Abnormalities In Platelet Arachidonic Acid Metabolism In Chronic Idiopathic Thrombocytopenic Purpura

Patients with chronic idiopathic thrombocytopenic purpura (CITP) have been described to have bleeding times (B.Ts) that were shorter than would be predicted by their platelet counts. This phenomenon was explained by the presence in CITP of a young platelet population with increased hemostatic competence (NEJM 287:155, ’72). In contradistinction, we have observed patients with CITP to have a bleeding tendency at platelet counts >75,000/cu mm. We therefore evaluated B.Ts and platelet arachidonic acid (AA) metabolism in 7 patients with CITP who demonstrated increased amounts of platelet associated IgG (PAIgG >3fg per platelet) and compared them to 20 healthy controls. 3/7 patients with CITP and platelet counts of >75,000/cu mm demonstrated marked prolongations in their B.Ts. (10’, 12’ and 14’, normal <7’). Marked abnormalities in the metabolism of AA through the cyclo-oxygenase (Thromboxane B2 and HHT) and lipoxygenase (HETE) pathways were also observed in patients with CITP. Platelets in CITP synthesized less amounts (p <0.005) of Thromboxane B2 (10.3 ± 3.1%) in comparison to controls (22.9 ± 1.8). Values for HHT were decreased (23.7 ± 4.9 vs 39.7 ± 1.9; p<0.005), while HETE production was increased (59.5 ± 7.8 vs 30.7 ± 1.8; p<0.001). No correlation was observed between PAIgG and platelet Thromboxane B2 formation. However, an inverse correlation (r=0.81, p<0.05 was observed between the B.T. and platelet Thromboxane B2 formation in patients with chronic ITP. We have demonstrated platelet dysfunction and impaired Thromboxane B2 formation in CITP. This association should be investigated in the individual patient, since the bleeding tendency in these patients is exacerbated by the superimposed impairment in platelet function.