Editing Thrombosis (section)

=== Pathogenesis ===
{{Main|Virchow's triad}}The main causes of thrombosis are given in [[Virchow's triad]] which lists [[thrombophilia]], [[endothelial cell]] injury, and disturbed [[blood flow]]. Generally speaking the risk for thrombosis increases over the life course of individuals, depending on life style factors like smoking, diet, and physical activity, the presence of other diseases like cancer or autoimmune disease, while also platelet properties change in aging individuals which is an important consideration as well.<ref>{{cite journal|last1=Faria|first1=Alessandra V.S. |last2= Andrade|first2=Sheila S|last3=Peppelenbosch|first3=Maikel P.|last4=Ferreira-Halder| first4=Carmen V.|last5=Fuhler|first5=Gwenny M.|title=Platelets in aging and cancer-"double-edged sword"| journal=Cancer and Metastasis Reviews |date=December 2020|volume=39|issue=4|pages=1205–1221|doi=10.1007/s10555-020-09926-2|pmid=32869161|pmc=458881| doi-access=free}}</ref>

==== Hypercoagulability ====
{{Main|Thrombophilia}}
Hypercoagulability or ''thrombophilia'', is caused by, for example, [[genetic disorder|genetic deficiencies]] or [[autoimmune disease|autoimmune disorder]]s. Recent studies indicate that white blood cells play a pivotal role in deep vein thrombosis, mediating numerous pro-thrombotic actions.<ref>{{cite journal|last1=Swystun|first1=L. L.|last2=Liaw|first2=P. C.|title=The role of leukocytes in thrombosis|journal=Blood|date=June 27, 2016|volume=128|issue=6|pages=753–762|doi=10.1182/blood-2016-05-718114|pmid=27354721|doi-access=free}}</ref>

==== Endothelial cell injury ====
Any inflammatory process, such as trauma, surgery or infection, can cause damage to the [[endothelium|endothelial lining]] of the vessel's wall. The main mechanism is exposure of [[tissue factor]] to the blood coagulation system.<ref name="labtestsonline">[http://www.labtestsonline.org/understanding/conditions/hypercoagulable_disorders-3.html labtestsonline > Hypercoagulable Disorders] {{Webarchive|url=https://web.archive.org/web/20070618165003/http://www.labtestsonline.org/understanding/conditions/hypercoagulable_disorders-3.html |date=June 18, 2007 }} This article was last reviewed on May 23, 2007, and was last modified on March 6, 2010.</ref> Inflammatory and other stimuli (such as [[hypercholesterolemia]]) can lead to changes in [[gene expression]] in endothelium producing to a pro-thrombotic state.<ref name=":0" /> When this occurs, endothelial cells [[Downregulation and upregulation|downregulate]] substances such as [[thrombomodulin]], which is a key modulator of thrombin activity.<ref>{{Cite journal|last1=Ito|first1=Takashi|last2=Kakihana|first2=Yasuyuki|last3=Maruyama|first3=Ikuro|date=January 1, 2016|title=Thrombomodulin as an intravascular safeguard against inflammatory and thrombotic diseases|journal=Expert Opinion on Therapeutic Targets|volume=20|issue=2|pages=151–158|doi=10.1517/14728222.2016.1086750|issn=1744-7631|pmid=26558419|s2cid=207486815}}</ref> The result is a sustained activation of thrombin and reduced production of [[protein C]] and tissue factor inhibitor, which furthers the pro-thrombotic state.<ref name=":0" />

Endothelial injury is almost invariably involved in the formation of thrombi in arteries, as high rates of blood flow normally hinder clot formation. In addition, arterial and cardiac clots are normally rich in platelets–which are required for clot formation in areas under high stress due to blood flow.<ref name=":0">{{Cite book|title=Robbins and Cotran Pathologic Basis of Disease|last=Kumar|first=Vinay|publisher=Elsevier|year=2015|isbn=978-1-4557-2613-4|location=Philadelphia|pages=122–130}}</ref>

