Yutaka Oguma

Clinical effect of low molecular weight heparin (Fragmin) on DIC : A multicenter cooperative study in Japan

A multicenter cooperative study was carried out involving 47 nationwide institutes in Japan to assess the efficacy and safety of low molecular weight heparin (Fragmin) on DIC. Fifty-six DIC cases were challenged by Fragmin injection principally for 5 days with the doses of 75 U/kg/day in the I group (n = 27) and 150 U/kg/day in the II group (n = 29). Scoring points were defined based on the severity of bleeding symptoms, organ failures and abnormal coagulation-fibrinolytic examinations, and therapeutic effect of Fragmin was evaluated objectively according to the improvement degrees of these scores. Six cases (10.7%) died of the underlying diseases or complications other than DIC and hemorrhagic side effects occurred in 3.7 and 10.3% cases of the I and II groups, respectively. However, in bleeding symptoms, 45.5 and 31.6% cases of the I and II groups improved excellently or moderately. In organ failures and coagulation-fibrinolytic examinations, remarkable improvement was observed in 31.6 and 66.7% cases of the I group, while they remained 14.3 and 51.7% in the II group, respectively. The overall utility of Fragmin was 66.7% in the I group and 58.6% in the II group. These results demonstrate that Fragmin is effective on DIC with a dose of 75 U/kg/day.

Heparin enhances thrombin-stimulated prostaglandin I2 production by cultured endothelial cells

Endothelial cells from human umbilical vein were incubated in vitro with thrombin in the absence or presence of unfractionated heparin (UFH), low molecular weight heparin (LMWH) or dermatan sulfate (DS) to clarify the effect of these glycosaminoglycans on thrombin-stimulated prostaglandin I2 (PGI2) production. Although DS did not affect the thrombin stimulation, UFH and LMWH each enhanced it about 1.5-fold. Pretreatment of cells with either UFH or LMWH also enhanced the thrombin stimulation. In addition, UFH and LMWH each enhanced PGI2 production stimulated by calcium ionophore A23187, but did not affect that stimulated by arachidonic acid. From these results, it was suggested that UFH and LMWH might cause a physical change of cell membrane, which would caused an easier liberation of arachidonic acid by phospholipases.