HEPARIN-RELEASABLE PLATELET FACTOR 4 IN PATIENTS WITH CORONARY-ARTERY DISEASE

Recently, platelet factor 4 (PF4) release by heparin (heparin-releasable PF4) has been examined as a useful marker of the interaction between the substances liberated from circulating platelets and the vascular endothelium. We compared the plasma levels of PF4 and beta-thromboglobulin (beta-TG) after intravenous heparin injection in patients with coronary artery disease (CAD) and normal control subjects. We also studied the effects of low-dose aspirin (81 mg/day) on the plasma level of heparin-releasable PF4 in the CAD patients. Blood samples were obtained before and 5 min after the intravenous injection of heparin (1,000 IU) from 23 patients with CAD and 15 normal control subjects. Although the plasma beta-TG level remained unchanged after heparin injection, the plasma PF4 level markedly increased in both groups. There was a significant difference in plasma PF4 levels at 5 min after heparin injection between the CAD group (100.1 +/- 38.1) and the control group (61.0 +/- 24.0) (p < 0.01). The PF4/beta-TG ratio after heparin injection was also higher in the CAD group than in the control group (p < 0.01). There was a correlation between the PF4/beta-TG ratio after heparin and the Gensini CAD score, which defines the severity of coronary atherosclerosis (r = 0.489, n = 23, p < 0.01). Low-dose aspirin was administered to 11 CAD patients for 246.0 +/-28.8 days. Blood samples for the assay of PF4 and beta-TG were obtained as stated above, and platelet aggregation, thromboxane B2 (TxB2), and 6-keto-prostaglandin F1-alpha (6-keto-PGF-1-alpha) levels were also measured before and during aspirin administration. Aspirin significantly reduced the PF4 level and the PF4/beta-TG ratio after heparin injection (p < 0.05) in accordance with the reduction in platelet aggregation (ADP induced: p < 0.01, collagen-induced: p < 0.01, epinephrine-induced: p < 0.05). Although there were no statistically significant changes in TxB2 and 6-keto-PGF-1-alpha levels during aspirin administration, the TxB2 level was decreased by aspirin in 7 of 11 CAD patients. The decrease in the PF4/beta-TG ratio after heparin injection was significantly correlated with the changes of ADP- and epinephrine-induced platelet aggregation (r = 0.717, p < 0.01 and r = 0.577, p < 0.05, respectively). These results suggest that heparin-releasable PF4 (the PF4 level and/or PF4/beta-TG ratio after heparin injection) has the potential to be used as a marker of increased platelet aggregability in CAD patients.