Deep vein thrombosis

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Symptoms classically affect a leg and typically develop over hours or days,{{cite journal | vauthors = Ratchford EV, Evans NS | title = Approach to lower extremity edema | journal = Current Treatment Options in Cardiovascular Medicine | volume = 19 | issue = 3 | pages = 16 | date = March 2017 | pmid = 28290004 | doi = 10.1007/s11936-017-0518-6 | s2cid = 34922038 }} though they can develop suddenly or over a matter of weeks.{{cite journal | vauthors = Moll S | title = A clinical perspective of venous thromboembolism | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 28 | issue = 3 | pages = 373–79 | date = March 2008 | pmid = 18296592 | doi = 10.1161/ATVBAHA.108.162818 | doi-access = free}} The legs are primarily affected, with 4–10% of DVT occurring in the arms. Despite the signs and symptoms being highly variable, the typical symptoms are pain, swelling, and redness. However, these symptoms might not manifest in the lower limbs of those unable to walk.{{cite journal | vauthors = Lloyd NS, Douketis JD, Moinuddin I, Lim W, Crowther MA | title = Anticoagulant prophylaxis to prevent asymptomatic deep vein thrombosis in hospitalized medical patients: a systematic review and meta-analysis | journal = Journal of Thrombosis and Haemostasis | volume = 6 | issue = 3 | pages = 405–14 | date = March 2008 | pmid = 18031292 | doi = 10.1111/j.1538-7836.2007.02847.x | doi-access=free }} In those who are able to walk, DVT can reduce one's ability to do so.{{cite journal | vauthors = Conklin P, Soares GM, Dubel GJ, Ahn SH, Murphy TP | title = Acute deep vein thrombosis (DVT): evolving treatment strategies and endovascular therapy | journal = Medicine and Health, Rhode Island | volume = 92 | issue = 12 | pages = 394–97 | date = December 2009 | pmid = 20066826 | url = http://rimed.org/medhealthri/2009-12/2009-12-394.pdf | url-status = live | archive-url = https://web.archive.org/web/20130206233314/http://rimed.org/medhealthri/2009-12/2009-12-394.pdf | archive-date = 6 February 2013 }} The pain can be described as throbbing and can worsen with weight-bearing, prompting one to bear more weight with the unaffected leg.{{cite journal | vauthors = Stubbs MJ, Mouyis M, Thomas M | title = Deep vein thrombosis | journal = BMJ | volume = 360 | issue = 8142 | pages = k351 | date = February 2018 | pmid = 29472180 | doi = 10.1136/bmj.k351 | s2cid = 3454404 }}

Additional signs and symptoms include tenderness, pitting edema (see image), dilation of surface veins, warmth, discoloration, a "pulling sensation", and even cyanosis (a blue or purplish discoloration) with fever. DVT can also exist without causing any symptoms. Signs and symptoms help in determining the likelihood of DVT, but they are not used alone for diagnosis.

At times, DVT can cause symptoms in both arms or both legs, as with bilateral DVT.{{cite journal |vauthors=Casella IB, Bosch MA, Sabbag CR |title=Incidence and risk factors for bilateral deep venous thrombosis of the lower limbs |journal=Angiology |volume=60 |issue=1 |pages=99–103 |date=2009 |pmid=18504268 |doi=10.1177/0003319708316897|s2cid=30043830 }} Rarely, a clot in the inferior vena cava can cause both legs to swell.{{cite journal | vauthors = Kennedy D, Setnik G, Li J | title = Physical examination findings in deep venous thrombosis | journal = Emergency Medicine Clinics of North America | volume = 19 | issue = 4 | pages = 869–76 | date = November 2001 | pmid = 11762276 | doi = 10.1016/s0733-8627(05)70223-6 | url = https://www.researchgate.net/publication/11596077}} Superficial vein thrombosis, also known as superficial thrombophlebitis, is the formation of a blood clot (thrombus) in a vein close to the skin. It can co-occur with DVT and can be felt as a "palpable cord". Migratory thrombophlebitis (Trousseau's syndrome) is a noted finding in those with pancreatic cancer and is associated with DVT.{{cite journal | vauthors = Campello E, Ilich A, Simioni P, Key NS | title = The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues | journal = British Journal of Cancer | volume = 121 | issue = 5 | pages = 359–71 | date = August 2019 | pmid = 31327867 | pmc = 6738049 | doi = 10.1038/s41416-019-0510-x }}

A pulmonary embolism (PE) occurs when a blood clot from a deep vein (a DVT) detaches from a vein (embolizes), travels through the right side of the heart, and becomes lodged as an embolus in a pulmonary artery that supplies deoxygenated blood to the lungs for oxygenation. Up to one-fourth of PE cases are thought to result in sudden death. When not fatal, PE can cause symptoms such as sudden onset shortness of breath or chest pain, coughing up blood (hemoptysis), and fainting (syncope). The chest pain can be pleuritic (worsened by deep breaths){{cite journal |vauthors=Doherty S |title=Pulmonary embolism: an update |journal=Australian Family Physician |volume=46 |issue=11 |pages=816–20 |date=November 2017 |pmid=29101916 |url=https://www.racgp.org.au/afp/2017/november/pulmonary-embolism/}} and can vary based upon where the embolus is lodged in the lungs. An estimated 30–50% of those with PE have detectable DVT by compression ultrasound.

A rare and massive DVT that causes significant obstruction and discoloration (including cyanosis) is phlegmasia cerulea dolens.{{cite journal | vauthors = Chinsakchai K, Ten Duis K, Moll FL, de Borst GJ | title = Trends in management of phlegmasia cerulea dolens | journal = Vascular and Endovascular Surgery | volume = 45 | issue = 1 | pages = 5–14 | date = January 2011 | pmid = 21193462 | doi = 10.1177/1538574410388309 | s2cid = 64951 }}{{cite journal | vauthors = ((Turner DPB)) | title = A case of phlegmasia cerulea dolens | journal = British Medical Journal | volume = 2 | issue = 4795 | pages = 1183–85 | date = November 1952 | pmid = 12997687 | pmc = 2021962 | doi = 10.1136/bmj.2.4795.1183 }} It is life-threatening, limb-threatening, and carries a risk of venous gangrene.{{cite journal | vauthors = Aggarwal DG, Bhojraj SS, Behrainwalla AA, Jani CK, Mehta SS | title = Phlegmasia cerulea dolens following heparin-induced thrombocytopenia | journal = Indian Journal of Critical Care Medicine | volume = 22 | issue = 1 | pages = 51–52 | date = January 2018 | pmid = 29422736 | pmc = 5793026 | doi = 10.4103/ijccm.IJCCM_183_16 | doi-access = free }} Phlegmasia cerulea dolens can occur in the arm but more commonly affects the leg.{{cite web |url=http://www.acssurgery.com/acs/chapters/ch0606.htm |title=Management of venous thromboembolism | vauthors = Owings JT |year=2005 |work=ACS Surgery |publisher=American College of Surgeons |access-date=16 January 2012 |url-status=dead |archive-url=https://web.archive.org/web/20120127090223/http://www.acssurgery.com/acs/chapters/ch0606.htm |archive-date=27 January 2012 }}{{cite journal | vauthors = Mazer BA, Hughes PG | title = Pacemaker-associated phlegmasia cerulea dolens treated with catheter-directed thrombolysis | journal = Clinical Practice and Cases in Emergency Medicine | volume = 2 | issue = 4 | pages = 316–19 | date = November 2018 | pmid = 30443615 | pmc = 6230348 | doi = 10.5811/cpcem.2018.8.39444 }} If found in the setting of acute compartment syndrome, an urgent fasciotomy is warranted to protect the limb.{{cite journal | vauthors = Abdul W, Hickey B, Wilson C | title = Lower extremity compartment syndrome in the setting of iliofemoral deep vein thrombosis, phlegmasia cerulea dolens and factor VII deficiency | journal = BMJ Case Reports | volume = 2016 | date = April 2016 | pages = bcr2016215078 | pmid = 27113791 | pmc = 4854131 | doi = 10.1136/bcr-2016-215078 }} Superior vena cava syndrome is a rare complication of arm DVT.

DVT is thought to be able to cause a stroke in the presence of a heart defect. This is called a paradoxical embolism because the clot abnormally travels from the pulmonary circuit to the systemic circuit while inside the heart. The defect of a patent foramen ovale is thought to allow clots to travel through the interatrial septum from the right atrium into the left atrium.{{cite journal | vauthors = Zietz A, Sutter R, De Marchis GM | title = Deep vein thrombosis and pulmonary embolism among patients with a cryptogenic stroke linked to patent foramen ovale – a review of the literature | journal = Frontiers in Neurology | volume = 11 | issue = | pages = 336 | date = 2020 | pmid = 32431661 | pmc = 7214694 | doi = 10.3389/fneur.2020.00336 | doi-access = free }}{{cite journal | vauthors = Pristipino C, Sievert H, D'Ascenzo F, Mas JL, Meier B, Scacciatella P, Hildick-Smith D, Gaita F, Toni D, Kyrle P, Thomson J, Derumeaux G, Onorato E, Sibbing D, Germonpré P, Berti S, Chessa M, Bedogni F, Dudek D, Hornung M, Zamorano J | display-authors = 6| title = European position paper on the management of patients with patent foramen ovale. General approach and left circulation thromboembolism | journal = EuroIntervention | volume = 14 | issue = 13 | pages = 1389–402 | date = January 2019 | pmid = 30141306 | doi = 10.4244/EIJ-D-18-00622 | doi-access = free| hdl = 2318/1691212 | hdl-access = free }}

File:SaddlePE.PNG|alt=A computed tomography image depicting PE in the pulmonary arteries|A CT image with red arrows indicating PE (grey) in the pulmonary arteries (white)

File:PCD2016.jpg|alt=Image showing marked discoloration of a leg with phlegmasia cerulea dolens|A case of phlegmasia cerulea dolens in the left leg

Patent-foramen-ovale-en.png|alt=A drawing depicting a patent foramen ovale|A depiction of a patent foramen ovale

In most suspected cases, DVT is ruled out after evaluation.{{cite journal | vauthors = Bates SM, Jaeschke R, Stevens SM, Goodacre S, Wells PS, Stevenson MD, Kearon C, Schunemann HJ, Crowther M, Pauker SG, Makdissi R, Guyatt GH | display-authors = 6 | title = Diagnosis of DVT: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines | journal = Chest | volume = 141 | issue = 2 Suppl | pages = e351S–e418S | date = February 2012 | pmid = 22315267 | pmc = 3278048 | doi = 10.1378/chest.11-2299 }} Cellulitis is a frequent mimic of DVT, with its triad of pain, swelling, and redness. Symptoms concerning for DVT are more often due to other causes, including cellulitis, ruptured Baker's cyst, hematoma, lymphedema, and chronic venous insufficiency. Other differential diagnoses include tumors, venous or arterial aneurysms, connective tissue disorders,{{cite journal | vauthors = Arumilli BR, Lenin Babu V, Paul AS | title = Painful swollen leg – think beyond deep vein thrombosis or Baker's cyst | journal = World Journal of Surgical Oncology | volume = 6 | pages = 6 | date = January 2008 | pmid = 18205917 | pmc = 2244628 | doi = 10.1186/1477-7819-6-6 | doi-access = free }} superficial vein thrombosis, muscle vein thrombosis, and varicose veins.{{cite journal | vauthors = Bauersachs RM | title = Clinical presentation of deep vein thrombosis and pulmonary embolism | journal = Best Practice & Research Clinical Haematology | volume = 25 | issue = 3 | pages = 243–51 | date = September 2012 | pmid = 22959541 | doi = 10.1016/j.beha.2012.07.004 | doi-access = free}}

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DVT and PE are the two manifestations of the cardiovascular disease venous thromboembolism (VTE). VTE can occur as DVT only, DVT with PE, or PE only. About two-thirds of VTE manifests as DVT only, with one-third manifesting as PE with or without DVT. VTE, along with superficial vein thrombosis, are common types of venous thrombosis.{{cite journal | vauthors = Abbattista M, Capecchi M, Martinelli I | title = Treatment of unusual thrombotic manifestations | journal = Blood | volume = 135 | issue = 5 | pages = 326–34 | date = January 2020 | pmid = 31917405 | doi = 10.1182/blood.2019000918 | doi-access = free}}

DVT is classified as acute when the clots are developing or have recently developed, whereas chronic DVT persists more than 28 days. Differences between these two types of DVT can be seen with ultrasound.{{cite journal | vauthors = Karande GY, Hedgire SS, Sanchez Y, Baliyan V, Mishra V, Ganguli S, Prabhakar AM | display-authors = 6 | title = Advanced imaging in acute and chronic deep vein thrombosis | journal = Cardiovascular Diagnosis and Therapy | volume = 6 | issue = 6 | pages = 493–507 | date = December 2016 | pmid = 28123971 | pmc = 5220209 | doi = 10.21037/cdt.2016.12.06 | doi-access = free }} An episode of VTE after an initial one is classified as recurrent.{{Cite journal |last= |date=2019-10-31 |title=Significant risk of another thrombosis remains if anticoagulation is stopped |url=https://evidence.nihr.ac.uk/alert/significant-risk-of-another-thrombosis-remains-if-anticoagulation-is-stopped- |journal=NIHR Evidence |type=Plain English summary |doi=10.3310/signal-000830|s2cid=242392407 }} Bilateral DVT refers to clots in both limbs while unilateral means only a single limb is affected.{{cite journal | vauthors = Casella IB, Bosch MA, Sabbag CR | title = Incidence and risk factors for bilateral deep venous thrombosis of the lower limbs | journal = Angiology | volume = 60 | issue = 1 | pages = 99–103 | year = 2009 | pmid = 18504268 | doi = 10.1177/0003319708316897 | s2cid = 30043830 }}

