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Peter McPhedran, MD

Emeritus Professor of Laboratory Medicine and Internal Medicine

CB 462
203-688-2436
peter.mcphedran@yale.edu

AB 1958 Harvard
MD 1962 Harvard
Fellowship: Hematology, Yale 1968-1970

Platelet dysfunction is routinely evaluated by platelet aggregation, among other tests. At times an aspirin-like defect is identified which seems not to be caused by medication, but by a congenital enzyme deficiency affecting platelet arachidonic acid metabolism. We have identified three patients with such deficiency patterns; collaborators at the University of Texas have confirmed defective or absent platelet cyclooxygenase enzyme in these three patients, using molecular probes(1). There are three more patients with aspirin-like platelet defects awaiting molecular studies. We need also to determine whether the enzymopathy is confined to platelets, or is also present in other somatic cells.

Epidemiologic surveys of patients with prolonged bleeding time (123 cases and normal controls) and with unexplained anemia (202 anemic patients) have been carried out, and the relative frequency of causes of platelet dysfunction and anemia defined in our population. These studies should help to guide physicians in the efficient evaluation of bleeding disorders and anemia.

Thrombotic thrombocytopenic purpura is an aggressive hematologic disorder manifested by platelet microthrombi in arterioles, which is often managed effectively by plasmapheresis. Some patients tend to relapse, and may die during relapses. The drug ticlopidine interferes with platelet function by blocking the platelet surface receptor for fibrinogen. In our hands, it has led to prolonged remissions in four patients with relapsing TTP(2).

Red cell distribution width, or RDW, a measure of anisocytosis, is generally accepted as useful in selecting certain causes of anemia, such as iron deficiency among microcytic patients, B12 and folate deficiency among macrocytic patients, and major hemoglobinopathies among patients with abnormal hemoglobin. However, the RDW has never been tested prospectively in unselected patients. We have chosen a set of 100 patients with extreme abnormal RDWs (23 and higher, 5 s.d.s above the mean) to determine whether these extreme values actually select any specific disorders (compared to controls within RDWs less than 2 s.d.s from the mean).

1. Matijevic-Aleksic N, McPhedran P, Wu KW. Bleeding Disorder Due to Platelet Prostaglandin H Synthase-1 (PGH-1) Deficiency. Brit J Haematol 92:212-217, 1996.
   
2. McPhedran P and Mukamal K. Ticlopidine for Relapsing TTP. Blood 84:80a, 1994.