Plasma Levels of Platelet Factor 4 Measured by Radioimmunoassay

Abstract

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.

Increased plasma concentrations of platelet factor 4 in coronary artery disease: a measure of in vivo platelet activation and secretion.

“…1). Patients with significant coronary artery disease had a significantly higher plasma PF4 (16 ng/ml; CIl, [13][14][15][16][17][18][19] ng/ml) than patients with normal coronary angiograms (8.7 ng/ml; CI,6 5.9-13 ng/ml) (p < 0.02). Seven patients who had subcritical narrowing were analyzed separately and found to have a plasma PF4 concentration that was intermediate between the other two groups (12.3 ng/ml; CI.…”

Platelet factor 4 is a negative autocrine in vivo regulator of megakaryopoiesis: clinical and therapeutic implications

“…As shown in Figure 3A, addition of 20 g/mL of recombinant mPF4 to WT hematopoietic cells inhibited megakaryocyte-containing colonies by more than 40% (P Ͻ .009), comparable to the effect of hPF4 ( Figure 3A). Even though plasma levels of PF4 are relatively low, 32 recent data suggest that at the site of platelet activation, PF4 levels may be higher than 200 g/mL; 33 thus, these levels of 20 g/mL of PF4 are within the physiologic range. Addition of polyclonal anti-mPF4 antibody specifically reversed the inhibitory effect of supplemental mPF4, as did an anti-hPF4 antibody in the presence of recombinant hPF4 ( Figure 3A).…”

Endothelial expression of E-selectin is induced by the platelet-specific chemokine platelet factor 4 through LRP in an NF-κB–dependent manner

“…The serum concentrations of PF4 exceeds 8 g/mL during platelet activation. 53 Because the concentration of PF4 within ␣-granules is estimated to be 1500 g/mL, 54 even higher concentrations of PF4 may be present at the site of platelet activation. It is therefore likely that PF4 levels at sites of platelet activation would be sufficient to increase E-selectin expression by endothelial cells under pathophysiologic conditions such as vascular inflammation or atherosclerotic vascular disease or both.…”