Kouzou Minamikawa

Effect of lipoproteins on tissue factor activity and PAI-II antigen in human monocytes and macrophages

Expression of the tissue factor (TF) and the plasminogen activator inhibitor-II were induced in cultured human monocytes-macrophages by incubation with lipoproteins. Very low-density lipoprotein (VLDL) augmented the TF and PAI-II expression the most, followed by low-density lipoprotein (LDL) and a very weak effect by high-density lipoprotein (HDL). In macrophages pre-cultured for 3 days, oxidized LDL augmented the expression of TF activity in the macrophages to a greater extent than native LDL. These findings indicate that lipoproteins affect both monocytes and macrophages, and that they induce a hypercoagulable-hypofibrinolytic state. Thus hyperlipidemia may be a direct risk factor for thrombotic disease.

State-of-the-Art Review : Increased Activated Protein C: Protein C Inhibitor Complex and Decreased Protein C Inhibitor Levels in Patients with Chronic Renal Failure on Maintenance Hemodialysis

Hemostatic abnormalities were examined in 55 pa tients during maintenance hemodialysis (HD). Before HD, plasma protein C and protein S antigens were almost within the normal range, while plasma thrombin-antithrombin III complex (TAT III) and plasmin-plasmin inhibitor complex (PPIC) levels in HD patients were increased slightly, and plasminogen acti vator inhibitor 1 level was significantly increased, compared to that in normal volunteers. Plasma activated protein C (APC) and protein C inhibitor (PCI) complex and APC α1 antitrypsin (α1AT) complex were not detected in normal volunteers; how ever, plasma APC-PCI complex was increased in 36 of the patients and plasma APC-α1AT complex was increased in 25 patients. Plasma PCI levels in these patients before HD were significantly decreased. Plasma TAT, PPIC, and tissue type plasminogen activator levels were significantly higher before HD than after 1 hour HD and at the end of HD, while the changes in plasma protein C antigen, protein S antigen, PCI antigen, APC-PCI complex, and APC-α1AT complex were not significant after 1 hour of HD or at the end of HD compared to levels before HD. Plasma PCI levels were correlated with APC- PCI complex, suggesting that decreased PCI levels might be caused by the activation of protein C.

State-of-the-Art Review : Coagulation Tests and Anti-Phospholipid Antibodies in Patients Positive for Lupus Anticoagulant

We examined activated partial thromboplastin time, kaolin clotting time, mixing with normal plasma in kaolin clotting time, dilute Russells viper venom time, dilute Rus sells viper venom time at high lipid concentrations, anti phospholipid antibodies, and anti-cardiolipin-β2-glycoprotein I complex antibody in 135 patients with prolongation of acti vated partial thromboplastin time and diagnosed 86 patients positive for lupus anticoagulant. The sensitivity of activated partial thromboplastin time and dilute Russells viper venom time/dilute Russells viper venom time-high lipid concentra tions ratio for lupus anticoagulant were markedly high, but the specificity of activated partial thromboplastin time for lupus anticoagulant was not markedly high. The specificity, but not the sensitivity, of kaolin clotting time-mixing with normal plasma in kaolin clotting time was markedly high. In summary, dilute Russells viper venom time to dilute Russells viper venom time-high lipid concentrations ratio gave high sensitiv ity as well as specificity, being the only assay to confirm this. Of the patients positive for lupus anticoagulant, 25% were posi tive for anti-phospholipid antibodies and 17% were positive for anti-cardiolipin-β2-glycoprotein I complex antibody. Of the lu pus anticoagulant-positive patients with thrombosis, 45% were positive for anti-phospholipid antibodies, 35% were positive for anti-cardiolipin-β2-glycoprotein I complex antibody, 60% were positive for both anti-phospholipid antibodies and anti cardiolipin-β2-glycoprotein I complex antibody, and only 17% were negative for anti-phospholipid antibodies and anti cardiolipin-β2-glycoprotein I complex antibody. These find ings suggest that lupus anticoagulant can be diagnosed by di lute Russells viper venom time/dilute Russells viper venom time-high lipid concentrations ratio, and that thrombosis in lupus anticoagulant-positive may be predictable from both anti-phospholipid antibodies and anti-cardiolipin-β2- glycoprotein I complex antibody. Plasma tissue type plasmin ogen activator level in lupus anticoagulant patients was signifi cantly increased, and plasma tissue type plasminogen activator and fibrin-D-dimer levels in lupus anticoagulant-positive pa tients with thrombosis were significantly higher than in those without thrombosis, suggesting that the diagnosis of thrombo sis by hemostatic markers might be important in lupus antico agulant.

Acute promyelocytic leukemia with del(6)(p23)

We report a unique case of de novo acute promyelocytic leukemia (APL) with cryptic 15;17 rearrangements. Cytogenetically, structural rearrangements of the 6p23 region has been reported mainly in secondary leukemia. This patient had a karyotype of 46, XY, del(6)(p23) and no additional chromosomal abnormalities. Molecular analyses revealed the presence of PML-RAR alpha fusion genes. Deletion of the 6p23 region is extremely rare in APL.