A COMPARATIVE-STUDY OF HEPARIN RESPONSES IN ARTERIAL AND VENOUS THROMBOEMBOLISM USING MOLECULAR MARKERS FOR THROMBOSIS

Background. Compared with the therapy of venous thromboembolism, there is little consensus regarding guidelines for heparin anticoagulation of patients with arterial thrombosis. This study aimed to identify the quantitative differences in the activation of the coagulation cascade and platelets in these two syndromes and to characterize their specific biological responses to heparin therapy. Methods and Results. Eighteen patients receiving intravenous heparin to treat venous (n = 9) or arterial (n=9) thromboembolism were prospectively studied for an average of 4 days each. Clinical responses to treatment, activated partial thromboplastin time (aPTT), and molecular markers for thrombosis were measured regularly. Although both groups received equivalent doses of heparin (almost-equal-to 1100 units/h), the resulting aPTTs and plasma heparin activity were significantly lower in the arterial patients (P<.05 and P<.01, respectively). The plasma levels of beta-thromboglobulin (a marker for platelet activation and granule release) were significantly higher in the arterial patients (109+/-9.5 versus 79+/-7.1 ng/mL, mean+/-SEM, P<.05). In vivo fibrin formation, as evidenced by plasma levels of fibrinopeptide A, was less effectively suppressed in the patients with arterial versus venous thrombosis (18.5+/-3.2 versus 10.4+/-2 ng/mL, P<.05). Prothrombin fragments 1+2, a marker for prothrombinase complex activity, was nearly normal in both heparinized groups. Conclusions. The anticoagulant response to heparin is blunted in patients with arterial thrombosis, at least in. part by the antagonistic actions of increased platelet activation. Comparing arterial with venous thrombosis, higher doses of heparin on the average may be required to achieve comparable aPTTs, plasma heparin activity, and comparable suppression of fibrin formation.