Prevalence of hereditary antithrombin deficiency (hATd)

with hereditary AT deficiency have at least one clot by age 5010

with hereditary AT deficiency have recurrent blood clots10

  • hATd affects 1 in every 500 to 5000 individuals9,14
    • This range suggests that approximately 65,000 to 650,000 people in the United States are affected15
  • Approximately 50% of individuals with hereditary AT deficiency will develop at least one clot in their lifetime (usually after adolescence).16
  • 85% of patients with hATd will have at least 1 thrombotic episode by age 57
  • ~70% of all patients with hATd will have a thrombotic event before the age of 357
  • Up to 70% of pregnant women with hATd may experience thromboembolic complications17
  • About 6 in 10 patients with hereditary AT deficiency have recurrent blood clots19
  • Inherited blood-clotting disorders are diagnosed with a test called a thrombophilia panel. This test can help to diagnose hereditary antithrombin deficiency or another inherited blood-clotting disorder, like factor V Leiden, or protein C or protein S deficiency

hATd has one of the highest thrombotic risks of all of the inherited thrombophilias18

hATd is a hereditary autosomal dominant disorder that typically reduces functional antithrombin levels to 40% to 60% of normal19

Patients with hereditary antithrombin deficiency are about 20 times more likely to have a VTE compared with the general population19

The risk of VTE is much higher in hereditary antithrombin-deficient patients than it is in patients with other thrombophilias like factor V Leiden or prothrombin gene mutation19

Risk increases progressively with lower antithrombin levels20,21

Of the estimated 547,596 patients hospitalized for VTE each year in the United States, up to 3% (~16,500) of these patients may have hATd22

hATd has 3 distinct features that set it apart from other thrombophilias

hATd presents the highest risk of thrombosis among inherited thrombophilias18

Can be prevented and treated by replacing the missing AT

Can be the reason why surgical patients do not have the expected response to their anticoagulation23†

†Heparin and enoxaparin.
*Patients heterozygous for factor V Leiden have approximately a 5-fold greater risk of venous thrombosis, while homozygotes have approximately an 80-fold greater risk. Chart adapted from Franchini et al.

AT and the coagulation cascade

AT activity inhibits many clotting factors in the coagulation cascade in 3 key steps2-4

  1. Procoagulation factors bind to AT
  2. Once bound to AT, procoagulation factors are cleared
  3. The expansion of existing clots and formation of new clots are prevented
  • Antithrombin is a thromboprotective protein that inhibits the coagulation enzymes in a slow, progressive manner when heparin is absent. These enzymes include factor Xa and thrombin, and to a lesser extent, factors IXa, XIa, XIIa, and VIIa24
  • Antithrombin plays a key role in anticoagulation by preventing the activation of coagulation-promoting proteins except at the site of injury25
  • Antithrombin participates in a feedback loop in which blood can clot rapidly when needed but does not clot all of the time25
 
 

THROMBATE III reduces VTE Risk

Dr. Bader talks about surgery in patients with hATd

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The Risks of Low AT

See how THROMBATE III replaces missing AT

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Causes of Heparin Resistance

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THROMBATE III Tools and Resources

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Important Safety Information

THROMBATE III® (antithrombin III [human]) is indicated in patients with hereditary antithrombin deficiency for treatment and prevention of thromboembolism and for prevention of perioperative and peripartum thromboembolism.

Hypersensitivity reactions may occur. Should evidence of an acute hypersensitivity reaction be observed, promptly interrupt the infusion and begin appropriate treatment.

Because THROMBATE III is made from human blood, it may carry a risk of transmitting infectious agents, eg, viruses, the variant Creutzfeldt-Jakob disease (vCJD) agent, and, theoretically, the Creutzfeldt-Jakob disease (CJD) agent. There is also the possibility that unknown infectious agents may be present in the product.

Perform coagulation tests to avoid excessive or insufficient anticoagulation and monitor for bleeding or thrombosis. Measure functional plasma AT levels with amidolytic or clotting assays; do not use immunoassays.

In clinical studies, the most common adverse reactions (≥ 5% of subjects) were dizziness, chest discomfort, nausea, dysgeusia, and pain (cramps).

The anticoagulant effect of heparin is enhanced by concurrent treatment with THROMBATE III in patients with hereditary AT deficiency. Thus, in order to avoid bleeding, the dosage of heparin (or low molecular weight heparin) may need to be reduced during treatment with THROMBATE III.

Please see full Prescribing Information for THROMBATE III.

You are encouraged to report negative side effects of prescription drugs to the FDA. Visit http://www.fda.gov/medwatch, or call 1-800-FDA-1088.