DVT in a leg above the knee is termed proximal DVT (proximal). DVT in a leg below the knee is termed distal DVT (distal), also called calf DVT when affecting the calf,{{cite journal | vauthors = Johnson SA, Stevens SM, Woller SC, Lake E, Donadini M, Cheng J, Labarère J, Douketis JD | display-authors = 6 | title = Risk of deep vein thrombosis following a single negative whole-leg compression ultrasound: a systematic review and meta-analysis | journal = JAMA | volume = 303 | issue = 5 | pages = 438–45 | date = February 2010 | pmid = 20124539 | doi = 10.1001/jama.2010.43 | doi-access = free }}{{cite journal | vauthors = Scarvelis D, Wells PS | title = Diagnosis and treatment of deep-vein thrombosis | journal = Canadian Medical Association Journal | volume = 175 | issue = 9 | pages = 1087–92 | date = October 2006 | pmid = 17060659 | pmc = 1609160 | doi = 10.1503/cmaj.060366 }}
{{cite journal | vauthors = Scarvelis D, Wells PS | title = Correction: Diagnosis and treatment of deep-vein thrombosis | journal = Canadian Medical Association Journal | volume = 177 | issue = 11 | pages = 1392 | date = November 2007 | pmc=2072980| doi = 10.1503/cmaj.071550 | pmid = }} and has limited clinical significance compared to proximal DVT.{{cite journal | vauthors = Galanaud JP, Bosson JL, Quéré I | title = Risk factors and early outcomes of patients with symptomatic distal vs. proximal deep-vein thrombosis | journal = Current Opinion in Pulmonary Medicine | volume = 17 | issue = 5 | pages = 387–91 | date = September 2011 | pmid = 21832920 | doi = 10.1097/MCP.0b013e328349a9e3 | s2cid = 33536953 }} Calf DVT makes up about half of DVTs.{{cite journal | vauthors = Utter GH, Dhillon TS, Salcedo ES, Shouldice DJ, Reynolds CL, Humphries MD, White RH | display-authors = 6 | title = Therapeutic anticoagulation for isolated calf deep vein thrombosis | journal = JAMA Surgery | volume = 151 | issue = 9 | pages = e161770 | date = September 2016 | pmid = 27437827 | doi = 10.1001/jamasurg.2016.1770 | doi-access = free}} Iliofemoral DVT is described as involving either the iliac, or common femoral vein;{{cite journal | vauthors = Comerota AJ, Kearon C, Gu CS, Julian JA, Goldhaber SZ, Kahn SR, Jaff MR, Razavi MK, Kindzelski AL, Bashir R, Patel P, Sharafuddin M, Sichlau MJ, Saad WE, Assi Z, Hofmann LV, Kennedy M, Vedantham S |display-authors = 6 | title = Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis | journal = Circulation | volume = 139 | issue = 9 | pages = 1162–73 | date = February 2019 | pmid = 30586751 | doi = 10.1161/CIRCULATIONAHA.118.037425 |pmc = 6389417 | doi-access = free}} elsewhere, it has been defined as involving at a minimum the common iliac vein, which is near the top of the pelvis.{{cite journal | vauthors = Tran HA, Gibbs H, Merriman E, Curnow JL, Young L, Bennett A, Tan C, Chunilal SD, Ward CM, Baker R, Nandurkar H | display-authors = 6 |title = New guidelines from the Thrombosis and Haemostasis Society of Australia and New Zealand for the diagnosis and management of venous thromboembolism | journal = The Medical Journal of Australia | volume = 210 | issue = 5 | pages = 227–35 | date = March 2019 | pmid = 30739331 | doi = 10.5694/mja2.50004 | hdl = 11343/285435 | s2cid = 73433650 | hdl-access = free }}

DVT can be classified into provoked and unprovoked categories. For example, DVT that occurs in association with cancer or surgery can be classified as provoked. However, the European Society of Cardiology in 2019 urged for this dichotomy to be abandoned to encourage more personalized risk assessments for recurrent VTE.{{cite journal | vauthors = Ageno W, Farjat A, Haas S, Weitz JI, Goldhaber SZ, ((Turpie AGG)), Goto S, Angchaisuksiri P, Dalsgaard Nielsen J, Kayani G, Schellong S, Bounameaux H, Mantovani LG, Prandoni P, Kakkar AK | display-authors = 6 | title = Provoked versus unprovoked venous thromboembolism: Findings from GARFIELD-VTE | journal = Research and Practice in Thrombosis and Haemostasis | volume = 5 | issue = 2 | pages = 326–41 | date = February 2021 | pmid = 33733032 | pmc = 7938631 | doi = 10.1002/rth2.12482 }} The distinction between these categories is not always clear.{{Cite web| vauthors = Piazza G |date=19 October 2019|title=Clot Chronicles: unprovoked vs. provoked VTE|url=https://natfonline.org/2019/10/clot-chronicles-unprovoked-vs-provoked-vte/|url-status=live|access-date=8 May 2021|website=North American Thrombosis Forum|archive-url=https://web.archive.org/web/20210508190314/https://natfonline.org/2019/10/clot-chronicles-unprovoked-vs-provoked-vte/ |archive-date=8 May 2021 }}

File:Blausen 0290 DeepVeinThrombosis.png

Traditionally, the three factors of Virchow's triad—venous stasis, hypercoagulability, and changes in the endothelial blood vessel lining—contribute to VTE and were used to explain its formation.{{cite journal | vauthors = Najem MY, Couturaud F, Lemarié CA | title = Cytokine and chemokine regulation of venous thromboembolism | journal = Journal of Thrombosis and Haemostasis | volume = 18 | issue = 5 | pages = 1009–19 | date = May 2020 | pmid = 32020753 | doi = 10.1111/jth.14759 | s2cid = 211037046 | url = | doi-access = free }} More recently, inflammation has been identified as playing a clear causal role.{{cite journal |vauthors=Borgel D, Bianchini E, Lasne D, Pascreau T, Saller F |title=Inflammation in deep vein thrombosis: a therapeutic target? |journal=Hematology |volume=24 |issue=1 |pages=742–50 |date=December 2019 |pmid=31736432 |doi=10.1080/16078454.2019.1687144 | doi-access = free}} Other related causes include activation of immune system components, the state of microparticles in the blood, the concentration of oxygen, and possible platelet activation. Various risk factors contribute to VTE, including genetic and environmental factors, though many with multiple risk factors never develop it.{{cite journal | vauthors = Kujovich JL | title = Factor V Leiden thrombophilia | journal = Genetics in Medicine | volume = 13 | issue = 1 | pages = 1–16 | date = January 2011 | pmid = 21116184 | doi = 10.1097/GIM.0b013e3181faa0f2 |doi-access=free}}

Acquired risk factors include the strong risk factor of older age, which alters blood composition to favor clotting.{{cite journal | vauthors = Tzoran I, Hoffman R, Monreal M | title = Hemostasis and thrombosis in the oldest old | journal = Seminars in Thrombosis and Hemostasis | volume = 44 | issue = 7 | pages = 624–31 | date = October 2018 | pmid = 29920621 | doi = 10.1055/s-0038-1657779 | s2cid = 49313388 }} Previous VTE, particularly unprovoked VTE, is a strong risk factor. A leftover clot from a prior DVT increases the risk of a subsequent DVT.{{cite journal |vauthors=Previtali E, Bucciarelli P, Passamonti SM, Martinelli I |title=Risk factors for venous and arterial thrombosis |journal=Blood Transfusion |volume=9 |issue=2 |pages=120–38 |date=April 2011 |pmid=21084000 |pmc=3096855 |doi=10.2450/2010.0066-10}} Major surgery and trauma increase risk because of tissue factor from outside the vascular system entering the blood. Minor injuries, lower limb amputation,{{cite journal | vauthors = Wong P, Baglin T | title = Epidemiology, risk factors and sequelae of venous thromboembolism | journal = Phlebology | volume = 27 | issue = Suppl 2 | pages = 2–11 | year = 2012 | pmid = 22457300 | doi = 10.1258/phleb.2012.012S31 | s2cid = 13564168 }} hip fracture, and long bone fractures are also risks. In orthopedic surgery, venous stasis can be temporarily provoked by a cessation of blood flow as part of the procedure. Inactivity and immobilization contribute to venous stasis, as with orthopedic casts,{{cite journal | vauthors = Rosendaal FR, Reitsma PH | title = Genetics of venous thrombosis | journal = Journal of Thrombosis and Haemostasis | volume = 7 | issue = Suppl 1 | pages = 301–04 | date = July 2009 | pmid = 19630821 | doi = 10.1111/j.1538-7836.2009.03394.x | doi-access=free }} paralysis, sitting, long-haul travel, bed rest, hospitalization,{{cite journal | vauthors = Martinelli I, Bucciarelli P, Mannucci PM | title = Thrombotic risk factors: basic pathophysiology | journal = Critical Care Medicine | volume = 38 | issue = 2 Suppl | pages = S3-9 | date = February 2010 | pmid = 20083911 | doi = 10.1097/CCM.0b013e3181c9cbd9 | s2cid = 34486553 }} catatonia,{{cite journal | vauthors = Ishida T, Sakurai H, Watanabe K, Iwashita S, Mimura M, Uchida H | title = Incidence of deep vein thrombosis in catatonic patients: A chart review | journal = Psychiatry Research | volume = 241 | issue = | pages = 61–5 | date = July 2016 | pmid = 27156025 | doi = 10.1016/j.psychres.2016.04.105| s2cid = 207452463 }} and in survivors of acute stroke.{{cite journal | vauthors = Winstein CJ, Stein J, Arena R, Bates B, Cherney LR, Cramer SC, Deruyter F, Eng JJ, Fisher B, Harvey RL, Lang CE, MacKay-Lyons M, Ottenbacher KJ, Pugh S, Reeves MJ, Richards LG, Stiers W, Zorowitz RD | display-authors = 6 | title = Guidelines for adult stroke rehabilitation and recovery: a guideline for healthcare professionals from the American Heart Association/American Stroke Association | journal = Stroke | volume = 47 | issue = 6 | pages = e98–e169 | date = June 2016 | pmid = 27145936 | doi = 10.1161/STR.0000000000000098 | doi-access = free }} Conditions that involve compromised blood flow in the veins are May–Thurner syndrome, where a vein of the pelvis is compressed, and venous thoracic outlet syndrome, which includes Paget–Schroetter syndrome, where compression occurs near the base of the neck.{{cite journal | vauthors = Béliard S, Feuvrier D, Ducroux E, Salomon du Mont L | title = May Thurner syndrome revealed by left calf venous claudication during running, a case report | journal = BMC Sports Science, Medicine & Rehabilitation | volume = 10 | pages = 3 | date = 2018 | pmid = 29435334 | pmc = 5796503 | doi = 10.1186/s13102-018-0092-6 | doi-access = free }}{{cite journal | vauthors = Hangge P, Rotellini-Coltvet L, Deipolyi AR, Albadawi H, Oklu R | title = Paget-Schroetter syndrome: treatment of venous thrombosis and outcomes | journal = Cardiovascular Diagnosis and Therapy | volume = 7 | issue = Suppl 3 | pages = S285–90 | date = December 2017 | pmid = 29399532 | pmc = 5778512 | doi = 10.21037/cdt.2017.08.15 | doi-access = free }}{{cite journal | vauthors = Jabri H, Mukherjee S, Sanghavi D, Chalise S | title = Bilateral upper extremity DVT in a 43-year-old man: is it thoracic outlet syndrome?! | journal = Case Reports in Medicine | volume = 2014 | pages = 758010 | date = 2014 | pmid = 25140182 | pmc = 4129160 | doi = 10.1155/2014/758010 | doi-access = free }}

Infections, including sepsis, COVID-19, HIV, and active tuberculosis, increase risk.{{cite journal | vauthors = Beristain-Covarrubias N, Perez-Toledo M, Thomas MR, Henderson IR, Watson SP, Cunningham AF | title = Understanding infection-induced thrombosis: lessons learned from animal models | journal = Frontiers in Immunology | volume = 10 | pages = 2569 | date = 2019 | pmid = 31749809 | pmc = 6848062 | doi = 10.3389/fimmu.2019.02569 | doi-access = free }}{{cite journal | vauthors = Kaplan D, Casper TC, Elliott CG, Men S, Pendleton RC, Kraiss LW, Weyrich AS, Grissom CK, Zimmerman GA, Rondina MT | display-authors=6 | title = VTE incidence and risk factors in patients with severe sepsis and septic shock | journal = Chest | volume = 148 | issue = 5 | pages = 1224–30 | date = November 2015 | pmid = 26111103 | pmc = 4631038 | doi = 10.1378/chest.15-0287 }}{{cite journal |vauthors=Jiménez D, García-Sanchez A, Rali P, Muriel A, Bikdeli B, Ruiz-Artacho P, Le Mao R, Rodríguez C, Hunt BJ, Monreal M | display-authors=6 |title=Incidence of VTE and bleeding among hospitalized patients with coronavirus disease 2019: a systematic review and meta-analysis |journal=Chest |volume=159 |issue=3 |pages=1182–96 |date=March 2021 |pmid=33217420 |pmc=7670889 |doi=10.1016/j.chest.2020.11.005 }}{{cite journal | vauthors = Rokx C, Borjas Howard JF, Smit C, Wit FW, Pieterman ED, Reiss P, Cannegieter SC, Lijfering WM, Meijer K, Bierman W, Tichelaar V, ((Rijnders BJA)) | display-authors=6 | title = Risk of recurrent venous thromboembolism in patients with HIV infection: A nationwide cohort study | journal = PLOS Medicine | volume = 17 | issue = 5 | pages = e1003101 | date = May 2020 | pmid = 32407386 | pmc = 7224453 | doi = 10.1371/journal.pmed.1003101 | doi-access=free }}{{cite journal |vauthors=Danwang C, Bigna JJ, Awana AP, Nzalie RN, Robert A |title=Global epidemiology of venous thromboembolism in people with active tuberculosis: a systematic review and meta-analysis |journal=Journal of Thrombosis and Thrombolysis |volume=51 |issue=2 |pages=502–12 |date=February 2021 |pmid=32627124 |doi=10.1007/s11239-020-02211-7 |s2cid=220337035 |url=}} Chronic inflammatory diseases and some autoimmune diseases,{{cite journal | vauthors = Borjas-Howard JF, Leeuw K, Rutgers A, Meijer K, ((Tichelaar VYIG)) | title = Risk of recurrent venous thromboembolism in autoimmune diseases: a systematic review of the literature | journal = Seminars in Thrombosis and Hemostasis | volume = 45 | issue = 2 | pages = 141–49 | date = March 2019 | pmid = 29954011 | doi = 10.1055/s-0038-1661387 | s2cid = 49606106 | url = https://pure.rug.nl/ws/files/63682337/s_0038_1661387.pdf }} such as inflammatory bowel disease,{{cite journal | vauthors = Branchford BR, Carpenter SL | title = The role of inflammation in venous thromboembolism | journal = Frontiers in Pediatrics | volume = 6 | issue = | pages = 142 | date = 2018 | pmid = 29876337 | pmc = 5974100 | doi = 10.3389/fped.2018.00142| doi-access = free }} systemic sclerosis,{{cite journal | vauthors = Henke PK, Kahn SR, Pannucci CJ, Secemksy EA, Evans NS, Khorana AA, Creager MA, Pradhan AD | display-authors = 6 | title = Call to action to prevent venous thromboembolism in hospitalized patients: a policy statement from the American Heart Association | journal = Circulation | volume = 141 | issue = 24 | pages = e914–31 | date = June 2020 | pmid = 32375490 | doi = 10.1161/CIR.0000000000000769 | doi-access = free}} Behçet's syndrome,{{cite journal | vauthors = Becatti M, Emmi G, Bettiol A, Silvestri E, Di Scala G, Taddei N, Prisco D, Fiorillo C | title = Behçet's syndrome as a tool to dissect the mechanisms of thrombo-inflammation: clinical and pathogenetic aspects | journal = Clinical and Experimental Immunology | volume = 195 | issue = 3 | pages = 322–33 | date = March 2019 | pmid = 30472725 | pmc = 6378375 | doi = 10.1111/cei.13243 | doi-access = free}} primary antiphospholipid syndrome, and systemic lupus erythematosus (SLE){{cite journal | vauthors = Knight CL, Nelson-Piercy C | title = Management of systemic lupus erythematosus during pregnancy: challenges and solutions | journal = Open Access Rheumatology: Research and Reviews| volume = 9 | pages = 37–53 | date = 2017 | pmid = 28331377 | pmc = 5354538 | doi = 10.2147/OARRR.S87828 | doi-access = free }} increase risk. SLE itself is frequently associated with secondary antiphospholipid syndrome.{{cite journal | vauthors = Svenungsson E, Antovic A | title = The antiphospholipid syndrome – often overlooked cause of vascular occlusions? | journal = Journal of Internal Medicine | volume = 287| issue = 4| pages = 349–72| date = January 2020 | pmid = 31957081 | doi = 10.1111/joim.13022 | doi-access = free}}

