Coagulation
Hereditary thrombophilia / hypercoagulopathies
Antithrombin deficiency

Author: Jeremy Parsons, M.D. (see Authors page)

Revised: 28 April 2016, last major update June 2012

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Antithrombin deficiency [title]

Cite this page: Antithrombin deficiency. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/coagulationantithrombindef.html. Accessed December 3rd, 2016.
Definition / General
  • Hereditary deficiencies occur in 0.07 - 0.17% of general population
  • Present in 1 - 9% of patients with venous thrombosis
  • Higher risk for venous and arterial thrombosis than protein C or S deficiency or activated protein C resistance; overall 50% have thrombosis
  • First thrombotic event occurs between ages 10 - 50 years
  • Often occurs with other genetic or acquired risk factors
  • Heterozygotes have levels 35 - 75% of normal
Etiology
  • Acute hemolytic transfusion reaction
  • Acute thrombotic episodes
  • Burns (extensive)
  • Heparin therapy
  • Inflammatory bowel disease
  • L-asparaginase therapy
  • Liver disease
  • Malignancy
  • Malnutrition
  • Nephrotic syndrome
  • Plasmapheresis
  • Preeclampsia
  • Protein poor diet
  • Thrombosis-recent or active (including DIC)
Treatment
  • Heparin (unfractionated or low molecular weight), followed by warfarin
  • May need increased doses of heparin or antithrombin concentrates / fresh frozen plasma if resistant to heparin
  • Should monitor antithrombin levels (should be 80 - 120%)
Molecular / Cytogenetics Description
  • Many mutations exist (qualitative or quantitative)
  • Usually autosomal dominant
  • Homozygosity is very rare, usually incompatible with life due to neonatal thrombosis, except for those with a heparin-binding mutation subtype, who have severe thrombosis but may survive

  • Type I mutations: quantitative deficiency with 50% of normal levels; due to any of 80 point mutations

  • Type II mutations: dysfunctional protein; often asymptomatic
    • IIa: mutations affect reactive site of target protease and heparin binding site
    • IIb: mutations affect reactive site of target protease
    • IIc: isolated decreased heparin binding