Ja. Fernandez et al., Dermatan sulfate and LMW heparin enhance the anticoagulant action of activated protein C, THROMB HAEM, 82(5), 1999, pp. 1462-1468
Unfractionated heparin potentiates the anticoagulant action of activated pr
otein C (APC) through several mechanisms, including the recently described
enhancement of proteolytic inactivation of factor V. Possible anticoagulant
synergism between APC and physiologic glycosaminoglycans, pharmacologic lo
w molecular weight heparins (LMWHs), and other heparin derivatives was stud
ied. Dermatan sulfate showed potent APC-enhancing effect. Commercial LMWHs
showed differing abilities to promote APC activity, and the molecular weigh
t of LMWHs correlated with enhancement of APC activity. Degree of sulfation
of the glycosaminoglycans influenced APC enhancement. However, because dex
tran sulfates did not potentiate APC action, the presence of sulfate groups
pei se on a polysaccharide is not sufficient for APC enhancement. As previ
ously for unfractionated heparin, APC anticoagulant activity was enhanced b
y glycosaminoglycans when factor V but not factor Va was the substrate. Thu
s, dermatan sulfate and LMWHs exhibit APC enhancing activity in vitro that
could be of physiologic and pharmacologic significance.