==== Disturbed blood flow ====
{{Further|Blood flow}}
[[File:Potential Mechanisms of Cancer-Related Hypercoagulability.png|thumb|Cancer-associated thrombosis can result from: (1) stasis, i.e., direct pressure on blood vessels by the tumor mass, poor performance status, and bed rest following surgical procedures; (2) iatrogenic, due to treatment with antineoplastic medications; and (3) secretion of heparanase from malignant tumors that results in degradation of endogenous heparin.<ref>{{Cite journal|last1=Nasser|first1=Nicola J.|last2=Fox|first2=Jana|last3=Agbarya|first3=Abed|date=March 2020|title=Potential Mechanisms of Cancer-Related Hypercoagulability|journal=Cancers|language=en|volume=12|issue=3|pages=566|doi=10.3390/cancers12030566|pmc=7139427|pmid=32121387|doi-access=free}}</ref>]]
Causes of disturbed blood flow include stagnation of blood flow past the point of injury, or [[venous stasis]] which may occur in heart failure,<ref name=labtestsonline /> or after long periods of sedentary behaviour, such as sitting on a long airplane flight. Also, [[atrial fibrillation]], causes stagnant blood in the left atrium (LA), or [[left atrial appendage]] (LAA), and can lead to a [[thromboembolism]].<ref name=labtestsonline /> [[Cancers]] or [[malignancies]] such as [[leukemia]] may cause increased risk of thrombosis by possible activation of the coagulation system by cancer cells or secretion of procoagulant substances ([[paraneoplastic syndrome]]), by external compression on a blood vessel when a solid tumor is present, or (more rarely) extension into the vasculature (for example, renal cell cancers extending into the renal veins).<ref name=labtestsonline /> Also, treatments for cancer (radiation, chemotherapy) often cause additional hypercoagulability.<ref name=labtestsonline /> There are scores that correlate different aspects of patient data (comorbidities, vital signs, and others) to risk of thrombosis, such as the POMPE-C, which stratifies risk of mortality due to pulmonary embolism in patients with cancer, who typically have higher rates of thrombosis.<ref>{{cite journal|last1=van der Hulle|first1=T|last2=den Exter|first2=PL|last3=Kooiman|first3=J|last4=van der Hoeven|first4=JJ|last5=Huisman|first5=MV|last6=Klok|first6=FA|title=Meta-analysis of the efficacy and safety of new oral anticoagulants in patients with cancer-associated acute venous thromboembolism.|journal=J Thromb Haemost|date=2014|volume=12|issue=7|pages=1116–20|pmid=24819040|doi=10.1111/jth.12605|s2cid=19395326}}</ref> Also, there are several predictive scores for thromboembolic events, such as Padua,<ref>{{Cite journal|last1=BARBAR|first1=S.|last2=NOVENTA|first2=F.|last3=ROSSETTO|first3=V.|last4=FERRARI|first4=A.|last5=BRANDOLIN|first5=B.|last6=PERLATI|first6=M.|last7=DE BON|first7=E.|last8=TORMENE|first8=D.|last9=PAGNAN|first9=A.|last10=PRANDONI|first10=P.|date=November 2010|title=A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score|journal=Journal of Thrombosis and Haemostasis|volume=8|issue=11|pages=2450–2457|doi=10.1111/j.1538-7836.2010.04044.x|pmid=20738765|issn=1538-7933|doi-access=free}}</ref> Khorana,<ref>{{Cite journal|last1=Khorana|first1=Alok A.|last2=Francis|first2=Charles W.|last3=Culakova|first3=Eva|last4=Fisher|first4=Richard I.|last5=Kuderer|first5=Nicole M.|last6=Lyman|first6=Gary H.|date=January 20, 2006|title=Thromboembolism in Hospitalized Neutropenic Cancer Patients|journal=Journal of Clinical Oncology|volume=24|issue=3|pages=484–490|doi=10.1200/jco.2005.03.8877|pmid=16421425|issn=0732-183X|doi-access=free}}</ref><ref>{{Cite journal|last1=Khorana|first1=Alok A.|last2=Kuderer|first2=Nicole M.|last3=Culakova|first3=Eva|last4=Lyman|first4=Gary H.|last5=Francis|first5=Charles W.|date=May 15, 2008|title=Development and validation of a predictive model for chemotherapy-associated thrombosis|journal=Blood|volume=111|issue=10|pages=4902–4907|doi=10.1182/blood-2007-10-116327|pmid=18216292|pmc=2384124|issn=0006-4971|doi-access=free}}</ref> and [[ThroLy score]].<ref>{{Cite journal|last1=Antic|first1=Darko|last2=Milic|first2=Natasa|last3=Nikolovski|first3=Srdjan|last4=Todorovic|first4=Milena|last5=Bila|first5=Jelena|last6=Djurdjevic|first6=Predrag|last7=Andjelic|first7=Bosko|last8=Djurasinovic|first8=Vladislava|last9=Sretenovic|first9=Aleksandra|last10=Vukovic|first10=Vojin|last11=Jelicic|first11=Jelena|date=July 22, 2016|title=Development and validation of multivariable predictive model for thromboembolic events in lymphoma patients|journal=American Journal of Hematology|volume=91|issue=10|pages=1014–1019|doi=10.1002/ajh.24466|pmid=27380861|s2cid=1724916|issn=0361-8609|doi-access=free}}</ref>