Because of the high prevalence of thrombotic complications in patients with sickle cell anemia (SCA), we investigated platelet function in patients with sickle hemoglobinopathies. Platelet aggregation induced by epinephrine, ADP, and collagen, except for absent secondary wave in 3 of 10 patients with SCA, was qualitatively normal. However, ristocetin-induced platelet aggregation (RIPA) with a final concentration 1.12 mg/ml was markedly abnormal-absent or virtually absent in 9 of 10 patients with SCA, 3 of 3 patients with hemoglobin S-C disease, and 2 of 3 patients with sickle trait. All 8 controls used in these experiments repeatedly demonstrated normal RIPA. Addition of normal plasma failed to correct abnormal RIPA in sickle hemoglobinopathy patients. All patients demonstrated normal RIPA with a ristocetin dose of 2.24 mg/ml and aggregated with bovine fibrinogen. Recombinant mixing experiments demonstrated that washed SCA platelets support RIPA (1.12 mg/ml) when resuspended in normal plasma or high dilutions of SCA plasma, but not in undiluted SCA plasma. Washed normal platelets do not support RIPA (1.12 mg/ml) when resuspended in SCA plasma. These findings suggest the presence of a plasma inhibitor of RIPA in patients with sickle hemoglobinopathies.

A role for coagulation in the pathogenesis of sickle cell anemia (SCA) pain crisis has long been suspected. We have observed evidence for in vivo coagulation in patients with SCA during pain crisis utilizing a radioimmunoassay for fibrinopeptide A (FPA). Since the proteolytic activity of thrombin results in the release of FPA from fibrinogen, plasma levels of FPA may be used as an index of in vivo thrombin activity. In 20 normal controls FPA plasma levels had a range of 0.6-1.4 ng/ml and a mean of 0.7 * 0.2 ng/ml. We observed elevations of FPA, values greater than the mean plus 4 standard deviations of the control group, in 21 consecutive plasma samples obtained from 8 SCA patients during pain crisis. FPA determinations on 7 of 10 plasma specimens obtained from 10 SCA patients during pain-free periods were within the normal range. Elevations of FPA in 2 of 3 of these pain-free patients could be explained by recent extensive oral surgery and faulty venopuncture, conditions known t o cause elevated levels of the peptide. Plasma specimens were obtained from 2 SCA patients with subjective complaints of pain, but who were suspected of malingering prior t o FPA determination. In both instances, FPA was within the normal range.In summary, plasma levels of FPA appear t o be elevated in SCA patients during crisis as contrasted t o pain-free periods and normal controls. This study provides new evidence for the occurrence of intravascular coagulation during SCA pain crisis. Further studies are needed t o assess whether this activation of the coagulation system is a cause or an effect of pain crisis.

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Summary: A case of severe thrombocytopenia and leukopenia secondary to quinidine is presented. The white cell count and platelet count returned to normal within five days after initiation of corticosteroid therapy and cessation of quinidine. Of interest is the fact that the patient had developed a purpuric rash twelve months earlier after drinking gin and tonic.