Abstract
BackgroundChronic anticoagulation is a standard of care in idiopathic pulmonary arterial hypertension (IPAH). However, hemostatic abnormalities in this disease remain poorly understood. Therefore, we aimed to study markers of thrombogenesis and fibrinolysis in patients with IPAH.MethodsWe studied 27 consecutive patients (67% female) with IPAH aged 50.0 years (IQR: 41.0 - 65.0) and 16 controls without pulmonary hypertension. Prothrombin fragment 1+2 (F1+2) and thrombin-antithrombin (TAT) complexes were measured to assess thrombogenesis; tissue-type plasminogen activator (tPA) antigen and plasmin-anti-plasmin complex to characterize activation of fibrinolysis; plasminogen activator inhibitor 1 (PAI-1) to measure inhibition of fibrinolysis; and endothelin-1 (ET-1) and interleukin-6 (IL-6) to assess endothelial activation and systemic inflammation, respectively. In addition, in treatment-naive IPAH patients these markers were assessed after 3 months of PAH-specific therapies.ResultsTPA (10.1[6.8-15.8] vs 5.2[3.3-7.3] ng/ml, p<0.001), plasmin-anti-plasmin (91.5[60.3-94.2] vs 55.8[51.1-64.9] ng/ml, p<0.001), IL-6 (4.9[2.5-7.9] vs 2.1[1.3-3.8] pg/ml, p=0.001) and ET-1 (3.7 [3.3-4.5] vs 3.4[3.1-3.5], p= 0.03) were higher in patients with IPAH than in controls. In IPAH patients plasmin-anti-plasmin and tPA correlated positively with IL-6 (r=0.39, p=0.04 and r=0.63, p<0.001, respectively) and ET-1 (r=0.55, p=0.003 and r=0.59, p=0.001, respectively). No correlation was found between tPA or plasmin-anti-plasmin and markers of thrombogenesis. Plasmin-anti-plasmin decreased after 3 months of PAH specific therapy while the other markers remained unchanged.ConclusionsIn the present study we showed that markers of fibrynolysis were elevated in patients with IPAH however we did not find a clear evidence for increased thrombogenesis in this group of patients. Fibrinolysis, inflammation, and endothelial activation were closely interrelated in IPAH.
Highlights
Histopathological studies have shown a high prevalence of in situ thrombosis in patients with idiopathic pulmonary arterial hypertension (IPAH) [1,2]
Seventeen (63%) IPAH patients were in WHO functional class III, 8 patients in functional class II and 2 patients in class IV at study entry
In the present study we have shown that markers of fibrinolysis were elevated in patients with IPAH while markers of thrombogenesis were not different from controls without PH
Summary
Histopathological studies have shown a high prevalence of in situ thrombosis in patients with idiopathic pulmonary arterial hypertension (IPAH) [1,2]. The use of vitamin K antagonists (VKA) has become a standard of care in IPAH [4]. This indication, has been questioned recently with the introduction of advanced PAH specific therapy which relieved many patients from bed resting [5,6]. Recent data suggested an increased bleeding risk in patients with IPAH compared to patients taking VKA for other reasons [7]. Chronic anticoagulation is a standard of care in idiopathic pulmonary arterial hypertension (IPAH). We aimed to study markers of thrombogenesis and fibrinolysis in patients with IPAH. Plasmin-anti-plasmin decreased after 3 months of PAH specific therapy while the other markers remained unchanged. Fibrinolysis, inflammation, and endothelial activation were closely interrelated in IPAH
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