References

  1. THROMBATE III [Prescribing Information]. Research Triangle Park, NC: Grifols Therapeutics LLC
  2. Maclean PS, Tait RC. Hereditary and acquired antithrombin deficiency: epidemiology, pathogenesis, and treatment options. Drugs. 2007;67(10):1429-1440
  3. Li W, Johnson DJD, Esmon CT, Huntington JA. Structure of the antithrombin–thrombin–heparin ternary complex reveals the antithrombotic mechanism of heparin. Nat Struct Mol Biol. 2004;11(9):857-862
  4. James AH, Konkle BA, Bauer KA. Prevention and treatment of venous thromboembolism in pregnancy and patients with hereditary antithrombin deficiency. Int J Womens Health. 2013;5:233-241
  5. Wolberg AS. Thrombin generation and fibrin clot structure. Blood Rev. 2007;21(3):131-142
  6. Davi G, Patrono C. Platelet activation and atherothrombosis. N Engl J Med. 2007;357(24): 2482-2494
  7. Kottke-Marchant K, Duncan A. Antithrombin deficiency: issues in laboratory diagnosis. Arch Pathol Lab Med. 2002;126(11):1326-1336
  8. Mitton BA, Steineck A. Antithrombin deficiency. eMedicine from WebMD. http://emedicine.medscape.com/article/198573-overview. Updated July 22, 2022. Accessed November 28, 2022
  9. Patnaik MM, Moll S. Inherited antithrombin deficiency: a review. Haemophilia. 2008;14(6):1229-1239
  10. Pabinger I, Schneider B. Thrombotic risk in hereditary antithrombin III protein C, or protein S deficiency. Arteroscler Thromb Vasc Biol. 1996;16(6):742-748
  11. Ranucci M. Antithrombin III: key factor in extracorporeal circulation. Minerva Anestesiol. 2002;68(5):454-457
  12. Foy P, Moll S. Thrombophilia: 2009 update. Curr Treat Options Cardiovasc Med. 2009;11(2):114-128
  13. AABB, American Red Cross, America’s Blood Centers, Armed Services Blood Program. Circular of information for the use of human blood and blood components. https://www.aabb.org/docs/default-source/default-document-library/resources/circular-of-information-watermark.pdf?sfvrsn=7f5d28ab_5 December 2021. Accessed November 28, 2022
  14. Tengborn L et al. Scand J Clin Lab Invest. 1981;41(5):469-477
  15. Wells PS, Blajchman MA, Henderson P, et al. Am J Hematol. 1994;45:321-324
  16. US Census Bureau, Population Division. US and World Population Clock. http://www.census.gov/ popclock/. Accessed November 28, 2022
  17. Khawar H, Kelley W,Guzman N. Fresh frozen plasma. In: StatPearls. https://www.ncbi.nlm.nih.gov/books/NBK513347/. Updated September 19, 2022. Accessed November 28, 2022 
  18. Hellgren M, Tengborn T, Abildgaard U. Pregnancy in women with congenital antithrombin III deficiency: experience of treatment with heparin and antithrombin. Gynecol Obstet Invest. 1982;14:127-141
  19. Franchini M, Veneri D, Salvagno GL, Manzato F, Lippi G. Inherited thrombophilia. Crit Rev Clin Lab Sci. 2006;43(3):249-290
  20. Rodgers GM. Role of antithrombin concentrate in hereditary antithrombin deficiency: an update. Thromb Haemost. 2009;101(5):806-812
  21. Di Minno MND, Dentali F, Lupoli R, Ageno W. Mild antithrombin deficiency and risk of recurrent venous thromboembolism. Circulation. 2014;129(4):497-503
  22. Bucciarelli P, Passamonti SM, Biguzzi E, et al. Low borderline plasma levels of antithrombin, protein C and protein S are risk factors for venous thromboembolism. J Thromb Haemost. 2012;10(9):1783-1791
  23. Centers for Disease Control and Prevention. Venous thromboembolism in adult hospitalizations – United States, 2007-2009. MMWR Morb Mortal Wkly Rep. 2012;61(22):401-404
  24. Finley A, Greenberg C. Review article: heparin sensitivity and resistance: management during cardiopulmonary bypass. Anesth Analg. 2013;116(6):1210-1222
  25. Kovács B, Bereczky Z, Oláh Z, et al. The superiority of anti-FXa assay over anti-FIIa assay in detecting heparin-binding site antithrombin deficiency. Am J Clin Pathol. 2013;140(5):675-679
  26. Olson E, Whitney M, Friedman B et al. In vivo fluorescence imaging of atherosclerotic plaques with activatable cell-penetrating peptides targeting thrombin activity, Integrative Biology, 2012;4(6):595–605
  27. Lloyd-Jones D, Adams RJ, Brown TM, et al; on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Circulation. 2010;121:e46-e215