Recombinant human thrombomodulin for pneumonia-induced severe ARDS complicated by DIC in children: a preliminary study

Abstract

Purpose 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 preliminary study, we reported the feasibility of using rTM for the treatment of pneumonia-induced severe ARDS complicated by DIC in children. Methods Six children (age: median 10 months old) with pneumonia-induced severe ARDS complicated by DIC were enrolled in this preliminary study. rTM (380 U/kg) was administered for a maximum of 6 days, in addition to conventional therapies 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, and were discharged from the hospital with no complications. In survived children, levels of soluble receptors for advanced glycation end products, interleukin-6, interleukin-8 and monocyte chemotactic protein-1 decreased after administration of rTM compared to those before rTM. Conclusions The rTM administration is feasible as an adjunctive therapeutic strategy for children over 2 months with pneumonia-induced severe ARDS complicated by DIC.

Antioxidants as Therapeutic Agents in Acute Respiratory Distress Syndrome (ARDS) Treatment—From Mice to Men

“…In addition to the effect of ROS on cell–cell interactions, ROS are also involved in altering coagulation and fibrinolysis, contributing to ARDS ( Figure 5 ) [ 159 , 160 , 161 ]. However, further research is necessary to understand the underlying principles in detail [ 162 ].…”

Endothelial Dysfunction after Hematopoietic Stem Cell Transplantation: A Review Based on Physiopathology

“…TM may have a physiopathologic role in thromboembolic disorders, ischemia-reperfusion syndromes, sepsis, malignant hypertension, and ARDS [108][109][110]. A single study reported that administration of recombinant TM significantly reduced acute GVHD (a-GVHD) and ameliorated OS after allogeneic hematopoietic stem cell transplantation [111].…”

“…A single study reported that administration of recombinant TM significantly reduced acute GVHD (a-GVHD) and ameliorated OS after allogeneic hematopoietic stem cell transplantation [111]. TM has been found clinically helpful as a therapy for DIC in children [112][113][114] and ARDS [108]. ure 8).…”

“…TM has been found clinically helpful as a therapy for DIC in children [112][113][114] and for ARDS [108]. After allogeneic hematopoietic stem cell transplantation, a study reported that TM administration significantly reduced a-GVHD and ameliorated OS [111].…”

Attempt for a Recombinant Thrombomodulin Alpha Treatment in a Rat Disseminated Intravascular Coagulation Model Using Yamakagashi (Rhabdophis tigrinus) Venom

“…A clinical trial of this soluble human thrombomodulin was conducted, and a manufacturing and marketing approval application was submitted for the treatment of DIC in 2006, following which the drug was approved in January 2008 [ 17 , 18 ]. Studies have reported that rTM exerts a therapeutic effect on DIC caused by infectious diseases, malignant tumors, trauma, and gynecological diseases [ 19 , 20 , 21 ]. The mechanism underlying the action of rTM involves promoting the activation of protein C by thrombin, and the generated activated protein C decomposes the coagulation-promoting factors Va and VIIIa using protein S as a coagulation factor to generate thrombin [ 22 ].…”