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| {{Infobox_Disease |
| | __NOTOC__ |
| Name = {{PAGENAME}} |
| | {{Thrombophilia}} |
| Image = |
| | {{CMG}}; {{AE}} [[User:Kashish Goel|Kashish Goel, M.D.]], {{asiri}},{{M.B}}, {{MKA}}, {{S.G.}}, {{JK}} |
| Caption = |
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| DiseasesDB = 29080 |
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| ICD10 = |
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| ICD9 = |
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| ICDO = |
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| OMIM = 188050 |
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| MedlinePlus = |
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| eMedicineSubj = |
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| eMedicineTopic = |
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| MeshID = D019851 |
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| }} | |
| {{SI}} | |
| {{CMG}};'''Associate Editor(s)-In-Chief:''' [[Kashish Goel|Kashish Goel, M.D.]] | |
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| '''''Synonyms and Keywords:''''' Hypercoagulability, coagulability, hypercoagulable state
| | {{SK}} Hypercoagulability, coagulability, hypercoagulable state; thrombosis risk elevation; thrombotic tendency; prothrombotic state; clotting disorder; |
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| ==Overview== | | == [[Thrombophilia overview|Overview]] == |
| '''Thrombophilia''' is defined as an increased risk of [[thrombosis]] in the body, due to an abnormality in the system of [[coagulation]]. Thrombophilia can be congenital or acquired. More than 50% of the cases of thrombosis are associated with an underlying thrombophilia. Thrombophilias are mostly associated with venous thromboembolism like deep vein thrombosis in lower extremities or pulmonary embolism. Relatively less is known about thrombophilias that predispose to arterial thromboembolism<ref name="pmid11309638">{{cite journal |author=Seligsohn U, Lubetsky A |title=Genetic susceptibility to venous thrombosis |journal=N. Engl. J. Med. |volume=344 |issue=16 |pages=1222–31 |year=2001 |month=April |pmid=11309638 |doi=10.1056/NEJM200104193441607 |url=}}</ref>.
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| ==Classification== | | == [[Thrombophilia historical perspective|Historical Perspective]]== |
| Thrombophilia can be classified in various forms.
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| * The most common classification is by the nature of the thrombosis: [[artery|arterial]], [[vein|venous]] or combined.
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| * Crowther & Kelton (2003) propose to classify the abnormality by the molecular deficiency, type I being the (severe) deficiencies of inhibitors, and type II being the less severe elevation of coagulation factors.<ref>{{cite journal |author=Crowther MA, Kelton JG |title=Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system |journal=Ann. Intern. Med. |volume=138 |issue=2 |pages=128-34|year=2003 |pmid=12529095 |doi= |url=http://www.annals.org/cgi/reprint/138/2/128}}</ref>
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| * Acquired vs. congenital
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| ==Pathophysiology== | | == [[Thrombophilia classification|Classification]] == |
| The Virchow's triad has been described classically as the patho-physiologic mechanism responsible for any thrombosis, which includes 3 components:
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| * Endothelial dysfunction
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| * Venous stasis
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| * Hypercoaguability
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| The mechanism of thrombophilia involves affecting the pathway of thrombosis<ref name="pmid11309638">{{cite journal |author=Seligsohn U, Lubetsky A |title=Genetic susceptibility to venous thrombosis |journal=N. Engl. J. Med. |volume=344 |issue=16 |pages=1222–31 |year=2001 |month=April |pmid=11309638 |doi=10.1056/NEJM200104193441607 |url=}}</ref>:
| | == [[Thrombophilia pathophysiology|Pathophysiology]] == |
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| [[Image: Figure_thrombophilia_mechanism.jpg]] | | == [[Thrombophilia causes|Causes]] == |
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| Adapted from: N Engl J Med. 2001 Apr 19;344(16):1222-31.
| | == [[Thrombophilia differential diagnosis|Differentiating Thrombophilia from Other Diseases]] == |
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| ==Epidemiology and Demographics== | | == [[Thrombophilia epidemiology and demographics|Epidemiology and Demographics]]== |
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| ==Risk factors== | | == [[Thrombophilia risk factors|Risk Factors]] == |
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| ==Causes== | | == [[Thrombophilia screening|Screening]]== |
| Common types:
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| * [[Factor V Leiden|Factor V, Leiden type]] (5% of the population are [[heterozygous]] for FVL).
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| * [[Prothrombin]] mutation (G20210A, 5'UTR).
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| * High [[homocysteine]] levels due to [[MTHFR]] mutation or vitamin deficiency (vitamins B6, B12 and folic acid).
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| * [[Antiphospholipid antibodies]]
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| ** [[anti-cardiolipin antibodies]] and/or
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| ** [[lupus anticoagulant]]s
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| * [[Kidney|Renal disease]] (renal loss of antithrombin)
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| Rare forms:
| | == [[Thrombophilia natural history, complications and prognosis|Natural History, Complications and Prognosis]] == |
| * [[Plasminogen]] and [[fibrinolysis]] disorders.
