Antithrombin III Deficiency Medication

  • Author: James L Harper, MD; Chief Editor: Robert J Arceci, MD, PhD   more...
 
Updated: Aug 1, 2011
 

Medication Summary

Antithrombin III (ATIII) deficiency may be quickly corrected with infusions of antithrombin III concentrates. Long-term therapy for congenital deficiency is generally not indicated, as an asymptomatic period may last decades. Once thrombosis has occurred, warfarin therapy is generally undertaken.

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Antithrombin-III concentrates

Class Summary

Antithrombin III concentrate (Thrombate III [Bayer Corporation]) is used for replacement therapy. This product is a plasma-derived concentrate made from pooled human plasma using modified Cohn ethanol separation and heat-treated for viral inactivation. The vials have no preservatives and are labeled in international units calibrated against a World Health Organization (WHO) standard.

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Antithrombin, recombinant (ATryn)

 

Recombinant AT made in goats. AT regulates hemostasis by inhibiting thrombin and factor Xa, key proteases for blood coagulation. Indicated for prevention of perioperative and peripartum thromboembolic events in patients with hereditary AT deficiency. Not indicated for treatment of thromboembolic events. Available as a lyophilized powder that is reconstitution for IV infusion. Normally administered as a continuous IV infusion medication.

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Antithrombin III (Thrombate III)

 

Alpha2-globulin that inactivates thrombin; plasmin; and other serine proteases of coagulation including factors IXa, Xa, XIa, XIIa, and VIIa, which, in turn, inhibits coagulation.

Mean recovery in healthy patients is 1.6% activity/U/kg infused (ie, 160% activity when 100 U/kg is infused) based on immunologic ATIII assays. Recovery based on functional assays is 1.4% activity/U/kg (ie, 140% activity when 100 U/kg is infused). Functional assay results are most commonly used to calculate dose. Half-life of ATIII is approximately 22 h. This number should be considered in light of patient's underlying clinical problems, as the rate of ATIII consumption may be increased, which would affect extent of recovery and half-life.

A target of 120% is the upper limit of the reference range for ATIII and is chosen as a target value to allow for maximum amount of time to elapse before clearance and consumption of ATIII drops the level in patient's plasma to < 80%.

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Anticoagulants

Class Summary

In patients with congenital ATIII deficiency, anticoagulation reduces the incidence of thrombosis. The duration of therapy is likely to be indefinite.

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Warfarin (Coumadin)

 

Inhibits vitamin K–dependent gamma carboxylation of procoagulant proteins factor II, VII, IX, X, as well as the anticoagulant factor, protein C. Tailor dose to maintain an INR in the range of 2-2.5. The length of time to achieve target INR is age dependent. In infants, the median time to achieve the target INR is 5 d and in adolescents, 3 d.

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Enoxaparin (Lovenox)

 

Produced by partial chemical or enzymatic depolymerization of unfractionated heparin (UFH). Binds to ATIII, enhancing its therapeutic effect. The heparin-ATIII complex binds to and inactivates activated factor X (Xa) and factor II (thrombin).

Does not actively lyse but is able to inhibit further thrombogenesis. Prevents reaccumulation of clot after spontaneous fibrinolysis.

Advantages include intermittent dosing and decreased requirement for monitoring. Heparin antifactor Xa levels may be obtained if needed to establish adequate dosing.

LMWH differs from UFH by having a higher ratio of antifactor Xa to antifactor IIa compared with UFH.

Prevents DVT, which may lead to pulmonary embolism in patients undergoing surgery who are at risk for thromboembolic complications. Used for prevention in hip replacement surgery (during and following hospitalization), knee replacement surgery, or abdominal surgery in those at risk of thromboembolic complications, or in nonsurgical patients at risk of thromboembolic complications secondary to severely restricted mobility during acute illness.

Used for the treatment of DVT or PE in conjunction with warfarin, for the inpatient treatment of acute DVT with or without PE, or for the outpatient treatment of acute DVT without PE.

No use in checking aPTT (drug has wide therapeutic window and aPTT does not correlate with anticoagulant effect). Average duration of treatment is 7-14 d.