Cancer can grow in and around veins, causing venous stasis, and can also stimulate increased levels of tissue factor.{{cite journal | vauthors = Falanga A, Russo L, Milesi V, Vignoli A | title = Mechanisms and risk factors of thrombosis in cancer | journal = Critical Reviews in Oncology/Hematology | volume = 118 | pages = 79–83 | date = October 2017 | pmid = 28917273 | doi = 10.1016/j.critrevonc.2017.08.003 }} Cancers of the blood, lung, pancreas, brain, stomach, and bowel are associated with high VTE risk.{{cite journal | vauthors = Fernandes CJ, ((Morinaga LTK)), Alves JL, Castro MA, Calderaro D, ((Jardim CVP)), Souza R | display-authors= 6 | title = Cancer-associated thrombosis: the when, how and why | journal = European Respiratory Review | volume = 28 | issue = 151 | date = March 2019 | page= 180119 | pmid = 30918022 | doi = 10.1183/16000617.0119-2018 | pmc= 9488553 | doi-access = free}} Solid tumors such as adenocarcinomas can contribute to both VTE and disseminated intravascular coagulation. In severe cases, this can lead to simultaneous clotting and bleeding.{{cite journal | vauthors = Levi M, Scully M | title = How I treat disseminated intravascular coagulation | journal = Blood | volume = 131 | issue = 8 | pages = 845–54 | date = February 2018 | pmid = 29255070 | doi = 10.1182/blood-2017-10-804096 | doi-access = free}} Chemotherapy treatment also increases risk.{{cite journal|vauthors=Bovill EG, van der Vliet A|year=2011|title=Venous valvular stasis-associated hypoxia and thrombosis: what is the link?|journal=Annual Review of Physiology|volume=73|pages=527–45|doi=10.1146/annurev-physiol-012110-142305|pmid=21034220}} Obesity increases the potential of blood to clot, as does pregnancy. In the postpartum, placental tearing releases substances that favor clotting. Oral contraceptives{{efn|Third-generation combined oral contraceptives (COCs) have an approximate two to three times higher risk than second-generation COCs. Progestogen-only pill use is not associated with increased VTE risk.{{cite journal | vauthors = Mantha S, Karp R, Raghavan V, Terrin N, Bauer KA, Zwicker JI | title = Assessing the risk of venous thromboembolic events in women taking progestin-only contraception: a meta-analysis | journal = BMJ | volume = 345 | issue = 7872 | pages = e4944 | date = August 2012 | pmid = 22872710 | pmc = 3413580 | doi = 10.1136/bmj.e4944 }}}} and hormonal replacement therapy increase the risk through a variety of mechanisms, including altered blood coagulation protein levels and reduced fibrinolysis.{{cite journal | vauthors = Reitsma PH, Versteeg HH, Middeldorp S | title = Mechanistic view of risk factors for venous thromboembolism | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 32 | issue = 3 | pages = 563–68 | date = March 2012 | pmid = 22345594 | doi = 10.1161/ATVBAHA.111.242818 | doi-access = free }}

File:Coagulation in vivo.png system, often described as a "cascade", includes a group of proteins that regulate clotting. DVT risk can be altered by abnormalities in the cascade. The regulators, antithrombin (ᾳTHR) and activated protein C (APC), are shown in green above the clotting factors they affect.|alt=Imagine showing the coagulation, which includes a group of proteins that regulate clots. DVT risk can be altered by abnormalities in the cascade.]]

Dozens of genetic risk factors have been identified, and they account for approximately 50 to 60% of the variability in VTE rates. As such, family history of VTE is a risk factor for a first VTE. Factor V Leiden, which makes factor V resistant to inactivation by activated protein C,{{cite journal | vauthors = Shaheen K, Alraies MC, Alraiyes AH, Christie R | title = Factor V Leiden: how great is the risk of venous thromboembolism? | journal = Cleveland Clinic Journal of Medicine | volume = 79 | issue = 4 | pages = 265–72 | date = April 2012 | pmid = 22473726 | doi = 10.3949/ccjm.79a.11072 | s2cid = 23139811 | url = https://www.ccjm.org/content/79/4/265.long | url-access = registration | doi-access = free }} mildly increases VTE risk by about three times. Deficiencies of three proteins that normally prevent blood from clotting—protein C, protein S, and antithrombin—contribute to VTE. These deficiencies in antithrombin, protein C, and protein S{{efn|Type I}} are rare but strong, or moderately strong, risk factors. They increase risk by about 10 times.{{cite journal | vauthors = Varga EA, Kujovich JL | title = Management of inherited thrombophilia: guide for genetics professionals | journal = Clinical Genetics | volume = 81 | issue = 1 | pages = 7–17 | date = January 2012 | pmid = 21707594 | doi = 10.1111/j.1399-0004.2011.01746.x | s2cid = 9305488 }} Having a non-O blood type roughly doubles VTE risk. Non-O blood type is common globally, making it an important risk factor.{{cite journal | vauthors = Dentali F, Sironi AP, Ageno W, Turato S, Bonfanti C, Frattini F, Crestani S, Franchini M | display-authors = 6 | title = Non-O blood type is the commonest genetic risk factor for VTE: results from a meta-analysis of the literature | journal = Seminars in Thrombosis and Hemostasis | volume = 38 | issue = 5 | pages = 535–48 | date = July 2012 | pmid = 22740183 | doi = 10.1055/s-0032-1315758 | s2cid = 5203474 }} Individuals without O blood type have higher blood levels of von Willebrand factor and factor VIII than those with O blood type, increasing the likelihood of clotting. Those homozygous for the common fibrinogen gamma gene variant rs2066865 have about a 1.6 times higher risk of VTE.{{cite journal | vauthors = Paulsen B, Skille H, Smith EN, Hveem K, Gabrielsen ME, Brækkan SK, Rosendaal FR, Frazer KA, Gran OV, Hansen JB | display-authors=6 | title = Fibrinogen gamma gene rs2066865 and risk of cancer-related venous thromboembolism | journal = Haematologica | volume = 105| issue = 7| pages = 1963–68| date = October 2019 | pmid = 31582554 | doi = 10.3324/haematol.2019.224279 | pmc=7327659 | doi-access = free}} The genetic variant prothrombin G20210A, which increases prothrombin levels, increases risk by about 2.5 times. Additionally, approximately 5% of people have been identified with a background genetic risk comparable to the factor V Leiden and prothrombin G20210A mutations.

Blood alterations including dysfibrinogenemia, low free protein S, activated protein C resistance, homocystinuria,{{cite journal | vauthors = Eslamiyeh H, Ashrafzadeh F, Akhondian J, Beiraghi Toosi M | title = Homocystinuria: a rare disorder presenting as cerebral sinovenous thrombosis | journal = Iranian Journal of Child Neurology | volume = 9 | issue = 2 | pages = 53–57 | date = 2015 | pmid = 26221164 | pmc = 4515342 }} hyperhomocysteinemia, high fibrinogen levels, high factor IX levels, and high factor XI levels are associated with increased risk. Other associated conditions include heparin-induced thrombocytopenia, catastrophic antiphospholipid syndrome,{{cite journal | vauthors = Ortel TL, Erkan D, Kitchens CS | title = How I treat catastrophic thrombotic syndromes | journal = Blood | volume = 126 | issue = 11 | pages = 1285–93 | date = September 2015 | pmid = 26179082 | doi = 10.1182/blood-2014-09-551978 | doi-access = free }} paroxysmal nocturnal hemoglobinuria,{{cite journal | vauthors = Lazo-Langner A, Kovacs MJ, Hedley B, Al-Ani F, Keeney M, Louzada ML, Chin-Yee I | display-authors = 6 | title = Screening of patients with idiopathic venous thromboembolism for paroxysmal nocturnal hemoglobinuria clones | journal = Thrombosis Research | volume = 135 | issue = 6 | pages = 1107–09 | date = June 2015 | pmid = 25890452 | doi = 10.1016/j.thromres.2015.04.006 }} nephrotic syndrome,{{cite journal | vauthors = Lijfering WM, Rosendaal FR, Cannegieter SC | title = Risk factors for venous thrombosis – current understanding from an epidemiological point of view | journal = British Journal of Haematology | volume = 149 | issue = 6 | pages = 824–33 | date = June 2010 | pmid = 20456358 | doi = 10.1111/j.1365-2141.2010.08206.x | doi-access=free}} chronic kidney disease,{{cite journal | vauthors = Lu HY, Liao KM | title = Increased risk of deep vein thrombosis in end-stage renal disease patients | journal = BMC Nephrology | volume = 19 | issue = 1 | pages = 204 | date = August 2018 | pmid = 30115029 | pmc = 6097196 | doi = 10.1186/s12882-018-0989-z | doi-access = free }} polycythemia vera, essential thrombocythemia,{{cite journal |vauthors=Reikvam H, Tiu RV |title=Venous thromboembolism in patients with essential thrombocythemia and polycythemia vera |journal=Leukemia |volume=26 |issue=4 |pages=563–71 |date=April 2012 |pmid=22076463 |doi=10.1038/leu.2011.314 |url=|doi-access=free }} intravenous drug use,{{cite journal | vauthors = Kyrle PA, Eichinger S | title = Deep vein thrombosis | journal = Lancet | volume = 365 | issue = 9465 | pages = 1163–74 | date = 2005 | pmid = 15794972 | doi = 10.1016/S0140-6736(05)71880-8 | s2cid = 54379879 }} and smoking.{{efn|"It is important to note that smoking is not an independent risk factor, although it increases the risk for cancers and other comorbidities and works synergistically with other independent risk factors."{{cite journal |vauthors=McLendon K, Goyal A, Bansal P, Attia M |title=Deep venous thrombosis risk factors |location=Treasure Island, FL |journal=StatPearls [Internet] |year=2020 |pmid=29262230 |url=https://www.ncbi.nlm.nih.gov/books/NBK470215/}}}}

Some risk factors influence the location of DVT within the body. In isolated distal DVT, the profile of risk factors appears distinct from proximal DVT. Transient factors, such as surgery and immobilization, appear to dominate, whereas thrombophilias{{efn|The term 'thrombophilia' as used here applies to the five inherited abnormalities of antithrombin, protein C, protein S, factor V, and prothrombin, as is done elsewhere.{{cite journal | vauthors = Middeldorp S | title = Is thrombophilia testing useful? | journal = Hematology. American Society of Hematology. Education Program | volume = 2011 | issue = 1 | pages = 150–55 | year = 2011 | pmid = 22160027 | doi = 10.1182/asheducation-2011.1.150| doi-access = free }} These 5 genetic factors have been referred to as the classical thrombophilias.{{cite journal | vauthors = Zöller B, Svensson PJ, Dahlbäck B, Lind-Hallden C, Hallden C, Elf J | title = Genetic risk factors for venous thromboembolism | journal = Expert Review of Hematology | volume = 13 | issue = 9 | pages = 971–81 | date = September 2020 | pmid = 32731838 | doi = 10.1080/17474086.2020.1804354 | doi-access = free }}}} and age do not seem to increase risk.{{cite journal | vauthors = Palareti G, Schellong S | title = Isolated distal deep vein thrombosis: what we know and what we are doing | journal = Journal of Thrombosis and Haemostasis | volume = 10 | issue = 1 | pages = 11–19 | date = January 2012 | pmid = 22082302 | doi = 10.1111/j.1538-7836.2011.04564.x | doi-access=free }} Common risk factors for having an upper extremity DVT include having an existing foreign body (such as a central venous catheter, a pacemaker, or a triple-lumen PICC line), cancer, and recent surgery.{{cite journal | vauthors = Heil J, Miesbach W, Vogl T, Bechstein WO, Reinisch A | title = Deep vein thrombosis of the upper extremity | journal = Deutsches Ärzteblatt International | volume = 114 | issue = 14 | pages = 244–49 | date = April 2017 | pmid = 28446351 | pmc = 5415909 | doi = 10.3238/arztebl.2017.0244 }}

File:2136ab Lower Limb Veins Anterior Posterior.jpg

Blood has a natural tendency to clot when blood vessels are damaged (hemostasis) to minimize blood loss.{{cite journal | vauthors = Chapin JC, Hajjar KA | title = Fibrinolysis and the control of blood coagulation | journal = Blood Reviews | volume = 29 | issue = 1 | pages = 17–24 | date = January 2015 | pmid = 25294122 | pmc = 4314363 | doi = 10.1016/j.blre.2014.09.003 }} Clotting is activated by the coagulation cascade and the clearing of clots that are no longer needed is accomplished by the process of fibrinolysis. Reductions in fibrinolysis or increases in coagulation can increase the risk of DVT.

DVT often develops in the calf veins and "grows" in the direction of venous flow, towards the heart.{{cite journal | vauthors = Mukhopadhyay S, Johnson TA, Duru N, Buzza MS, Pawar NR, Sarkar R, Antalis TM | display-authors = 6 | title = Fibrinolysis and inflammation in venous thrombus resolution | journal = Frontiers in Immunology | volume = 10 | issue = | pages = 1348 | date = 2019 | pmid = 31258531 | pmc = 6587539 | doi = 10.3389/fimmu.2019.01348 | doi-access = free }}{{cite journal | vauthors = Chan WS, Spencer FA, Ginsberg JS | title = Anatomic distribution of deep vein thrombosis in pregnancy | journal = Canadian Medical Association Journal | volume = 182 | issue = 7 | pages = 657–60 | date = April 2010 | pmid = 20351121 | pmc = 2855912 | doi = 10.1503/cmaj.091692 }} DVT most frequently affects veins in the leg or pelvis{{cite journal | vauthors = Phillippe HM | title = Overview of venous thromboembolism | journal = The American Journal of Managed Care | volume = 23 | issue = 20 Suppl | pages = S376–82 | date = December 2017 | pmid = 29297660 | url = https://www.ajmc.com/journals/supplement/2017/direct-oral-anticoagulants-assessing-clinical-and-economic-value/overview-of-venous-thromboembolism | access-date = 30 January 2020 | archive-date = 30 January 2020 | archive-url = https://web.archive.org/web/20200130164826/https://www.ajmc.com/journals/supplement/2017/direct-oral-anticoagulants-assessing-clinical-and-economic-value/overview-of-venous-thromboembolism | url-status = dead }} including the popliteal vein (behind the knee), femoral vein (of the thigh), and iliac veins of the pelvis. Extensive lower-extremity DVT can even reach into the inferior vena cava (in the abdomen).{{cite web | vauthors = Kim ES, Bartholomew JR | url = http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/venous-thromboembolism/ | title = Venous thromboembolism | access-date = 15 February 2011 | work = Disease Management Project | publisher = Cleveland Clinic | url-status = live | archive-url = https://web.archive.org/web/20110223211240/http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/cardiology/venous%2Dthromboembolism/ | archive-date = 23 February 2011}} Upper extremity DVT most commonly affects the subclavian, axillary, and jugular veins.

