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Effect of dextran on factor VIII/von Willebrand factor structure and function.
Thrombosis and Haemostasis
|October 30, 1985
Summary
Dextran 70 infusion significantly decreased levels of Factor VIII and von Willebrand factor (vWF) in healthy volunteers, impacting vWF multimer structure. This effect mimics certain types of von Willebrand disease.
Area of Science:
- Hematology
- Clinical Pharmacology
Background:
- Dextran 70 is a plasma volume expander.
- Its effects on hemostatic factors, particularly Factor VIII and von Willebrand factor (vWF), are not fully understood.
Purpose of the Study:
- To investigate the impact of Dextran 70 infusion on Factor VIII and vWF parameters in healthy individuals.
- To characterize changes in vWF multimeric structure and platelet function post-infusion.
Main Methods:
- Analysis of Factor VIII procoagulant activity, Factor VIII-related antigen, and ristocetin cofactor activity before and after Dextran 70 infusion.
- Assessment of ristocetin-induced platelet agglutination (RIPA) in platelet-rich plasma (PRP).
- Multimeric analysis of von Willebrand factor (vWF).
Main Results:
- A significant decrease in Factor VIII/vWF activities and antigen levels was observed, peaking at six hours post-infusion.
- The reduction in vWF levels did not correlate with hemodilution.
- vWF multimeric analysis revealed a progressive loss of all multimers, with larger multimers affected most significantly.
- RIPA and vWF triplet structure remained unchanged; in vitro incubation showed no direct effect of dextran.
Conclusions:
- Dextran 70 administration alters Factor VIII and von Willebrand factor levels and structure in vivo.
- The observed changes in vWF, particularly the loss of large multimers, resemble findings in von Willebrand disease subtype Ib.
- Dextran 70's effects appear to be systemic rather than a direct interaction with plasma components in vitro.