| |
|
|
|
|
|
|
|||
|
FA Ofosu, GJ Modi, LM Smith, AL Cerskus, J Hirsh and MA Blajchman
Heparan with a low affinity for antithrombin III has previously been
demonstrated to inhibit thrombin generation in both normal plasma and
plasma depleted of antithrombin III. In addition, standard heparin and
heparin with a low affinity for antithrombin III have been demonstrated to
have equivalent inhibitory actions on thrombin generation in plasma
depleted of antithrombin III. These observations prompted the investigation
of the effects of four normal vessel wall glycosaminoglycans (heparan
sulfate, dermatan sulfate, chondroitin-4- sulfate, and
chondroitin-6-sulfate) on the intrinsic pathway generation of thrombin and
factor Xa and on the inactivation of thrombin and factor Xa in plasma.
Heparan sulfate inhibited thrombin generation and accelerated the
inactivation of added thrombin and factor Xa in normal plasma but not in
antithrombin III-depleted plasma. In contrast, dermatan sulfate inhibited
thrombin generation in both normal and antithrombin III-depleted plasma. In
addition, heparan sulfate was an effective inhibitor of factor Xa
generation, while dermatan sulfate was not. Neither chondroitin-4-sulfate
nor chondroitin-6-sulfate inhibited the generation of thrombin or factor Xa
nor did they accelerate the inactivation of factor Xa or thrombin by
plasma. These results suggest that heparan sulfate acts primarily by
potentiating antithrombin III, while dermatan sulfate acts by potentiating
heparin cofactor II. The inhibition of thrombin generation by heparan
sulfate and dermatan sulfate thus appears to occur by complementary
pathways, both of which may contribute to the anticoagulation of blood in
vivo.
This article has been cited by other articles:
| |||||||||||
| Copyright © 1984 by American Society of Hematology Online ISSN: 1528-0020 | |||||||||