The process of fibrinolysis, where DVT clots can be dissolved back into the blood, acts to temper the process of thrombus growth.{{cite journal | vauthors = Saha P, Humphries J, Modarai B, Mattock K, Waltham M, Evans CE, Ahmad A, Patel AS, Premaratne S, Lyons OT, Smith A | display-authors = 6 | title = Leukocytes and the natural history of deep vein thrombosis: current concepts and future directions | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 31 | issue = 3 | pages = 506–12 | date = March 2011 | pmid = 21325673 | pmc = 3079895 | doi = 10.1161/ATVBAHA.110.213405 }} This is the preferred process. Aside from the potentially deadly process of embolization, a clot can resolve through organization, which can damage the valves of veins, cause vein fibrosis, and result in non-compliant veins.{{cite journal | vauthors = Ro A, Kageyama N, Mukai T | title = Pathophysiology of venous thromboembolism with respect to the anatomical features of the deep veins of lower limbs: a review | journal = Annals of Vascular Diseases | volume = 10 | issue = 2 | pages = 99–106 | date = June 2017 | pmid = 29034034 | pmc = 5579784 | doi = 10.3400/avd.ra.17-00035 }} Organization of a thrombus into the vein can occur at the third stage of its pathological development, in which collagen becomes the characteristic component. The first pathological stage is marked by red blood cells, and the second is characterized by medium-textured fibrin.{{cite journal | vauthors = Nicklas JM, Gordon AE, Henke PK | title = Resolution of deep venous thrombosis: proposed immune paradigms | journal = International Journal of Molecular Sciences | volume = 21 | issue = 6 | date = March 2020 | page = 2080 | pmid = 32197363 | pmc = 7139924 | doi = 10.3390/ijms21062080 | doi-access = free }}

File:2134 Thoracic Upper Limb Veins.jpg and brachiocephalic veins (not pictured). The cephalic and basilic veins, however, are superficial veins.|alt=An image showing major arm veins]]

In arterial thrombosis, blood vessel wall damage is required, as it initiates coagulation,{{cite journal | vauthors = López JA, Chen J | title = Pathophysiology of venous thrombosis | journal = Thrombosis Research | volume = 123 | issue = Suppl 4 | pages = S30–34 | year = 2009 | pmid = 19303501 | doi = 10.1016/S0049-3848(09)70140-9 }} but clotting in the veins mostly occurs without any such mechanical damage. The beginning of venous thrombosis is thought to arise from "activation of endothelial cells, platelets, and leukocytes, with initiation of inflammation and formation of microparticles that trigger the coagulation system" via tissue factor. Vein wall inflammation is likely the inciting event. Importantly, the activated endothelium of veins interacts with circulating white blood cells (leukocytes). While leukocytes normally help prevent blood from clotting (as does normal endothelium), upon stimulation, leukocytes facilitate clotting. Neutrophils are recruited early in the process of venous thrombi formation. They release pro-coagulant granules and neutrophil extracellular traps (NETs) or their components, which play a role in venous thrombi formation. NET components are pro-thrombotic through both the intrinsic and extrinsic coagulation pathways.{{cite journal | vauthors = Thålin C, Hisada Y, Lundström S, Mackman N, Wallén H | title = Neutrophil extracellular traps: villains and targets in arterial, venous, and cancer-associated thrombosis | journal = Arteriosclerosis, Thrombosis, and Vascular Biology | volume = 39 | issue = 9 | pages = 1724–38 | date = September 2019 | pmid = 31315434 | pmc = 6703916 | doi = 10.1161/ATVBAHA.119.312463 }} NETs provide "a scaffold for adhesion" of platelets, red blood cells, and multiple factors that potentiate platelet activation.{{cite journal | vauthors = Laridan E, Martinod K, De Meyer SF | title = Neutrophil Extracellular Traps in Arterial and Venous Thrombosis | journal = Seminars in Thrombosis and Hemostasis | volume = 45 | issue = 1 | pages = 86–93 | date = February 2019 | pmid = 30634198 | doi = 10.1055/s-0038-1677040 | s2cid = 58594612 | url = https://lirias.kuleuven.be/handle/123456789/633069}} In addition to the pro-coagulant activities of neutrophils, multiple stimuli cause monocytes to release tissue factor.{{cite journal | vauthors = Swystun LL, Liaw PC | title = The role of leukocytes in thrombosis | journal = Blood | volume = 128 | issue = 6 | pages = 753–62 | date = August 2016 | pmid = 27354721 | doi = 10.1182/blood-2016-05-718114 | doi-access = free}} Monocytes are also recruited early in the process.

Tissue factor, via the tissue factor–factor VIIa complex, activates the extrinsic pathway of coagulation and leads to conversion of prothrombin to thrombin, followed by fibrin deposition. Fresh venous clots are red blood cell and fibrin rich. Platelets and white blood cells are also components. Platelets are not as prominent in venous clots as they are in arterial ones, but they can play a role. In cancer, tissue factor is produced by cancer cells. Cancer also produces unique substances that stimulate factor Xa, cytokines that promote endothelial dysfunction, and plasminogen activator inhibitor-1, which inhibits the breakdown of clots (fibrinolysis).

File:D-dimer production.pdf

Often, DVT begins in the valves of veins. The blood flow pattern in the valves can cause low oxygen concentrations in the blood (hypoxemia) of a valve sinus. Hypoxemia, which is worsened by venous stasis, activates pathways—ones that include hypoxia-inducible factor-1 and early-growth-response protein 1. Hypoxemia also results in the production of reactive oxygen species, which can activate these pathways, as well as nuclear factor-κB, which regulates hypoxia-inducible factor-1 transcription. Hypoxia-inducible factor-1 and early-growth-response protein 1 contribute to monocyte association with endothelial proteins, such as P-selectin, prompting monocytes to release tissue factor-filled microvesicles, which presumably begin clotting after binding to the endothelial surface.

D-dimers are a fibrin degradation product, a natural byproduct of fibrinolysis that is typically found in the blood. An elevated level{{efn|An elevated level is greater than 250 ng/mL D-dimer units (DDU) or greater than 0.5 μg/mL fibrinogen equivalent units (FEU). A normal level is below these values.}} can result from plasmin dissolving a clot—or other conditions.{{cite web |url=http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9290 |title=DDI/9290 clinical: D-dimer, plasma |publisher=Mayo Medical Laboratories |access-date=27 August 2012 |url-status=dead |archive-url=https://web.archive.org/web/20121008203101/http://www.mayomedicallaboratories.com/test-catalog/Clinical+and+Interpretive/9290 |archive-date=8 October 2012 }} Hospitalized patients often have elevated levels for multiple reasons. Anticoagulation, the standard treatment for DVT, prevents further clot growth and PE, but does not act directly on existing clots.{{cite journal | vauthors = Vedantham S, Goldhaber SZ, Kahn SR, Julian J, Magnuson E, Jaff MR, Murphy TP, Cohen DJ, Comerota AJ, Gornik HL, Razavi MK, Lewis L, Kearon C |display-authors=6 | title = Rationale and design of the ATTRACT Study: a multicenter randomized trial to evaluate pharmacomechanical catheter-directed thrombolysis for the prevention of postthrombotic syndrome in patients with proximal deep vein thrombosis | journal = American Heart Journal | volume = 165 | issue = 4 | pages = 523–530.e3 | date = April 2013 | pmid = 23537968 | pmc = 3612268 | doi = 10.1016/j.ahj.2013.01.024 }}

==Diagnosis==

A clinical probability assessment using the Wells score (see column in the table below) to determine if a potential DVT is "likely" or "unlikely" is typically the first step of the diagnostic process. The score is used in suspected first lower extremity DVT (without any PE symptoms) in primary care and outpatient settings, including the emergency department. The numerical result (possible score −2 to 9) is most commonly grouped into either "unlikely" or "likely" categories. A Wells score of two or more means DVT is considered "likely" (about a 28% chance), while those with a lower score are considered "unlikely" to have DVT (about a 6% chance). In those unlikely to have DVT, a diagnosis is excluded by a negative D-dimer blood test. In people with likely DVT, ultrasound is the standard imaging used to confirm or exclude a diagnosis. Imaging is also needed for hospital inpatients with suspected DVT and those initially categorized as unlikely to have DVT but who have a positive D-dimer test.

While the Wells score is the predominant and most studied clinical prediction rule for DVT,{{cite journal | vauthors = Geersing GJ, Zuithoff NP, Kearon C, Anderson DR, Ten Cate-Hoek AJ, Elf JL, Bates SM, Hoes AW, Kraaijenhagen RA, Oudega R, Schutgens RE, Stevens SM, Woller SC, Wells PS, Moons KG | display-authors = 6 | title = Exclusion of deep vein thrombosis using the Wells rule in clinically important subgroups: individual patient data meta-analysis | journal = BMJ | volume = 348 | issue = 7949 | pages = g1340 | date = March 2014 | pmid = 24615063 | pmc = 3948465 | doi = 10.1136/bmj.g1340 }} it does have drawbacks. The Wells score requires a subjective assessment regarding the likelihood of an alternate diagnosis and performs less well in the elderly and those with a prior DVT. The Dutch Primary Care Rule has also been validated for use. It contains only objective criteria but requires obtaining a D-dimer value.{{cite journal | vauthors = Pyzocha N | title = Diagnosing DVT in nonpregnant adults in the primary care setting | journal = American Family Physician | volume = 100 | issue = 12 | pages = 778–80 | date = December 2019 | pmid = 31845779 | url = https://www.aafp.org/afp/2019/1215/p778.html}} With this prediction rule, three points or less means a person is at low risk for DVT. A result of four or more points indicates an ultrasound is needed. Instead of using a prediction rule, experienced physicians can make a DVT pre-test probability assessment using clinical assessment and gestalt, but prediction rules are more reliable.

Compression ultrasonography for suspected deep vein thrombosis is the standard diagnostic method, and it is highly sensitive for detecting an initial DVT. A compression ultrasound is considered positive when the vein walls of normally compressible veins do not collapse under gentle pressure. Clot visualization is sometimes possible, but is not required.{{cite journal | vauthors = Le Gal G, Righini M | title = Controversies in the diagnosis of venous thromboembolism | journal = Journal of Thrombosis and Haemostasis | volume = 13 | pages = S259–65 | date = June 2015 | issue = Suppl 1 | pmid = 26149033 | doi = 10.1111/jth.12937 | doi-access = free}} Three compression ultrasound scanning techniques can be used, with two of the three methods requiring a second ultrasound some days later to rule out the diagnosis.{{cite journal | vauthors = Wells PS, Ihaddadene R, Reilly A, Forgie MA | title = Diagnosis of venous thromboembolism: 20 years of progress | journal = Annals of Internal Medicine | volume = 168 | issue = 2 | pages = 131–40 | date = January 2018 | pmid = 29310137 | doi = 10.7326/M17-0291 | s2cid = 34220435 }} Whole-leg ultrasound is the option that does not require a repeat ultrasound, but proximal compression ultrasound is frequently used because distal DVT is only rarely clinically significant.{{cite journal | vauthors = Stone J, Hangge P, Albadawi H, Wallace A, Shamoun F, Knuttien MG, Naidu S, Oklu R | display-authors=6 | title = Deep vein thrombosis: pathogenesis, diagnosis, and medical management | journal = Cardiovascular Diagnosis and Therapy | volume = 7 | issue = Suppl 3 | pages = S276–84 | date = December 2017 | pmid = 29399531 | pmc = 5778510 | doi = 10.21037/cdt.2017.09.01 | doi-access=free }} Ultrasound methods including duplex and color flow Doppler can be used to further characterize the clot and Doppler ultrasound is especially helpful in the non-compressible iliac veins.

CT scan venography, MRI venography, or a non-contrast MRI are also diagnostic possibilities. The gold standard for judging imaging methods is contrast venography, which involves injecting a peripheral vein of the affected limb with a contrast agent and taking X-rays, to reveal whether the venous supply has been obstructed. Because of its cost, invasiveness, availability, and other limitations, this test is rarely performed.

File:DVTUS.PNG|An ultrasound with a blood clot visible in the left common femoral vein. (The common femoral vein is distal to the external iliac vein.)

File:Ultrasonography of deep vein thrombosis of the femoral vein -annotated.jpg|Doppler ultrasonography showing absence of flow and hyperechogenic content in a clotted femoral vein (labeled subsartorial{{efn|Subsartorial is a proposed name for a section of the femoral vein.{{cite journal|vauthors = Häggström, M|title = Subsartorial vessels as replacement names for superficial femoral vessels|journal = International Journal of Anatomy, Radiology and Surgery|volume = 8|issue = 1|pages = AV01–02|date = January 2019|doi = 10.7860/IJARS/2019/40329:2458|doi-access = free|url = http://www.ijars.net/articles/PDF/2458/40329_CE%5BRa1%5D_F(SHU)_PF1(A_SHU)_PFA(A_SHU)_PF2(AKA_SHU)_PN(SHU).pdf}}}}) distal to the branching point of the deep femoral vein. When compared to this clot, clots that instead obstruct the common femoral vein (proximal to this branching point) cause more severe effects due to impacting a significantly larger portion of the leg.{{cite journal|vauthors = Jaff MR, McMurtry MS, Archer SL, Cushman M, Goldenberg N, Goldhaber SZ, Jenkins JS, Kline JA, Michaels AD, Thistlethwaite P, Vedantham S, White RJ, Zierler BK|display-authors = 6|title = Management of massive and submassive pulmonary embolism, iliofemoral deep vein thrombosis, and chronic thromboembolic pulmonary hypertension: a scientific statement from the American Heart Association|journal = Circulation|volume = 123|issue = 16|pages = 1788–830|date = April 2011|pmid = 21422387|doi = 10.1161/CIR.0b013e318214914f|doi-access=free }}

File:Iliac vein deep vein thrombosis.JPEG|An abdominal CT scan demonstrating an iliofemoral DVT, with the clot in the right common iliac vein of the pelvis

File:Vascular anatomy lower extremity for DVT POCUS.png|Vascular anatomy for deep venous thrombosis (DVT) point of care ultrasound (POCUS)

Treatment for DVT is warranted when the clots are either proximal, distal and symptomatic, or upper extremity and symptomatic.{{cite journal | vauthors = Bartholomew JR | title = Update on the management of venous thromboembolism | journal = Cleveland Clinic Journal of Medicine | volume = 84 | issue = 12 Suppl 3 | pages = 39–46 | date = December 2017 | pmid = 29257737 | doi = 10.3949/ccjm.84.s3.04 | s2cid = 3707226 | url = https://www.ccjm.org/content/84/12_suppl_3/39 | url-access = registration| doi-access = free }} Providing anticoagulation, or blood-thinning medicine, is the typical treatment after patients are checked to make sure they are not subject to bleeding.{{efn|Evidence for anticoagulation comes from studies other than definitive randomized controlled trials that demonstrate efficacy and safety for anticoagulation vs. placebo or using NSAIDs.{{cite journal | vauthors = Cundiff DK, Manyemba J, Pezzullo JC | title = Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism | journal = The Cochrane Database of Systematic Reviews | issue = 1 | pages = CD003746 | date = January 2006 | volume = 2006 | pmid = 16437461 | doi = 10.1002/14651858.CD003746.pub2 | pmc = 7389637 | veditors = Cundiff DK }}}} However, treatment varies depending upon the location of DVT. For example, in cases of isolated distal DVT, ultrasound surveillance (a second ultrasound after 2 weeks to check for proximal clots), might be used instead of anticoagulation.{{cite journal | vauthors = Fleck D, Albadawi H, Wallace A, Knuttinen G, Naidu S, Oklu R | title = Below-knee deep vein thrombosis (DVT): diagnostic and treatment patterns | journal = Cardiovascular Diagnosis and Therapy | volume = 7 | issue = Suppl 3 | pages = S134–39 | date = December 2017 | pmid = 29399516 | pmc = 5778527 | doi = 10.21037/cdt.2017.11.03 | doi-access = free }} Although, those with isolated distal DVT at a high risk of VTE recurrence are typically anticoagulated as if they had proximal DVT. Those at a low risk for recurrence might receive a four- to six-week course of anticoagulation, lower doses, or no anticoagulation at all. In contrast, those with proximal DVT should receive at least 3 months of anticoagulation.

