The clinical characteristics and treatment outcomes of patients with DIC and suspected DIC that was treated with TM-α between May 2008 and April 2010 were retrospectively analyzed in a subgroup analysis of PMS data. The original PMS study was an open-label, multicenter, non-interventional, prospective, observational cohort study of patients with DIC who received TM-α . The PMS for TM-α was conducted in accordance with the Japanese Society on Thrombosis and Hemostasis Post-Marketing Surveillance Committee for Recomodulin Injection and the guidelines for Good Postmarketing Study Practice, as required by the Japanese Ministry of Health, Labour, and Welfare (JMHLW). We used existing data without personally identifiable information throughout our study. The original PMS study was therefore exempted from local institutional review and formal approval, as well as the requirement for informed consent. In the PMS for TM-α, all patients were diagnosed with DIC and suspected DIC by attending physicians based on JMHLW or JAAM diagnostic criteria.
The PMS data included 3204 patients with DIC and suspected DIC (patients with infectious diseases, n = 2083; patients with hematological diseases, n = 1121). The underlying diseases of the patients with infectious diseases were as follows; sepsis (n = 837), pneumonia (n = 359), peritonitis (n = 260), urinary tract infection (n = 163), hepatobiliary pancreatic system infection (n = 117), skin and muscle infections (n = 55), gastrointestinal infections (n = 53), meningitis (n = 37), viral infection (n = 25), wound infection (n = 24), pleural infection (n = 18), and others (n = 135). The underlying diseases of the patients with hematological diseases were as follows; acute myeloid leukemia (n = 235), acute promyelocytic leukemia (n = 167), non-Hodgkin's lymphoma (n = 156), acute lymphocytic leukemia (n = 144), acute myelomonocytic leukemia (n = 55), myelodysplastic syndromes (n = 51), acute monocytic leukemia (n = 47), multiple myeloma (n = 35), adult T cell leukemia (n = 18), hematopoietic stem cell transplantation (n = 17), chronic myelogenous leukemia (n = 17), hemophagocytic syndrome (n = 14), acute erythroid leukemia (n = 13), febrile neutropenia (n = 11), acute megakaryoblastic leukemia (n = 7), chronic lymphocytic leukemia (n = 7), aplastic anemia (n = 5), Hodgkin's lymphoma (n = 5), and others (n = 117).
The DIC resolution rate, 28-day survival rate, rates of adverse drug reaction and bleeding-related adverse drug reactions were investigated. The degree of coagulopathy was evaluated by calculating DIC scores according to the DIC diagnostic criteria of the JAAM  for infectious diseases and those of the JMHW  and ISTH  for hematological diseases. After treatment with TM-α, resolution of DIC was defined as a score ≤3 using the diagnostic criteria of the JAAM, ≤2 using the diagnostic criteria of the JMHW for DIC in patients with hematological diseases, ≤5 using the diagnostic criteria of the JMHW for infectious diseases, and ≤4 using the diagnostic criteria of the ISTH for both diseases. The PMS for TM-α started before the establishment of the JSTH DIC diagnostic criteria. As a result, there were few records that included “change of platelet count” or a few data for SF and TAT; thus, the JSTH scores could not be calculated. Survival was calculated at 28 days from the beginning of TM-α treatment or at the end of observation.
In patients with infectious diseases, the severity of organ failure was assessed using the sequential organ failure assessment (SOFA) score . The symptoms of organ failure were decided by the attending physician based on clinical signs indicating organ dysfunction due to DIC . Laboratory tests such as the white blood cell (WBC) count and platelet count, and the measurement of hemoglobin, albumin, lactate dehydrogenase (LDH), total bilirubin (T-Bil), creatine and C-reactive protein (CRP) levels, and hemostatic tests such as the prothrombin time (PT)-international ratio (INR), activated partial thromboplastin time (APTT), fibrinogen, fibrinogen, fibrin degradation products (FDP), D-dimer, AT, protein C, thrombin-AT complex (TAT) and plasmin-α2 plasmin inhibitor complex (PIC) were performed in each participating institute. Patients with fibrinogen < 1.5 g/L were considered to have hypofibrinogenemia. The rates of adverse drug reaction and bleeding-related adverse drug reaction were evaluated from the start of TM-α treatment to day 28 after the end of TM-α treatment. The safety data were coded using preferred terms from the Japanese translation of the Medical Dictionary for Regulatory Activities (version 13.1)
In the descriptive analyses of baseline characteristics, numerical data were expressed as the median (Q1, Q3; interquartile range). The chi-square test and the Wilcoxon signed-rank test were performed as statistical analyses. P values of < 0.05 were considered to indicate statistical significance. Multiplicity adjustment was not considered. All analyses were performed using SAS version 9.4 (SAS Institute, Cary, NC) by EPS Corporation (Tokyo, Japan) according to the plan for the statistical analysis.