Prospective Double-Blind Comparison between Fragmin and Conventional Low-Dose Heparin: Thromboprophylactic Effect and Bleeding Complications

The effects on primary haemostasis of unfractionated heparin and of the two low molecular weight heparins, enoxaparin and fragmin, were compared in two rat models, one employing the gastric mucosa and the other the tail skin. All three heparin preparations prolonged the bleeding time and increased the blood loss dose dependently. The prolongation of the bleeding time per unit dose caused by unfractionated heparin was significantly greater than the prolongation caused by either one of the two low molecular weight heparins. In the gastric mucosa, but not in the tail skin, enoxaparin prolonged the bleeding time significantly less than fragmin (p < 0.05).

Section: Discussionmentioning

confidence: 99%

Haemorrhagic Effects of Unfractionated and Two Low Molecular Weight Heparins, Enoxaparin and Fragmin, in Rats

Bang

Berstad²,

Talstad³

1991

“…Kabi 2165 and other LM W heparins have been shown to be effective and safe prepara tions for the prophylaxis of DVT in several groups of immobilized patients when used in doses according to their individual anticoag ulant and bleeding properties [18][19][20][21][22][23]. In general surgical patients (less prone to de velop DVT compared to stroke patients) an effective and safe dose of Kabi 2165 seems to be 2,500 anti-Xa U s.c./24 h [24,25], Turpie et al [26] used LMW heparin ORG10172 in stroke patients to prevent DVT and concluded that treated patients developed less DVT and did not suffer from major bleeding accidents.…”

Section: Discussionmentioning

confidence: 99%

Prophylaxis of Deep Venous Thrombosis with a Low-Molecular-Weight Heparin (Kabi 2165/Fragmin®) in Stroke Patients

Prins¹,

Gelsema

Sing

et al. 1989

In a group of 60 patients in the acute phase of an ischemic stroke the assumption that low-molecular-weight heparin Kabi 2165 in the dose of 2 × 2,500 anti-Xa units s.c. could prevent thromboembolic complications was tested using a double-blind, placebo-controlled, randomized trial design. Thirty patients were allocated to each group. Both treatment groups were comparable with regard to neurological status and general condition. In the Kabi 2165 group there were 6 cases of deep venous thrombosis (DVT) compared to 15 in the placebo group (p = 0.05). In the placebo group there were 4 deaths during the trial versus 9 in the Kabi-2165-treated group (NS). Cerebral bleeding complicated 2 cases in the placebo group versus 4 in the Kabi 2165 group (NS). These results indicate that in ischemic stroke patients Kabi 2165 2 × 2,500 anti-Xa units s.c./24 h reduces the frequency of DVT. Because of the small number of patients it is impossible to evaluate the safety.

“…In ad dition, most of the reported bleeding studies were carried out in the intravenous acute studies. The LMW heparins are generally used in the subcutaneous prophylaxis of ve nous thrombosis over a period of 7-15 days [21,22], The bleeding models, therefore, must be consistent with this mode of therapy and the data must be carefully evaluated. Utilizing the rabbit ear bleeding index mod el, we studied the bleeding effects of various LMW heparins and calculated the bleeding index for each of the agents.…”

Section: Discussionmentioning

confidence: 99%

Comparative Study on the in vitro and in vivo Activities of Seven Low-Molecular-Weight Heparins

Fareed

Jm²,

Hoppensteadt³

et al. 1988

Different low-molecular-weight (LMW) heparins are produced by fractionation, enzymatic and chemical methods. Although the manufacturer’s assigned molecular weights of these agents are similar (around 5,000 daltons), they exhibit considerable molecular structural heterogeneity due to the variations in the manufacturing process. In vitro standardization of these LMW heparins produces highly variable results due to the variability of assay specificity. In a comparative study with seven LMW heparins, differences were found in molecular weight distribution, antifactor Xa activity, antifactor Πa activity, Heptest® activity, USP potency, platelet interactions, protamine and platelet factor 4 neutralization and charge density ratios. Relative antithrombotic actions varied between the seven agents and the ratio of the intravenous:subcutaneous effects were inconsistent with expected results based on in vitro properties or observed ex vivo effects. These products were not bioequivalent in equigravimetric or equipharmacopeial dosages (antifactor Xa, USP). Although the intravenous bioavailability was proportional to the potency for an individual agent, the subcutaneous bioavailability of the same agent showed differences from that of the intravenous regimen. In addition, significant differences between the bleeding profiles of these agents were noted in both intravenous and subcutaneous routes. The bleeding profiles did not correlate well with the relative proportion of the antifactor Xa component. However, some relationship to the bleeding effect was observed with the antifactor Xa and activated-partial-thromboplastin-time activities. These LMW heparins produced different effects on platelets as studied in the heparin-induced thrombocytopenia and platelet activation systems. These observations suggest that the individual composition of each LMW heparin determines its in vivo behavior which may account for the different safety/efficacy ratios observed in clinical trials.