6,9 In this regard, the population of COMPERA are considered to be at Paclitaxel molecular weight intermediate risk for worse outcome (WHO function class III in 75% of patients, mean 6 minutes walk test of 294 m; mean right atrial pressure of 8.8 mmHg and mean cardiac output index of 2.2 L/min/m2). Another point to be considered is how early anticoagulant therapy should be initiated in PAH patients. Introduction of anticoagulant therapy at an early stage of the disease may carry the possible advantage of slowing the progression of

luminal narrowing in PAH. However, this strategy may be associated with increased life-time exposure to anticoagulant therapy with increased bleeding risk. Alternatively, the use of anticoagulant therapy in patients in an advanced stage of the disease is expected to offer more protection, since these patients have low cardiopulmonary reserve that cannot withstand further arterial obstruction. Nevertheless, these patients may be also at increased bleeding risk related to hepatic and gastrointestinal

congestion. Risk of bleeding Bleeding in PAH patients is important for two reasons: it occurs in relatively higher rates compared with other diseases; and it may be associated with serious sequelae. In a retrospective single centre study, major bleeding ranged from 2.4 per 100 patient-years for chronic thromboembolic pulmonary hypertension and 5.4 per 100 patient-years for idiopathic PAH,

to 19 per 100 patient-years for PAH associated with connective tissue disease. 10 These rates are considered high compared to the reported rates of major bleeding in patients with atrial fibrillation receiving oral anticoagulants (2.0 per 100 patient-years). 11–12 The occurrence of an otherwise mild bleeding can be a catastrophic event in PAH patients. These patients are volume sensitive and acute blood loss may induce a fatal vicious circle of cardiopulmonary decompensation that leads to irreversible cardiogenic shock. Chronic blood loss will impair cardiopulmonary reserve and in severe anemia both tissue hypoxia and lactic acidosis contribute to increase pulmonary GSK-3 artery pressure. A number of factors should be considered to assess risk of bleeding in these patients. [4] Type of PAH: bleeding risk is increased in 3 groups of patients with PAH: (a) patients with connective tissue diseases, specially patients with scleroderma in whom the risk of gastrointestinal bleeding is increased due to the presence of luminal telangiectasia 13 ; (b) patients with PAH related to congenital heart disease and (c) patients with portopulmonary hypertension with increased risk for gastrointestinal bleeding owing to the presence of varices and abnormal coagulation profile.