Activated protein C resistance

An estimated 64 percent of patients with venous thromboembolism may have APC resistance.{{cite journal |author =Sheppard DR |s2cid=20016675 |title=Activated protein C resistance: the most common risk factor for venous thromboembolism |journal=J Am Board Fam Pract |volume=13 |issue=2 |pages=111–5 |year=2000 |pmid=10764192 |doi=10.3122/15572625-13-2-111|doi-access=free }}{{update inline|date=February 2020}}

The disorder can be acquired or inherited, the hereditary form having an autosomal dominant inheritance pattern.{{cite journal |pmid=7902898 |date=December 1993 |vauthors =Koster T, Rosendaal FR, De Ronde H, Briët E, Vandenbroucke JP, Bertina RM |s2cid=54283312 |title=Venous thrombosis due to poor anticoagulant response to activated protein C: Leiden Thrombophilia Study |volume=342 |issue=8886–8887 |pages=1503–6 |issn=0140-6736 |journal=Lancet |doi=10.1016/S0140-6736(05)80081-9}}

APC (with protein S as a cofactor) degrades Factor Va and Factor VIIIa. APC resistance is the inability of protein C to cleave Factor Va and/or Factor VIIIa, which allows for longer duration of thrombin generation and may lead to a hypercoagulable state. This may be hereditary or acquired.{{cite journal |vauthors =Nicolaes GA, Dahlbäck B |title=Congenital and acquired activated protein C resistance |journal=Semin Vasc Med |volume=3 |issue=1 |pages=33–46 |year=2003 |pmid=15199491 |doi=10.1055/s-2003-38331}} The best known and most common hereditary form is Factor V Leiden, which is responsible for more than 95% of cases. Other genetic causes include Factor V Cambridge (VThr306) and the factor V HR2 haplotype (A4070G mutation).{{cite book | title = Advances in Experimental Medicine and Biology | last1 = Hotoleanu | first1 = Cristina | chapter = Genetic Risk Factors in Venous Thromboembolism | date = 2016 | volume = 906 | pages = 253–272 | publisher = Springer International Publishing | issn = 0065-2598 | eissn = 2214-8019 | doi = 10.1007/5584_2016_120 | pmid = 27638626 | isbn = 978-3-319-22107-6 | url = }} Acquired forms of APC resistance occur in the presence of elevated Factor VIII concentrations.{{cn|date=November 2021}} Antiphospholipid antibodies,{{cite journal | vauthors = Kujovich JL | title = Factor V Leiden thrombophilia | journal = Genet Med | volume = 13 | issue = 1 | pages = 1–16 | date = January 2011 | pmid = 21116184 | doi = 10.1097/GIM.0b013e3181faa0f2 | s2cid = 220861191 | url = | doi-access = free }} pregnancy, and certain forms of estrogen therapy, such as ethinylestradiol-containing birth control pills, have been found to produce acquired APC resistance.{{cite journal | vauthors = Tchaikovski SN, Rosing J | title = Mechanisms of estrogen-induced venous thromboembolism | journal = Thromb Res | volume = 126 | issue = 1 | pages = 5–11 | date = July 2010 | pmid = 20163835 | doi = 10.1016/j.thromres.2010.01.045 | url = }}{{cite journal | vauthors = Hemelaar M, van der Mooren MJ, Rad M, Kluft C, Kenemans P | title = Effects of non-oral postmenopausal hormone therapy on markers of cardiovascular risk: a systematic review | journal = Fertil Steril | volume = 90 | issue = 3 | pages = 642–72 | date = September 2008 | pmid = 17923128 | doi = 10.1016/j.fertnstert.2007.07.1298 | url = | doi-access = free }}{{cite journal | vauthors = Morimont L, Haguet H, Dogné JM, Gaspard U, Douxfils J | title = Combined Oral Contraceptives and Venous Thromboembolism: Review and Perspective to Mitigate the Risk | journal = Front Endocrinol (Lausanne) | volume = 12 | issue = | pages = 769187 | date = 2021 | pmid = 34956081 | pmc = 8697849 | doi = 10.3389/fendo.2021.769187 | url = | doi-access = free }}{{cite journal | vauthors = Douxfils J, Morimont L, Bouvy C | title = Oral Contraceptives and Venous Thromboembolism: Focus on Testing that May Enable Prediction and Assessment of the Risk | journal = Semin Thromb Hemost | volume = 46 | issue = 8 | pages = 872–886 | date = November 2020 | pmid = 33080636 | doi = 10.1055/s-0040-1714140 | s2cid = 224821517 | url = }}{{cite journal | vauthors = Reda S, Morimont L, Douxfils J, Rühl H | title = Can We Measure the Individual Prothrombotic or Prohemorrhagic Tendency by Global Coagulation Tests? | journal = Hamostaseologie | volume = 40 | issue = 3 | pages = 364–378 | date = August 2020 | pmid = 32726831 | doi = 10.1055/a-1153-5824 | s2cid = 220878363 | url = | doi-access = free }}{{cite journal | vauthors = Clark P | title = Changes of hemostasis variables during pregnancy | journal = Semin Vasc Med | volume = 3 | issue = 1 | pages = 13–24 | date = February 2003 | pmid = 15199489 | doi = 10.1055/s-2003-38329 | url = }}{{cite journal | vauthors = Asscheman H, T'Sjoen G, Lemaire A, Mas M, Meriggiola MC, Mueller A, Kuhn A, Dhejne C, Morel-Journel N, Gooren LJ | title = Venous thrombo-embolism as a complication of cross-sex hormone treatment of male-to-female transsexual subjects: a review | journal = Andrologia | volume = 46 | issue = 7 | pages = 791–5 | date = September 2014 | pmid = 23944849 | doi = 10.1111/and.12150 | hdl = 11585/413984 | s2cid = 5363824 | url = | doi-access = free }}{{cite journal | vauthors = Toorians AW, Thomassen MC, Zweegman S, Magdeleyns EJ, Tans G, Gooren LJ, Rosing J | title = Venous thrombosis and changes of hemostatic variables during cross-sex hormone treatment in transsexual people | journal = J Clin Endocrinol Metab | volume = 88 | issue = 12 | pages = 5723–9 | date = December 2003 | pmid = 14671159 | doi = 10.1210/jc.2003-030520 | url = | doi-access = free }}{{citation overkill|date=April 2022}}

