Clopidogrel: risk of acquired haemophilia

Reports of acquired haemophilia have been received in association with clopidogrel.

From:
Medicines and Healthcare products Regulatory Agency
Published
11 December 2014
Therapeutic area:
Cardiovascular disease and lipidology

Article date: December 2013

Clopidogrel is a thienopyridine, inhibiting platelet activation and aggregation. It is indicated for prevention of:

  • atherothrombotic events in patients with acute coronary syndrome, ischaemic stroke, or established peripheral arterial disease
  • atherothrombotic and thromboembolic events in patients with atrial fibrillation and at least one other risk factor, who are unsuitable for treatment with vitamin K antagonists

Acquired haemophilia [footnote 1] [footnote 2] is a very rare condition that affects between one and four men or women per million people per year; it generally occurs in the elderly. About half of cases are idiopathic and half associated with illness (eg, rheumatoid arthritis, cancer). Occasionally, cases of acquired haemophilia may occur in association with drug treatment.

Morbidity and mortality associated with acquired haemophilia are high. The condition tends to cause bleeding into the skin and soft tissues; by contrast with severe congenital haemophilia, bleeding into the joints is unusual.

A total of 11 cases of acquired haemophilia A and one case of acquired haemophilia B have been received worldwide by the licence (marketing authorisation) holder in association with clopidogrel, four of which were published case reports.[footnote 3] [footnote 4] [footnote 5] This number of reports should be considered in the context of the very high use of clopidogrel (more than 153 million patients worldwide).

The case reports described patients aged between 65 years and 81 years, with no previous history of abnormal haemostasis. In six cases, it was reported that symptoms of acquired haemophilia resolved after stopping clopidogrel and corrective treatment (including steroids). Although no cases had a fatal outcome, two were considered life-threatening. Although these events are very rare, it is important to be aware of the possibility that a patient may develop acquired haemophilia, as distinct from the risk of bleeding associated with clopidogrel.

Advice for healthcare professionals:

  • Healthcare professionals should be aware of the risk of acquired haemophilia in association with clopidogrel
  • Prompt diagnosis is required to minimise the time the patient is at risk of bleeding and to avoid major bleeding
  • Acquired haemophilia should be considered in the event of isolated prolonged activated partial thromboplastin time (aPTT)
  • Patients with confirmed acquired haemophilia should be managed by specialists, and clopidogrel should be discontinued. Invasive procedures should be avoided    

Further information

Letter sent to healthcare professionals, September 2013

Summary of Product Characteristics

 

Article citation: Drug Safety Update volume 7 issue 5, December 2013: A2.

  1. Franchini M, et al. Am J Hematol 2005; 80: 55–63. ↩

  2. Delgado J, et al. Br J Haematol 2003; 121: 21–35. ↩

  3. Hwang HW, et al. Korean J Hematol 2012; 47: 80–82. ↩

  4. Haj M, et al. BMJ 2004; 329: 323. ↩

  5. Foley PW, et al. J R Soc Med 2004; 97: 542–43. ↩

Updates to this page

Published 11 December 2014
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