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| * [[Paroxysmal nocturnal hemoglobinuria]]
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| * [[Protein C deficiency]].
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| * [[Protein S deficiency]].
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| * [[Antithrombin|Antithrombin III]] deficiency.
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| ==Differential diagnosis of thrombophilia== | | == Diagnosis == |
| (By organ system)
| | [[Thrombophilia history and symptoms|History and Symptoms]] | [[Thrombophilia physical examination|Physical Examination]] | [[Thrombophilia laboratory findings|Laboratory Findings]] | [[Thrombophilia x ray|X Ray]] | [[Thrombophilia CT|CT]] | [[Thrombophilia MRI|MRI]] | [[Thrombophilia echocardiography or ultrasound|Ultrasound]] | [[Thrombophilia other imaging findings|Other Imaging Studies]] | [[Thrombophilia other diagnostic studies|Other Diagnostic Studies]] |
| {|style="width:75%; height:100px" border="1"
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| |style="height:100px"; style="width:25%" border="1" bgcolor="LightSteelBlue" | '''Cardiovascular'''
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| |style="height:100px"; style="width:75%" border="1" bgcolor="Beige" | • [[Cerebral vein thrombosis]] • [[Acute myocardial infarction]] • [[Deep vein thrombophlebitis]] • [[Portal vein thrombosis]] • [[Pelvic thrombophlebitis]]
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| |-bgcolor="LightSteelBlue"
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| | '''Drug Side Effect''' | |
| |bgcolor="Beige"| • [[Asparaginase]] • [[Bevacizumab]] • [[Combined oral contraceptive pill]] • [[Cyproterone]] • [[Diethylstilboestrol]] • [[Drospirenone]] • [[Eltrombopag]] • [[Erythropoietin]] • [[Ethinylestradiol]] • [[Fosfestrol]] • [[Granulocyte-macrophage colony stimulating factor]] • [[Heparin]] • [[Hormone replacement therapy]] • [[Lenalidomide]] • [[Peginesatide]] • [[Polyestradiol]] • [[Raloxifene]] • [[Strontium ranelate]] • [[Tamoxifen]] • [[Tobacco smoking]] • [[Tranexamic acid]] • [[Vorinostat]]
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| |-bgcolor="LightSteelBlue"
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| | '''Endocrine'''
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| |bgcolor="Beige"| • [[Hyperosmolar non-ketotic diabetic coma]]
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| |-bgcolor="LightSteelBlue" | |
| | '''Gastroenterologic'''
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| |bgcolor="Beige"| • Acute [[pancreatitis]] • [[Portal hypertension]]
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| |- | |
| |-bgcolor="LightSteelBlue"
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| | '''Genetic'''
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| |bgcolor="Beige"| [[Congenital Dysfibrinogenemia]] • [[Factor II mutation]] • [[Hereditary thrombophlebitis]] • [[Antithrombin III deficiency]] • [[Factor V Leiden mutation]] • [[Protein C deficiency]] • [[Protein S deficiency]] • [[Klippel-Trenaunay syndrome]] • [[Klinefelter syndrome]] • [[Sickle cell disease]] • [[Carbohydrate-deficient glycoprotein syndrome type 1b]] • [[Factor XII deficiency]] • [[Haemoglobin SC disease]] • [[Hyperprothrombinemia 20210G-A]] • [[Plasminogen deficiency]] • [[Activated protein C resistance]] • [[CD59 antigen deficiency]] • [[Cystathionine beta-synthase deficiency]]
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| |-bgcolor="LightSteelBlue"
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| | '''Hematologic'''
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| |bgcolor="Beige"| • [[Polycythemia vera]] • [[Essential thrombocythemia]] • [[Myeloproliferative disease]] • [[Hyperviscosity]] syndrome • [[Paroxysmal Nocturnal Hemoglobinuria]] • [[Thrombocytosis]] • Raised homocysteine levels
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| |-bgcolor="LightSteelBlue"
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| | '''Iatrogenic'''
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| |bgcolor="Beige"| • Surgical complication | |
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| |-bgcolor="LightSteelBlue"
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| | '''Infectious Disease'''
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| |bgcolor="Beige"| • [[Intraperitoneal abscess]] • [[Acute peritonitis]] • [[Visceral abscess]] • [[Diverticulitis]] • [[Intravenous catheter infection]]
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| |-bgcolor="LightSteelBlue"
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| | '''Musculoskeletal / Ortho'''
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| |bgcolor="Beige"| • Orthopedic surgeries • Abdominal surgery
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| |-bgcolor="LightSteelBlue"
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| | '''Nutritional / Metabolic'''
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| |bgcolor="Beige"| • Cystathionuria • Homocystinuria • Methyltetrahydrofolate reductase deficiency • [[Metabolic Syndrome]] • [[Insulin resistance]] • Folic acid deficiency • [[Obesity]]
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| |-bgcolor="LightSteelBlue"
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| | '''Obstetric/Gynecologic'''
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| |bgcolor="Beige"| • [[Pregnancy]] • [[Puerperium period]] • [[Ovarian hyperstimulation syndrome]]
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| |-bgcolor="LightSteelBlue"
