Trombomulina

Trombomulina, known in English as thrombomodulin, is an endothelial cell surface glycoprotein that functions as a key cofactor in the protein C anticoagulant pathway. In humans, the THBD gene encodes the protein, which is a type I membrane protein expressed on vascular endothelium and, in soluble form, can be found in plasma after shedding or alternative splicing. The protein consists of an extracellular domain containing a lectin-like region, six epidermal growth factor (EGF)-like repeats, a serine/threonine-rich mucin-like domain, followed by a transmembrane segment and a short cytoplasmic tail.

Mechanistically, thrombin binds to thrombomodulin on the endothelial surface, and the thrombin–thrombomodulin complex markedly accelerates activation of protein C to activated protein C (APC). APC, with protein S, inactivates coagulation factors Va and VIIIa, reducing thrombin generation and exerting an anticoagulant effect. The lectin-like N-terminal domain of thrombomodulin also contributes to anti-inflammatory effects, including interactions that dampen NF-κB signaling and HMGB1 activity.

Physiologically, thrombomodulin participates in maintaining vascular integrity and modulating inflammation. Clinically, soluble thrombomodulin forms are used as biomarkers of endothelial injury, and recombinant human soluble thrombomodulin has been explored as a therapeutic for disseminated intravascular coagulation in some countries, notably Japan. Regulatory approval and evidence for efficacy vary by region, and bleeding risk remains a consideration.

Research continues into broader applications, including sepsis and microvascular dysfunction, with interest in exploiting thrombomodulin’s anticoagulant and anti-inflammatory properties. Thrombomodulin biology is an example of how endothelial surface proteins coordinate coagulation and inflammatory responses.