Some anticoagulants can be taken by mouth, and these oral medicines include warfarin (a vitamin K antagonist), rivaroxaban (a factor Xa inhibitor), apixaban (a factor Xa inhibitor), dabigatran (a direct thrombin inhibitor), and edoxaban (a factor Xa inhibitor). Other anticoagulants cannot be taken by mouth. These parenteral (non-oral) medicines include low-molecular-weight heparin, fondaparinux, and unfractionated heparin. Some oral medicines are sufficient when taken alone, while others require the use of an additional parenteral blood thinner. Rivaroxaban and apixaban are the typical first-line medicines, and they are sufficient when taken orally. Rivaroxaban is taken once daily, and apixaban is taken twice daily. Warfarin, dabigatran, and edoxaban require the use of a parenteral anticoagulant to initiate oral anticoagulant therapy. When warfarin is initiated for VTE treatment, a 5-day minimum of a parenteral anticoagulant{{efn|The international normalized ratio should be ≥ 2.0 for 24 hours minimum, but if the ratio is > 3.0, then the parenteral anticoagulant is not needed for five days.{{cite journal | vauthors = Kearon C, Akl EA, Comerota AJ, Prandoni P, Bounameaux H, Goldhaber SZ, Nelson ME, Wells PS, Gould MK, Dentali F, Crowther M, Kahn SR | display-authors = 6 | title = Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines | journal = Chest | volume = 141 | issue = 2 Suppl | pages = e419S–96S | date = February 2012 | pmid = 22315268 | pmc = 3278049 | doi = 10.1378/chest.11-2301 }}}} together with warfarin is given, which is followed by warfarin-only therapy. Warfarin is taken to maintain an international normalized ratio (INR){{efn|An INR is determined from the ratio of a patient's prothrombin time (PT) to a standardized control PT. A normal INR for those not on anticoagulation is 1.0. A value of 5.0 or higher is considered a critical finding because of an increased risk of bleeding.{{cite journal |vauthors=Shikdar S, Vashisht R, Bhattacharya PT |title=International normalized ratio (INR) |year=2021 |location=Treasure Island, FL |journal=StatPearls [Internet] |pmid=29939529 |url=https://www.ncbi.nlm.nih.gov/books/NBK507707/}}}} of 2.0–3.0, with 2.5 as the target.Guyatt et al. 2012, p. 22S: 3.2. The benefit of taking warfarin declines as the duration of treatment extends,{{cite journal | vauthors = Middeldorp S, Prins MH, Hutten BA | title = Duration of treatment with vitamin K antagonists in symptomatic venous thromboembolism | journal = The Cochrane Database of Systematic Reviews | issue = 8 | pages = CD001367 | date = August 2014 | volume = 2014 | pmid = 25092359 | doi = 10.1002/14651858.CD001367.pub3 | pmc = 7074008 }} and the risk of bleeding increases with age.{{cite journal|vauthors=de Jong PG, Coppens M, Middeldorp S|date=August 2012|title=Duration of anticoagulant therapy for venous thromboembolism: balancing benefits and harms on the long term|journal=British Journal of Haematology|volume=158|issue=4|pages=433–41|doi=10.1111/j.1365-2141.2012.09196.x|pmid=22734929|doi-access=free}} Periodic INR monitoring is not necessary when first-line direct oral anticoagulants are used. Overall, anticoagulation therapy is complex, and many circumstances can affect how these therapies are managed.{{cite journal | vauthors = Witt DM, Nieuwlaat R, Clark NP, Ansell J, Holbrook A, Skov J, Shehab N, Mock J, Myers T, Dentali F, Crowther MA, Agarwal A, Bhatt M, Khatib R, Riva JJ, Zhang Y, Guyatt G | display-authors = 6 | title = American Society of Hematology 2018 guidelines for management of venous thromboembolism: optimal management of anticoagulation therapy | journal = Blood Advances | volume = 2 | issue = 22 | pages = 3257–91 | date = November 2018 | pmid = 30482765 | pmc = 6258922 | doi = 10.1182/bloodadvances.2018024893 }}

{{multiple image

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| image1 = Heparin-2D-skeletal.png

| alt1 = Heparin

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| image2 = Fondaparinux.svg

| alt2 = Fondaparinux

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| footer = Structural representations of the backbone of heparins (left), which vary in the size of their chain, and the synthetic pentasaccaride (five-sugar) fondaparinux (right)

}}

The duration of anticoagulation therapy (whether it will last 4 to 6 weeks, 6 to 12 weeks, 3 to 6 months, or indefinitely) is a key factor in clinical decision making.{{cite journal | vauthors = Kearon C, Kahn SR | title = Long-term treatment of venous thromboembolism | journal = Blood | volume = 135 | issue = 5 | pages = 317–25 | date = January 2020 | pmid = 31917402 | doi = 10.1182/blood.2019002364 | doi-access = free }} When proximal DVT is provoked by surgery or trauma a 3-month course of anticoagulation is standard. When a first VTE is proximal DVT that is either unprovoked or associated with transient non-surgical risk factor, low-dose anticoagulation beyond 3 to 6 months might be used. In those with an annual risk of VTE in excess of 9%, as after an unprovoked episode, extended anticoagulation is a possibility.{{cite journal | vauthors = Keeling D, Baglin T, Tait C, Watson H, Perry D, Baglin C, Kitchen S, Makris M | display-authors = 6 | title = Guidelines on oral anticoagulation with warfarin – fourth edition | journal = British Journal of Haematology | volume = 154 | issue = 3 | pages = 311–24 | date = August 2011 | pmid = 21671894 | doi = 10.1111/j.1365-2141.2011.08753.x | doi-access=free}} Those who finish warfarin treatment after idiopathic VTE with an elevated D-dimer level show an increased risk of recurrent VTE (about 9% vs about 4% for normal results), and this result might be used in clinical decision making.{{cite journal | vauthors = Douketis J, Tosetto A, Marcucci M, Baglin T, Cushman M, Eichinger S, Palareti G, Poli D, Tait RC, Iorio A | display-authors = 6 | title = Patient-level meta-analysis: effect of measurement timing, threshold, and patient age on ability of D-dimer testing to assess recurrence risk after unprovoked venous thromboembolism | journal = Annals of Internal Medicine | volume = 153 | issue = 8 | pages = 523–31 | date = October 2010 | pmid = 20956709 | doi = 10.7326/0003-4819-153-8-201010190-00009 | s2cid = 10659607 }} Thrombophilia test results rarely play a role in the length of treatment.{{cite journal | vauthors = Baglin T | title = Inherited and acquired risk factors for venous thromboembolism | journal = Seminars in Respiratory and Critical Care Medicine | volume = 33 | issue = 2 | pages = 127–37 | date = April 2012 | pmid = 22648484 | doi = 10.1055/s-0032-1311791 | s2cid = 6925903 }}

Treatment for acute leg DVT is suggested to continue at home for uncomplicated DVT instead of hospitalization. Factors that favor hospitalization include severe symptoms or additional medical issues.{{cite journal |vauthors=Ortel TL, Neumann I, Ageno W, Beyth R, Clark NP, Cuker A, Hutten BA, Jaff MR, Manja V, Schulman S, Thurston C, Vedantham S, Verhamme P, Witt DM, D Florez I, Izcovich A, Nieuwlaat R, Ross S, J Schünemann H, Wiercioch W, Zhang Y, Zhang Y |display-authors=6 |title=American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism |journal=Blood Advances |volume=4 |issue=19 |pages=4693–738 |date=October 2020 |pmid=33007077 |pmc=7556153 |doi=10.1182/bloodadvances.2020001830 |url=}} Early walking is suggested over bedrest.{{cite report |vauthors=Chatsis V, Visintini S |title=Early mobilization for patients with venous thromboembolism: a review of clinical effectiveness and guidelines |publisher=Canadian Agency for Drugs and Technologies in Health |location=Ottawa, ON |date=January 2017 |url=https://www.ncbi.nlm.nih.gov/books/NBK531715/ |pmid=30303669}} Graduated compression stockings—which apply higher pressure at the ankles and a lower pressure around the knees can be trialed for symptomatic management of acute DVT symptoms, but they are not recommended for reducing the risk of post-thrombotic syndrome,{{cite journal | vauthors = Kearon C, Akl EA, Ornelas J, Blaivas A, Jimenez D, Bounameaux H, Huisman M, King CS, Morris TA, Sood N, Stevens SM, ((Vintch JRE)), Wells P, Woller SC, Moores L | display-authors = 6 | title = Antithrombotic therapy for VTE disease: CHEST guideline and expert panel report | journal = Chest | volume = 149 | issue = 2 | pages = 315–52 | date = February 2016 | pmid = 26867832 | doi = 10.1016/j.chest.2015.11.026 }} as the potential benefit of using them for this goal "may be uncertain". Nor are compression stockings likely to reduce VTE recurrence.{{cite journal | vauthors = Berntsen CF, Kristiansen A, Akl EA, Sandset PM, Jacobsen EM, Guyatt G, Vandvik PO | display-authors = 6 | title = Compression Stockings for Preventing the Postthrombotic Syndrome in Patients with Deep Vein Thrombosis | journal = The American Journal of Medicine | volume = 129 | issue = 4 | pages = 447.e1–447.e20 | date = April 2016 | pmid = 26747198 | doi = 10.1016/j.amjmed.2015.11.031 }} They are, however, recommended in those with isolated distal DVT.

If someone decides to stop anticoagulation after an unprovoked VTE instead of being on lifelong anticoagulation, aspirin can be used to reduce the risk of recurrence,{{cite journal | vauthors = Wigle P, Hein B, Bernheisel CR | title = Anticoagulation: updated guidelines for outpatient management | journal = American Family Physician | volume = 100 | issue = 7 | pages = 426–34 | date = October 2019 | pmid = 31573167 | url = https://www.aafp.org/afp/2019/1001/p426.html}} but it is only about 33% as effective as anticoagulation in preventing recurrent VTE. Statins have also been investigated for their potential to reduce recurrent VTE rates, with some studies suggesting effectiveness.{{cite journal | vauthors = Wallace A, Albadawi H, Hoang P, Fleck A, Naidu S, Knuttinen G, Oklu R | display-authors=6 | title = Statins as a preventative therapy for venous thromboembolism | journal = Cardiovascular Diagnosis and Therapy | volume = 7 | issue = Suppl 3 | pages = S207–18 | date = December 2017 | pmid = 29399524 | pmc = 5778529 | doi = 10.21037/cdt.2017.09.12 | doi-access=free }}

An unprovoked VTE might signal the presence of an unknown cancer, as it is an underlying condition in up to 10% of unprovoked cases. A thorough clinical assessment is needed and should include a physical examination, a review of medical history, and universal cancer screening done in people of that age. A review of prior imaging is considered worthwhile, as is "reviewing baseline blood test results including full blood count, renal and hepatic function, PT and APTT."{{Cite web |date=2020-03-26 |title=Overview {{!}} Venous thromboembolic diseases: diagnosis, management and thrombophilia testing {{!}} Guidance {{!}} NICE |url=https://www.nice.org.uk/guidance/ng158 |access-date=2024-10-16 |website=www.nice.org.uk}} It is not recommended practice to obtain tumor markers or a CT of the abdomen and pelvis in asymptomatic individuals. NICE recommends that further investigations are unwarranted in those without relevant signs or symptoms.

Thrombolysis is the injection of an enzyme into the veins to dissolve blood clots, and while this treatment has been proven effective against the life-threatening emergency clots of stroke and heart attacks, randomized controlled trials{{cite journal | vauthors = Enden T, Haig Y, Kløw NE, Slagsvold CE, Sandvik L, Ghanima W, Hafsahl G, Holme PA, Holmen LO, Njaastad AM, Sandbæk G, Sandset PM | display-authors = 6 | title = Long-term outcome after additional catheter-directed thrombolysis versus standard treatment for acute iliofemoral deep vein thrombosis (the CaVenT study): a randomised controlled trial | journal = Lancet | volume = 379 | issue = 9810 | pages = 31–38 | date = January 2012 | pmid = 22172244 | doi = 10.1016/S0140-6736(11)61753-4 | s2cid = 21801157 }}{{cite journal | vauthors = Haig Y, Enden T, Grøtta O, Kløw NE, Slagsvold CE, Ghanima W, Sandvik L, Hafsahl G, Holme PA, Holmen LO, Njaaastad AM, Sandbæk G, Sandset PM | display-authors = 6 | title = Post-thrombotic syndrome after catheter-directed thrombolysis for deep vein thrombosis (CaVenT): 5-year follow-up results of an open-label, randomised controlled trial | journal = The Lancet Haematology | volume = 3 | issue = 2 | pages = e64–71 | date = February 2016 | pmid = 26853645 | doi = 10.1016/S2352-3026(15)00248-3 }}{{cite journal | vauthors = Vedantham S, Goldhaber SZ, Julian JA, Kahn SR, Jaff MR, Cohen DJ, Magnuson E, Razavi MK, Comerota AJ, Gornik HL, Murphy TP, Lewis L, Duncan JR, Nieters P, Derfler MC, Filion M, Gu CS, Kee S, Schneider J, Saad N, Blinder M, Moll S, Sacks D, Lin J, Rundback J, Garcia M, Razdan R, VanderWoude E, Marques V, Kearon C | display-authors = 6 | title = Pharmacomechanical catheter-directed thrombolysis for deep-vein thrombosis | journal = The New England Journal of Medicine | volume = 377 | issue = 23 | pages = 2240–52 | date = December 2017 | pmid = 29211671 | pmc = 5763501 | doi = 10.1056/NEJMoa1615066 }} have not established a net benefit in those with acute proximal DVT.{{Cite news|url=https://medicine.wustl.edu/news/clot-busting-drugs-not-recommended-most-patients-with-blood-clots/|title=Clot-busting drugs not recommended for most patients with blood clots| vauthors = Bhandari T |date=6 December 2017|work=Washington University School of Medicine|access-date=21 January 2020}} Drawbacks of catheter-directed thrombolysis (the preferred method of administering the clot-busting enzyme) include a risk of bleeding, complexity,{{efn|"Up to 83% of patients treated by any catheter-based therapy, need adjunctive angioplasty, and stenting".}} and the cost of the procedure. Although, while anticoagulation is the preferred treatment for DVT, thrombolysis is a treatment option for those with the severe DVT form of phlegmasia cerula dorens (bottom left image) and in some younger patients with DVT affecting the iliac and common femoral veins. Of note, a variety of contraindications to thrombolysis exist. In 2020, NICE kept their 2012 recommendations that catheter-directed thrombolysis should be considered in those with iliofemoral DVT who have "symptoms lasting less than 14 days, good functional status, a life expectancy of 1 year or more, and a low risk of bleeding."

