Heparin‐releasable platelet factor 4 in patients with coronary artery disease

Abstract 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 β‐thromboglobulin (β‐TG) after intravenous heparin injection in patients wtih 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 β‐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/β‐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/β‐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 β‐TG were obtained as stated above, and platelet aggregation, thromboxane B 2 (T×B 2 ), and 6‐keto‐prostaglandin F 1 α (6‐keto‐PGF 1 α) levels were also measured before and during aspirin administration. Aspirin significantly reduced the PF4 level and the PF4/β‐TG ratio after heparin injection (p<0.05) in accoradance 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 T×B 2 and 6‐keto‐PGF 1 α levels during aspirin administration, the T×B 2 level was decreased by aspirin in 7 of 11 CAD patients. The decrease in the PF4/β‐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/β‐TG ratio after heparin injection) has the potential to be used as a marker of increased platelet aggregability in CAD patients.