Postmarketing Surveillance of Recombinant Human Soluble Thrombomodulin (Thrombomodulin α) in Pediatric Patients With Disseminated Intravascular Coagulation

Abstract

Recombinant human soluble thrombomodulin (thrombomodulin α [TM-α]) has been marketed as a novel anticoagulant for disseminated intravascular coagulation (DIC) in Japan since 2008. Postmarketing surveillance (PMS) has been conducted since its approval. As effectiveness and safety were not previously determined in pediatric patients, this study evaluated PMS data and examined the usefulness of TM-α in treating pediatric DIC. After excluding newborn infants, data for 210 pediatric patients were analyzed and compared to 3786 adult patients. The day after the last TM-α administration, DIC had resolved in 58.5% of the patients. At 28 days after the last TM-α administration, the survival rate was 71.6%. Nineteen episodes of adverse drug reactions were observed in 11 patients but no significant differences were noted for effectiveness and safety. Although this study was limited by its retrospective design, including selection biases and no limitation on concomitant use of other anticoagulants, TM-α appears to be useful for the treatment of DIC in both pediatric and adult patients.

Population pharmacokinetics of thrombomodulin alfa in pediatric patients with hematological malignancy and disseminated intravascular coagulation

“…Failure to detect a significant difference may have been be due to the small sample size, while it might indicate that the trough concentration may not correlate with effectiveness in children. Postmarketing surveillance of TM‐α showed that the DIC resolution rate after administration of TM‐α was 58.5% in children . The rate of achieving the target trough concentration in our study was approximately equivalent to that of DIC resolution found in postmarketing surveillance.…”

“…Postmarketing surveillance of TM-showed that the DIC resolution rate after administration of TM-was 58.5% in children. 14 The pharmacokinetic values used in this study were for a typical patient who weighed 27 kg. The pharmacokinetic values used in Tsuruta et al's study were for a typical patient who weighed 53.5 kg.…”

“…In children, several studies have reported high anti‐DIC activity of TM‐α and postmarketing surveillance has been conducted . However, to date, the pharmacokinetics of TM‐α in pediatric patients with DIC have not been reported.…”

“…11 In children, several studies have reported high anti-DIC activity of TM- 12,13 and postmarketing surveillance has been conducted. 14 However, to date, the pharmacokinetics of TM-in pediatric patients with DIC have not been reported. The pharmacokinetics of TM-in pediatric patients may differ from those of adults as a result of changes in body composition and maturation of organ function.…”

Successful treatment of pneumonia-induced severe ARDS complicated with DIC in two infants using recombinant human thrombomodulin

“…Recombinant human soluble thrombomodulin (rhTM), which was primarily developed for the treatment of DIC in adults [6], is now widely administered for treating pediatric patients with DIC [7,8]. While previous evidences have shown that the safety and efficacy of rhTM for DIC, recent studies in adults have implicated the efficacy of rhTM on ARDS via anti-inflammatory effects [9,10].…”