A mechanical thrombectomy device can remove DVT clots, particularly in acute iliofemoral DVT (DVT of the major veins in the pelvis), but there is limited data on its efficacy. It is usually combined with thrombolysis, and sometimes temporary IVC filters are placed to protect against PE during the procedure.{{Cite web |date=2019-06-12 |title=Overview {{!}} Percutaneous mechanical thrombectomy for acute deep vein thrombosis of the leg {{!}} Guidance {{!}} NICE |url=https://www.nice.org.uk/guidance/ipg651 |access-date=2024-10-16 |website=www.nice.org.uk}} Catheter-directed thrombolysis with thrombectomy against iliofemoral DVT has been associated with a reduction in the severity of post-thrombotic syndrome at an estimated cost-effectiveness ratio of about $138,000{{efn|Estimated in United States dollars, estimate published in 2019}} per gained QALY.{{cite journal | vauthors = Comerota AJ, Kearon C, Gu CS, Julian JA, Goldhaber SZ, Kahn SR, Jaff MR, Razavi MK, Kindzelski AL, Bashir R, Patel P, Sharafuddin M, Sichlau MJ, Saad WE, Assi Z, Hofmann LV, Kennedy M, Vedantham S | display-authors= 6 | title = Endovascular thrombus removal for acute iliofemoral deep vein thrombosis | journal = Circulation | volume = 139 | issue = 9 | pages = 1162–73 | date = February 2019 | pmid = 30586751 | pmc= 6389417 | doi = 10.1161/CIRCULATIONAHA.118.037425 }}{{cite journal | vauthors = Magnuson EA, Chinnakondepalli K, Vilain K, Kearon C, Julian JA, Kahn SR, Goldhaber SZ, Jaff MR, Kindzelski AL, Herman K, Brady PS, Sharma K, Black CM, Vedantham S, Cohen DJ | display-authors= 6 | title = Cost-effectiveness of pharmacomechanical catheter-directed thrombolysis versus standard anticoagulation in patients with proximal deep vein thrombosis: results from the ATTRACT trial | journal = Circulation: Cardiovascular Quality and Outcomes | volume = 12 | issue = 10 | pages = e005659 | date = October 2019 | pmid = 31592728 | pmc= 6788761 | doi = 10.1161/CIRCOUTCOMES.119.005659 }} Phlegmasia cerulea dolens might be treated with catheter-directed thrombolysis and/or thrombectomy.

In DVT in the arm, the first (topmost) rib can be surgically removed as part of the typical treatment when the DVT is due to thoracic outlet syndrome or Paget–Schroetter syndrome. This treatment involves initial anticoagulation followed by thrombolysis of the subclavian vein and staged first rib resection to relieve the thoracic outlet compression and prevent recurrent DVT.{{cite journal |vauthors=Jones MR, Prabhakar A, Viswanath O, Urits I, Green JB, Kendrick JB, Brunk AJ, Eng MR, Orhurhu V, Cornett EM, Kaye AD | display-authors = 6 |title=Thoracic outlet syndrome: a comprehensive review of pathophysiology, diagnosis, and treatment |journal=Pain and Therapy |volume=8 |issue=1 |pages=5–18 |date=June 2019 |pmid=31037504 |pmc=6514035 |doi=10.1007/s40122-019-0124-2 }}

File:Gray966.png|The first rib, which is removed in a first rib resection surgery, is labeled 1 in this image

File:A-case-of-Paget-Schroetter-syndrome-(PSS)-in-a-young-judo-tutor-a-case-report-13256 2016 848 Fig1 HTML.jpg|A venogram before catheter-directed thrombolysis for Paget–Schroetter syndrome, a rare and severe arm DVT shown here in a judo practitioner, with highly restricted blood flow shown in the vein

File:A-case-of-Paget-Schroetter-syndrome-(PSS)-in-a-young-judo-tutor-a-case-report-13256 2016 848 Fig2 HTML.jpg|After treatment with catheter-directed thrombolysis, blood flow in the axillary and subclavian vein were significantly improved. Afterwards, a first rib resection allowed decompression. This reduces the risk of recurrent DVT and other sequelae from thoracic outlet compression.

File:Inferior vena cava filter.jpg

The placement of an inferior vena cava filter (IVC filter) is possible when either the standard treatment for acute DVT, anticoagulation, is absolutely contraindicated (not possible), or if someone develops a PE despite being anticoagulated. However, a 2020 NICE review found "little good evidence" for their use. A 2018 study associated IVC filter placement with a 50% reduction in PE, a 70% increase in DVT, and an 18% increase in 30 day mortality when compared to no IVC placement.{{cite journal | vauthors = Turner TE, Saeed MJ, Novak E, Brown DL | title = Association of inferior vena cava filter placement for venous thromboembolic disease and a contraindication to anticoagulation with 30-day mortality | journal = JAMA Network Open | volume = 1 | issue = 3 | pages = e180452 | date = July 2018 | pmid = 30646021 | pmc = 6324296 | doi = 10.1001/jamanetworkopen.2018.0452 }} Other studies including a systematic review and meta-analysis did not find a difference in mortality with IVC placement.{{cite journal | vauthors = Konstantinides SV, Meyer G, Becattini C, Bueno H, Geersing GJ, Harjola VP, Huisman MV, Humbert M, Jennings CS, Jiménez D, Kucher N, Lang IM, Lankeit M, Lorusso R, Mazzolai L, Meneveau N, Ní Áinle F, Prandoni P, Pruszczyk P, Righini M, Torbicki A, Van Belle E, Zamorano JL | display-authors=6 | title = 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS) | journal = European Heart Journal | volume = 41 | issue = 4 | pages = 543–603 | date = January 2020 | pmid = 31504429 | doi = 10.1093/eurheartj/ehz405 | doi-access = free}} If someone develops a PE despite being anticoagulated, care should be given to optimize anticoagulation treatment and address other related concerns before considering IVC filter placement.

Patients with a history of DVT might be managed by primary care, general internal medicine, hematology, cardiology, vascular surgery, or vascular medicine.{{Cite web|url=http://patientblog.clotconnect.org/2012/05/09/what-kind-of-doctor-do-i-need/|title=What kind of doctor do I need?|vauthors=Moll S|date=9 May 2012|website=Clot Connect|access-date=28 January 2020|archive-date=28 January 2020|archive-url=https://web.archive.org/web/20200128174155/http://patientblog.clotconnect.org/2012/05/09/what-kind-of-doctor-do-i-need/|url-status=dead}} Patients suspected of having an acute DVT are often referred to the emergency department for evaluation.{{cite journal | vauthors = Kitchen L, Lawrence M, Speicher M, Frumkin K | title = Emergency department management of suspected calf-vein deep venous thrombosis: a diagnostic algorithm | journal = The Western Journal of Emergency Medicine | volume = 17 | issue = 4 | pages = 384–90 | date = July 2016 | pmid = 27429688 | pmc = 4944794 | doi = 10.5811/westjem.2016.5.29951 }} Interventional radiology is the specialty that typically places and retrieves IVC filters,{{Cite web|url=https://www.hopkinsmedicine.org/health/treatment-tests-and-therapies/inferior-vena-cava-ivc-filter-placement|title=Inferior Vena Cava (IVC) Filter Placement | date=2020|website=Johns Hopkins Medicine|access-date=28 January 2020}} and vascular surgery might do catheter directed thrombosis for some severe DVTs.

For the prevention of blood clots in the general population, incorporating leg exercises while sitting down for long periods, or having breaks from a sitting position and walking around, having an active lifestyle, and maintaining a healthy body weight are recommended.{{Cite web|url=https://www.cdc.gov/ncbddd/dvt/facts.html|title=What is Venous Thromboembolism?|date=14 March 2019|website=Centers for Disease Control and Prevention|access-date=6 January 2020}} Walking increases blood flow through the leg veins.{{cite journal | vauthors = Partsch H, Blättler W | title = Compression and walking versus bed rest in the treatment of proximal deep venous thrombosis with low molecular weight heparin | journal = Journal of Vascular Surgery | volume = 32 | issue = 5 | pages = 861–69 | date = November 2000 | pmid = 11054217 | doi = 10.1067/mva.2000.110352 | doi-access = free}} Excess body weight is modifiable unlike most risk factors, and interventions or lifestyle modifications that help someone who is overweight or obese lose weight reduce DVT risk. Avoiding both smoking and a Western pattern diet are thought to reduce risk.{{cite journal | vauthors = Folsom AR, Cushman M | title = Exploring opportunities for primary prevention of unprovoked venous thromboembolism: ready for prime time? | journal = Journal of the American Heart Association | volume = 9 | issue = 23 | pages = e019395 | date = December 2020 | pmid = 33191841 | pmc = 7763794 | doi = 10.1161/JAHA.120.019395 }} Statins have been investigated for primary prevention (prevention of a first VTE), and the JUPITER trial, which used rosuvastatin, has provided some tentative evidence of effectiveness.{{cite journal | vauthors = Li L, Zhang P, Tian JH, Yang K | title = Statins for primary prevention of venous thromboembolism | journal = The Cochrane Database of Systematic Reviews | issue = 12 | pages = CD008203 | date = December 2014 | volume = 2014 | pmid = 25518837 | doi = 10.1002/14651858.CD008203.pub3 | doi-access = free | pmc = 11127252 }} Of the statins, rosuvastatin appears to be the only one with the potential to reduce VTE risk.{{cite journal | vauthors = Kunutsor SK, Seidu S, Khunti K | title = Statins and primary prevention of venous thromboembolism: a systematic review and meta-analysis | journal = The Lancet Haematology | volume = 4 | issue = 2 | pages = e83–e93 | date = February 2017 | pmid = 28089655 | doi = 10.1016/S2352-3026(16)30184-3 | url = https://research-information.bris.ac.uk/files/99752833/Statins_VTE_Lancet_Accepted.pdf | hdl = 1983/5a398e70-6c7c-40bd-a8d4-53c24d84f1a2 | s2cid = 24036108 | hdl-access = free }} If so, it appears to reduce risk by about 15%. However, the number needed to treat to prevent one initial VTE is about 2000, limiting its applicability.{{cite journal | vauthors = Biere-Rafi S, Hutten BA, Squizzato A, Ageno W, Souverein PC, de Boer A, Gerdes VE, Büller HR, Kamphuisen PW |display-authors=6 | title = Statin treatment and the risk of recurrent pulmonary embolism | journal = European Heart Journal | volume = 34 | issue = 24 | pages = 1800–06 | date = June 2013 | pmid = 23396492 | doi = 10.1093/eurheartj/eht046 | doi-access = free}}

Acutely ill hospitalized patients are suggested to receive a parenteral anticoagulant, although the potential net benefit is uncertain. Critically ill hospitalized patients are recommended to either receive unfractionated heparin or low-molecular weight heparin instead of foregoing these medicines.

File:Knee Replacement.jpg, a procedure that can precipitate DVT formation]]

Major orthopedic surgery—total hip replacement, total knee replacement, or hip fracture surgery—has a high risk of causing VTE.{{cite journal | vauthors = Sobieraj DM, Lee S, Coleman CI, Tongbram V, Chen W, Colby J, Kluger J, Makanji S, Ashaye AO, White CM | display-authors = 6 | title = Prolonged versus standard-duration venous thromboprophylaxis in major orthopedic surgery: a systematic review | journal = Annals of Internal Medicine | volume = 156 | issue = 10 | pages = 720–27 | date = May 2012 | pmid = 22412039 | doi = 10.7326/0003-4819-156-10-201205150-00423 | s2cid = 22797561 }} If prophylaxis is not used after these surgeries, symptomatic VTE has about a 4% chance of developing within 35 days.{{cite journal | vauthors = Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, Ortel TL, Pauker SG, Colwell CW | display-authors = 6 | title = Prevention of VTE in orthopedic surgery patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines | journal = Chest | volume = 141 | issue = 2 Suppl | pages = e278S–e325S | date = February 2012 | pmid = 22315265 | pmc = 3278063 | doi = 10.1378/chest.11-2404 }} Following major orthopedic surgery, a blood thinner or aspirin is typically paired with intermittent pneumatic compression, which is the preferred mechanical prophylaxis over graduated compression stockings.

Options for VTE prevention in people following non-orthopedic surgery include early walking, mechanical prophylaxis, and blood thinners (low-molecular-weight heparin and low-dose-unfractionated heparin) depending upon the risk of VTE, risk of major bleeding, and person's preferences.{{cite journal | vauthors = Gould MK, Garcia DA, Wren SM, Karanicolas PJ, Arcelus JI, Heit JA, Samama CM | display-authors = 6 | title = Prevention of VTE in nonorthopedic surgical patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines | journal = Chest | volume = 141 | issue = 2 Suppl | pages = e227S–77S | date = February 2012 | pmid = 22315263 | pmc = 3278061 | doi = 10.1378/chest.11-2297 }} After low-risk surgeries, early and frequent walking is the best preventive measure.{{cite journal | vauthors = Anderson DR, Morgano GP, Bennett C, Dentali F, Francis CW, Garcia DA, Kahn SR, Rahman M, Rajasekhar A, Rogers FB, Smythe MA, ((Tikkinen KAO)), Yates AJ, Baldeh T, Balduzzi S, Brożek JL, Ikobaltzeta IE, Johal H, Neumann I, Wiercioch W, Yepes-Nuñez JJ, Schünemann HJ, Dahm P | display-authors= 6 | title = American Society of Hematology 2019 guidelines for management of venous thromboembolism: prevention of venous thromboembolism in surgical hospitalized patients | journal = Blood Advances | volume = 3 | issue = 23 | pages = 3898–944 | date = December 2019 | pmid = 31794602 | pmc = 6963238 | doi = 10.1182/bloodadvances.2019000975 }}

The risk of VTE is increased in pregnancy by about four to five times because of a more hypercoagulable state that protects against fatal postpartum hemorrhage.{{cite journal | vauthors = Turetz M, Sideris AT, Friedman OA, Triphathi N, Horowitz JM | title = Epidemiology, pathophysiology, and natural history of pulmonary embolism | journal = Seminars in Interventional Radiology | volume = 35 | issue = 2 | pages = 92–98 | date = June 2018 | pmid = 29872243 | pmc = 5986574 | doi = 10.1055/s-0038-1642036 }} Preventive measures for pregnancy-related VTE were suggested by the American Society of Hematology in 2018. Warfarin, a common vitamin K antagonist, can cause birth defects and is not used for prevention during pregnancy.{{cite journal | vauthors = Bates SM, Greer IA, Middeldorp S, Veenstra DL, Prabulos AM, Vandvik PO | title = VTE, thrombophilia, antithrombotic therapy, and pregnancy: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines | journal = Chest | volume = 141 | issue = 2 Suppl | pages = e691S–e736S | date = February 2012 | pmid = 22315276 | pmc = 3278054 | doi = 10.1378/chest.11-2300 }}

