The efficacy of recombinant human soluble thrombomodulin for obstetric disseminated intravascular coagulation: a retrospective study

Abstract

IntroductionRecombinant human soluble thrombomodulin (rhTM) is a novel anti-coagulant agent that regulates the imbalanced coagulation system by reducing the excessive activation of thrombin. rhTM potentially reduces the morbidity and mortality in patients with sepsis-induced disseminated intravascular coagulation (DIC). However, the efficacy of rhTM in obstetric DIC has not yet been established. We performed this study to examine whether the administration of rhTM was a potentially effective treatment for DIC induced by one or more underlying obstetric disorders.MethodsThis is a single-center, retrospective cohort study conducted between January 2007 and February 2015 using the records of the Department of Obstetrics at the Perinatal Medical Center of TOYOTA Memorial Hospital, Aichi, Japan. The eligibility criteria were known or suspected obstetric DIC documented on the basis of clinical and laboratory data and association with one or more major underlying obstetric disorders. Baseline imbalance between patients with and without treatment of rhTM was adjusted using an inverse probability of treatment weighting using propensity scores composed of the following independent variables: severe postpartum hemorrhage, placental abruption, and preeclampsia/eclampsia, including hemolysis, elevated liver enzymes, and low platelet syndrome, initial platelet counts, D-dimer levels, fibrinogen levels, and prothrombin time–international normalized ratio (PT–INR). We evaluated laboratory changes and clinical outcomes in the early phase of obstetric DIC.ResultsIn total, 66 of 4627 patients admitted to our department during the study period fulfilled the required criteria; of these, 37 and 29 patients were included in the rhTM and control group, respectively. After adjustment, treatment with rhTM was associated with significant improvements in platelet counts, D-dimer levels, fibrinogen levels, and PT–INR compared with the control group. The platelet concentrate transfusion volume was significantly lower in the rhTM treatment group (3.02 vs 6.03 units, P = 0.016). None of the adjusted group differences were statistically significant for all types of organ damage and failure.ConclusionrhTM administration was associated with clinical and laboratory improvement in patients with DIC caused by underlying obstetric conditions. Further clinical research is needed to clarify the optimal application of rhTM in each of the causative obstetric disorders.

Analysis of the role of thrombomodulin in all-trans retinoic acid treatment of coagulation disorders in cancer patients

“…Overall, our findings indicate the key role of TM in RA treatment of blood coagulation abnormalities in cancer patients. These results are in line with recent clinical observations regarding the therapeutic effects of recombinant human thrombomodulin, an anticoagulant drug with the same external structure of TM, in the treatment of DIC [65–69].…”

Impact of uterus‐preserving surgery on Stage I primary mucinous epithelial ovarian carcinoma: A multi‐institutional study with propensity score‐weighted analysis

“…Cohorts were adjusted for the probability of treatment by using the inverse probability of treatment weighting (IPTW) approach, where each individual was weighted by the inverse probability of receiving treatment, equal to 1/PS for treated individuals and 1/(1 − PS) for control individuals. Because there is no sample loss in the IPTW approach, this design was considered appropriate for the present observational study 14 . Standardized differences 15 in the independent variables prior to and after adjustment were calculated to evaluate the balance of variables and effectiveness of the PS‐based IPTW analysis.…”

DIC in obstetrics: Diagnostic score, highlights in management, and international registry‐communication from the DIC and Women's Health SSCs of the International Society of Thrombosis and Haemostasis

“…Yoshihara et al. have also reported that treatment with recombinant human thrombomodulin was associated with significant improvements in platelet counts, D‐dimer, fibrinogen, and prothrombin time …”