Plasma thrombomodulin (TM) levels were significantly elevated at disease onset in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC), but was not in those with essential thrombocythemia and idiopathic thrombocytopenic purpura. However, in patients with TTP and DIC, TM levels decreased significantly after they achieved complete remission. In both TTP and DIC patients, plasma TM levels at onset in those with poor prognosis were higher than that in those with good prognosis. Among DIC patients, the plasma TM level was higher in those with organ failure than in those without, but there were no differences among patients with various underlying diseases associated with DIC. It is speculated that the plasma TM level reflects damage to vascular endothelial cells or organ failure and that it is useful in assessing prognosis for patients with DIC and TTP.

We found that patients with thrombotic thrombocytopenic purpura (TTP) have significantly elevated plasma thrombin antithrombin III complex (TAT) and FDP-D-dimer levels, while the plasmin-alpha 2 plasmin inhibitor complex (PIC) level was only slightly increased. The tissue-type plasminogen activator (t-PA) level was increased, but it was well correlated with the plasminogen activator inhibitor-I (PAI-I) level. These findings suggest that hypercoagulable and hypofibrinolytic states coexist in these patients, in contrast to patients with disseminated intravascular coagulation, who exhibit coexisting hypercoagulable and hyperfibrinolytic states. Levels of vascular endothelial cell markers, such as PAI-I, thrombomodulin (TM), and t-PA, were increased at the onset of TTP, but the level of von Willebrand factor (vWF) antigen was not increased. The outcome in TTP patients was correlated with plasma t-PA and TM levels but not with TAT or PIC. These results suggest that vascular endothelial cell markers, such as TM and t-PA, are released from injured or stimulated endothelial cells, reflecting the degree of vascular endothelial damage, and that the main factor in the pathogenesis of TTP is vascular endothelial cell injury.

Therapy with alectinib alone was significantly superior to therapy with crizotinib alone in terms of TTF, PFS, and OS, and sequential therapy with crizotinib and alectinib after crizotinib failure tended to provide a better OS benefit than did therapy with alectinib alone in patients with ALK-positive NSCLC. However, large-scale prospective studies are needed to confirm these observations.

Plasma cytokine levels were examined in 13 patients with thrombotic thrombocytopenic purpura (TTP). Auto-antibodies, platelet-associated immunoglobulin G, and platelet aggregating factor were detected in many of these patients and high-molecular-weight bands of von Willebrand factor multimers were reduced in 9 of 10 patients examined. Complete remission (CR) was attained in 7 of the 13 patients, but 6 died. Tumor necrosis factor (TNF), Interleukin (IL)-1 beta, IL-6, and soluble IL-2 receptor showed marked increases at onset and decreased at CR. The prognosis tended to be poor in patients with increased IL-6 and soluble IL-2 receptor levels. These findings suggest that immunological mechanisms, such as the activation of macrophage, are involved in the pathogenesis of TTP and are reflected in the plasma cytokine levels.

Hypercholesterolemia is associated with an increased incidence of vascular complications. To assess the actual degree of activation of coagulation systems and vascular disorders in hypercholesterolemia, plasma levels of vascular endothelial cell markers, such as thrombomodulin (TM), tissue-type plasminogen activator, plasminogen activator inhibitor-I (PAI-I), and von Willebrand factor, were measured in 51 patients with hypercholesterolemia. We also investigated the effects of Pravastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on plasma lipid, lipoprotein a, and hemostatic markers. The mean plasma levels of thrombin-antithrombin III complex (TAT), fibrinopeptide A (FPA), TM, and PAI-I were significantly elevated in hypercholesterolemia. Of the hemostatic markers, only TM was significantly increased in patients with ischemic heart diseases (IHD). The mean concentration of total cholesterol and levels of TAT, FPA, PAI-I, and TM were significantly reduced after the Pravastatin treatment. The PIC/TAT ratio was significantly increased in non-IHD patients after treatment, this was not the case in IHD patients. These findings suggested the presence of a thrombogenic state and vascular endothelial cell disorders in hypercholesterolemia; such a state might well be related to hypofibrinolysis.

No abstract

The plasma level of tumor necrosis factor (TNF) was determined in 20 normal individuals, 52 patients with disseminated intravascular coagulation (DIC), 22 pre-DIC patients, and 39 non-DIC patients. TNF was not detected in the normal subjects, and the level was very low in non-DIC patients. However, the TNF level was significantly elevated in DIC patients, and it was moderately increased in pre-DIC patients shortly before the onset of DIC. This increase in circulating TNF may be associated with DIC. TNF was higher in DIC associated with solid cancer than in DIC associated with leukemia or sepsis. The increase in plasma TNF level was mildly correlated with DIC score, and it was significantly increased in patients with poor prognosis. However, the plasma TNF level in DIC patients with organ failure was not significantly different from those without organ failure. We conclude that the increase in circulating TNF reflects the pathogenic factors in DIC rather than being a consequence of organ failure due to DIC.

SummaryThe plasma level of interleukin-1β (IL-1β) was determined in normal individuals, patients with disseminated intravascular coagulation (DIC), patients in the pre-DIC period (within 7 days before the onset of DIC), and non-DIC patients to examine the relationship between DIC and the plasma ILlp level. The plasma IL-1β level was 0-0.085 ng/ml in normal individuals, with little difference being seen according to related age. It was significantly higher in the DIC group (0.19 ± 0.19 ng/ml) than in the pre-DIC group (0.05 ± 0.08 ng/ml) or the non-DIC group (0.09 ± 0.01 ng/ml). The plasma IL-1β level was not markedly elevated in leukemia patients, even in the DIC group, but it was significantly increased in the DIC group of solid cancer patients and was generally elevated in patients with sepsis. It was markedly elevated to 0.39 ± 0.26 ng/ml in patients with organ failure. When mononuclear cells were incubated with lipopolysaccharide, it was found that IL-1β, tumor necrosis factor, and tissue factor (TF) were released into the medium, and there was an increase of TF release from endothelial cells incubated with this medium. These results suggest that the increase in IL-Iβ reflected the activation of monocytes and may be an important factor in DIC and its associated organ failure.