Background and Goal of Study
In sepsis, platelet activation and increase of coagulation factors induce hypercoagulable state. Activated platelets secrete platelet-derived growth factor (PDGF)-AB and release soluble CD40(sCD40) ligand.  PDGF-AB is a mitogenic mediator and plays a key role in the development of arteriosclerosis. sCD40 ligand is one of the inflammatory mediators in atherosclerosis process.  Antithrombin-III (AT-III) therapy is currently performed to treat hypercoagulable state in sever sepsis. In our previous studies, we found that pretreatment of AT-III inhibits collagen-stimulated platelet activation.  However, it is impossible to administrate AT-III before platelets activation as treatment for septic coagulopathy. In this study, we investigated the effect of AT-III on the activated platelet by collagen.
Materials and Methods
Twelve healthy volunteers, who have not been taking any antiplatelet medicines, were enrolled in this study. Platelet-rich plasma (PRP) was obtained from blood samples by centrifugation. After the PRP stimulation with collagen, AT-III was administrated 15, 30, 45, 60, 90 or 120 sec later. Platelet aggregation was followed in an aggregometer. The mixture was centrifuged and isolated supernatant for measurement of PDGF-AB and sCD40L by ELISA. The data were analyzed by Student’s t-test.
Results and Discussion
The administration of AT-III until 45 sec after stimulation of collagen markedly suppressed platelets aggregation and the secretion of PDGF-AB. AT-III administration within 60 sec after collagen stimulation significantly inhibited the sCD40L release. These results strongly suggest that the administration of AT-III very early period after the platelet activation drastically attenuate the platelet activation, in terms of both platelet aggregation and the release of atherosclerotic or inflammatory mediators.
Conclusions
In septic coagulopathy, we suggest that administration of AT-III, just after platelet activation, may provide an anti-coagulant and anti-inflammatory effect. However, all platelets are not activated at once in septic patients, start of AT-III therapy as soon as possible after diagnosis of coagulopathy may be more effective.

02 / Antithrombin-III suppresses collagen-induced human platelets activation