Clopidogrel ( Plavix ) is a platelet aggregation inhibitor indicated for conditions such as myocardial infarction, stroke or established peripheral arterial disease, acute coronary syndrome and atrial fibrillation.
Acquired hemophilia is a rare bleeding disorder caused by autoantibodies directed against plasma coagulation factors, most notably factor VIII ( i.e., acquired hemophilia A ). While the cause is unknown in half of patients, associations with malignancy, pregnancy, autoimmune disease and drugs have been described.
Clinically, it is characterized by spontaneous and often severe bleeding in patients with no history of bleeding.
Control of acute bleeding is a priority because of the high risk of early mortality.
Typical laboratory findings of acquired hemophilia A include a prolonged activated partial thromboplastin time ( aPTT ) and a low factor VIII level.
The thrombin and prothrombin times are normal, as are both the platelet count and function.
Investigation for an antifactor VIII inhibitor should be considered if indicated by a prolonged aPTT.
Management involves treatment of active bleeding and suppression of the inhibitory antibody.
In September 2013, the manufacturer of Plavix advised physicians in the UK of 11 cases of acquired hemophilia A and one case of acquired hemophilia B in patients treated with Clopidogrel since the launch of the product.
Patients were 65 to 81-years-old.
In some cases, no previous history of abnormal hemostasis had been reported. Time to onset ranged from a few days to 4 months after starting Clopidogrel treatment.
No fatal cases were reported.
Acquired hemophilia suspected of being associated with the use of clopidogrel has been reported in the scientific literature.
As of Sept. 30, 2013, there were no reports of acquired hemophilia suspected of being associated with Clopidogrel in Canada.
Health care professionals should be aware of the potential association between acquired hemophilia and the use of Clopidogrel. Increased bruising should not be attributed to the antiplatelet action of Clopidogrel, unless the platelet count and coagulation screen are found to be normal.
In cases of confirmed isolated aPTT prolongation with or without bleeding, acquired hemophilia should be considered.
Patients with a confirmed diagnosis of acquired hemophilia should be managed and treated by specialists, and Clopidogrel should be discontinued.
Acquired hemophilia has been included in the Warnings and Precautions and certain Post-Market Adverse Drug Reactions sections of some of the Clopidogrel Canadian product monographs. ( Xagena )
Source: Health Canada, 2014