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Contributor Information and Disclosures
Author

James L Harper, MD  Associate Professor, Department of Pediatrics, Division of Hematology/Oncology and Bone Marrow Transplantation, Associate Chairman for Education, Department of Pediatrics, University of Nebraska Medical Center; Assistant Clinical Professor, Department of Pediatrics, Creighton University School of Medicine; Director, Continuing Medical Education, Children's Memorial Hospital; Pediatric Director, Nebraska Regional Hemophilia Treatment Center

James L Harper, MD is a member of the following medical societies: American Academy of Pediatrics, American Association for Cancer Research, American Federation for Clinical Research, American Society of Hematology, American Society of Pediatric Hematology/Oncology, Council on Medical Student Education in Pediatrics, and Hemophilia and Thrombosis Research Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Gary R Jones, MD  Associate Medical Director, Clinical Development, Berlex Laboratories

Gary R Jones, MD is a member of the following medical societies: American Academy of Pediatrics, American Society of Pediatric Hematology/Oncology, and Western Society for Pediatric Research

Disclosure: Nothing to disclose.

Mary L Windle, PharmD  Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Gary D Crouch, MD  Program Director of Pediatric Hematology-Oncology Fellowship, Department of Pediatrics, Associate Professor, Uniformed Services University of the Health Sciences

Gary D Crouch, MD is a member of the following medical societies: American Academy of Pediatrics and American Society of Hematology

Disclosure: Nothing to disclose.

David Pallares, MD  Clinical Assistant Professor, Department of Pediatrics, Division of Allergy and Immunology, University of Louisville School of Medicine

David Pallares, MD is a member of the following medical societies: American Academy of Allergy Asthma and Immunology

Disclosure: Nothing to disclose.

Chief Editor

Robert J Arceci, MD, PhD  King Fahd Professor of Pediatric Oncology, Professor of Pediatrics, Oncology and the Cellular and Molecular Medicine Graduate Program, Kimmel Comprehensive Cancer Center at Johns Hopkins University School of Medicine

Robert J Arceci, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Pediatric Society, American Society of Hematology, and American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

References

  1. Beauchamp NJ, Pike RN, Daly M, et al. Antithrombins Wibble and Wobble (T85M/K): archetypal conformational diseases with in vivo latent-transition, thrombosis, and heparin activation. Blood. Oct 15 1998;92(8):2696-706. [Medline].

  2. Kuhle S, Lane DA, Jochmanns K, et al. Homozygous antithrombin deficiency type II (99 Leu to Phe mutation) and childhood thromboembolism. Thromb Haemost. Oct 2001;86(4):1007-11. [Medline].

  3. [Guideline] Institute for Clinical Systems Improvement (ICSI). Venous thromboembolism. ICSI. Jun 2007;[Full Text].

  4. Mitchell L, Andrew M, Hanna K, et al. Trend to efficacy and safety using antithrombin concentrate in prevention of thrombosis in children receiving l-asparaginase for acute lymphoblastic leukemia. Results of the PAARKA study. Thromb Haemost. Aug 2003;90(2):235-44. [Medline].

  5. Vossen CY, Conard J, Fontcuberta J, et al. Risk of a first venous thrombotic event in carriers of a familial thrombophilic defect. The European Prospective Cohort on Thrombophilia (EPCOT). J Thromb Haemost. Mar 2005;3(3):459-64. [Medline].

  6. [Best Evidence] Young G, Albisetti M, Bonduel M, et al. Impact of inherited thrombophilia on venous thromboembolism in children: a systematic review and meta-analysis of observational studies. Circulation. Sep 23 2008;118(13):1373-82. [Medline].

  7. Andrews M, Monagale PT, Brooker L. Thromboembolic Complications During Infancy and Childhood. London: BC Decker, Inc. Hamilton; 2000:321-60.

  8. ATryn, Antithrombin (recombinant) [package insert]. GTC Biotherapeutics, inc; 2009. [Full Text].

  9. Bucur SZ, Levy JH, Despotis GJ, et al. Uses of antithrombin III concentrate in congenital and acquired deficiency states. Transfusion. May 1998;38(5):481-98. [Medline].

  10. Corral J, Hernandez-Espinosa D, Soria JM, Gonzalez-Conejero R, Ordonez A, Gonzalez-Porras JR. Antithrombin Cambridge II (A384S): an underestimated genetic risk factor for venous thrombosis. Blood. May 15 2007;109(10):4258-63. [Medline].

