They are derived from unfractionated heparin by either enzymatic or chemical depolymerisation. Their mean molecular weight is between 4 and 6.5 kDa, with a range of 2 to 8 kDa. The mean number of saccharide units is between 13 and 22.
Low molecular weight heparins do not prolong the activated partial thromboplastin time. They possess higher anti-Xa than antithrombin effect, i.e. reduced anti-IIa activity relative to anti-Xa activity. Activity is measured by anti-Xa assay. The target range for anti-Xa activity in blood samples drawn 4-6 hours after a dose should be between 0.5 and 1.0 unit/ml. Advantages:
Predictable anticoagulant dose-response relationship.
High bioavailability; less non-specific binding to cationic plasma proteins and to cell surfaces as a result of less negative charge density. Longer plasma half-life (greater than 30 minutes).
Therapeutic anticoagulant effect with once or twice daily subcutaneous injections at fixed, weight-adjusted doses. Reduced binding to platelet factor IV (reduced risk of heparin-induced thrombocytopenia). Less interference with the physiological activation of protein C. Reduced binding to osteoclasts (reduced risk of heparin-induced osteoporosis).
More difficult to reverse with protamine. Too small to inactivate IIa well.
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