Trousseau sign of malignancy

Armand Trousseau first described this finding in the 1860s; he later found the same sign in himself, was subsequently diagnosed with gastric cancer and died soon thereafter.{{cite journal |vauthors=Samuels MA, King ME, Balis U |title=Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises. Case 31-2002. A 61-year-old man with headache and multiple infarcts |journal=N. Engl. J. Med. |volume=347 |issue=15 |pages=1187–94 |date=2002 |pmid=12374880 |doi=10.1056/NEJMcpc020117 }}

Trousseau presciently attributed thromboembolism in malignancy to changes in blood composition rather than local inflammatory or mechanical forces. By correlating clinical observation with surgical and autopsy findings, Trousseau recognized that a localized cancer could induce a generalized hypercoagulable state in which thrombosis could occur elsewhere in the body, such as in extremities with visceral malignancy. Trousseau described several cases in which recurrent thrombosis was the presenting feature of visceral cancer, and his confidence in the utility of this connection led him to say, "So great, in my opinion, is the semiotic value of phlegmasia in the cancerous cachexia, that I regard this phlegmasia as a sign of the cancerous diathesis as certain as sanguinolent effusion into the serous cavities."

Some malignancies, especially gliomas (25%), as well as adenocarcinomas of the pancreas and lung, are associated with hypercoagulability (the tendency to form blood clots) for reasons that are incompletely understood, but may be related to factors secreted by the tumors, in particular a circulating pool of cell-derived tissue factor-containing microvesicles.{{cite journal | author = Del Conde I, Bharwani LD, Dietzen DJ, Pendurthi U, Thiagarajan P, López JA | year = 2007 | title = Microvesicle-associated tissue factor and Trousseau's syndrome. | journal = J Thromb Haemost | volume = 5 | issue = 1| pages = 70–4 | doi=10.1111/j.1538-7836.2006.02301.x| pmid = 17239164 | pmc = 3410746}} Some adenocarcinomas secrete mucin that can interact with selectin found on platelets, thereby causing small clots to form.{{cite journal |vauthors=Wahrenbrock M, Borsig L, Le D, Varki N, Varki A | year = 2003 | title = Selectin-mucin interactions as a probable molecular explanation for the association of Trousseau syndrome with mucinous adenocarcinomas | journal = J Clin Invest | volume = 112 | issue = 6| pages = 853–862 | doi=10.1172/jci200318882| pmid = 12975470 | pmc = 193671}}{{Cite journal | doi = 10.1182/blood-2006-10-053736 | issn = 0006-4971 | volume = 110 | issue = 6 | pages = 1723–1729 | last = Varki | first = Ajit | title = Trousseau's syndrome: multiple definitions and multiple mechanisms | journal = Blood

| date = 2007 | pmid = 17496204 | pmc = 1976377}} Moreover, most malignant tumors overexpress and secrete heparanase,{{Cite journal|last1=Edovitsky|first1=Evgeny|last2=Elkin|first2=Michael|last3=Zcharia|first3=Eyal|last4=Peretz|first4=Tamar|last5=Vlodavsky|first5=Israel|date=2004-08-18|title=Heparanase gene silencing, tumor invasiveness, angiogenesis, and metastasis|journal=Journal of the National Cancer Institute|volume=96|issue=16|pages=1219–1230|doi=10.1093/jnci/djh230|issn=1460-2105|pmid=15316057|doi-access=free}} an enzyme that degrade heparan sulfate {{Cite journal|last1=Vlodavsky|first1=I.|last2=Friedmann|first2=Y.|last3=Elkin|first3=M.|last4=Aingorn|first4=H.|last5=Atzmon|first5=R.|last6=Ishai-Michaeli|first6=R.|last7=Bitan|first7=M.|last8=Pappo|first8=O.|last9=Peretz|first9=T.|last10=Michal|first10=I.|last11=Spector|first11=L.|date=July 1999|title=Mammalian heparanase: gene cloning, expression and function in tumor progression and metastasis|url=https://pubmed.ncbi.nlm.nih.gov/10395325/|journal=Nature Medicine|volume=5|issue=7|pages=793–802|doi=10.1038/10518|issn=1078-8956|pmid=10395325|s2cid=38895589 }} and endogenous heparin,{{Cite journal|last1=Nasser|first1=N. J.|last2=Sarig|first2=G.|last3=Brenner|first3=B.|last4=Nevo|first4=E.|last5=Goldshmidt|first5=O.|last6=Zcharia|first6=E.|last7=Li|first7=J. P.|last8=Vlodavsky|first8=I.|date=March 2006|title=Heparanase neutralizes the anticoagulation properties of heparin and low-molecular-weight heparin|journal=Journal of Thrombosis and Haemostasis|volume=4|issue=3|pages=560–565|doi=10.1111/j.1538-7836.2006.01792.x|issn=1538-7933|pmid=16460439|doi-access=free}} and thus contribute to the hypercoagulable state in cancer patients.{{Cite journal|last1=Nasser|first1=Nicola J.|last2=Na'amad|first2=Mira|last3=Weinberg|first3=Ido|last4=Gabizon|first4=Alberto A.|date=January 2015|title=Pharmacokinetics of low molecular weight heparin in patients with malignant tumors|url=https://pubmed.ncbi.nlm.nih.gov/25280062/|journal=Anti-Cancer Drugs|volume=26|issue=1|pages=106–111|doi=10.1097/CAD.0000000000000176|issn=1473-5741|pmid=25280062|s2cid=6639067 }}{{Cite journal|last=Rickles|first=F. R.|date=March 2006|title=If heparanase is the answer, what is the question?|url=https://pubmed.ncbi.nlm.nih.gov/16460438/|journal=Journal of Thrombosis and Haemostasis|volume=4|issue=3|pages=557–559|doi=10.1111/j.1538-7836.2006.01828.x|issn=1538-7933|pmid=16460438|s2cid=5631803 |doi-access=free}}{{Cite journal|last1=Nasser|first1=Nicola J.|last2=Fox|first2=Jana|last3=Agbarya|first3=Abed|date=2020-02-29|title=Potential Mechanisms of Cancer-Related Hypercoagulability|journal=Cancers|volume=12|issue=3|page=566 |doi=10.3390/cancers12030566|issn=2072-6694|pmc=7139427|pmid=32121387|doi-access=free }}

File:Potential Mechanisms of Cancer-Related Hypercoagulability.png

In patients with malignancy-associated hypercoagulable states, the blood may spontaneously form clots in the portal vessels (portal vein thrombosis), the deep veins of the limbs (deep vein thrombosis), or the superficial veins (superficial vein thrombosis) anywhere on the body. These clots present as visibly swollen blood vessels (thrombophlebitis), especially the veins, or as intermittent pain in the affected areas.

{{reflist|2}}

{{Bleeding and clotting disorders}}

Category:Medical signs