Low MolecularWeight Heparins and Heparinoids

The multiple effects of UFH on the coagulation cascade may increase its potential to cause hemorrhage.4 Anticoagulants with more specific sites of action may confer a better safety profile. Two such anticoagulants are low-molecular-weight heparin (LMWH) and heparinoids.

Natural UFH consists of molecular chains of molecular weights varying from 5000 to more than 40,000 Da. In practice, its anticoagulant effect may be difficult to predict, requiring regular monitoring of the prothrombin time (PTT) and dose adjustment. In contrast, LMWHs consist of only short chains of polysaccharide having an average molecular weight of less than 8000 Da.

LMWHs are formed by various methods of fractionation or depolymerization of polymeric heparin (Table 7.1). Although they are enzymatically derived from UFH, they have a different site of action and can be administered subcutaneously. LMWHs exert their anticoagulant effect by inhibiting factor Xa and augmenting tissue-factor-pathway inhibitor, but minimally affect thrombin or factor IIa (Figs. 7.1 and 7.2).4-6 Thus, the PTT, a measure of antithrombin (anti-factor IIa) activity, is not used to measure the activity of LMWHs.

Heparinoid is a term used to describe naturally occurring and synthetic glycosoaminoglycans of structure similar to heparin. Heparinoids have specific

Low-molecular-weight heparin

Antithrombin

Low-molecular-weight heparin

Antithrombin

Inactivated Factor Ha still factor Xa activated

Minimal anti-factor I la activity

Inactivated Factor Ha still factor Xa activated

Minimal anti-factor I la activity

FIGURE 7.2 LMWH inhibits factor Xa and minimally affects factor Ila; thus, activated partial thromboplastin time is not used to measure its anticoagulant activity. (Reprinted from the American Family Physician published by the American Academy of Family Physicians, February 15th, 1999, in an article entitled ''Low-molecular-weight heparin in outpatient treatment of DVT.'')

antithrombin activity.4,7 They are often used as an alternative to heparin in patients with HITS (Table 7.2).

0 0

Post a comment