File:Stuetzstrumpf 04 (fcm).jpg

Travelling "is an often cited yet relatively uncommon" cause of VTE. Suggestions for at-risk{{efn|Including those with "previous VTE, recent surgery or trauma, active malignancy, pregnancy, estrogen use, advanced age, limited mobility, severe obesity, or known thrombophilic disorder"}} long-haul travelers include calf exercises, frequent walking, and aisle seating in airplanes to ease walking.{{cite journal | vauthors = Kahn SR, Lim W, Dunn AS, Cushman M, Dentali F, Akl EA, Cook DJ, Balekian AA, Klein RC, Le H, Schulman S, Murad MH | display-authors = 6 | title = Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines | journal = Chest | volume = 141 | issue = 2 Suppl | pages = e195S–e226S | date = February 2012 | pmid = 22315261 | pmc = 3278052 | doi = 10.1378/chest.11-2296 }} See section 6.0, Long-Distance Travel{{cite web |url=http://www.chestnet.org/News/Press-Releases/2012/02/ACCP-Antithrombotic-and-Economy-Class-Syndrome |title=New DVT guidelines: No evidence to support "economy-class syndrome" | quote = oral contraceptives, sitting in a window seat, advanced age, and pregnancy increase DVT risk in long-distance travelers |date=7 February 2012 |publisher=American College of Chest Physicians |access-date=10 February 2012 |url-status=live |archive-url=https://web.archive.org/web/20160603075103/http://www.chestnet.org/News/Press-Releases/2012/02/ACCP-Antithrombotic-and-Economy-Class-Syndrome |archive-date=3 June 2016}} Graduated compression stockings have sharply reduced the levels of asymptomatic DVT in airline passengers, but the effect on symptomatic DVT, PE, or mortality is unknown, as none of the individuals studied developed these outcomes.{{cite journal |vauthors=Clarke MJ, Broderick C, Hopewell S, Juszczak E, Eisinga A |title=Compression stockings for preventing deep vein thrombosis in airline passengers |journal=The Cochrane Database of Systematic Reviews |volume=2021 |issue= 4|pages=CD004002 |date=April 2021 |pmid=33878207 |doi=10.1002/14651858.CD004002.pub4 |pmc=8092568 |url=https://ora.ox.ac.uk/objects/uuid:5636a717-65b5-4d1e-984b-f8c3d980a0dd/download_file?safe_filename=Clarke_et_al-2016-The_Cochrane_Library.sup-2%2B%25281%2529.pdf&file_format=application%2Fpdf&type_of_work=Journal+article }} However, graduated compression stockings are not suggested for long-haul travelers (>4 hours) without risk factors for VTE. Likewise, neither aspirin nor anticoagulants are suggested in the general population undertaking long-haul travel. Those with significant VTE risk factors{{efn|For example "recent surgery, history of VTE, postpartum women, active malignancy, or ≥2 risk factors, including combinations of the above with hormone replacement therapy, obesity, or pregnancy"}} undertaking long-haul travel are suggested to use either graduated compression stockings or LMWH for VTE prevention. If neither of these two methods are feasible, then aspirin is suggested.{{cite journal | vauthors = Schünemann HJ, Cushman M, Burnett AE, Kahn SR, Beyer-Westendorf J, Spencer FA, Rezende SM, Zakai NA, Bauer KA, Dentali F, Lansing J, Balduzzi S, Darzi A, Morgano GP, Neumann I, Nieuwlaat R, Yepes-Nuñez JJ, Zhang Y, Wiercioch W | display-authors = 6 | title = American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients | journal = Blood Advances | volume = 2 | issue = 22 | pages = 3198–225 | date = November 2018 | pmid = 30482763 | pmc = 6258910 | doi = 10.1182/bloodadvances.2018022954 }}

DVT is most frequently a disease of older age that occurs in the context of nursing homes, hospitals, and active cancer. It is associated with a 30-day mortality rate of about 6%, with PE being the cause of most of these deaths. Proximal DVT is frequently associated with PE, unlike distal DVT, which is rarely if ever associated with PE. Around 56% of those with proximal DVT also have PE, although a chest CT is not needed simply because of the presence of DVT.{{cite journal | vauthors = Kruger PC, Eikelboom JW, Douketis JD, Hankey GJ | title = Deep vein thrombosis: update on diagnosis and management | journal = The Medical Journal of Australia | volume = 210 | issue = 11 | pages = 516–24 | date = June 2019 | pmid = 31155730 | doi = 10.5694/mja2.50201 | s2cid = 173995098 }} If proximal DVT is left untreated, in the following 3 months approximately half of people will experience symptomatic PE.

Another frequent complication of proximal DVT, and the most frequent chronic complication, is post-thrombotic syndrome, where individuals have chronic venous symptoms. Symptoms can include pain, itching, swelling, paresthesia, a sensation of heaviness, and in severe cases, leg ulcers. After proximal DVT, an estimated 20–50% of people develop the syndrome, with 5–10% experiencing severe symptoms.{{cite journal | vauthors = Galanaud JP, Monreal M, Kahn SR | title = Epidemiology of the post-thrombotic syndrome | journal = Thrombosis Research | volume = 164 | pages = 100–09 | date = April 2018 | pmid = 28844444 | doi = 10.1016/j.thromres.2017.07.026 }} Post-thrombotic syndrome can also be a complication of distal DVT, though to a lesser extent than with proximal DVT.{{cite journal | vauthors = Galanaud JP, Righini M, Le Collen L, Douillard A, Robert-Ebadi H, Pontal D, Morrison D, Barrellier MT, Diard A, Guénnéguez H, Brisot D, Faïsse P, Accassat S, Martin M, Delluc A, Solymoss S, Kassis J, Carrier M, Quéré I, Kahn SR | display-authors= 6 | title = Long-term risk of postthrombotic syndrome after symptomatic distal deep vein thrombosis: The CACTUS-PTS study | journal = Journal of Thrombosis and Haemostasis | volume = 18| issue = 4| pages = 857–64| date = January 2020 | pmid = 31899848 | doi = 10.1111/jth.14728 | doi-access = free}}

In the 10 years following an initial VTE, about 30% of people will have a recurrence. VTE recurrence in those with prior DVT is more likely to recur as DVT than PE.{{cite journal | vauthors = Konstantinides SV, Torbicki A, Agnelli G, Danchin N, Fitzmaurice D, Galiè N, Gibbs JS, Huisman MV, Humbert M, Kucher N, Lang I, Lankeit M, Lekakis J, Maack C, Mayer E, Meneveau N, Perrier A, Pruszczyk P, Rasmussen LH, Schindler TH, Svitil P, Vonk Noordegraaf A, Zamorano JL, Zompatori M | display-authors = 6 | title = 2014 ESC guidelines on the diagnosis and management of acute pulmonary embolism | journal = European Heart Journal | volume = 35 | issue = 43 | pages = 3033–69, 3069a–69k | date = November 2014 | pmid = 25173341 | doi = 10.1093/eurheartj/ehu283 | doi-access = free }} Cancer{{cite journal | vauthors = Mazzolai L, Aboyans V, Ageno W, Agnelli G, Alatri A, Bauersachs R, Brekelmans MP, Büller HR, Elias A, Farge D, Konstantinides S, Palareti G, Prandoni P, Righini M, Torbicki A, Vlachopoulos C, Brodmann M | display-authors = 6 | title = Diagnosis and management of acute deep vein thrombosis: a joint consensus document from the European Society of Cardiology working groups of aorta and peripheral vascular diseases and pulmonary circulation and right ventricular function | journal = European Heart Journal | volume = 39 | issue = 47 | pages = 4208–18 | date = December 2018 | pmid = 28329262 | doi = 10.1093/eurheartj/ehx003 |doi-access=free}} and unprovoked DVT are strong risk factors for recurrence. After initial proximal unprovoked DVT with and without PE, 16–17% of people will have recurrent VTE in the 2 years after they complete their course of anticoagulants. VTE recurrence is less common in distal DVT than proximal DVT.{{cite journal |vauthors=Khan F, Rahman A, Carrier M, Kearon C, Weitz JI, Schulman S, Couturaud F, Eichinger S, Kyrle PA, Becattini C, Agnelli G, Brighton TA, Lensing AW, Prins MH, Sabri E, Hutton B, Pinede L, Cushman M, Palareti G, Wells GA, Prandoni P, Büller HR, Rodger MA | display-authors = 6 | title = Long term risk of symptomatic recurrent venous thromboembolism after discontinuation of anticoagulant treatment for first unprovoked venous thromboembolism event: systematic review and meta-analysis | journal = BMJ | volume = 366 | issue = 8209 | pages = l4363 | date = July 2019 | pmid = 31340984 | pmc = 6651066 | doi = 10.1136/bmj.l4363 }} In upper extremity DVT, annual VTE recurrence is about 2–4%. After surgery, a provoked proximal DVT or PE has an annual recurrence rate of only 0.7%.

About 1.5 out of 1000 adults a year have a first VTE in high-income countries.{{cite journal | vauthors = Johannesen CD, Flachs EM, Ebbehøj NE, Marott JL, Jensen GB, Nordestgaard BG, Schnohr P, Bonde JP | display-authors = 6 | title = Sedentary work and risk of venous thromboembolism | journal = Scandinavian Journal of Work, Environment & Health | volume = 46 | issue = 1 | pages = 69–76 | date = January 2020 | pmid = 31385593 | doi = 10.5271/sjweh.3841 |doi-access=free}} The condition becomes much more common with age. VTE rarely occurs in children, but when it does, it predominantly affects hospitalized children.{{cite journal | vauthors = Monagle P, Cuello CA, Augustine C, Bonduel M, Brandão LR, Capman T, ((Chan AKC)), Hanson S, Male C, Meerpohl J, Newall F, O'Brien SH, Raffini L, van Ommen H, Wiernikowski J, Williams S, Bhatt M, Riva JJ, Roldan Y, Schwab N, Mustafa RA, Vesely SK | display-authors=6 | title = American Society of Hematology 2018 Guidelines for management of venous thromboembolism: treatment of pediatric venous thromboembolism | journal = Blood Advances | volume = 2 | issue = 22 | pages = 3292–316 | date = November 2018 | pmid = 30482766 | pmc = 6258911 | doi = 10.1182/bloodadvances.2018024786 }} Children in North America and the Netherlands have VTE rates that range from 0.07 to 0.49 out of 10,000 children annually. Meanwhile, almost 1% of those aged 85 and above experience VTE each year. About 60% of all VTEs occur in those 70 years of age or older. Incidence is about 18% higher in males than in females,{{cite journal | vauthors = Crous-Bou M, Harrington LB, Kabrhel C | title = Environmental and genetic risk factors associated with venous thromboembolism | journal = Seminars in Thrombosis and Hemostasis | volume = 42 | issue = 8 | pages = 808–20 | date = November 2016 | pmid = 27764878 | pmc = 5146955 | doi = 10.1055/s-0036-1592333 }} though there are ages when VTE is more prevalent in women.{{cite journal |vauthors=Wendelboe AM, Raskob GE |title=Global burden of thrombosis: epidemiologic aspects |journal=Circulation Research |volume=118 |issue=9 |pages=1340–47 |date=April 2016 |pmid=27126645 |doi=10.1161/CIRCRESAHA.115.306841 |doi-access=free}} VTE occurs in association with hospitalization or nursing home residence about 60% of the time, active cancer about 20% of the time, and a central venous catheter or transvenous pacemaker about 9% of the time.{{cite journal | vauthors = Heit JA, Spencer FA, White RH | title = The epidemiology of venous thromboembolism | journal = Journal of Thrombosis and Thrombolysis | volume = 41 | issue = 1 | pages = 3–14 | date = January 2016 | pmid = 26780736 | pmc = 4715842 | doi = 10.1007/s11239-015-1311-6 }}

During pregnancy and after childbirth, acute VTE occurs in about 1.2 of 1000 deliveries. Despite it being relatively rare, it is a leading cause of maternal morbidity and mortality.{{cite journal | vauthors = Bates SM, Rajasekhar A, Middeldorp S, McLintock C, Rodger MA, James AH, Vazquez SR, Greer IA, Riva JJ, Bhatt M, Schwab N, Barrett D, LaHaye A, Rochwerg B |display-authors= 6 | title = American Society of Hematology 2018 guidelines for management of venous thromboembolism: venous thromboembolism in the context of pregnancy | journal = Blood Advances | volume = 2 | issue = 22 | pages = 3317–59 | date = November 2018 | pmid = 30482767 | pmc = 6258928 | doi = 10.1182/bloodadvances.2018024802 }} After surgery with preventive treatment, VTE develops in about 10 of 1000 people after total or partial knee replacement, and in about 5 of 1000 after total or partial hip replacement.{{cite journal | vauthors = Januel JM, Chen G, Ruffieux C, Quan H, Douketis JD, Crowther MA, Colin C, Ghali WA, Burnand B | display-authors = 6 | title = Symptomatic in-hospital deep vein thrombosis and pulmonary embolism following hip and knee arthroplasty among patients receiving recommended prophylaxis: a systematic review | journal = JAMA | volume = 307 | issue = 3 | pages = 294–303 | date = January 2012 | pmid = 22253396 | doi = 10.1001/jama.2011.2029 | doi-access = free }} About 400,000 Americans develop an initial VTE each year, with 100,000 deaths or more attributable to PE.{{cite journal | vauthors = Grosse SD, Nelson RE, Nyarko KA, Richardson LC, Raskob GE | title = The economic burden of incident venous thromboembolism in the United States: A review of estimated attributable healthcare costs | journal = Thrombosis Research | volume = 137 | pages = 3–10 | date = January 2016 | pmid = 26654719 | pmc = 4706477 | doi = 10.1016/j.thromres.2015.11.033 }} Asian, Asian-American, Native American, and Hispanic individuals have a lower VTE risk than Whites or Blacks. Populations in Asia have VTE rates at 15 to 20% of what is seen in Western countries, with an increase in incidence seen over time. In North American and European populations, around 4–8% of people have a thrombophilia, most commonly factor V leiden and prothrombin G20210A. For populations in China, Japan, and Thailand, deficiences in protein S, protein C, and antithrombin predominate.{{cite journal | vauthors = Margaglione M, Grandone E | title = Population genetics of venous thromboembolism. A narrative review | journal = Thrombosis and Haemostasis | volume = 105 | issue = 2 | pages = 221–31 | date = February 2011 | pmid = 20941456 | doi = 10.1160/TH10-08-0510 | s2cid = 17552169 }} Non-O blood type is present in around 50% of the general population and varies with ethnicity, and it is present in about 70% of those with VTE.{{cite web | url = http://www.redcrossblood.org/learn-about-blood/blood-types | title = Blood types | access-date = 15 August 2012 | publisher = American Red Cross | url-status = live | archive-url = https://web.archive.org/web/20120814050932/http://www.redcrossblood.org/learn-about-blood/blood-types | archive-date = 14 August 2012}}

DVT occurs in the upper extremities in about 4–10% of cases, with an incidence of 0.4–1.0 people out of 10,000 a year. A minority of upper extremity DVTs are due to Paget–Schroetter syndrome, also called effort thrombosis, which occurs in 1–2 people out of 100,000 a year, usually in athletic males around 30 years of age or in those who do significant amounts of overhead manual labor.{{cite journal | vauthors = Ijaopo R, Oguntolu V, DCosta D, Garnham A, Hobbs S | title = A case of Paget-Schroetter syndrome (PSS) in a young judo tutor: a case report | journal = Journal of Medical Case Reports | volume = 10 | pages = 63 | date = March 2016 | pmid = 26987584 | pmc = 4797165 | doi = 10.1186/s13256-016-0848-0 | doi-access = free }}

File:Serena Williams at 2013 US Open.jpg has spoken at length about a frightening encounter she had with VTE while she was hospitalized in 2017.]]

