Severity of pulmonary hypertension during vaso‐occlusive pain crisis and exercise in patients with sickle cell disease

Pulmonary hypertension is increasingly recognised as a complication of sickle cell disease. Despite mild to moderate increases in pulmonary arterial pressures, the 2-year mortality associated with the disease approaches 50% in adult patients. (Castro et al, 2003). We recently demonstrated that in adult patients with sickle cell disease, even mild pulmonary hypertension [defined by a tricuspid regurgitant jet velocity (TRV) ≥2·5 m/s] is a major independent risk factor for death (relative risk, 10·1; 95%confidence interval, 2·7–44), suggesting that these mild to moderate increases in pulmonary pressures are poorly tolerated (Gladwin et al, 2004). Sudden or unexplained death is a well-described phenomenon in patients with sickle cell disease, both in steady state and during vaso-occlusive crisis, occurring in 12–26% of all deaths in the Co-operative Study of Sickle Cell Disease (Charache, 1994; Platt et al, 1994). Acute increases in pulmonary pressures during stress in these patients with severe anaemia and mild to moderate pulmonary hypertension could result in cardiovascular collapse and potentially explain some of these events. Vasoocclusive pain crisis is associated with pathological changes, such as worsening anaemia, enhanced red cell adhesion, vasoconstriction and hypoxemia, which could certainly promote or exacerbate pulmonary hypertension in patients with sickle cell disease. Similarly, during physical exertion, patients with pulmonary vascular diseases become more symptomatic, mainly because of the inability of their right ventricles to overcome the increased right ventricular afterload, and are unable to adequately increase cardiac output for the demands of exercise. Based on these observations, we hypothesised that vasoocclusive crisis and exercise are associated with worsening pulmonary hypertension in patients with sickle cell disease. To test this hypothesis, we evaluated the effects of vaso-occlusive pain crises and exercise on pulmonary artery pressures, as well as the blood laboratory parameters associated with vasoocclusive pain crisis and changes in pulmonary pressures.