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Severe Acquired Hemophilia with Factor VIII Inhibition Associated with Acetaminophen and Chlorpheniramine

Clinical Researcher, Department of Internal Medicine, San Camillo Hospital, Rome, Italy

Silvia De Maria, MD

Clinical Researcher, Department of Internal Medicine, San Camillo Hospital

Giovanni Minisola, MD

Professor, Department of Internal Medicine, San Camillo Hospital

Giulio Cesare Nicotra, MD

Professor, Department of Internal Medicine, San Camillo Hospital

Reprints: Giuseppe Famularo MD PhD, Department of Internal Medicine, San Camillo Hospital, Circonvallazione Gianicolense, 00152, Rome, Italy, fax 0039-6-7847528, gfamularo{at}scamilloforlanini.rm.it

OBJECTIVE: To report a case of acquired hemophilia with a high-titer factor VIII inhibitor associated with the use of acetaminophen and chlorpheniramine in combination.

CASE SUMMARY: An 83-year-old woman presented with a severe bleeding disorder 2 weeks after she was prescribed acetaminophen and chlorpheniramine for treatment of a flu-like illness. Laboratory studies showed severe anemia with greatly reduced factor VIII activity and the presence of a high-titer factor VIII inhibitor at 228 Bethesda units. Treatment with high-dose corticosteroids, transfusion of several units of red blood cells, and repeated infusions of factor VIII bypassing activity was successful. Complete clinical and laboratory remission was achieved after 4 weeks of treatment. Use of the Naranjo probability scale suggested a possible association between this adverse event and treatment with acetaminophen and chlorpheniramine.

DISCUSSION: Acquired hemophilia due to factor VIII inhibitor(s) has been associated with the use of drugs such as thioxanthenes, interferon, and fludarabine. As of this writing, to the best of our knowledge, no other case has been reported among patients receiving acetaminophen or chlorpheniramine.

CONCLUSIONS: We suggest that acquired hemophilia due to factor VIII inhibitor(s) should be considered in the appropriate setting when patients present with unexplained and even minor bleeding while on treatment with acetaminophen or chlorpheniramine alone or combined.

Key Words: acetaminophen, acquired hemophilia, chlorpheniramine, factor VIII inhibitor(s)

Published Online, July 20, 2004. www.theannals.com, DOI 10.1345/aph.1E100