Thrombin, the enzyme that converts fibrinogen into fibrin during blood clot formation, may play multiple roles in the pathogenesis and progression of pulmonary arterial hypertension (PAH), according to a new study published in Thrombosis Research.

Researchers believe thrombin’s many functions could be important in PAH pathogenesis. These include the secretion of vasoconstrictive mediators, increase of endothelial permeability, and regulation of smooth muscle cell migration, proliferation, and hypertrophy, indicating that thrombin plays a role in pulmonary vessel remodeling, vascular obstruction, and obliteration.

Olga Melnichnikova, PhD, of the Personalized Medicine Centre at Almazov National Medical Research Centre in Saint Petersburg, Russian Federation, and the coauthors of the study wrote, Further detailed study of hemostasis combined with analysis of clinical data and assessment of biomarkers of vascular wall damage could facilitate the development of personalized medicine approaches for PAH patients.”


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To investigate the possible role of thrombin in PAH pathogenesis, the authors enrolled 24 patients with PAH and 26 healthy volunteers. Of the 24 patients with PAH, 17 had idiopathic disease and 7 had systemic scleroderma-associated PAH.

They found that the parameters analyzed in the plasma of PAH patients and controls differed significantly. For example, patients with idiopathic PAH had an increased time of thrombin generation and a decreased velocity index, indicating a hypocoagulable phenotype. 

“We associated these results with the ‘exhaustion effect’ of coagulation factors followed activation of the hemostatic system in patients with [idiopathic] PAH,” the authors wrote. 

The researchers’ findings also indicated the activation of thrombin generation in patients with systemic scleroderma-associated PAH. Moreover, they suggested a more severe course of disease in these patients.

The authors concluded that due to its pleiotropic effects on endothelial cells and vascular tone, thrombin may play multiple roles in PAH pathogenesis. 

Reference

Melnichnikova O, Simakova M, Moiseeva O, et al. The dynamics of thrombin formation in patients with pulmonary arterial hypertension. Thromb Res. Published online August 4, 2021. doi:10.1016/j.thromres.2021.07.015s