Thombomodulin Identified as Unique Biomarker for Diagnosing Necrotizing Soft-Tissue Infections

Thrombomodulin, a protein present in blood plasma, is a biomarker that may be useful for diagnosing necrotizing soft-tissue infections.

Necrotizing soft tissue infections (NSTI) are bacterial infections characterized by rapid tissue degradation. NSTIs are rapidly progressing infections frequently complicated by septic shock and associated with high mortality. Early diagnosis is critical for patient outcome, but challenging due to vague initial symptoms.

Investigators at Karolinska Institutet (Stockholm, Sweden) searched for useful biomarkers to aid in the diagnosis of NSTIs. For the search, the investigators used Luminex (Austin, TX, USA) multiplex assays to analyze 36 soluble factors in blood plasma from the 311 NSTI patients included in the international INFECT study. Control groups included patients with suspected NSTI and sepsis, respectively.

Results of the study pointed to thrombomodulin as being a unique biomarker for detection of NSTI. Thrombomodulin is an integral membrane protein expressed on the surface of endothelial cells and serves as a cofactor for thrombin. It reduces blood coagulation by converting thrombin to an anticoagulant enzyme from a procoagulant enzyme. In humans, thrombomodulin is encoded by the THBD gene. The protein has a molecular mass of 74 kiloDaltons, and consists of a single chain with six tandemly repeated EGF-like domains, a serine/threonine-rich spacer, and a transmembrane domain.

Senior author Dr. Anna Norrby-Teglund, professor of medicine at Karolinska Institutet, said, "The new biomarker, thrombomodulin, proved to be superior to the laboratory parameters used clinically today. There are currently no tools for safe, rapid diagnosis in life-threatening soft tissue infections. Our findings are consequently very interesting as the biomarkers identified are possible candidates for improved diagnostics. The results are also relevant for individualized treatment in the future."

The study was published in the July 15, 2021, online edition of the Journal of Clinical Investigation.

Related Links:
Karolinska Institutet
Luminex