Thrombophilia causes

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Asiri Ediriwickrema, M.D., M.H.S. [2]

Overview

Thrombophilia may be caused by either acquired, inherited, or, more commonly, a combination of both conditions.

Causes

Inherited

Common inherited causes of thrombophilia include:

  • Factor V Leiden: Factor V is a procoagulant which upon activation promotes the formation of thrombin. In 1994, Bertina and colleagues identified a single nucleotide polymorphism (guanine to adenine substitution in nucleotide 1691), which rendered factor V resistant to proteolytic inactivation by activated protein C (APC).[1]
  • Prothrombin G20210A: Prothrombin, or factor II, is a precursor to throbmin. A single nucleotide polymorphism (guanine to adenonine substitution in in nucleotide 20210) was first identied by Poort and colleages in 1996. The mutation was associated with elevated prothrombin, thought to be due to increased translation efficiency, and an increased risk of thrombosis.[2]
  • Coinheritance of multiple thrombophilias is not infrequent, and does increase the thrombotic risk in affected patients.

Rare causes of thrombophilia include:

Causes of Thrombophilia by Organ System

Cardiovascular Cerebral vein thrombosisAcute myocardial infarctionDeep vein thrombophlebitisPortal vein thrombosisPelvic thrombophlebitis
Drug Side Effect Asparaginasebevacizumabcombined oral contraceptive pillcertolizumab pegolCcproteronediethylstilboestroldrospirenoneeltrombopagerythropoietinethinylestradiolfosfestrolgranulocyte-macrophage colony stimulating factorheparinhormone replacement therapylenalidomidepeginesatidepolyestradiolraloxifenestrontium ranelatetamoxifentobacco smokingtranexamic acidvorinostat
Endocrine Hyperosmolar non-ketotic diabetic coma
Gastroenterologic • Acute pancreatitisPortal hypertension
Genetic Congenital DysfibrinogenemiaFactor II mutationHereditary thrombophlebitisAntithrombin III deficiencyFactor V Leiden mutationProtein C deficiencyProtein S deficiencyKlippel-Trenaunay syndromeKlinefelter syndromeSickle cell diseaseCarbohydrate-deficient glycoprotein syndrome type 1bFactor XII deficiencyHaemoglobin SC diseaseHyperprothrombinemia 20210G-APlasminogen deficiencyActivated protein C resistanceCD59 antigen deficiencyCystathionine beta-synthase deficiency
Hematologic Polycythemia veraEssential thrombocythemiaMyeloproliferative diseaseHyperviscosity syndrome • Paroxysmal Nocturnal HemoglobinuriaThrombocytosis • Raised homocysteine levels
Iatrogenic • Surgical complication
Infectious Disease Intraperitoneal abscessAcute peritonitisVisceral abscessDiverticulitisIntravenous catheter infection
Musculoskeletal / Ortho • Orthopedic surgeries • Abdominal surgery
Nutritional / Metabolic CystathionuriaHomocystinuriaMethyltetrahydrofolate reductase deficiencyMetabolic SyndromeInsulin resistanceFolic acid deficiencyObesity
Obstetric/Gynecologic PregnancyPuerperium periodOvarian hyperstimulation syndrome
Oncologic MalignancyPeritoneal metastasisAdenocarcinoma of cecumAdenocarcinoma of colon • Occult malignancy • LeukemiaPancreatic cancerGlucagonoma
Renal / Electrolyte Chronic renal failureParoxysmal Nocturnal HemoglobinuriaNephrotic syndrome
Rheum / Immune / Allergy Antiphospholipid SyndromeCirculating anticoagulantHeparin induced thrombocytopeniaInflammatory bowel diseaseCrohn's diseaseBehcet diseaseHughes-Stovin syndromePolyarteritis NodosaSLE
Trauma TraumaAbdominal trauma
Miscellaneous Paraneoplastic syndromeHypereosinophilic syndromeImmobility

References

  1. Bertina RM, Koeleman BP, Koster T, Rosendaal FR, Dirven RJ, de Ronde H; et al. (1994). "Mutation in blood coagulation factor V associated with resistance to activated protein C." Nature. 369 (6475): 64–7. doi:10.1038/369064a0. PMID 8164741.
  2. Poort SR, Rosendaal FR, Reitsma PH, Bertina RM (1996). "A common genetic variation in the 3'-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis". Blood. 88 (10): 3698–703. PMID 8916933.

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