A 79 year old man suffering from arthralgia on bilateral shoulders and knee joints since March 1995 was followed at the orthopedic outpatient clinic in our hospital. Because of persistent edema on both feet, loss of body weight, and a low grade fever with arthralgia, he was admitted to our hospital at the internal medicine. Laboratory data showed a mild increase in platelet counts, C-reactive protein, immunoglobulin G and rheumatic factor. Levels of plasma fibrinogen, fibrin/fibrinogen degradation products, the D dimer, the thrombin-antithrombin complex, the plasmin α₂-plasmin inhibitor complex and interleukin 6 were found to be also increased. Based on these data, a diagnosis of chronic rheumatic arthritis accompanied by hypercoagulable states was made. One week after the administration of beraprost sodium, an PGI₂ analogue, at 60μg per day, the edema disappeared and the disturbed hemostasis apparently ameliorated as evidenced by a trend to normalize all these markers for hemostasis. In view of a report that this drug augmented expression of thrombomodulin on the vascular endothelial cell surface in vitro, the observed amendment of hypercoagulable states in this patient could also be, if not totally but at least partly, attributed to augmented thrombomodulin expression together with suppression of interleukin 6. Further studies are needed in order to clarify the mechanisms involved in the improvement of such disease conditions upon administration of this drug.

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We investigated the effects of liposomes on the factor VIII activation by thrombin. The liposome consisting of phosphatidylserine and phosphatidylcholine (20:80, molar ratio) inhibited thrombin-activation of factor VIII in a dose-dependent manner with maximum 12% of the control, while PC liposome had no effect on the activation. Addition of PS/PC liposome apparently attenuated factor VIII activation rate during 20min time course. However, the thrombin cleavages of factor VIII heavy and light chains were comparable either in the presence of PS/PC liposome or PC liposome. Addition of PS/PC liposome after maximum activation of factor VIII led to rapid inactivation of factor VIII when compared to the addition of the control PC liposome. These results indicates that phosphatidylserine-containing liposome unstabilizes thrombin-activated factor VIII by a non-proteolytic mechanism.

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