Rationale behind the development of low molecular weight heparin derivatives.
There is now considerable evidence that the antithrombotic and the hemorrhagic effects of heparin can be dissociated by using low molecular weight heparins and by using heparin with low affinity to AT III. The findings with low-affinity heparin suggest that hemorrhage is contributed to by heparin properties that are independent of AT III binding and thus of their major anticoagulant effect. The current evidence supports the suggestion that the hemorrhagic effect of heparin is contributed to by a reversible platelet functional defect that is relatively less important than its AT III dependent anticoagulant effect for preventing experimental venous thrombosis. Whether these promising results in animals also apply to human thromboembolism disease will require careful evaluation by suitably designed clinical trials.
Hirsh
J
J
Ofosu
F
F
Buchanan
M
M
D000818:Animals; D000990:Antithrombin III / Q000378:metabolism; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D003871:Dermatan Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005170:Factor X / Q000037:antagonists & inhibitors; D015951:Factor Xa; D006470:Hemorrhage / Q000139:chemically induced; D006493:Heparin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D008970:Molecular Weight; D010426:Pentosan Sulfuric Polyester / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects; D011516:Prothrombin / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013431:Sulfates; D013927:Thrombosis / Q000188:drug therapy
D013431:Sulfates; D003871:Dermatan Sulfate; D010426:Pentosan Sulfuric Polyester; D000990:Antithrombin III; D011516:Prothrombin; D005170:Factor X; C025337:Factor IIa; D006493:Heparin; D015951:Factor Xa