Dosage, anticoagulant, and antithrombotic effects of heparin and low-molecular-weight heparin in the treatment of deep vein thrombosis

We have performed a prospective, randomized, controlled trial comparing continuous intravenous unfractionated heparin with twice-daily subcutaneous (s.c.) high-dose low-molecular-weight (LMW) heparin in the initial treatment of 50 patients with acute proximal deep vein thrombosis. In this article we analyze the relationship between the dosage of the heparins, the anticoagulant effects on aPTT, and thrombin and factor Xa inhibition to the improvement of the Marder score after a 10-day treatment period. Improvement of the Marder score was observed in about 70% of patients without regard to administration of unfractionated or LMW heparin.(1) Patients in both treatment categories were divided into two groups, namely, those who showed an improvement of the Marder score and those who did not. In the group of patients with unfractionated heparin and regression of thrombus size the mean dosage was 33,000 U/day, whereas the mean dosage was 37,000 U/day in the patients with status idem of the Marder score after the 10-day treatment period. Thrombin clotting time values were in contrast to the dosage. Patients with regression of thrombosis showed higher thrombin clotting time values compared with those with status idem. These results were also seen with aPTT and the Heptest coagulation assay, but the differences between the two groups were less pronounced. No differences between these two groups of patients were seen or detected with the S2222 chromogenic anti-factor Xa method. Patients receiving 2 x 12,000 IU s.c./day LMW heparin did not show these differences, the dosage being adjusted by the anti-Xa levels, ranging from 0.6 to 1.0 U/mL 4 hours after the s.c. Injection. The groups of patients categorized as to improvement or not of the Marder score did not show differences in the daily dose. The anti-Xa activity was higher in patients with regression of thrombosis compared with patients without regression. The other coagulation parameters did not show any relation to the clinical outcome of thrombus regression. The relationship between the change of the Marder score at day 10 and the anticoagulant effect on the different coagulation systems correlated weakly for patients receiving unfractionated heparin. The highest correlation was found for the improvement of Marder score and thrombin inhibition in the heparin group with r = 0.42. For LMW heparin no correlation could be detected. Heptest coagulation values were in the same range for patients receiving unfractionated and LMW heparin. In contrast to the chromogenic anti-Xa assay, aPTT, thrombin clotting time, and prothrombin time values differed substantially in the two treatment regimens. Treatment of recent deep vein thrombosis with unfractionated heparin profits from laboratory monitoring, whereas monitoring of the anticoagulant effect during the treatment with s.c. LMW heparin does not influence the outcome on thrombus regression.