  11. de Galan-Roosen AE, Kuijpers JC, Rosendaal FR, Steegers EA, van Beers WA, Ponjee GA. Maternal and paternal thrombophilia: risk factors for perinatal mortality. BJOG. Mar 2005;112(3):306-11. [Medline].

  12. Feero WG. Genetic thrombophilia. Prim Care. Sep 2004;31(3):685-709, xi. [Medline].

  13. Fyfe A, Tait RC. Antithrombin-a for the prophylaxis of venous thrombosis in congenital antithrombin deficiency. Expert Rev Hematol. Oct 2009;2(5):499-507. [Medline].

  14. Haire WD. Antithrombin III in hematopoietic stem cell transplantation. Semin Thromb Hemost. 1997;23(6):591-601. [Medline].

  15. Haire WD, Ruby EI, Stephens LC, et al. A prospective randomized double-blind trial of antithrombin III concentrate in the treatment of multiple-organ dysfunction syndrome during hematopoietic stem cell transplantation. Biol Blood Marrow Transplant. 1998;4(3):142-50. [Medline].

  16. Hayek S, Kenet G, Lubetsky A, et al. Does thrombophilia play an aetiological role in Legg-Calve-Perthes disease?. J Bone Joint Surg Br. Jul 1999;81(4):686-90. [Medline].

  17. Khor B, Van Cott EM. Laboratory tests for antithrombin deficiency. Am J Hematol. Dec 2010;85(12):947-50. [Medline].

  18. Kurnik K, Kosch A, Strater R, Schobess R, Heller C, Nowak-Gottl U. Recurrent thromboembolism in infants and children suffering from symptomatic neonatal arterial stroke: a prospective follow-up study. Stroke. Dec 2003;34(12):2887-92. [Medline].

  19. Langlois NJ, Wells PS. Risk of venous thromboembolism in relatives of symptomatic probands with thrombophilia: a systematic review. Thromb Haemost. Jul 2003;90(1):17-26. [Medline].

  20. Luxembourg B, Delev D, Geisen C, Spannagl M, Krause M, Miesbach W, et al. Molecular basis of antithrombin deficiency. Thromb Haemost. Apr 2011;105(4):635-46. [Medline].

  21. Maclean PS, Tait RC. Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis and treatment options. Drugs. 2007;67(10):1429-40. [Medline].

  22. Medical Economics, ed. Physicians' Desk Reference. 54th ed. Thomson PDR; 2000:735-6. [Full Text].

  23. Medical Economics, ed. Physicians' Desk Reference. 55th ed. Thomson PDR; 2001:899.

  24. Mitsuguro M, Sakata T, Okamoto A, et al. Usefulness of antithrombin deficiency phenotypes for risk assessment of venous thromboembolism: type I deficiency as a strong risk factor for venous thromboembolism. Int J Hematol. Oct 2010;92(3):468-73. [Medline].

  25. Muszbek L, Bereczky Z, Kovacs B, Komaromi I. Antithrombin deficiency and its laboratory diagnosis. Clin Chem Lab Med. Dec 2010;48 Suppl 1:S67-78. [Medline].

  26. Nagaraja D, Christopher R, Tripathi M. Plasma antithrombin III deficiency in ischaemic stroke in the young. Neurol India. Jun 1999;47(2):155-6. [Medline].

  27. Ota K, Akizawa T, Hirasawa Y, et al. Effects of argatroban as an anticoagulant for haemodialysis in patients with antithrombin III deficiency. Nephrol Dial Transplant. Aug 2003;18(8):1623-30. [Medline].

  28. Pal N, Kertai MD, Lakshminarasimhachar A, Avidan MS. Pharmacology and clinical applications of human recombinant antithrombin. Expert Opin Biol Ther. Jul 2010;10(7):1155-68. [Medline].

  29. Picard V, Nowak-Göttl U, Biron-Andreani C, Fouassier M, Frere C, Goualt-Heilman M. Molecular bases of antithrombin deficiency: twenty-two novel mutations in the antithrombin gene. Hum Mutat. Jun 2006;27(6):600. [Medline].

  30. Schinzel H, Weilemann LS. Antithrombin substitution therapy. Blood Coagul Fibrinolysis. Nov 1998;9 Suppl 3:S17-21; discussion S21-2. [Medline].

 
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Antithrombin (AT) sites of action.
 
 
 
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