ristocetin and Anemia--Sickle-Cell

Several investigators have reported defective ristocetin-induced platelet aggregation (RIPA) in individuals whose red blood cells contain sickle haemoglobin, but the race of control subjects in these studies was not stated. Therefore, maximal amplitude of RIPA was examined in 75 normal whites and blacks, of 16 of whom had sickle trait defined by haemoglobin electrophoresis and sickle prep. Final ristocetin concentrations in platelet rich plasma were 1.1, 1.2 and 1.5 mg/ml. Mean aggregation at 1.1 mg/ml was significantly less in blacks (mean 31%) than in whites (mean 72%) (P less than 0.001). 60% of blacks but only 11% of whites had less than 50% RIPA at 1.1 mg/ml. RIPA was entirely absent in 19% of blacks. Differences in RIPA between black and white subjects were also present at ristocetin concentrations of 1.2 and 1.5 mg/ml but were less striking. RIPA in 25 children with homozygous sickle cell anaemia was similar to that in the normal AA and AS blacks. Differences in RIPA could not be explained by age, sex, presence of sickle haemoglobin, or medications. Addition of normal plasma or platelets did not correct reduced RIPA in seven blacks, and their plasma inhibited normal RIPA responses. Reduced platelet aggregation to low concentrations of ristocetin is a normal finding in many blacks, is not related to the presence of sickle haemoglobin, and appears to be due to a plasma inhibitor against RIPA.

Topics: Adolescent; Adult; Anemia, Sickle Cell; Black People; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Fibrinogen; Humans; Male; Middle Aged; Platelet Aggregation; Ristocetin; von Willebrand Factor; White People

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.

Topics: Anemia, Sickle Cell; Blood Platelets; Collagen; Epinephrine; Factor VIII; Fibrinogen; Humans; Platelet Aggregation; Ristocetin