Korean J Hematol.  2012 Mar;47(1):80-82. 10.5045/kjh.2012.47.1.80.

A patient with acquired hemophilia A induced by clopidogrel

• Hwang HW
• Kong JH
• Yu DW
• Kim WT
• Kim HS
• Lee CI

• KMID: 2251976
• DOI: http://doi.org/10.5045/kjh.2012.47.1.80

Abstract

Acquired hemophilia A (AHA) is a rare bleeding disorder caused by autoantibodies against factor VIII (FVIII). Treatment with clopidogrel is a cause of AHA, but its clinical course is unknown. Recently, we treated a 65-year-old man who was hospitalized for cerebellar infarction and had a prolonged activated partial thromboplastin time (aPTT) with soft tissue oozing after 3 weeks of clopidogrel use. We terminated clopidogrel administration and transfused the patient with fresh frozen plasma. However, the aPTT increased up to 98.8 seconds, and the FVIII and FVIII inhibitor levels were <1% and 5.4 Bethesda units/mL, respectively. Clopidogrel-associated AHA was considered, and we began steroid treatment. Two months later, FVIII, FVIII inhibitor, and aPTT values were normalized. No further bleeding or aPTT prolongation has been reported during the 2-year follow-up period. AHA should be considered in patients taking clopidogrel and experiencing bleeding, unless the platelet count and coagulation screen are normal.

Keyword

Acquired hemophilia; Clopidogrel; Factor VIII; FVIII autoantibodies

MeSH Terms

Aged
Autoantibodies
Factor VIII
Follow-Up Studies
Hemophilia A
Hemorrhage
Humans
Infarction
Partial Thromboplastin Time
Plasma
Platelet Count
Ticlopidine
Autoantibodies
Factor VIII
Ticlopidine

Figure

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  Fig. 1 Changes in aPTT, FVIII, and FVIII inhibitor levels as well as the use of blood products or medication after clopidogrel treatment. Abbreviations: aPTT, activated partial thromboplastin time; FVIII, factor VIII; FFP, fresh frozen plasma.

Reference

1. Green D, Lechner K. A survey of 215 non-hemophilic patients with inhibitors to factor VIII. Thromb Haemost. 1981. 45:200–203.

2. Delgado J, Jimenez-Yuste V, Hernandez-Navarro F, Villar A. Acquired haemophilia: review and meta-analysis focused on therapy and prognostic factors. Br J Haematol. 2003. 121:21–35.

3. Toschi V, Baudo F. Diagnosis, laboratory aspects and management of acquired hemophilia A. Intern Emerg Med. 2010. 5:325–333.

4. Zeitler H, Ulrich-Merzenich G, Hess L, et al. Treatment of acquired hemophilia by the Bonn-Malmo Protocol: documentation of an in vivo immunomodulating concept. Blood. 2005. 105:2287–2293.

5. Haj M, Dasani H, Kundu S, Mohite U, Collins PW. Acquired haemophilia A may be associated with clopidogrel. BMJ. 2004. 329:323.

6. Franchini M, Capra F, Nicolini N, et al. Drug-induced anti-factor VIII antibodies: a systematic review. Med Sci Monit. 2007. 13:RA55–RA61.

7. Balamuthusamy S, Arora R. Hematologic adverse effects of clopidogrel. Am J Ther. 2007. 14:106–112.

8. Mehta SR, Yusuf S. The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme; rationale, design and baseline characteristics including a meta-analysis of the effects of thienopyridines in vascular disease. Eur Heart J. 2000. 21:2033–2041.

9. CAPRIE Steering Committee. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). Lancet. 1996. 348:1329–1339.

10. Elmi F, Peacock T, Schiavone J. Isolated profound thrombocytopenia associated with clopidogrel. J Invasive Cardiol. 2000. 12:532–535.

11. Bennett CL, Connors JM, Carwile JM, et al. Thrombotic thrombocytopenic purpura associated with clopidogrel. N Engl J Med. 2000. 342:1773–1777.

12. Medina PJ, Sipols JM, George JN. Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. Curr Opin Hematol. 2001. 8:286–293.

13. Cohen AJ, Kessler CM. Acquired inhibitors. Baillieres Clin Haematol. 1996. 9:331–354.

14. Hay CR. Acquired haemophilia. Baillieres Clin Haematol. 1998. 11:287–303.

15. Green D, Blanc J, Foiles N. Spontaneous inhibitors of factor VIII: kinetics of inactivation of human and porcine factor VIII. J Lab Clin Med. 1999. 133:260–264.