A new type of familial macrothrombocytopenia with increased platelet calpain activity

An 8 years old Japanese boy born in non-sanguineous parents has been in good health until he was found to have macrothrombocytic thrombocytopenia when he developed purpura after common cold and ingestion of aspirin. His hearing ability and renal function were normal. He had no cataract. Hematological studies revealed normal hemoglobin, normal white cell counts with normal differentials and mild thrombocytopenia (94×103/μl). Numerous giant platelets larger than red cells were identified on blood films. Döhle bodies and other inclusion bodies were not found in his neutrophils. The patient's platelet in platelet-rich plasma did not aggregate spontaneously and caused normal aggregation/agglutination in response to epinephrine, ADP, collagen and ristocetin, respectively. Major platelet membrane glycoproteins such as GPIa/IIa, Ib/IX, IIIa, and so on were indistinguishable from those of normal platelets. Clot retraction and coagulation studies were normal. However, calpain activity in the patient's platelets solubilized with 1% Triton X-100 was found to be 218.3% of that in platelets from normal control donors (n=6) when calculated per platelet and 135.7% of the controls when calculated per protein concentration. The patient's mother also showed moderate numbers of giant platelets and moderately increased activity of platelet calpain. Thus, the patient's platelets can not be classified into any congenital platelet disorder so far known and seem to be a new congenital disease in which giant platelets are associated with increased platelet calpain acitvity.