Coagulation Profiles of Pulmonary Arterial Hypertension Patients, Assessed by Non-Conventional Hemostatic Tests and Markers of Platelet Activation and Endothelial Dysfunction

Abstract

Many pathophysiologic processes of pulmonary arterial hypertension (PAH), namely, excess vasoconstriction, vascular remodeling and in situ thrombosis, involve the coagulation cascade, and more specifically, platelets. The aim of this study was to globally assess coagulation processes in PAH, by using non-conventional hemostatic tests, along with markers of platelet activation and endothelial dysfunction. We studied 44 new PAH patients (22 with idiopathic PAH and 22 with connective tissue disease) and 25 healthy controls. The following tests were performed: platelet function analyzer-100 (PFA-100), light transmission aggregometry (LTA), rotational thromboelastometry (ROTEM), endogenous thrombin potential (ETP), serotonin, thromboxane A2 and p-selectin plasma levels, and von Willebrand antigen (VWF:Ag) and activity (VWF:Ac). Our results showed that PAH patients had diminished platelet aggregation, presence of disaggregation, defective initiation of the clotting process and clot propagation, and diminished thrombin formation capacity. Serotonin, thromboxane A2 and p-selectin levels were increased, and VWF:Ag and VWF:Ac decreased in the same population. The results of this study suggest that the platelets of PAH patients are activated and present functional abnormalities. The procoagulant activity, in general, appears to be impaired probably due to a sustained and prolonged activation of the procoagulant processes. Larger observational studies are warranted to confirm these laboratory findings.

Integrated analysis of m6A mRNA methylation in rats with monocrotaline-induced pulmonary arterial hypertension

“…In addition, the molecular functions of the up-regulated m 6 A methylation genes were related to PDGF binding and extracellular matrix structural constituents. KEGG pathway analysis demonstrated that genes with upregulated methylation participate in extracellular matrix (ECM)-receptor interaction, PI3K/AKT signaling pathway and platelet activation, which has been shown to play a major role in the pathogenesis of PAH [ 33 – 35 ]. Further GSEA result also showed the similar results ( Supplementary Figure 1 ).…”

Platelets, extracellular vesicles and coagulation in pulmonary arterial hypertension

“…52 Subsequent studies have shown low and lownormal levels of vWF antigen and activity in PAH. 53,54 These results were attributed to an acquired von Willebrand syndrome in the context of a 'high-shear highflow' circulation.…”

“…55 Increased thrombin formation was subsequently demonstrated by Tournier et al in 16 patients with IPAH, using a method called calibrated automated thrombography. 10 Curiously, reduced thrombin generation was later shown using the same method by Vrigkou et al 53 These conflicting results may reflect differences in sample preparation (platelet rich plasma versus platelet poor plasma) and patient population (IPAH versus IPAH and connective tissue disease-associated PAH), and will require additional investigation. Indeed this could signal that increased thrombin generation is isolated to specific subgroups of PAH, which may account for differing responses to anticoagulation observed in some retrospective studies.…”

Tissue Factor and Tissue Factor Pathway Inhibitor in Men and Women Affected with Hypertension

“…Prevalence and control of hypertension appear to be different according to age, sex, and other factors such as obesity, physical activity and caffeine abuse (8) . Among pathophysiological effects of arterial hypertension are vasoconstriction, increase incidence of thrombosis, disturbances of coagulation pathways and platelets function (26) . Tissue factor is essential factors of blood clotting, it is expressed by vascular and nonvascular cells of the body and exerts prominent role in hemostasis through its function which involves initiation of blood coagulation (18) .…”