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==Overview==
==Overview==
'''Thrombosis''' is the formation of a [[thrombus]] (medical term for a [[clot]]) inside a [[blood vessel]]. This can dislodge from the site it was formed and can move along the flow of blood to distant places in the body. A piece of thrombus that is transported in this way is called an embolus (plural emboli). This process of formation an emboli, from a thrombus is called thromboembolism. The term was coined in 1848 by [[Rudolph Carl Virchow]].


The most important sites of thrombosis formation, based on their frequency and clinical effect are coronary arteries and deep veins of the legs. Former, the most important site of arterial thrombosis and latter the most important site of venous thrombosis.
==Pathophysiology==
==Pathophysiology==
[[Rudolf Virchow]] noted several factors affecting the clot formation, which are as follows:
[[Rudolf Virchow]] noted several factors affecting the clot formation, which are as follows:
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{| class="wikitable"
{| class="wikitable"
|-
|-
! Virchow's<ref name="isbn1-4020-6649-X">{{cite book |author=Agutter, Paul S. |title=The Aetiology of Deep Venous Thrombosis: A Critical, Historical and Epistemological Survey |publisher=Springer |location=Berlin |year=2008 |pages=84  |isbn=1-4020-6649-X |oclc= |doi= |accessdate=}}</ref>
! Virchow's
! Modern
! Modern
! Notes
! Notes
|-
|-
| Phenomena of interrupted [[blood]]-flow
| Phenomena of interrupted [[blood]]-flow
| "Stasis" or "[[venous stasis]]"<ref name="pmid15692260">{{cite journal |author=Lowe GD |title=Virchow's triad revisited: abnormal flow |journal=Pathophysiol. Haemost. Thromb. |volume=33 |issue=5-6 |pages=455–7 |year=2003 |pmid=15692260 |doi=10.1159/000083845 |url=http://content.karger.com/produktedb/produkte.asp?doi=10.1159/000083845&typ=pdf}}</ref>
| "Stasis" or "[[venous stasis]]"
| The first category, alterations in normal [[blood]] flow, refers to several situations. These include [[turbulence]], [[stasis (medicine)|stasis]], [[mitral stenosis]], and [[varicose veins]]. The equivalence of [[Virchow's triad|Virchow's]] version and the modern version has been disputed.<ref name="urlFurther reflections on Virchows triad. - Free Online Library">{{cite web |url=http://www.thefreelibrary.com/Further+reflections+on+Virchow%27s+triad.(Letter+to+the+Editor)-a0128075135 |title=Further reflections on Virchow's triad. - Free Online Library |format= |work= |accessdate=2009-02-10}}</ref>
| The first category, alterations in normal [[blood]] flow, refers to several situations. These include [[turbulence]], [[stasis (medicine)|stasis]], [[mitral stenosis]], and [[varicose veins]]. The equivalence of [[Virchow's triad|Virchow's]] version and the modern version has been disputed.
|-
|-
| Phenomena associated with irritation of the [[vessel]] and its vicinity
| Phenomena associated with irritation of the [[vessel]] and its vicinity
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| Phenomena of [[blood]]-[[coagulation]]
| Phenomena of [[blood]]-[[coagulation]]
| "[[Hypercoagulability]]"
| "[[Hypercoagulability]]"
| The last category, alterations in the constitution of blood,<ref name="pmid15692259">{{cite journal |author=Chung I, Lip GY |title=Virchow's triad revisited: blood constituents |journal=Pathophysiol. Haemost. Thromb. |volume=33 |issue=5-6 |pages=449–54 |year=2003 |pmid=15692259 |doi=10.1159/000083844 |url=http://content.karger.com/produktedb/produkte.asp?doi=10.1159/000083844&typ=pdf}}</ref> has numerous possible [[risk factors]] such as [[hyperviscosity]], deficiency of [[antithrombin]] III, [[nephrotic syndrome]], changes after severe [[Physical trauma|trauma]] or burn, disseminated [[cancer]], late [[pregnancy]] and [[delivery]], race, age, whether the patient is a smoker, and [[obesity]].  All of these [[risk factors]] lead to  [[hypercoagulability]].
| The last category, alterations in the constitution of blood,  has numerous possible [[risk factors]] such as [[hyperviscosity]], deficiency of [[antithrombin]] III, [[nephrotic syndrome]], changes after severe [[Physical trauma|trauma]] or burn, disseminated [[cancer]], late [[pregnancy]] and [[delivery]], race, age, whether the patient is a smoker, and [[obesity]].  All of these [[risk factors]] lead to  [[hypercoagulability]].
|}
|}


