Plasma thrombomodulin (TM) level was measured in case of acute leukemia. The cases was acute non-lymphoblastic leukemia (ANLL) (n=40), acute lymphoblastic leukemia (ALL) (n=16) and others (n=4). Plasma TM level was significantly higher in the cases at acute stage than that in the cases at remission. Plasma TM level, however, was not different between the cases with and without DIC in ANLL as well as ALL. When correlation of plasma TM level was examined to the other hematological parameters, significant correlation was found to white blood cell count (r=0.627) and leukemic cell count (r=0.591), but not to FDP, D-dimer or PIC. It was suggested that the increase of plasma TM in cases of acute leukemia was not induced by complication of DIC but by the increase of white blood cells, particularly of leukemic cells. The amount of TM of normal white blood cells was 1.2-6.5ng/107 WBC, which suggested that only the smallest fraction of plasma TM was derived from white blood cells in normal subjects. It was also suggested that the increased plasma TM in cases of acute leukemia was not derived from leukemic cells, as TM content and mRNA were markedly reduced in leukemic cells. It was concluded that the increased plasma TM in cases of acute leukemia was derived mostly from injured endothelial cells and the increase of white blood cells and leukemic cells was related to its increase.
Injury of human endothelial cells by leukemic cells was investigated. Isolated leukocyte fraction was applied on cultured human umbilical endothelial cells (HUVEC) and endothelial injury was monitored by an increase of thrombomodulin (TM) in the supernate and its decrease in HUVEC. It was revealed that the results were classified into 3 types with the use of leukocyte fraction of 10 cases of acute leukemia. Type A (6/10): The leukemic cells showed no effect on HUVEC as TM in the supernate or in HUVEC was not changed at all. Type B (3/10): Apparent endothelial injury was found by the co-incubation of the leukocyte fraction with HUVEC, whether the leukocytes were stimulated with LPS or not. Type C (1/10): TM in the supernate was not increased, whereas it was apparently decreased in HUVEC by the addition of the leukemic cells. Plasma concentration of elastase-α1 proteinase inhibitor complex was markedly increased in this case. The identical results was obtained by the addition of elastase to HUVEC. And the antigenicity of purified human TM was decreased by the addition of elastase. It was postulated from these results that elastase was involved in the endothelial damage by the leukemic cells of this case. It was concluded that leukemic cells in one third of acute leukemia had injuring activity to endothelial cells. In the exceptional cases, however, leukemic elastase will contribute endothelial injury and decrease the level of plasma TM.
We studied diagnostic significance of measuring the plasma levels of heparin cofactor II (HC II) and thrombin-heparin cofactor II complex (T-HC II) in patients with disseminated intravascular coagulation (DIC). The plasma levels of HC II, T-HC II and other factors—thrombin-antithrombin III complex (TAT), antithrombin III (AT III), α2-plasmin inhibitor-plasmin complex (PIC), FDP-E, protein C (PC), protein C inhibitor (PCI), and fibrinogen—were measured in 9 patients with DIC and 31 control subjects. HC II activity was measured by a chromogenic assay. HC II antigen was measured by immunoelectrophoresis. T-HC II was measured by enzyme immunoassay. HC II activity was correlated with its antigen. In the patients with DIC, HC II was correlated with AT III, PC, PCI and fibrinogen. T-HC II increased in all patients with DIC (vs control value, p<0.01), and it was correlated with TAT, PIC and FDP-E. Therefore determination of HC II and T-HC II could be valuable for the diagnosis of DIC.