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Circulating glycosaminoglycan anticoagulants associated with suramin treatment
M K Horne1, C A Stein, R V LaRocca
1Clinical Pathology Department, National Cancer Institute, Bethesda, MD 20892.
Abstract:
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.
Insights
Suramin treatment caused complex coagulopathy in women with adrenocortical carcinoma. A unique inhibitor, linked to glycosaminoglycans and hepatic injury, was identified.
Area of Science:
- Biochemistry
- Pharmacology
- Hematology
Background:
- Metastatic adrenocortical carcinoma treatment often involves chemotherapy.
- Suramin is a drug used in treating certain cancers, including adrenocortical carcinoma.
- Coagulopathy is a significant concern in cancer patients undergoing treatment.
Observation:
- Three women receiving suramin developed a complex coagulopathy.
- Hepatocellular dysfunction contributed to the coagulopathy.
- A unique inhibitor of thrombin clotting time was present in the patients' plasma.
Findings:
- The anticoagulant's potency increased with hepatic injury exacerbations.
- The inhibitor was associated with high-charge glycosaminoglycans, specifically heparan sulfate and dermatan sulfate.
- Suramin may inhibit glycosaminoglycan-degrading enzymes, leading to their accumulation.
Implications:
- This suggests a novel mechanism of drug-induced coagulopathy.
- Understanding this mechanism could lead to improved patient monitoring and management strategies.
- Further research is needed to elucidate the precise interactions between suramin, glycosaminoglycans, and coagulation pathways.