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.