Plasma levels of soluble fibrin (SF) were measured in 1184 patients with disseminated intravascular coagulation (DIC) according to Japanese Ministry of Health and Welfare (JMHW) criteria. The usefulness of SF for the diagnosis of DIC was compared with other hemostatic molecular markers. Most hemostatic markers were significantly increased in patients with DIC than in those without DIC. Plasma levels of fibrin and fibrinogen degradation products, thrombin-antihtrombin complex, plasmin-plasmin inhibitor complex, D-dimer, thrombomodulin, and SF levels were also significantly higher in those with pre-DIC than in those without DIC. In classification of overt DIC by International Society of Thrombosis and Haemostasis (ISTH) criteria, most hemostatic markers were significantly increased in patients with overt DIC than in those without overt DIC. Plasma levels of SF 'in patients with DIC were significantly higher than those in patients with pre-DIC, which were significantly higher than in those without DIC. Plasma levels of SF were also significantly higher in patients with overt DIC than in those with non-overt DIC. The correlation between plasma SF levels and DIC score according to JMHW criteria or ISTH criteria was good. Receiver operating characteristic analysis shows that SF was the best marker for the diagnosis of DIC or overt DIC. These findings suggest that plasma SF might be useful marker for the diagnosis of DIC or overt DIC.

We measured the plasma level of fibrinogen in 560 patients with disseminated intravascular coagulation (DIC) and evaluated its relationship with outcome and with other hemostatic markers. Forty-seven percent of patients had >200 mg/dL of plasma fibrinogen and 24% had <100 mg/dl of plasma fibrinogen, suggesting that plasma fibrinogen level is not a sensitive marker for DIC. In our analysis of outcome and plasma fibrinogen levels, the rate of death was high in leukemia/lymphoma patients with high fibrinogen concentration, but no significant difference in outcome was observed in relation to plasma fibrinogen concentration in non-leukemia/lymphoma patients with DIC. Among patients with leukemia/lymphoma, the frequency of organ failure was markedly high in patients with high plasma levels of fibrinogen. Among patients without leukemia/lymphoma, the frequency of organ failure increased concomitantly with the increase in plasma fibrinogen levels. The international normalized ratio was significantly increased in leukemia/ lymphoma patients with low fibrinogen. FDP levels were slightly increased in patients with low fibrinogen. Platelet count was significantly low in patients without leukemia/ lymphoma with high fibrinogen. DIC score increased concomitantly with the reduction in plasma fibrinogen levels. Plasma levels of thrombomodulin and tissue factor were significantly high in patients with high fibrinogen levels. Plasma levels of antiplasmin and plasminogen were significantly decreased in patients with low fibrinogen. Plasma levels of plasmin plasmin-inhibitor complex and tissue type plasminogen activator/ plasminogen activator inhibitor-1 complex (PAI-I) were significantly higher in patients with low fibrinogen than in those with high fibrinogen. Plasma levels of PAI-I and IL-6 were significantly higher in patients with high fibrinogen than in those with low fibrinogen. Patients with high fibrinogen levels showed less activation of secondary fibrinolysis, which might explain the occurrence of organ failure and poor outcome. Am. J. Hematol. 72:1-7, 2003.

Vascular events caused by atherosclerosis are the major cause of death in patients undergoing hemodialysis (HD). The relationship between the tests of atherosclerosis and hemostasis in 84 patients with HD was examined. Abnormal test results indicting the occurrence of atherosclerosis were found in 66% by the Fontaine score, in 33% by ankle blood pressures, and in 79% by aortic calcification index (ACI). When HD was prolonged, the mean Fontaine score and ACI were further increased. Particularly, the ACI tended to correlate with HD duration. The ankle-brachial index (ABI) was decreased in patients with HD duration of more than 10 years. Before HD, the plasma levels of fibrinogen, plasmin-plasmin inhibitor complex (PIC), thrombomodulin (TM), and D-dimer were increased, while the plasma levels of protein C (PC), antithrombin (AT), thrombin-antithrombin complex (TAT), and tissue plasminogen activator (tPA)-plasminogen activator inhibitor-I (PAI-I) complex (tPA-PAI-1 complex) were decreased. With prolonged HD, the plasma levels of AT and PC were decreased, while those of D-dimer were increased. The plasma levels of TAT and TPA-PAI-1 complex were significantly increased and those of PIC, soluble fibrin (SF) and D-dimer tended to be high in patients with less than 0.7 of ABI. The plasma levels of D-dimer, TPA-PAI-1 complex, TAT, PIC, and SF tended to be high in patients with more than 0.5 in ABI. These findings suggest that patients undergoing HD have progressive atherosclerosis and that this is associated with some hemostatic abnormalities.

Vascular events caused by arteriosclerosis are the major cause of death in patients under hemodialysis (HD). Arteriosclerosis is associated with lipoprotein abnormalities such as increased serum levels of low-density lipoprotein (LDL), especially of modified LDL (M-LDL) and oxidized LDL (Ox-LDL). We examined the relationship between markers of arteriosclerosis, hemostasis, and lipid metabolism in patients with chronic renal failure, hyperlipidemia, and healthy volunteers. In patients under HD, the serum levels of total cholesterol, LDL, and triglyceride (TG) were decreased, but the serum levels of M-LDL were increased compared to HL and healthy volunteers. In patients with CRF, the serum levels of Ox-LDL in patients under HD were lower than in those under continuous ambulatory peritoneal dialysis or conservative therapy. The plasma levels of antithrombin and protein C were significantly lower and the plasma levels of thrombomodulin were significantly higher in patients under HD compared to those under conservative therapy. These data show that patients under HD were more in hypercoagulable state than those under conservative therapy. Among patients under HD, only the plasma levels of von Willebrand factor were significantly increased in patients with more than 30 U/L of Ox-LDL compared to those with less than 30 U/L of Ox-LDL. There was no significant difference in the tests of arteriosclerosis among M-LDL values and Ox-LDL values. These findings suggest that abnormalities of lipid are not the main risk factor for arteriosclerosis disease in patients under HD.

Serum levels of lipids and lipoproteins were examined in individuals with hyperlipidemia treated with atorvastatin or colestimide and in healthy volunteers. Modified low-density lipoprotein (LDL) was measured by its faster electrophoretic mobility and expressed as charge modification frequency (CMF). Serum levels of total cholesterol (t-chol), triglyceride (TG), very low-density lipoprotein (VLDL)-chol, low-density lipoprotein (LDL)-chol, and CMF were significantly higher in hyperlipidemia, but there was no significant difference in serum high-density lipoprotein (HDL)-chol levels between hyperlipidemic and healthy subjects. Treatment with atorvastatin resulted in significant decreases of serum t-chol, TG, and LDLchol levels but not serum HDL-chol and VLDL-chol. Treatment with colestimide significantly reduced serum t-chol, HDL-chol, and LDL-chol levels but not those of TG and VLDL-chol. CMF was significantly reduced by treatment with atorvastatin but not by colestimide. Atorvastatin significantly reduced plasma levels of thrombomodulin, thrombin antithrombin complex (TAT) and tissue type plasminogen activator-plasminogen activator inhibitor-I complex. Colestimide moderately prolonged activated partial thromboplastin time and reduction of TAT. Based on its actions of lowering modified LDL and improving hemostatic abnormalities, we postulate that atorvastatin might inhibit the onset of ischemic diseases.