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von Willebrand factor release induced by endotoxin.
H R Gralnick1, L P McKeown, O M Wilson
1Clinical Pathology Department, National Institutes of Health, Bethesda, MD 20892.
The Journal of Laboratory and Clinical Medicine
|January 1, 1989
Summary
Endotoxin administration in humans significantly elevates von Willebrand factor (vWF) and factor VIII levels within hours. This study observed increased vWF antigen, activity, and larger multimers following endotoxin exposure.
Area of Science:
- Hematology
- Immunology
- Endocrinology
Background:
- In vitro studies show endothelial cells release von Willebrand factor (vWF) in response to stimuli.
- Understanding vWF synthesis, storage, and release is crucial for hemostasis research.
Purpose of the Study:
- To investigate the in vivo effects of endotoxin administration on vWF and factor VIII levels and multimeric organization in normal volunteers.
Main Methods:
- Intravenous administration of endotoxin (Escherichia coli, 4 ng/kg) to 11 healthy individuals.
- Monitoring of factor VIII, vWF antigen, vWF activity (ristocetin cofactor assay), and vWF multimeric structure over 48 hours.
- Analysis of plasma samples using agarose gel electrophoresis to assess vWF multimer size distribution.
Main Results:
- Significant increases in factor VIII, vWF antigen, and vWF activity were observed within 2 hours post-endotoxin, peaking at 4-6 hours.
- Elevated vWF antigen and activity persisted for at least 48 hours, while factor VIII levels returned to baseline by 24 hours.
- Endotoxin induced an increase in the largest vWF multimers and the appearance of larger-than-normal multimers, present for 2-4 hours.
Conclusions:
- Endotoxin triggers a rapid and significant release of vWF and factor VIII from endothelial cells in vivo.
- The observed changes in vWF multimeric composition suggest a complex response to endotoxin, potentially impacting hemostatic function.