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Coagulation protein function VI: augmentation of anticoagulant function by acetaldehyde-treated heparin
A S Brecher1, K Hellman, M H Basista
1Department of Chemistry, Bowling Green State University, Ohio 43403, USA.
Digestive Diseases and Sciences
|September 18, 1999
Summary
Acetaldehyde potentiates heparin's anticoagulant effects by altering its structure, potentially explaining effects in alcoholics. Acetaldehyde-treated protamine sulfate also proved a more effective anticoagulant than protamine sulfate alone.
Area of Science:
- Biochemistry
- Pharmacology
- Hematology
Background:
- Heparin is a widely used anticoagulant that functions by binding to antithrombin III and thrombin.
- Acetaldehyde (AcH), a metabolite of ethanol, is present in individuals with alcohol use disorders.
- The interaction between acetaldehyde and heparin's anticoagulant properties is not well understood.
Purpose of the Study:
- To investigate the effect of acetaldehyde on heparin's anticoagulant activity.
- To explore the potential structural modifications of heparin induced by acetaldehyde.
- To examine the combined effects of acetaldehyde, heparin, and protamine sulfate on plasma clotting time.
Main Methods:
- Plasma clotting time assays were performed using varying concentrations of heparin, acetaldehyde, ethanol, and protamine sulfate.
- Heparin and protamine sulfate were preincubated with acetaldehyde or ethanol before addition to plasma.
- The order of addition of reagents was varied to assess interactions.
Main Results:
- Acetaldehyde significantly potentiated heparin's anticoagulant effect, prolonging plasma clotting time.
- High concentrations of acetaldehyde rendered heparin completely ineffective at clotting plasma within 300 seconds.
- Ethanol also prolonged clotting time, suggesting an organic solvent effect, while acetaldehyde likely forms adducts with heparin.
- Acetaldehyde-treated protamine sulfate demonstrated enhanced anticoagulant activity compared to protamine sulfate alone.
- The order of mixing acetaldehyde, heparin, and protamine sulfate did not significantly alter the final clotting times.
Conclusions:
- Acetaldehyde alters heparin's structure, likely through adduct formation, enhancing its anticoagulant potency.
- These findings suggest a potential mechanism for altered coagulation in alcoholics due to acetaldehyde exposure.
- Acetaldehyde-modified protamine sulfate represents a potentially more effective anticoagulant agent.