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| | '''Oncologic''' | |
| |bgcolor="Beige"| • Malignancy • Peritoneal metastasis • Adenocarcinoma of cecum • Adenocarcinoma of colon • Occult malignancy • Leukemia • Pancreatic cancer • [[Glucagonoma]]
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| |-bgcolor="LightSteelBlue"
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| | '''Renal / Electrolyte'''
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| |bgcolor="Beige"| • [[Chronic renal failure]] • [[Paroxysmal Nocturnal Hemoglobinuria]] • [[Nephrotic syndrome]] | |
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| |-bgcolor="LightSteelBlue" | |
| | '''Rheum / Immune / Allergy'''
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| |bgcolor="Beige"| • [[Antiphospholipid Syndrome]] • [[Circulating anticoagulant]] • [[Heparin induced thrombocytopenia]] • [[Inflammatory bowel disease]] • [[Crohn's disease]]• [[Behcet disease]] • [[Hughes-Stovin syndrome]] • [[Polyarteritis Nodosa]] • [[SLE]]
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| | '''Trauma'''
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| |bgcolor="Beige"| • [[Trauma]] • [[Abdominal trauma]]
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| |-bgcolor="LightSteelBlue" | |
| | '''Miscellaneous'''
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| |bgcolor="Beige"| • [[Paraneoplastic syndrome]] • [[Hypereosinophilic syndrome]] • [[Immobility]]
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| |}
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| ==Indications for testing== | | == Treatment == |
| Searching for a coagulation abnormality is not normally undertaken in patients in whom thrombosis has an obvious other cause. For example, if the thrombosis is due to immobilisation after recent [[orthopedic surgery]], it is unlikely that an underlying cause is found. Comprehensive testing in any patient should include complete assessment of risk factors and its effect on long-term therapy. Some of the indications may include<ref name="pmid19289024">{{cite journal |author=Foy P, Moll S |title=Thrombophilia: 2009 update |journal=Curr Treat Options Cardiovasc Med |volume=11 |issue=2 |pages=114–28 |year=2009 |month=April |pmid=19289024 |doi= |url=}}</ref><ref name="pmid11309638">{{cite journal |author=Seligsohn U, Lubetsky A |title=Genetic susceptibility to venous thrombosis |journal=N. Engl. J. Med. |volume=344 |issue=16 |pages=1222–31 |year=2001 |month=April |pmid=11309638 |doi=10.1056/NEJM200104193441607 |url=}}</ref>:
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| * Unexplained venous thromboembolism at an age of less than 50 years
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| * Recurrent spontaneous thrombosis
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| * Unusual sites like portal, splenic, mesenteric, hepatic or renal veins
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| * Family history in first-degree relatives
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| * Recurrent pregnancy losses
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| * Recurrence of venous thromboembolism while adequately anticoagulated
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| * Warfarin-induced skin necrosis
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| * Unexplained arterial thromboembolism in a younger patient without significant arteriosclerosis risk factors and no cardioembolic source
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| Conversely, although thrombosis itself may occur in any person, repeated (two or more) unprovoked episodes of thrombosis and unusual sites and types of thrombosis (e.g. [[Budd-Chiari syndrome]]) may point towards a coagulation disorder.
| | [[Thrombophilia medical therapy|Medical Therapy]] | [[Thrombophilia surgery|Surgery]] | [[Thrombophilia primary prevention|Primary Prevention]] | [[Thrombophilia secondary prevention|Secondary Prevention]] | [[Thrombophilia future or investigational therapies|Future or Investigational Therapies]] | [[Thrombophilia cost-effectiveness of therapy | Cost Effectiveness of Therapy]] |
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| Increasingly, [[habitual abortion|recurrent miscarriage]] is seen as an indication for thrombophilia screening. <ref>Dawood, F., Farquharson, R., Quenby, S.''Recurrent miscarriage.'' Current Obstetrics & Gynaecology, 2004; 14:247-253.</ref>
| | ==Case Studies== |
| | | :[[Thrombophilia case study one|Case #1]] |
| Tests for thrombophilia include [[prothrombin time]] and INR, [[partial thromboplastin time]], [[thrombin time]], [[fibrinogen]] levels, [[antiphospholipid antibody]] levels (IgG- and IgM-anticardiolipin, dilute Russell viper venom time and lupus anticoagulant), [[protein C]], [[protein S]] and [[antithrombin]] (both levels and activity), activated protein C resistance (APC resistance), [[factor V Leiden]] and [[thrombin|prothrombin]] mutation. Many laboratories add on various other tests, depending on local policy and guidelines.
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| ==Treatment==
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| ==References==
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| {{Reflist|2}}
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| [[Category:Hematology]] | | [[Category:Hematology]] |
| | | [[Category:Disease]] |
| [[de:Thrombophilie]] | |
| [[fr:Thrombophilie]]
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| [[no:Trombofili]]
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| [[pl:Trombofilia]]
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| {{WH}} | | {{WH}} |
| {{WS}} | | {{WS}} |