Being on blood thinners because of DVT can be life-changing because it can prevent lifestyle activities such as contact or winter sports to prevent bleeding after potential injuries.{{cite journal | vauthors = Golemi I, Salazar Adum JP, Tafur A, Caprini J | title = Venous thromboembolism prophylaxis using the Caprini score | journal = Disease-a-Month | volume = 65 | issue = 8 | pages = 249–98 | date = August 2019 | pmid = 30638566 | doi = 10.1016/j.disamonth.2018.12.005 | s2cid = 58564402 }} Head injuries prompting brain bleeds are of particular concern. This has caused NASCAR driver Brian Vickers to forego participation in races. Professional basketball players including NBA players Victor Wembanyama, Chris Bosh, and hall of famer Hakeem Olajuwon have dealt with recurrent blood clots,{{Cite news|url=https://www.usatoday.com/story/sports/nba/heat/2016/02/16/chris-bosh-risk-blood-clot-recurrence/80453318/|title=Expert: Chris Bosh, like many, at risk of blood clot recurrence| vauthors = Perez AJ |date=17 February 2016|work=USA Today|access-date=22 January 2020}} and Bosh's career was significantly hampered by DVT and PE.{{Cite news|url=https://www.cnn.com/2016/05/04/sport/chris-bosh-absence-nba-playoffs/index.html|title=Chris Bosh officially out as Heat make playoff push| vauthors = Martin J |date=4 May 2016|work=CNN|access-date=22 January 2020}}

Tennis star Serena Williams was hospitalized in 2011 for PE thought to have originated from DVT.{{Cite news|url=https://abcnews.go.com/Health/Wellness/serena-williams-hospitalized-pulmonary-embolism/story?id=13036965|title=Serena Williams Hospitalized After Pulmonary Embolism| vauthors = Moisse K |date=2 March 2011|work=ABC News|access-date=22 January 2020}} Years later, in 2017, due to her knowledge of DVT and PE, Serena accurately advocated for herself to have a PE diagnosed and treated. During this encounter with VTE, she was hospitalized after a C-section surgery and was off of blood thinners. After feeling the sudden onset of a PE symptom, shortness of breath, she told her nurse and requested a CT scan and an IV heparin drip, all while gasping for air. She started to receive an ultrasound to look for DVT in the legs, prompting her to express dissatisfaction to the medical staff that they were not looking for clots where she had symptoms (her lungs), and they were not yet treating her presumed PE. After being diagnosed with PE and not DVT, and after receiving heparin by IV, the coughing from the PE caused her C-section surgical site to open and the heparin contributed to bleeding at the site. Serena later received an IVC filter while in the hospital.{{Cite web|url=https://www.vogue.com/article/serena-williams-vogue-cover-interview-february-2018|title=Serena Williams on motherhood, marriage, and making her comeback| vauthors = Haskell R |date=10 January 2018|website=Vogue|access-date=22 January 2020}}{{cite journal | vauthors = Andrews BL, Friedman Ross L | title = Black Women and Babies Matter | journal = The American Journal of Bioethics | volume = 21 | issue = 2 | pages = 93–95 | date = February 2021 | pmid = 33534674 | doi = 10.1080/15265161.2020.1861384 | s2cid = 231803661 }}

Other notable people have been affected by DVT. Former United States President Richard Nixon had recurrent DVT,{{cite journal | vauthors = Pascarella L, Pappas TN | title = Phlebitis, pulmonary emboli and presidential politics: Richard M. Nixon's complicated deep vein thrombosis | journal = The American Surgeon | volume = 79 | issue = 2 | pages = 128–34 | date = February 2013 | pmid = 23336651 | doi = 10.1177/000313481307900222 | doi-access = free }} and so has former Secretary of State Hillary Clinton. She was first diagnosed while First Lady in 1998 and again in 2009.{{Cite news|url=https://www.washingtonpost.com/politics/hillary-clinton-has-not-been-quick-to-share-health-information/2016/09/11/822b1b0c-784d-11e6-bd86-b7bbd53d2b5d_story.html|title=Hillary Clinton has not been quick to share health information| vauthors = Frankel TC |date=11 September 2016|newspaper=The Washington Post|access-date=22 January 2020}} Dick Cheney was diagnosed with an episode while Vice President,{{Cite news |url= https://www.theguardian.com/world/2007/mar/06/usa.dickcheney1 |title=Cheney diagnosed with deep-vein thrombosis | date=6 March 2007|work=The Guardian|access-date=22 January 2020}} and TV show host Regis Philbin had DVT after hip-replacement surgery.{{Cite web|url=https://www.everydayhealth.com/pictures/celebrities-who-battled-deep-vein-thrombosis/|title=11 Celebrities Who Battled Deep Vein Thrombosis Risk| vauthors = Rodriguez D |date=12 October 2018|website=Everyday Health|access-date=22 January 2020}} DVT has also contributed to the deaths of famous people. For example, DVT and PE played a role in rapper Heavy D's death at age 44.{{Cite web|url=https://www.cnn.com/2011/12/27/showbiz/heavy-d-autopsy/index.html|title=Coroner: Rapper Heavy D died of blood clot in lung | date=27 December 2011|website=CNN|access-date=22 January 2020}} NBC journalist David Bloom died at age 39 while covering the Iraq War from a PE that was thought to have progressed from a missed DVT,{{Cite news|url=https://www.today.com/news/my-husband-should-be-living-today-wbna7074940|title=My husband should be living today | date=3 March 2005|work=TODAY|access-date=22 January 2020}} and actor Jimmy Stewart had DVT that progressed to a PE when he was 89.{{cite book | vauthors = Eliot M |title=Jimmy Stewart: A Biography |date=2006 |publisher=Random House |location=New York |isbn=978-1400052226 |page=409}}

File:Rudolf Virchow-cropped.jpg

The book Sushruta Samhita, an Ayurvedic text published around 600–900 BC, contains what has been cited as the first description of DVT.{{cite journal | vauthors = Goodman LR | title = In search of venous thromboembolism: the first 2913 years | journal = American Journal of Roentgenology | volume = 201 | issue = 4 | pages = W576-81 | date = October 2013 | pmid = 24059395 | doi = 10.2214/AJR.13.10604 | doi-access=free }} In 1271, DVT symptoms in the leg of a 20-year-old male were described in a French manuscript, which has been cited as the first case or the first Western reference to DVT.{{cite journal | vauthors = Galanaud JP, Laroche JP, Righini M | title = The history and historical treatments of deep vein thrombosis | journal = Journal of Thrombosis and Haemostasis | volume = 11 | issue = 3 | pages = 402–11 | date = March 2013 | pmid = 23297815 | doi = 10.1111/jth.12127 | doi-access=free }}

In 1856, German physician and pathologist Rudolf Virchow published his analysis after the insertion of foreign bodies into the jugular veins of dogs, which migrated to the pulmonary arteries. These foreign bodies caused pulmonary emboli, and Virchow was focused on explaining their consequences.{{cite journal | vauthors = Kumar DR, Hanlin E, Glurich I, Mazza JJ, Yale SH | title = Virchow's contribution to the understanding of thrombosis and cellular biology | journal = Clinical Medicine & Research | volume = 8 | issue = 3–4 | pages = 168–72 | date = December 2010 | pmid = 20739582 | pmc = 3006583 | doi = 10.3121/cmr.2009.866 }} He cited three factors, which are now understood as hypercoagulability, stasis, and endothelial injury.{{cite journal | vauthors = Bagot CN, Arya R | title = Virchow and his triad: a question of attribution | journal = British Journal of Haematology | volume = 143 | issue = 2 | pages = 180–90 | date = October 2008 | pmid = 18783400 | doi = 10.1111/j.1365-2141.2008.07323.x |doi-access=free}} It was not until 1950 that this framework was cited as Virchow's triad, but the teaching of Virchow's triad has continued in light of its utility as a theoretical framework and as a recognition of the significant progress Virchow made in expanding the understanding of VTE.

Methods to observe DVT by ultrasound were established in the 1960s.{{cite journal | vauthors = Rahaghi FN, Minhas JK, Heresi GA | title = Diagnosis of deep venous thrombosis and pulmonary embolism: new imaging tools and modalities | journal = Clinics in Chest Medicine | volume = 39 | issue = 3 | pages = 493–504 | date = September 2018 | pmid = 30122174 | pmc = 6317734 | doi = 10.1016/j.ccm.2018.04.003 }} Diagnoses were commonly performed by impedance plethysmography in the 1970s and 1980s,{{sfn|Dalen|2003|p=3}} but ultrasound, particularly after utility of probe compression was demonstrated in 1986, became the preferred diagnostic method. Yet, in the mid-1990s, contrast venography and impedance plethysmography were still described as common.{{cite journal | vauthors = Line BR, Peters TL, Keenan J | title = Diagnostic test comparisons in patients with deep venous thrombosis | journal = Journal of Nuclear Medicine | volume = 38 | issue = 1 | pages = 89–92 | date = January 1997 | pmid = 8998158 | url = http://jnm.snmjournals.org/content/38/1/89.full.pdf }}

File:Warfarintablets5-3-1.jpg

Multiple pharmacological therapies for DVT were introduced in the 20th century: oral anticoagulants in the 1940s, subcutaneous injections of LDUH in 1962 and subcutaneous injections of LMWH in 1982.{{sfn|Dalen|2003|p=2}} 1974 was when vascular inflammation and venous thrombosis were first proposed to be interrelated.{{cite journal | vauthors = Myers DD | title = Pathophysiology of venous thrombosis | journal = Phlebology | volume = 30 | issue = 1 Suppl | pages = 7–13 | date = March 2015 | pmid = 25729062 | doi = 10.1177/0268355515569424 | s2cid = 22467822 }} For around 50 years, a months-long warfarin (Coumadin) regimen was the mainstay of pharmacological treatment.{{cite journal | vauthors = Franchini M, Mannucci PM | title = Direct oral anticoagulants and venous thromboembolism | journal = European Respiratory Review | volume = 25 | issue = 141 | pages = 295–302 | date = September 2016 | pmid = 27581829 | doi = 10.1183/16000617.0025-2016 | pmc = 9487211 | doi-access = free }} To avoid the blood monitoring required with warfarin and the injections required by heparin and heparin-like medicines, direct oral anticoagulants (DOACs) were developed. In the late 2000s to early 2010s, DOACs—including rivaroxaban (Xarelto), apixaban (Eliquis), and dabigatran (Pradaxa)—came to the market.{{cite journal | vauthors = Keeling D, Alikhan R | title = Management of venous thromboembolism – controversies and the future | journal = British Journal of Haematology | volume = 161 | issue = 6 | pages = 755–63 | date = June 2013 | pmid = 23531017 | doi = 10.1111/bjh.12306 |doi-access=free}} The New York Times described a "furious battle" among the three makers of these drugs "for the prescription pads of doctors".{{Cite news|url=https://www.nytimes.com/2015/01/08/upshot/the-drugs-that-companies-promote-to-doctors-are-rarely-breakthroughs.html|title=The drugs that companies promote to doctors are rarely breakthroughs| vauthors = Ornstein C, Jones RG |date=7 January 2015|work=The New York Times}}

VTE costs the US healthcare system about $7 to 10 billion dollars annually. Initial and average DVT costs for a hospitalized US patient is about $10,000 (2015 estimate).{{cite journal |vauthors=Dasta JF, Pilon D, Mody SH, Lopatto J, Laliberté F, Germain G, Bookhart BK, Lefebvre P, Nutescu EA |display-authors=6 |title=Daily hospitalization costs in patients with deep vein thrombosis or pulmonary embolism treated with anticoagulant therapy |journal=Thrombosis Research |volume=135 |issue=2 |pages=303–10 |date=February 2015 |pmid=25555319 |doi=10.1016/j.thromres.2014.11.024 |doi-access=free}} In Europe, the costs for an initial VTE hospitalization are significantly less, costing about €2000 to 4000 (2011 estimate).{{cite journal | vauthors = Ruppert A, Steinle T, Lees M | title = Economic burden of venous thromboembolism: a systematic review | journal = Journal of Medical Economics | volume = 14 | issue = 1 | pages = 65–74 | year = 2011 | pmid = 21222564 | doi = 10.3111/13696998.2010.546465 |doi-access=free}} Post-thrombotic syndrome is a significant contributor to DVT follow-up costs.{{cite journal | vauthors = Dobesh PP | title = Economic burden of venous thromboembolism in hospitalized patients | journal = Pharmacotherapy | volume = 29 | issue = 8 | pages = 943–53 | date = August 2009 | pmid = 19637948 | doi = 10.1592/phco.29.8.943 | s2cid = 8966676 }} Outpatient treatment significantly reduces costs, and treatment costs for PE exceed those of DVT.{{cite journal |vauthors=Fernandez MM, Hogue S, Preblick R, Kwong WJ |title=Review of the cost of venous thromboembolism |journal=ClinicoEconomics and Outcomes Research |volume=7 |issue= |pages=451–62 |date=2015 |pmid=26355805 |pmc=4559246 |doi=10.2147/CEOR.S85635 |url= |doi-access=free }}

A 2019 study published in Nature Genetics reported more than doubling the known genetic loci associated with VTE.{{cite journal | vauthors = Klarin D, Busenkell E, Judy R, Lynch J, Levin M, Haessler J, Aragam K, Chaffin M, Haas M, Lindström S, Assimes TL, Huang J, Min Lee K, Shao Q, Huffman JE, Kabrhel C, Huang Y, Sun YV, Vujkovic M, Saleheen D, Miller DR, Reaven P, DuVall S, Boden WE, Pyarajan S, Reiner AP, Trégouët DA, Henke P, Kooperberg C, Gaziano JM, Concato J, Rader DJ, Cho K, Chang KM, Wilson PW, Smith NL, O'Donnell CJ, Tsao PS, Kathiresan S, Obi A, Damrauer SM, Natarajan P | display-authors = 6 | title = Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease | journal = Nature Genetics | volume = 51 | issue = 11 | pages = 1574–79 | date = November 2019 | pmid = 31676865 | pmc = 6858581 | doi = 10.1038/s41588-019-0519-3 }} In their updated 2018 clinical practice guidelines, the American Society of Hematology identified 29 separate research priorities, most of which related to patients who are acutely or critically ill. Inhibition of factor XI, P-selectin, E-selectin, and a reduction in formation of neutrophil extracellular traps are potential therapies that might treat VTE without increasing bleeding risk.{{cite journal | vauthors = Metz AK, Diaz JA, Obi AT, Wakefield TW, Myers DD, Henke PK | title = Venous thrombosis and post-thrombotic syndrome: from novel biomarkers to biology | journal = Methodist DeBakey Cardiovascular Journal | volume = 14 | issue = 3 | pages = 173–81 | date = 2018 | pmid = 30410646 | pmc = 6217569 | doi = 10.14797/mdcj-14-3-173 }}

{{notelist|32em|notes=}}

{{reflist}}

Cited literature

{{refbegin}}

• {{cite book | vauthors = Dalen JE |title=Venous thromboembolism |url=https://books.google.com/books?id=u-3Fiw7yE5kC&pg=PA1 |year=2003 |publisher=CRC Press |isbn=978-0824756451 }}
• {{cite journal | vauthors = Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuünemann HJ | title = Executive summary: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines | journal = Chest | volume = 141 | issue = 2 Suppl | pages = 7S–47S | date = February 2012 | pmid = 22315257 | pmc = 3278060 | doi = 10.1378/chest.1412S3 }}

{{refend}}

{{Medical resources

| DiseasesDB = 3498

| ICD11 = {{ICD11|BD71.4}}

| ICD10 = {{ICD10|I|80|1|i|80}}, {{ICD10|I|80|2|i|80}}

| ICD9 = {{ICD9|453.40}}

| ICDO =

| OMIM =

| MedlinePlus = 000156

| eMedicineSubj = med

| eMedicineTopic = 2785

| MeshID = D020246

}}

{{Vascular diseases}}

Category:Coagulopathies

Category:Diseases of veins, lymphatic vessels and lymph nodes

Category:Hematology

Category:Wikipedia medicine articles ready to translate