Three consecutive randomized open studies have been carried out to determine the optimal dosage of low molecular weight heparin (LMWH) in the prevention of postoperative thrombosis in general surgery (892 patients). All patients undergoing abdominal, gynaecological, thoracic or urological surgery were over 40 years old and presented at least one of the following risk factors for thrombosis: previous thromboembolism, obesity, varicose veins, malignancy (30 per cent), pre-operative hospitalization over 5 days, oestrogen therapy, chronic cardiac disease or bronchitis. Isotopic venous thrombosis and bleeding complications were assessed after subcutaneous administration of a LMWH fragment (LMWH, Enoxaparine) or unfractionated heparin (UH). The three studies compared 3 X 5000 units UH daily with 1 X 60 mg, 1 X 40 mg, 1 X 20 mg LMWH daily. Thromboembolic events rates were not significantly different from group to group (UH: 3.8 per cent, 2.7 per cent, 7.6 per cent respectively compared with LMWH: 2.9 per cent, 2.8 per cent, 3.8 per cent). Bleeding episodes including wound haematoma formation, perioperative blood losses and systemic haemorrhage were not significantly different in patients receiving LMWH or UH. Significant decreases in haematocrit and haemoglobin were only observed in patients receiving 60 mg Enoxaparine (as compared to UH). An analysis using the 'intention to treat' approach gave results consistent with those of an analysis of good compliers. An overview of isotopic thromboses in the three studies gave no evidence of differences amongst the effects of the three doses of LMWH (P = 0.20), and pooling the results of the three studies using the Mantel-Haenszel procedure gave no evidence of a global difference between Enoxaparine and UH (P = 0.54). These results suggest that an optimal dosage of 20 mg/day of Enoxaparine is safe and effective in the prevention of postoperative thrombosis in this population.

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A new simple clotting test (Heptest) for low molecular weight heparins was compared to anti-Xa determination by an amidolytic assay in volunteers and in patients receiving standard calcium heparin or low molecular weight (LMW) heparin (Enoxaparin) by subcutaneous administration. The results obtained with both methods are in very good agreement. It seems that the Heptest, although influenced by various other clotting parameters, is nevertheless relatively specific for anti-Xa activity. Despite our positive first impression, we object to expressing the results in micrograms of heparin per milliliter or anti-Xa units. Until rigorous standardization is possible, we prefer to express the results as clotting times. Preliminary results warrant a more extensive study in order to assess the clinical relevance of Heptest in patients receiving unfractionated or LMW heparins.

Three consecutive randomized open studies have been carried out in 892 patients undergoing abdominal, gynecological, thoracic or urological surgery. They were over 40 years old and presented at least one of the following risk factors for thrombosis: previous thromboembolism, obesity, varicose veins, malignancy (30% in these studies), pre-operative hospitalization over 5 days, estrogen therapy, chronic cardiac disease or bronchitis. The two groups of each trial were well matched with regard to population characteristics. The third trial included higher rate of patients undergoing urologic surgery. Isotopic venous thromboses and bleeding complications were assessed after subcutaneous administration of a low molecular weight (LMW) heparin fragment (Enoxaparin, 1 mg = 100 Anti-Xa I.U.) or unfractionated heparin (UH). The 3 studies compared 3 × 5,000 IU UH daily with 1 × 60 mg, 1 × 40 mg, or 1 × 20 mg LMW heparin daily. Thromboembolic event rates were not significantly different among the groups (UH : 3.6, 2.8, 7.6% respectively compared to LMWH : 3, 2.8, 3.7%). Significant decrease of hematocrit and hemoglobin were only observed in patients receiving 60 mg Enoxaparin (as compared to UH) whilst in the 2 other trials no difference could be evidenced between the 2 populations. The metaanalysis of the three studies on the “intention to treat” patients gave results consistent with those observed in good compliers. The three consecutive studies showed homogeneous results (p = 0.20), the Mantel Haenszel test did not evidence a global difference between Enoxaparin and unfractionated Heparin (p = 0.54). These results suggest that an optimal dosage of 20 mg per day of Enoxaparin is safe and as efficient as UH 5,000 IU × 3 in the prevention of post-operative thrombosis in this population.