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* A [[thrombus]] is characteristically found to first develop in the calf [[veins]] and progressively grow in the direction of [[blood]] flow (leading to the [[heart]]).
* A [[thrombus]] is characteristically found to first develop in the calf [[veins]] and progressively grow in the direction of [[blood]] flow (leading to the [[heart]]).
* An exceedingly extensive thrombosis in [[Deep vein|deep veins]] can extend well into the [[iliac vein|iliac veins]] or [[inferior vena cava|the inferior vena cava]].
* An exceedingly extensive thrombosis in [[Deep vein|deep veins]] can extend well into the [[iliac vein|iliac veins]] or [[inferior vena cava|the inferior vena cava]].
* [[Atherosclerosis]] is a miss balance between [[lipid]]<nowiki/>s and the hemostasis system which caused clot in [[Artery|arteries]]. By occluding the artery [[myocardial infarction]], [[stroke]] could happen <ref name="pmid2083873">{{cite journal |vauthors=Prentice CR |title=Pathogenesis of thrombosis |journal=Haemostasis |volume=20 Suppl 1 |issue= |pages=50–9 |date=1990 |pmid=2083873 |doi=10.1159/000216161 |url=}}</ref>.
* [[Atherosclerosis]] is a miss balance between [[lipid]]<nowiki/>s and the hemostasis system which caused clot in [[Artery|arteries]]. By occluding the artery [[myocardial infarction]], [[stroke]] could happen .
* Thrombosis can happen in both Bare Metal Stent <nowiki/>(BMS) and Drug Eluting Stent (DES).   
* Thrombosis can happen in both Bare Metal Stent <nowiki/>(BMS) and Drug Eluting Stent (DES).   
Factors that serve as nidus for development stent thrombosis are:<blockquote>Delayed [[endothelialization]]<ref name="pmid17344324">{{cite journal| author=Camenzind E, Steg PG, Wijns W| title=Stent thrombosis late after implantation of first-generation drug-eluting stents: a cause for concern. | journal=Circulation | year= 2007 | volume= 115 | issue= 11 | pages= 1440-55; discussion 1455 | pmid=17344324 | doi=10.1161/CIRCULATIONAHA.106.666800 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17344324  }} </ref><ref name="pmid17684153">{{cite journal| author=Awata M, Kotani J, Uematsu M, Morozumi T, Watanabe T, Onishi T et al.| title=Serial angioscopic evidence of incomplete neointimal coverage after sirolimus-eluting stent implantation: comparison with bare-metal stents. | journal=Circulation | year= 2007 | volume= 116 | issue= 8 | pages= 910-6 | pmid=17684153 | doi=10.1161/CIRCULATIONAHA.105.609057 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=17684153  }} </ref><ref name="pmid16697331">{{cite journal| author=Kotani J, Awata M, Nanto S, Uematsu M, Oshima F, Minamiguchi H et al.| title=Incomplete neointimal coverage of sirolimus-eluting stents: angioscopic findings. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 10 | pages= 2108-11 | pmid=16697331 | doi=10.1016/j.jacc.2005.11.092 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16697331  }} </ref>.</blockquote><blockquote>Inflammatory response to the stent material<ref>Leon MB, Abizaid A, Moses JW. Subgroup analysis from the Cypher clinical trials. In: The Cypher Stent: A New Gold Standard in the Treatment of Coronary Artery Disease. New York, NY: Cardiovascular Research Foundation; 2003:54–57.</ref><ref name="pmid15710761">{{cite journal| author=Tanabe K, Serruys PW, Degertekin M, Grube E, Guagliumi G, Urbaszek W et al.| title=Incomplete stent apposition after implantation of paclitaxel-eluting stents or bare metal stents: insights from the randomized TAXUS II trial. | journal=Circulation | year= 2005 | volume= 111 | issue= 7 | pages= 900-5 | pmid=15710761 | doi=10.1161/01.CIR.0000155607.54922.16 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15710761  }} </ref>.</blockquote><blockquote>Hypersensitivity reaction around the stent material in DES serving as nidus for ST<ref name="pmid14744976">{{cite journal| author=Virmani R, Guagliumi G, Farb A, Musumeci G, Grieco N, Motta T et al.| title=Localized hypersensitivity and late coronary thrombosis secondary to a sirolimus-eluting stent: should we be cautious? | journal=Circulation | year= 2004 | volume= 109 | issue= 6 | pages= 701-5 | pmid=14744976 | doi=10.1161/01.CIR.0000116202.41966.D4 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=14744976  }} </ref><ref name="pmid16386683">{{cite journal| author=Nebeker JR, Virmani R, Bennett CL, Hoffman JM, Samore MH, Alvarez J et al.| title=Hypersensitivity cases associated with drug-eluting coronary stents: a review of available cases from the Research on Adverse Drug Events and Reports (RADAR) project. | journal=J Am Coll Cardiol | year= 2006 | volume= 47 | issue= 1 | pages= 175-81 | pmid=16386683 | doi=10.1016/j.jacc.2005.07.071 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16386683  }} </ref><ref name="pmid16814667">{{cite journal| author=Joner M, Finn AV, Farb A, Mont EK, Kolodgie FD, Ladich E et al.| title=Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk. | journal=J Am Coll Cardiol | year= 2006 | volume= 48 | issue= 1 | pages= 193-202 | pmid=16814667 | doi=10.1016/j.jacc.2006.03.042 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16814667  }} </ref><ref name="pmid15963413">{{cite journal| author=Ong AT, McFadden EP, Regar E, de Jaegere PP, van Domburg RT, Serruys PW| title=Late angiographic stent thrombosis (LAST) events with drug-eluting stents. | journal=J Am Coll Cardiol | year= 2005 | volume= 45 | issue= 12 | pages= 2088-92 | pmid=15963413 | doi=10.1016/j.jacc.2005.02.086 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15963413  }} </ref><ref name="pmid15464315">{{cite journal| author=Grube E, Lansky A, Hauptmann KE, Di Mario C, Di Sciascio G, Colombo A et al.| title=High-dose 7-hexanoyltaxol-eluting stent with polymer sleeves for coronary revascularization: one-year results from the SCORE randomized trial. | journal=J Am Coll Cardiol | year= 2004 | volume= 44 | issue= 7 | pages= 1368-72 | pmid=15464315 | doi=10.1016/j.jacc.2004.06.054 | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15464315  }} </ref>.</blockquote>
Factors that serve as nidus for development stent thrombosis are:<blockquote>Delayed [[endothelialization]].</blockquote><blockquote>Inflammatory response to the stent material.</blockquote><blockquote>Hypersensitivity reaction around the stent material in DES serving as nidus for ST.</blockquote>
* [[Pregnancy]] increases risk of having thrombosis in both veins and arteries because of hypercoagulate state <ref name="pmid26383185">{{cite journal |vauthors=James AH |title=Thrombosis in pregnancy and maternal outcomes |journal=Birth Defects Res. C Embryo Today |volume=105 |issue=3 |pages=159–66 |date=September 2015 |pmid=26383185 |doi=10.1002/bdrc.21106 |url=}}</ref>.
* [[Pregnancy]] increases risk of having thrombosis in both veins and arteries because of hypercoagulate state .
* Acquired risk factors for thrombosis are:
* Acquired risk factors for thrombosis are:
[[Oral contraceptive]] use,
[[Oral contraceptive]] use,
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Surgery
Surgery


