Thrombophilia - Definition and Overview

Thrombophilia is the propensity to develop thrombosis (blood clots) due to an abnormality in the system of coagulation.

Indications

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, habitual abortion is seen as an indication for thrombophilia screening. Up to 20% of women presenting with recurrent pregnancy loss may have a coagulation disorder.

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.
• Acquired vs. congenital

Types

Common types:

• Factor V, Leiden type (3% of the population are heterozygous for FVL).
• Prothrombin mutation (G20210A, 5'UTR).
• High homocysteine levels due to MTHFR mutation or vitamin deficiency (vitamins B6, B12 and folic acid).
• Antiphospholipid antibodies
  • anticardiolipin antibodies and/or
  • lupus anticoagulants
• Renal disease (renal loss of antithrombin)

Rare forms:

• Plasminogen and fibrinolysis disorders.
• Paroxysmal nocturnal hemoglobinuria
• Protein C deficiency.
• Protein S deficiency.
• Antithrombin III deficiency.

Testing

Tests for thrombophilia include prothrombin time and INR, partial thromboplastin time, thrombin time, fibrinogen levels, antiphospholipid antibody levels (IgG- and IgM-anticardiolipin, dillute Russell viper venom time and lupus anticoagulant), protein C, protein S and antithombin (both levels and activity), activated protein C resistance (APC resistance), factor V Leiden and thrombin mutation. Many laboratories add on various other tests, depending on local policy and guidelines.

Reference

• Crowther MA, Kelton JG. Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system. Ann Intern Med 2003;138:128-34. PDF fulltext. (http://www.annals.org/cgi/reprint/138/2/128) PMID 12529095.