EFFECTS OF PLATELETS AND WHITE BLOOD-CELLS AND ANTIPLATELET AGENT C7E3 (REOPRO(TM)) ON A NEW TEST OF PAF PROCOAGULANT ACTIVITY OF WHOLE-BLOOD

This study was designed to evaluate the effects of varying concentrati ons of platelets, white blood cells (WBC) and Fab fragments of a monoc lonal antibody (c7E3, Reopro(TM)) directed at the platelet GpIIb-IIIa receptor complex on ACT-based clot ratio values (hemoSTATUS assay) in healthy volunteers. These measurements were made in heparinized whole blood from 10 normal volunteers in which either platelet or WBC concen trations had been varied by differential centrifugation. In addition, blood collected in either heparin or argatroban was incubated with var ying concentrations of c7E3 (Reopro(TM)). Clot ratio values (%Maximal) in normal blood did not decrease until average platelet counts were l ess than 50,000. A marked reduction in clot ratios was observed when W BC concentration increased above or decreased below baseline clot rati os within each patient. Strong linear relationships were observed betw een white cell concentration and clot ratio values when white cell con centrations were either less or greater than baseline values. When arg atroban was used as an anticoagulant, inverse relationships were demon strated between clot ratio values and increasing c7E3 concentration (C h 3: r=-0.33, Ch4: r=-0.84, Ch5: r=-0.87, Ch 6: r=-0.71). ACT-based cl ot ratio values determined in heparinized whole blood presumably refle cting PAF inducible platelet procoagulant activity, are affected by pl atelet concentration when counts are less than 50,000/mu l. The hemoST ATUS test was also found to be affected by WBC concentration since clo t ratio values decreased when WBC counts were below 4,000/mu l or abov e 9,000/mu l. A dose-dependent reduction in clot ratio values was also observed with increasing concentrations of c7E3. This test can reliab ly detect platelet dysfunction only if the platelet count is > 50,000 and the WBC is normal. (C) 1997 Elsevier Science Ltd.