Adhesion of leukocytes and platelets to the vascular endothelial cells in endotoxemia induces microcirculatory disturbance that leads to the organ dysfunction. In this study, we investigated the role of leukocyte and platelet in the development of endotoxemic organ dysfunction in rats injected with 1.0 mg/kg of lipopolysaccharide (LPS) and observed the mesenteric microcirculation under an intravital microscope. One hour after the injection of LPS, rolling of leukocytes on the mesenteric endothelial cell surface was conspicuous and their number was significantly increased to that in the control group given the buffer alone (p<0.01). Three hours after the injection, leukocytes appeared to become adherent to the endothelial cell surface, and the adherent leukocytes were significantly increased to the control rats (p<0.05). At this time period, remarkable platelet adhesion to the endothelial cell surface was noted. Conversely, leukocytes in the circulating blood decreased significantly 1 hour after the injection, and the circulating platelet counts were reduced to nearly 1/3 of the initial level 3 hours after the injection (p<0.05). The levels of TNF α and IL-6 in plasma reached their maxima at 1 and 3 hours after the injection, respectively. The results together indicate that leukocytes and platelets adherent to the mesenteric endothelial cell surface may have contributed to the occlusion of the vessels leading to the organ dysfunction. Indeed, the markers selected for the organ damages, i.e. ALT, BUN and lactate were found to be significantly increased 15 hours after the injection.

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We report a successful treatment with recombinant activated factor VII (rFVIIa) of a life-threatening maxillopharyngeal hemorrhage that occurred after extraction of the left wisdom tooth in a hemophilia A patient associated with an inhibitor. Although the extraction of the tooth had been conducted under administration of 50 U/kg of the prothrombin complex concentrate (PCC), a hematoma developed in the submandibular soft tissue. Despite additional administration of PCC twice within 19 hours after the tooth extraction, the hamatoma enlarged and grew toward the pharynx and compressed the respiratory tract. To maintain the airway, a tracheotomy was performed under administration of the activated PCC, but bleeding started at the incision site 3 hours later and formed a hematoma that grew continuously. After a bolus infusion of 120 μg/kg of rFVIIa, we administered rFVIIa continuously for 12 hours at a rate of 30 μg/kg/h together with 1.0 g of tranexamic acid given at every 6 hours intravenously. Within 2 hours after the initiation of rFVIIa treatment, bleeding ceased and the hematoma began to diminish obviously. In this case, administration of rFVIIa brought about a remarkable sustained hemostatic effect for a life-threatening hematoma, for which PCC and activated PCC manifested only a transitory effect.

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