Prolonged immobilization like hospitalization <ref name="pmid27189130">{{cite journal |vauthors=Wolberg AS, Rosendaal FR, Weitz JI, Jaffer IH, Agnelli G, Baglin T, Mackman N |title=Venous thrombosis |journal=Nat Rev Dis Primers |volume=1 |issue= |pages=15006 |date=May 2015 |pmid=27189130 |doi=10.1038/nrdp.2015.6 |url=}}</ref>.
Prolonged immobilization like hospitalization .


'''This video explains the process of thrombosis:'''
'''This video explains the process of thrombosis:'''
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==Genetics==
==Genetics==
Genetic factors that play roles in causing thrombosis <ref name="pmid19630821">{{cite journal |vauthors=Rosendaal FR, Reitsma PH |title=Genetics of venous thrombosis |journal=J. Thromb. Haemost. |volume=7 Suppl 1 |issue= |pages=301–4 |date=July 2009 |pmid=19630821 |doi=10.1111/j.1538-7836.2009.03394.x |url=}}</ref>:
Genetic factors that play roles in causing thrombosis :
* Non-O blood groups  
* Non-O blood groups  
* Factor V Leiden mutation
* Factor V Leiden mutation
* Prothrombin G20210A gene variants
* Prothrombin G20210A gene variants
* Polymorphisms in factors IX17 or XI <ref name="pmid21232005">{{cite journal |vauthors=Austin H, De Staercke C, Lally C, Bezemer ID, Rosendaal FR, Hooper WC |title=New gene variants associated with venous thrombosis: a replication study in White and Black Americans |journal=J. Thromb. Haemost. |volume=9 |issue=3 |pages=489–95 |date=March 2011 |pmid=21232005 |pmc=4532311 |doi=10.1111/j.1538-7836.2011.04185.x |url=}}</ref>
* Polymorphisms in factors IX17 or XI  


