Abstract
To evaluate the antithrombogenic activity of endothelium, we intravenously injected heparin (60u/kg) in patients with DIC and healthy cotrols, and measured both plasma platelet factor 4 (PF4) and β-thromboglobulin (βTG).
Plasma PF4 increased transiently 5 minutes after heparin injection, while βTG did not. During this course urinary PF4 remarkably increased, however βTG decreased. This may suggest that PF4 was released from the heparin-like molecules on the surface of endothelium. As the heparin exerts its anticoagulant activities by potentiating the antithrombin III (ATIII) against the coagulation factor proteinases, more increasing amounts of PF4 released from endothelium neutralize larger heparin-like molecules on the endothelium and decrease the antithrombogenic activities of endothelium.
In healthy controls, there was direct correlation between βTG and PF4. Increased βTG was observed in healthy controls over 60 years old, but not in younger controls, while PF4 did not show significant changes with advancing age.
Four cases with DIC showed abnormal profile, whose levels of pre-βTG and PF4 were markedly higher than those of controls. DIC in large part, is regarded as a consequence of intravascular thrombin formation, which is immediately neutralized by the ATIII bound to the heparin-like molecules on endothelium. However, PF4 released from the activated platelets also immediately binds to the heparin-like molecules on endothelium. This way, with more increasing amounts of PF4 released from platelets, larger heparin-like molecules on the endothelium will be neutralized. This process may decrease the endothelial antithrombogenic activities in DIC.
The decreased antithrombogenic activity revealed by this heparin injection test, may play a role for the pathogenesis of DIC.
