Studies of human plate alpha-granule release in vivo

The clinical usefulness of measuring platelet factor 4 (PF4) and β-thromboglobulin (βTG) by radioimmunoassay in plasma, urine, and platelets has been evaluated in 105 normal subjects and 184 selected patients with suspected alterations in platelet reactivity. Since blood collection techniques are critical in minimizing in vitro artifact when measuring plasma PF4 and βTG, we developed a method for sampling and processing with respect to anticoagulant, inhibitory agents, temperature, centrifugation, and interval before processing. In 105 normal subjects, the levels of PF4 and βTG were 1.8 ± 1.0 (± 1 SD) and 6.0 ± 3.6 ng/ml, respectively, in plasma; 1.36 ± 0.24 and 4.29 ± 1.38 ng/fl × 10−6, respectively, in platelets; and 0.18 ± 0.16 ng PF4/mg creatinine in urine. Serum values for PF4 and βTG in these normal subjects, as well as in individuals with thrombocytopenia or thrombocytosis, correlated closely with the platelet concentration in whole blood (coefficient of correlation 0.947 and 0.826, respectively; p 0.2). Patients with acute events such as cardiopulmonary bypass showed parallel depletion of PF4 and βTG from platelets, striking elevation of these proteins in plasma and clearance of PF4 into urine. Untransfused, severely thrombocytopenic patients with aplastic anemia had low levels of PF4 and βTG in their plasma, i.e., 0.3 ± 0.3 (p 0.1). We conclude that measurements of PF4 and βTG in plasma and platelets and of PF4 in urine do not identify individuals with stable chronic atherosclerotic vascular disease and thus do not generally provide a means for identifying patients at risk or following the effects of therapy. In contrast, marked elevation in plasma levels and depletion of these proteins from circulating platelets occur with acute in vivo platelet activation and release.