Combinations of Low Doses of Unfractionated Heparin and of Low-Molecular-Weight Heparin Prevent Experimental Venous Thrombosis

Synergism between low-molecular-weight heparin and low doses of unfractionated heparin (UH) enhancing anti-factor Xa activity and the release of tissue factor pathway inhibitor was observed. The aim of this study was to verify whether this association is effective in preventing experimental venous thrombosis. Seventy rats were allocated into 7 groups: the control group treated with distilled water, the H350 group treated with UH 350 IU/kg, the E2 group treated with enoxaparin 2 mg/kg, the H175 group treated with UH 175 IU/kg, the E1 group treated with enoxaparin 1 mg/kg, the H175 + E1 group treated with UH 175 IU/kg plus enoxaparin 1 mg/kg, and the H100 + E0.5 group treated with UH 100 IU/kg plus enoxaparin 0.5 mg/kg. Forty minutes after subcutaneous injection, thrombosis was induced in vena cava. Three hours later, if present, thrombi were withdrawn and weighed. Bleeding time, activated partial thromboplastin time, thrombin time (TT), and anti-factor Xa were measured at the beginning and end of the experiment. Forty-eight other animals were treated, but without inducing thrombus, and tests were performed 40 min after injection. Thrombus developed in 90.9% of control animals, 20% of the H350 group, 22.2% of the E2 group, 10% of the H175 + E1 group, and 30% of the H100 + E0.5 group; there was a difference between group C and the other groups. Only in the H350 and H175 + E1 groups were TT and activated partial thromboplastin time prolonged in relation to control at the end of the experiment. Forty minutes after injection, TT was prolonged in the H350 and H175 + E1 groups. In conclusion, combinations of low doses of low-molecular-weight heparin and low doses of UH were as effective as high doses of each one used alone in preventing thrombus development in rat vena cava.