Pulmonary hypertension is a severe clinical condition characterized by molecular and anatomic changes in pulmonary circulation. It is associated with increased pulmonary vascular resistance, which leads to right-sided heart failure if left untreated and, ultimately, death. Treatment of patients with pulmonary arterial hypertension (PAH) involves a complex strategy that takes into consideration disease severity, general and supportive measures, and combination drug regimens. Abnormalities of blood coagulation factors, anti-thrombotic factors, and the fibrinolytic system may contribute to a prothrombotic state in patients with idiopathic PAH. These physiologic changes, in concert with the presence of non-specific risk factors for venous thromboembolism such as heart failure and immobility, are thought to be the basis for oral anticoagulation in PAH. Several observational studies provide helpful information in favor of anticoagulation use in idiopathic PAH but not in other pulmonary hypertension etiologies. Guideline recommendations are based on the lack of prospective comparative trials in this regard. For that reason, large differences exist in the use of anticoagulants in different countries and centers. More studies should be carried out to clarify the risks and the potential benefits of anticoagulant use in a heterogeneous population of patients who are already at considerable life risk.

The objective of this study is to evaluate the safety and tolerability of the pharmacological treatment of pulmonary hypertension in pediatric patients. It is a retrospective, longitudinal, observational study on pediatric patients undergoing treatment with pulmonary targeted therapies. 63 patients were included (51% male), with a median age of 3.4 years (IQR, 3.6 months-10 years) and a median weight 13 kg (IQR, 6-30 kg). Congenital heart disease was the etiology of pulmonary hypertension in the majority of cases (n = 33) and 28 patients were in NYHA functional class III-IV. The most commonly used drug was sildenafil (n = 79, 56%), followed by bosentan (n = 27, 23%), and a combination of both (n = 14, 41%). 34 patients had adverse reactions (54%) with an incidence rate of 1.02 per patient per year. The most commonly reported reactions were gastrointestinal symptoms (22%) and spontaneous erections (22%) in males. Nine severe adverse reactions (10%) occurred, requiring eight treatment withdrawal and one hospital admission. Treatment with targeted therapies for pulmonary hypertension is safe in the pediatric population. Severe ADRs were uncommon both in monotherapy and in combination therapy. Combination therapy was associated with a higher rate of ADRs. We observed similar survival rates in children receiving sildenafil doses according to the European Medicines Agency (EMA) recommendations or higher.

Anticoagulants are widely used in patients with pulmonary arterial hypertension (PAH) to prolong survival. However, there is a lack of robust evidence demonstrating the benefits of anticoagulants in PAH patients and very little is known about the complications of their use in this population. The objective of this study is to compare the safety of routine administration of oral anticoagulants between PAH patients who were and were not treated with oral anticoagulants. This observational, retrospective cohort study included consecutive patients with confirmed PAH from two centers: Brigham and Women’s Hospital in Boston and Hospital Universitario La Paz in Madrid from January 2009 to August 2015. The study group comprised patients who received therapeutic anticoagulation; patients who had never received anticoagulants were placed in the control group. Of the 201 included patients, 60.2% were treated with oral anticoagulants and 39.8% were not treated. The hazard ratio for major bleeding was 2.7 (95% confidence interval [CI] = 1.1–6.8; P = 0.036). The incidence rate for the anticoagulation group was 4.7 per 100 patient-years (95% CI = 2.5–8.0). The most frequent major hemorrhage was gastrointestinal bleeding with 24 cases (72.7%). Prior bleeding, poor anticoagulation, HAS-BLED score ≥3, diabetes, and number of medications were factors that increased the risk of major bleeding in patients using anticoagulants. The harmful effects of anticoagulants could outweigh the benefits in PAH patients. Therefore, anticoagulants should be prescribed on a case-by-case basis and should not be systematically recommended.

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Background High-dose methotrexate may cause acute nephrotoxicity because it is mostly excreted by the renal route. Carboxypeptidase G2 is an enzyme that hydrolyses methotrexate rapidly to the inactive metabolites DAMPA and glutamate. The criteria that justify the use of carboxypeptidase in the hospital studied are: methotrexate plasma concentration >10 µM/L, 48 h after administration or increase of creatinine by 100%, 24 h after infusion. Purpose The aim of this study was to check that carboxypeptidase was being used correctly according to the hospital's criteria and to evaluate patient response to treatment. Materials and methods Retrospective study of patients who received carboxypeptidase in the last five years. The data collected were: diagnosis, age, doses of methotrexate and carboxypeptidase, methotrexate and creatinine plasma levels. Results Eighty patients were treated with high dose methotrexate (5 g/m2) and 8 of them (10%), diagnosed with acute lymphoblastic leukaemia, needed a rescue with 50 IU/kg of carboxypeptidase 48 h after infusion. The mean age was 8.87 years (3-13). The mean time to recovery renal function was 7.28 days (4-17) after administration of carboxypeptidase. Conclusions All patients fulfilled at least one of the two criteria that justified carboxypeptidase administration. This drug offers an alternative rapid route for methotrexate elimination. The role of the pharmacist is important to ensure proper use of carboxypeptidase due to the high cost of the drug. DSL006 table 1 - METHOTREXATE LEVELS (μM/L) - CREATININE LEVELS (mg/dL) PATIENT - Before carboxy-peptidase -24 h after carboxy-peptidase -Before metho-trexate - After metho-trexate - 24 h after carboxy-peptidase - 1 - 57.27 - 6.39 - 0.47 - 2.54 - 2.66 - 2 - 56.69 - 3.88 - 0.33 - 2.48 - 2.49 - 3 - 91.25 - 8.37 - 0.69 - 1.50 - 1.50 - 4 - 29.96 - 5.67 - 0.40 - 2.61 - 2.48 - 5 219.09 - 0.77 - 0.50 no data no data - 6 - 40.48 - 9.44 - 0.80 - 4.01 - 4.73 - 7 - 51.32 - 6.87 - 0.32 - 1.94 - 1.90 - 8 - 45.49 - 9.23 - 0.42 - 2.21 - 4.33