Coagulation
Hereditary thrombophilia / hypercoagulopathies
Antithrombin deficiency
Author: Jeremy C. Parsons, M.D.
Last author update: 1 June 2012
Last staff update: 11 September 2020
Copyright: 2002-2023, PathologyOutlines.com, Inc.
PubMed Search: Antithrombin deficiency [title]
Table of Contents
Definition / general | Etiology | Treatment | Molecular / cytogenetics description | Additional referencesCite this page: Parsons JC. Antithrombin deficiency. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/coagulationantithrombindef.html. Accessed June 3rd, 2023.
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
