A radioimmunoassay has been developed to measure platelet factor 4 (PF4) in biological fluids both in vitro and in vivo. The assay has been shown to be highly specific for PF4 and has a sensitivity of 0.08 ng/assay tube and 1.6 ng/ml of plasma. The preparation of plasma for the measurement of in vivo levels of PF4 requires the use of an anticoagulant containing EDTA, theophylline and prostaglandin E1, the immediate cooling of the blood and high speed or prolonged centrifugation to reduce platelet contamination. Plasma levels of PF4 are normally between 4 and 24 ng/ml with a median of 7.4 ng/ml. Plasma PF4 levels are markedly increased during cardiopulmonary bypass surgery with shortened 51Cr-labelled platelet survival times and during arterial thrombosis. However, despite similarly shortened platelet survival times, the level of PF4 is normal in immune thrombocytopenia. Elevations of plasma PF4 levels are found following surgery, acute myocardial infarction and frequently during acute infections and in inflammatory states. On the contrary, normal levels are usual in disseminated malignancy, in severe hepatic and renal disease and in chronic arterial disease. The measurement of PF4 is a useful addition to the study of platelet pathophysiology. It is apparent, however, that raised levels are by no means specific for thromboembolic disease and similarly platelet destruction is not invariably associated with abnormally increased plasma PF4 levels.

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Relationships between platelet survival (51Cr) and plasma concentrations (radioimmunoassay) of β-thromboglobulin (βTC) and platelet factor 4 (PF4) were analysed in 91 studies of patients prior to and after coronary artery bypass surgery. Platelet lifespans were calculated using the linear, exponential, weighted mean (WM) and multiple hit (MH) models. The values obtained approximated normal distributions and all the indices correlated, r values ranging from 0.69 to 6 (p<0,001 in all cases).βTC had significant negative correlations with all indices of platelet survival, the most significant being with MH (r = -0.39, p<0.001). Of interest was the correlation of βTG with the number of hits (n) in MH (r = -0.29, p<0.01). PF4 correlated with all indices of platelet survival except n, the most significant correlation was with WM (r = 0.33, p<0.01). BTC and PF4 were highly correlated (r = 0.62, p<0.001), however no benefit was obtained by combining measurements of the two proteins in any regression with platelet lifespan.The results suggest that shortened platelet survival in vascular disease is associated with platelet release of BTG and PF4 and that these platelet specific proteins are comparable as markers of platelet activation in vivo.

Relationships between 51Cr platelet survival and plasma concentrations of beta-thromboglobulin (betaTG) and platelet factor 4 (PF4) were analyzed in 91 studies of patients with coronary artery disease. betaTG was significantly correlated with platelet life-span, turnover, and the number of hits in the multiple hit model. PF4 was significantly correlated with life-span and turnover. The most significant relationship involving platelet-specific protein concentrations and life-span estimates was between betaTG and life-span estimated using the multiple hit model (r = -0.39, p less than 0.001). There was a high correlation between betaTG and PF4 (r = 0.62, p less than 0.001), and no improvement could be obtained by combining the measurements of the two proteins in any regression with life-span or turnover. The results indicate that the patients with the shortest platelet survival time in this group tended to have the highest plasma concentration of betaTG and PF4 and thus probably increased in vivo release of betaTG and PF4. They strengthen the claim that these platelet-specific proteins may be indicators of platelet involvement in disease.