Thrombophilia

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Thrombophilia
OMIM 188050
DiseasesDB 29080
MeSH D019851

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-In-Chief: Kashish Goel, M.D.

Synonyms and Keywords: Hypercoagulability, coagulability, hypercoagulable state

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.

Classification

Thrombophilia can be classified in various forms.

  • The most common classification is by the nature of the thrombosis: arterial, venous or combined.
  • 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.[1]
  • Acquired vs. congenital

Pathophysiology

Epidemiology and Demographics

Risk factors

Causes

Common types:

Rare forms:

Differential diagnosis of thrombophilia

(By organ system)

Cardiovascular • Cerebral vein thrombosisAcute myocardial infarctionDeep vein thrombophlebitisPortal vein thrombosis • Pelvic thrombophlebitis
Drug Side Effect • 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
Endocrine Hyperosmolar non-ketotic diabetic coma
Gastroenterologic • Acute pancreatitisPortal hypertension
Genetic Congenital Dysfibrinogenemia • Factor II mutation • Hereditary thrombophlebitis • Antithrombin III deficiencyFactor V Leiden mutationProtein C deficiencyProtein S deficiencyKlippel-Trenaunay syndromeKlinefelter syndromeSickle 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
Hematologic Polycythemia veraEssential thrombocythemiaMyeloproliferative diseaseHyperviscosity syndrome • Paroxysmal Nocturnal HemoglobinuriaThrombocytosis • Raised homocysteine levels
Iatrogenic Surgical complication
Infectious Disease • Intraperitoneal abscess • Acute peritonitis • Visceral abscessDiverticulitis • Intravenous catheter infection
Musculoskeletal / Ortho • Orthopedic surgeries • Abdominal surgery
Nutritional / Metabolic • Cystathionuria • Homocystinuria • Methyltetrahydrofolate reductase deficiency • Metabolic SyndromeInsulin resistance • Folic acid deficiency • Obesity
Obstetric/Gynecologic • Pregnancy • Puerperium period • Ovarian hyperstimulation syndrome
Oncologic • Malignancy • Peritoneal metastasis • Adenocarcinoma of cecum • Adenocarcinoma of colon • Occult malignancy • Leukemia • Pancreatic cancer • Glucagonoma
Renal / Electrolyte Chronic renal failureParoxysmal Nocturnal HemoglobinuriaNephrotic syndrome
Rheum / Immune / Allergy Antiphospholipid Syndrome • Circulatin anticoagulant • Heparin induced thrombocytopeniaInflammatory bowel diseaseCrohn's disease • Behcet disease • Hughes-Stovin syndrome • Polyarteritis NodosaSLE
Trauma • Trauma • Abdominal trauma
Miscellaneous Paraneoplastic syndrome • Hypereosinophilic syndrome • Immobility

Indications for testing

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.

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.

Increasingly, recurrent miscarriage is seen as an indication for thrombophilia screening. [2]

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 prothrombin mutation. Many laboratories add on various other tests, depending on local policy and guidelines.

Treatment

References

  1. Crowther MA, Kelton JG (2003). "Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system". Ann. Intern. Med. 138 (2): 128–34. PMID 12529095.
  2. Dawood, F., Farquharson, R., Quenby, S.Recurrent miscarriage. Current Obstetrics & Gynaecology, 2004; 14:247-253.

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