LOW MOLECULAR WEIGHT HEPARIN (Enoxaparin) COMPARED WITH UNFRACTIONATED HEPARIN THRICE DAILY IN PREVENTION OF POSTOPERATIVE THROMBOSIS. A RANDOMIZED MULTICENTRE TRIAL

Abstract

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.

The low molecular weight heparin Enoxaparin inhibits the consumption of factor VII and prothrombin activation in vivo associated with elective knee replacement surgery

“…Plasmas of patients receiving Enoxaparin inactivated both exogenous thrombin and factor Xa more effectively than plasmas of patients on placebo. The increased capacity of plasma of the former patients to inactivate exogenous factor Xa is consistent with the results of previous studies (Planes et al, 1986;Samama et al, 1988;Leclerc et al, 1992). We could clearly demonstrate increased thrombin inhibition by all post-surgical plasmas in this study only when the enzyme was added to an equal volume of undiluted patient plasma.…”

Occurrence of thrombosis and haemorrhage, relationship with anti‐Xa, anti‐IIa activities, and D‐dimer plasma levels in patients receiving a low molecular weight heparin, enoxaparin or tinzaparin, to prevent deep vein thrombosis after hip surgery

“…In contrast, a significant relationship between plasma anti‐Xa activity and thrombosis has been observed in a few studies (Levine et al , 1989; Turpie et al , 1987; Samama et al , 1988) and a significant relationship between anti‐Xa and haemorrhages in three studies has also been found (Levine et al , 1989; Koller et al , 1986; Bergqvist et al , 1986). As Levine et al (1989) found a significant correlation between anti‐Xa activity measured just before injection, and thrombosis and bleeding, with 40 mg of enoxaparin administered once daily in the same surgical indication, it appeared pertinent to compare the effects of tinzaparin to that of enoxaparin in the prevention of thrombosis in patients undergoing hip surgery using a dose near to 4000 anti‐Xa‐IU.…”

Low Molecular Weight Heparins and Bleeding

“…Lower doses, although still effectively inhibiting venous thromboses, did not induce more bleeding than unfractionated heparin. This was also the case for the studies that have been performed with Enoxaparin [19][20][21][22] (Table 3). Here again, high doses (60 mg) led to a higher incidence of bleeding, whereas doses in the range of 20 mg twice daily or 40 mg once daily apparently did not increase the risk of bleeding.…”