The Serum Levels of N-Terminal Pro B-Type Natriuretic Peptide (NT-proBNP) Is a Strong Indicator of Pulmonary Hypertension in Patients with Sickle Cell/Beta Thalassemia.

Echocardiography studies have reported that approximately 30% of screened adult patients with sickle cell disease (SCD) have pulmonary hypertension (PH) defined as systolic pulmonary artery pressures of ≥ 35 mm Hg or regurgitant jet velocity value (TRV) of ≥ 2.5 m/sec. PH is increasingly observed in SCD and thalassemia. B-type natriuretic peptide (BNP) and the putatively inactive amino-terminal fragment of proBNP (NT-proBNP) are produced by the cleavage of proBNP, which is secreted from the ventricles during pressure strain. The serum concentration of NT-proBNP is considered as one of the strongest independent predictors for survival in patients with left ventricular dysfunction. The aim of this study was to evaluate the prevalence of PH in correlation with hemolytic findings and NT-proBNP levels in 73 patients with HbS/beta-thalassemia (HbS/β-thal; thal 0: 44 pts and thal +: 29 pts). The presence of PH was evaluated by using Doppler echocardiography and applying the modified Bernoulli equation (pulmonary artery systolic pressure=4V² +right atrial pressure). Exclusion criteria of this study include: evidence of left ventricular failure, vaso-occlussive crisis during the last 15 days, atrial fibrillation or ventricular tachycardia, mitral value regurtitation (MVR) >2/4+ or mitral value stenosis, and severe pericardial perfusion. In all pts we measured Hb, leukocyte, platelet, and reticulocyte counts, LDH, bilirubin, ferritin, creatinine, and Hb F. NT-proBNP levels were evaluated using an electrochemiluminescence immunoassay (Roche Diagnostics GmbH, Mannheim, Germany). Thirty-six patients (49%) were on hydroxyurea administration for a median time of 9 years. Nineteen patients (26%) had PH and experienced mild symptoms, such as fatigue or dyspnea on slight exertion. The administration of hydroxyurea did not affect the presence of PH. Patients with PH had elevated values of NT-pro BNP, reticulocyte counts and serum ferritin and a borderline increase of HbF compared with non PH patients (table). Even patients without PH had elevated concentrations of NT-proBNP compared with 20 controls of similar age and gender (mean±SD for controls: 48.1±22.1 pg/mL; p<0.0001). The results of this ongoing study have shown that the frequency of PH in our cohort of HbS/beta-thal patients is similar with that observed in patients with SCD. Serum NT-proBNP is a strong indicator of PH in this cohort of hemoglobinopathy patients. Furthermore, the correlation between PH with reticulocyte counts and ferritin suggests that the degree of hemolysis and iron overload is implicated in the pathogenesis of PH in HbS/beta-thal.