{{See also|Activated protein C resistance test}}

APC resistance can be evaluated using an APC resistance test.{{cite journal | vauthors = Amiral J, Vissac AM, Seghatchian J | title = Laboratory assessment of Activated Protein C Resistance/Factor V-Leiden and performance characteristics of a new quantitative assay | journal = Transfus Apher Sci | volume = 56 | issue = 6 | pages = 906–913 | date = December 2017 | pmid = 29162399 | doi = 10.1016/j.transci.2017.11.021 | url = }} There are two types of APC resistance tests with different properties: the activated partial thromboplastin (aPTT)-based test and the endogenous thrombin potential (ETP)-based test.{{cite journal | vauthors = de Visser MC, van Hylckama Vlieg A, Tans G, Rosing J, Dahm AE, Sandset PM, Rosendaal FR, Bertina RM | title = Determinants of the APTT- and ETP-based APC sensitivity tests | journal = J Thromb Haemost | volume = 3 | issue = 7 | pages = 1488–94 | date = July 2005 | pmid = 15978106 | doi = 10.1111/j.1538-7836.2005.01430.x | hdl = 1887/5044 | s2cid = 23567724 | url = | hdl-access = free }}

Asymptomatic individuals with APC resistance (e.g., heterozygous factor V Leiden) are not normally treated unless additional risk factors for thrombosis are also present.{{cite journal | vauthors = Nichols WL, Heit JA | title = Activated protein C resistance and thrombosis | journal = Mayo Clin Proc | volume = 71 | issue = 9 | pages = 897–8 | date = September 1996 | pmid = 8790269 | doi = 10.4065/71.9.897 | url = }} An example is surgery, in which perioperative short-term anticoagulation may be used. However, people with homozygous factor V Leiden, and people with heterozygous factor V Leiden who have an additional thrombophilic condition (e.g., antithrombin deficiency, protein C deficiency, or protein S deficiency), should be considered for lifelong oral anticoagulation therapy. People with APC resistance and initial DVT are treated with a standard anticoagulant regimen, for instance intravenous heparin therapy followed by oral anticoagulation.

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{{Medical resources

| DiseasesDB =

| ICD10 = D68.51

| ICDO =

| OMIM = 188055

| MedlinePlus =

| eMedicineSubj =

| eMedicineTopic =

| MeshID = D020016

}}

{{Diseases of megakaryocytes|us=y}}

Category:Coagulopathies

Category:Defects of enzyme cofactors