antithrombin deficiency

Etiology

• genetic
• acquired antithrombin deficiency:
  • oral contraceptives
    • estrogen can reduce antithrombin levels by 15%
  • nephrotic syndrome
    • antithrombin is lost in the urine along with other plasma proteins
  • liver disease
  • disseminated intravascular coagulation (DIC)
  • critical illness

Epidemiology

(genetic form)

• incidence 1 per 2000-5000
• accounts for 3-8% of thrombotic or thromboembolic events in the general population
• generally presents between age 10-35 with recurrent DVT (often with pulmonary embolism)

Pathology

• type 1 (reduced synthesis)
  • heterozygous (decreased synthesis)
  • homozygous (absence)
  • generally due to gene deletions or frameshift mutations
• type 2 (dysfunctional)
  • normal levels, but decreased functional activity
  • generally due to point mutations
    • point mutation in the heparin binding region is relatively common (1/500) but is associated with a low rate of thrombosis
    • mutations in the thrombin-binding regions are associated with an increased risk of thrombosis

Genetics

• autosomal dominant inheritance
• G20210A prothrombin mutation increases risk of initial venous thromboembolism

Laboratory

• antithrombin levels
• biological activity of antithrombin
• normal bleeding time
• normal platelet aggregation studies
• PTT may not prolong with heparin therapy
  • heparin binds to antithrombin III to inactivate coagulation factor 2, coagulation factor 9, coagulation factor 10, & coagulation factor 11

Management

• low molecular weight heparin
• oral anticoagulants (warfarin with INR of 2-3)
• antithrombin concentrates
  • maintain functional activity > 80%
• anti-platelet agents
• heparin may be ineffective

More general terms

• blood protein disorder
• hypercoagulability
• genetic disease of the blood/bone marrow

Additional terms

• antithrombin-III (ATIII, heparin cofactor, SERPINC1, AT3, PRO0309)