AT III deficiency and pregnancy - Section 1

Case Study: Pregnancy with hATd and History of Pulmonary Embolism (PE)

Patient History

  • Laura is a 37-year-old who is at ~5 weeks' gestation
  • African-American female diagnosed with hereditary antithrombin deficiency
  • Asymptomatic until age 27, when she experienced a massive PE requiring lytic therapy
  • Younger sibling died of massive PE at age 18
 
 

Initial Evaluation and Management

  • Maintained on warfarin since PE
  • Transitioned to enoxaparin 40 mg daily
  • Baseline pregnancy-related coagulation studies were obtained and were normal
  • Monitoring planned every 8–10 weeks
  • Labs included antithrombin level, anti-Xa, factors VII and VIII, and fibrinogen
 

Pregnancy Complications and Management

  • At 8 weeks, Laura developed a DVT despite no evidence of increased coagulation system activation
  • Enoxaparin increased to 80 mg BID to offset the hypermetabolic state
  • Anti-Xa level was in good therapeutic range at 0.8 IU/mL*
  • Antithrombin level (51%) had not decreased significantly, so no antithrombin supplementation was given
 

Delivery Plan

  • Meetings with maternal-fetal medicine specialist to discuss delivery options given history
  • Elective induction at 38 weeks was recommended
  • Plan was to bring patient into hospital 2 days in advance to give THROMBATE III to raise antithrombin level to 100% and check decay rate every 12 hours
  • Pharmacy was alerted to ensure adequate stocks as patient would need THROMBATE III for several days
  • Labs showed no abnormal increase in coagulation studies compared with normal pregnancy
 

Delivery Outcome

  • Patient went into spontaneous labor 2 days before scheduled induction
  • Patient was informed that she was not a candidate for epidural because there was no time to discontinue enoxaparin before delivery
  • AT level on admission was 38%
  • Patient was given 3000 units of THROMBATE III and antithrombin level increased to 112%
  • Patient delivered vaginally without issue
  • Post-delivery antithrombin level was 71%
 

Postpartum Management

  • Patient was maintained on 2000 units of THROMBATE III daily for 2 days postpartum
  • Peak antithrombin levels at 1-hour post dose were 108% and 116%
  • Trough antithrombin levels drawn before next dose were 44% and 59%, respectively
  • Patient was given 3000 units of THROMBATE III on day of discharge and continued on enoxaparin 80 mg BID
 

Postpartum Outcome

  • No significant post-delivery complications were noted
  • Mother and baby did well
  • Patient was transitioned back to warfarin after 6 weeks
 

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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.

Global_references

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 DJ, Esmon CT, Huntington JA. 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. Blood Rev. 2007;21(3):131-142. 6. Davi G, Patrono C. 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. Wells PS, Blajchman MA, Henderson P, et al. Am J Hematol. 1994;45:321-324. 15. US Census Bureau, Population Division. US and World Population Clock. http://www.census.gov/ popclock/. Accessed November 28, 2022. 16. 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. 17. 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. 18. Franchini M, Veneri D, Salvagno GL, Manzato F, Lippi G. Inherited thrombophilia. Crit Rev Clin Lab Sci. 2006;43(3):249-290. 19. Rodgers GM. Role of antithrombin concentrate in hereditary antithrombin deficiency: an update. Thromb Haemost. 2009;101(5):806-812. 20. Di Minno MND, Dentali F, Lupoli R, Ageno W. Mild antithrombin deficiency and risk of recurrent venous thromboembolism. Circulation. 2014;129(4):497-503. 21. 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. 22. 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. 23. Finley A, Greenberg C. Review article: heparin sensitivity and resistance: management during cardiopulmonary bypass. Anesth Analg. 2013;116(6):1210-1222. 24. 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. 25. 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. 26. 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.