Raised erythrocyte creatine in patients with pulmonary arterial hypertension - Evidence for subclinical hemolysis

Background: Pulmonary arterial hypertension (PAH) has been associated with hemolytic conditions such as sickle cell disease but the possible role of hemolysis in the pathogenesis or pathophysiology of other forms of PAH has not been studied. Erythrocyte lifespan is the gold-standard test of hemolysis and may be measured by assaying erythrocyte creatine (EC) levels. EC decreases as the erythrocyte ages, so patients with hemolysis have high EC levels. Methods: We measured EC and other parameters of hemolysis in patients with idiopathic and connective tissue associated PAH and normal controls. Results: In patients with PAH (n = 40), EC levels were higher than in controls n = 30 (patients EC 1.72 mcmol/g HgB 95%CI[1.51, 1.96], controls EC 1.05 mcmol/g HgB [0.93, 1.19], p < 0.0001). High levels of EC correlated with worse 6 min walk (r = -0.42, p < 0.0001) and worse functional class (p = 0.002). Other indirect indices of hemolysis (total lactate dehydrogenase, red cell distribution width) were also increased in patients with PAH relative to controls. Conclusions: There is evidence of subclinical hemolysis in patients with PAH, and higher levels of hemolysis are associated with poorer exercise capacity.