==Gross Pathology==
==Gross Pathology==
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Revision as of 15:59, 28 August 2018

Thrombosis Microchapters

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

Thrombosis is the formation of a thrombus (medical term for a clot) inside a blood vessel. This can dislodge from the site it was formed and can move along the flow of blood to distant places in the body. A piece of thrombus that is transported in this way is called an embolus (plural emboli). This process of formation an emboli, from a thrombus is called thromboembolism. The term was coined in 1848 by Rudolph Carl Virchow.

The most important sites of thrombosis formation, based on their frequency and clinical effect are coronary arteries and deep veins of the legs. Former, the most important site of arterial thrombosis and latter the most important site of venous thrombosis.

Pathophysiology

Rudolf Virchow noted several factors affecting the clot formation, which are as follows:

1) Alterations in blood flow (stasis): Blood flows throughout the circulatory system, without significantly stopping or slowing any where. In certain pathological conditions where the blood flow slows down or stops, it causes:

  • Increase in platelet to endothelium contact
  • Decrease the dilution of clotting factors

This increases the risk of clot formation and form microthrombi, which further grow and propagate.

2) Injury to the vascular endothelium: Intrinsic or secondary to external trauma (eg, catheterization) can cause intimal damage and stimulates clot formation. See Coagulation.

3) Alterations in the constitution of blood (hypercoagulability): It is the propensity to develop thrombosis due to an abnormality in the system of coagulation.

These three conditions are collectively known as Virchow's triad and lead to intravascular coagulation, forming a mass of red blood cells, leukocytes, and fibrin.

Shown below is a table depicting the elements of Virchow's triad and their modern counterparts.

Virchow's Modern Notes
Phenomena of interrupted blood-flow "Stasis" or "venous stasis" The first category, alterations in normal blood flow, refers to several situations. These include turbulence, stasis, mitral stenosis, and varicose veins. The equivalence of Virchow's version and the modern version has been disputed.
Phenomena associated with irritation of the vessel and its vicinity "Endothelial injury" or "vessel wall injury" The second category, injuries and/or trauma to endothelium includes damage to the veins arising from shear stress or hypertension.
Phenomena of blood-coagulation "Hypercoagulability" The last category, alterations in the constitution of blood, has numerous possible risk factors such as hyperviscosity, deficiency of antithrombin III, nephrotic syndrome, changes after severe trauma or burn, disseminated cancer, late pregnancy and delivery, race, age, whether the patient is a smoker, and obesity. All of these risk factors lead to hypercoagulability.

Thrombus Formation

  • Usually there is a balance between the coagulation and fibrinolysis systems in order to not having abnormal thrombosis in the body.
  • Factors that increase the risk for a homeostatic imbalance include:

Thrombophilia

Immobilization

Trauma

Factors that serve as nidus for development stent thrombosis are:

Delayed endothelialization.

Inflammatory response to the stent material.

Hypersensitivity reaction around the stent material in DES serving as nidus for ST.

  • Pregnancy increases risk of having thrombosis in both veins and arteries because of hypercoagulate state .
  • Acquired risk factors for thrombosis are:

Oral contraceptive use,

Hormone replacement therapy

Advanced age

Surgery

Prolonged immobilization like hospitalization .

This video explains the process of thrombosis:

{{#ev:youtube|X_POCRsy7i4}}

Genetics

Genetic factors that play roles in causing thrombosis :

  • Non-O blood groups
  • Factor V Leiden mutation
  • Prothrombin G20210A gene variants
  • Polymorphisms in factors IX17 or XI

Gross Pathology

  • Dull appearance.
  • Zahn line from platelets and fibrin with layers of RBCs in pulmonary venous thromboembolism.
  • Gross picture of thrombosis is different in live and dead person.

In live person it is gray and firm.

In dead person it is dark purple or yellow elastic called "chicken fat".

Microscopic Pathology

  • lamination
  • Zahn line


Classification

Arterial | Venous | Arterial and Venous Thrombosis: Differences and Similarities

Causes

Site of Thrombosis

Arterial | Venous

Differentiating Thrombosis from other Diseases

Arterial | Venous

Risk Factors

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Evaluation

Treatment

Risk Factor Modifications | Prevention

Related Chapters

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