Platelet function abnormalities in acquired hemophilia A

Background: The bleeding pattern in acquired hemophilia A (AHA) differs from that of inherited hemophilia, being characterized by soft tissue and muscle hematomas, mucocutaneous bleeding, but seldom joint bleeding. Platelet function disorders are inherited or acquired. The acquired forms may appear in association with medications, medical conditions, and autoimmune disorders. Objectives: We chose to investigate platelet function in a series of patients with AHA due to autoantibodies inactivating coagulation factor (F)VIII. Methods: Platelet function disorders were assessed at AHA diagnosis in platelet-rich plasma according to the Scientific Subcommittee of the International Society on Thrombosis and Haemostasis recommendations. In addition, the δ- and α-granule platelet content—that is, adenine nucleotides (ADP and ATP), serotonin and β-thromboglobulin—were measured. CD40L and soluble P-selectin were also measured in plasma to investigate in vivo platelet activation. Results: In 11 cases with AHA and a median age of 67 years, FVIII coagulant activity was unmeasurable, the inhibitor titer was <20 Bethesda Units in 5 cases (45%) and higher than 20 Bethesda Units in 6 cases (55%). All patients showed reduced platelet aggregation and secretion. Furthermore, 4 cases with monoclonal gammopathy of undetermined significance had worse aggregation responses and an abnormal δ-granule platelet content, supporting a diagnosis of δ storage pool disease. Following remission the intraplatelet levels of ADP and serotonin improved. Conclusion: This study demonstrates that acquired platelet function abnormalities may be present in patients with AHA and perhaps contribute to the severity of their bleeding tendency.