Circulating glycosaminoglycan anticoagulants associated with suramin
treatment
MK Horne , CA Stein, RV LaRocca and CE Myers
Clinical Pathology Department, National Cancer Institute, Bethesda, MD
20892.
A complex coagulopathy appeared in three women receiving suramin as
treatment for metastatic adrenocortical carcinoma. Although hepatocellular
dysfunction accounted for some of the abnormality, a unique feature of the
coagulopathy was the presence of an inhibitor of the thrombin clotting
time. The potency of this circulating anticoagulant increased markedly
during exacerbations of hepatic injury. The anticoagulant was removed from
plasma samples from two of the patients by passage over a column of
diethylaminoethyl (DEAE)- Sephacel. It eluted from the DEAE at salt
concentrations that removed "high-charge" glycosaminoglycans. Elimination
of the purified anticoagulant activity in vitro required a combination of
heparitinase and chondroitinase ABC, suggesting that the activity was
mediated by both heparan sulfate and dermatan sulfate. Suramin is
hypothesized to inhibit enzymes that normally degrade glycosaminoglycans,
resulting in accumulation of these substances, which are released from the
liver into the circulation during periods of hepatic injury.
Volume 71,
Issue 2,
pp. 273-279,
02/01/1988
Copyright © 1988 by The American Society of Hematology
