Recombinant Human Thrombomodulin for Pneumonia-Induced Severe Acute Respiratory Distress Syndrome Complicated by Disseminated Intravascular Coagulation in Children: A feasibility study

Abstract

Background Recombinant human soluble thrombomodulin (rTM) has been used to treat disseminated intravascular coagulation (DIC). Recent studies have shown the efficacy of rTM through its anti-inflammatory effects for treatment of adults with acute respiratory distress syndrome (ARDS). However, the safety and efficacy of rTM in children with severe ARDS complicated by DIC have not been reported. In this study, we investigated the feasibility of using rTM for the treatment of pneumonia-induced severe ARDS complicated by DIC in children. Methods Six children (age: median 10 month-old) with pneumonia-induced severe ARDS complicated by DIC were enrolled in this feasibility study. rTM (380 U/kg) was administered for a maximum of 6 days, in addition to conventional therapies including cardiopulmonary support, antibiotics and/or antivirus drugs administration, steroid administration and intravenous immunoglobulin after diagnosis of severe ARDS complicated by DIC. After administration of rTM, we measured changes in the plasma TM concentration and evaluated the clinical course, status of DIC and ARDS, and other laboratory findings, including levels of cytokines, chemokines, and biomarkers. Results In all six children, the plasma concentration of TM increased and DIC scores decreased after administration of rTM. Four of the six children recovered from the severe ARDS complicated by DIC after treatment in the pediatric intensive care unit, and were discharged from the hospital with no complications. In surviving children, levels of soluble receptors for advanced glycation end products, interleukin-6, interleukin-8 and monocyte chemotactic protein-1 decreased after administration of rTM. Conclusions The rTM administration is feasible as a therapeutic strategy for children over 2 months with pneumonia-induced severe ARDS complicated by DIC.