An overview of clinical trials of low molecular weight heparin fractions. 1988

M N Levine, and J Hirsh
Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

There is experimental evidence that low molecular weight heparin fractions are as effective as standard unfractionated heparin but cause less bleeding. In order to determine the efficacy and safety of low molecular weight heparins, we have conducted an overview of published randomized trials in which a low molecular weight heparin was compared to either placebo or to unfractionated heparin. In the two trials comparing low molecular weight heparin prophylaxis with placebo, the incidence of leg vein thrombosis was substantially reduced with low molecular weight heparin and there was no increased bleeding risk. There have been five trials which compared low molecular weight heparin with unfractionated heparin in high risk surgical patients. In one of these studies there was a statistically significant reduction in postoperative venous thrombosis in patients who received the low molecular weight heparin. In the remaining studies, thrombosis rates were relatively low in all groups and no difference was detected between low molecular weight heparin and unfractionated heparin. We found a significant relationship between ex vivo anti-factor Xa levels and clinically important bleeding, r = 0.54. We conclude that low molecular weight heparin is an effective method of prophylaxis and has a negligible risk of bleeding provided that the anti-factor Xa levels do not exceed 0.2 units per ml. There have been only three published randomized trials on the efficacy of low molecular weight heparin in the treatment of venous thrombosis. Much larger studies are required to establish the efficacy and safety of low molecular weight heparin fractions in the treatment of established venous thromboembolism.

UI MeSH Term Description Entries
D011897 Random Allocation A process involving chance used in therapeutic trials or other research endeavor for allocating experimental subjects, human or animal, between treatment and control groups, or among treatment groups. It may also apply to experiments on inanimate objects. Randomization,Allocation, Random
D002986 Clinical Trials as Topic Works about pre-planned studies of the safety, efficacy, or optimum dosage schedule (if appropriate) of one or more diagnostic, therapeutic, or prophylactic drugs, devices, or techniques selected according to predetermined criteria of eligibility and observed for predefined evidence of favorable and unfavorable effects. This concept includes clinical trials conducted both in the U.S. and in other countries. Clinical Trial as Topic
D004305 Dose-Response Relationship, Drug The relationship between the dose of an administered drug and the response of the organism to the drug. Dose Response Relationship, Drug,Dose-Response Relationships, Drug,Drug Dose-Response Relationship,Drug Dose-Response Relationships,Relationship, Drug Dose-Response,Relationships, Drug Dose-Response
D004311 Double-Blind Method A method of studying a drug or procedure in which both the subjects and investigators are kept unaware of who is actually getting which specific treatment. Double-Masked Study,Double-Blind Study,Double-Masked Method,Double Blind Method,Double Blind Study,Double Masked Method,Double Masked Study,Double-Blind Methods,Double-Blind Studies,Double-Masked Methods,Double-Masked Studies,Method, Double-Blind,Method, Double-Masked,Methods, Double-Blind,Methods, Double-Masked,Studies, Double-Blind,Studies, Double-Masked,Study, Double-Blind,Study, Double-Masked
D006470 Hemorrhage Bleeding or escape of blood from a vessel. Bleeding,Hemorrhages
D006495 Heparin, Low-Molecular-Weight Heparin fractions with a molecular weight usually between 4000 and 6000 kD. These low-molecular-weight fractions are effective antithrombotic agents. Their administration reduces the risk of hemorrhage, they have a longer half-life, and their platelet interactions are reduced in comparison to unfractionated heparin. They also provide an effective prophylaxis against postoperative major pulmonary embolism. LMWH,Low-Molecular-Weight Heparin,Low Molecular Weight Heparin,Heparin, Low Molecular Weight
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013924 Thrombophlebitis Inflammation of a vein associated with a blood clot (THROMBUS). Phlegmasia Alba Dolens,Dolens, Phlegmasia Alba,Thrombophlebitides
D015842 Serine Proteinase Inhibitors Exogenous or endogenous compounds which inhibit SERINE ENDOPEPTIDASES. Serine Endopeptidase Inhibitor,Serine Endopeptidase Inhibitors,Serine Protease Inhibitor,Serine Protease Inhibitors,Serine Proteinase Antagonist,Serine Proteinase Antagonists,Serine Proteinase Inhibitor,Serine Proteinase Inhibitors, Endogenous,Serine Proteinase Inhibitors, Exogenous,Serine Protease Inhibitors, Endogenous,Serine Protease Inhibitors, Exogenous,Antagonist, Serine Proteinase,Endopeptidase Inhibitor, Serine,Inhibitor, Serine Endopeptidase,Inhibitor, Serine Protease,Inhibitor, Serine Proteinase,Protease Inhibitor, Serine,Proteinase Antagonist, Serine,Proteinase Inhibitor, Serine
D015951 Factor Xa Activated form of factor X that participates in both the intrinsic and extrinsic pathways of blood coagulation. It catalyzes the conversion of prothrombin to thrombin in conjunction with other cofactors. Autoprothrombin C,Coagulation Factor Xa,Factor X, Activated,Thrombokinase,Activated Factor X,Blood Coagulation Factor X, Activated,Factor 10A,Factor Ten A,Factor Xa, Coagulation

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