Contents

Search

antithrombin deficiency

Etiology: 1) genetic 2) acquired antithrombin deficiency: a) oral contraceptives - estrogen can reduce antithrombin levels by 15% b) nephrotic syndrome - antithrombin is lost in the urine along with other plasma proteins c) liver disease d) disseminated intravascular coagulation (DIC) e) critical illness Epidemiology: (genetic form) 1) incidence 1 per 2000-5000 2) accounts for 3-8% of thrombotic or thromboembolic events in the general population 3) generally presents between age 10-35 with recurrent DVT (often with pulmonary embolism) Pathology: 1) type 1 (reduced synthesis) a) heterozygous (decreased synthesis) b) homozygous (absence) c) generally due to gene deletions or frameshift mutations 2) type 2 (dysfunctional) a) normal levels, but decreased functional activity b) generally due to point mutations 1] point mutation in the heparin binding region is relatively common (1/500) but is associated with a low rate of thrombosis 2] 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 [2] Laboratory: 1) antithrombin levels 2) biological activity of antithrombin 3) normal bleeding time 4) normal platelet aggregation studies 5) 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: 1) low molecular weight heparin 2) oral anticoagulants (warfarin with INR of 2-3) 3) antithrombin concentrates - maintain functional activity > 80% 4) anti-platelet agents 5) heparin may be ineffective

Related

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

General

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

References

  1. Contributions from Linda Kuribayashi MD, Dept of Medicine, UCSF Fresno
  2. Medical Knowledge Self Assessment Program (MKSAP) 11, 16, 18. 19. American College of Physicians, Philadelphia 1998, 2012, 2018, 2022.
  3. Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia. 2008 Nov;14(6):1229-39 PMID: 19141163
  4. Gaman AM, Gaman GD Deficiency Of Antithrombin III (AT III) - Case Report and Review of the Literature. Curr Health Sci J. 2014 Apr-Jun;40(2):141-3. PMID: 25729597 Free PMC Article