trombomoduliini

Trombomoduliini, known in English as thrombomodulin, is a transmembrane glycoprotein expressed predominantly on the surface of endothelial cells lining blood vessels. It serves as a key cofactor in anticoagulation by binding thrombin and altering its substrate specificity to favor activation of the anticoagulant protein C.

When thrombin binds to thrombomodulin on the endothelial surface, thrombomodulin facilitates the conversion of protein C to activated protein C (APC) in the presence of its cofactor protein S. APC then proteolytically inactivates coagulation factors Va and VIIIa, reducing further thrombin generation and clot formation. This thrombomodulin–thrombin–protein C pathway provides a negative feedback mechanism that helps prevent excessive coagulation after vascular injury. The pathway also intersects with anti-inflammatory and fibrinolytic processes, contributing to vascular homeostasis.

Structurally, thrombomodulin consists of an extracellular domain that binds thrombin, a single transmembrane region, and a cytoplasmic tail. A soluble form of thrombomodulin can be produced by proteolytic shedding from the endothelial surface and circulates in plasma; elevated levels of soluble thrombomodulin reflect endothelial injury or dysfunction and are used as a biomarker in some clinical settings.

Genetics and clinical relevance: the THBD gene encodes thrombomodulin. Altered expression or function of thrombomodulin has been linked to thrombotic disorders and endothelial dysfunction. Therapeutically, recombinant human soluble thrombomodulin has been used in some countries to treat disseminated intravascular coagulation and sepsis, though evidence of benefit varies by condition and study. Thrombomodulin remains a focus of research for its roles in coagulation, inflammation, and vascular biology.