The inherited
hemoglobin disorders
sickle cell disease and
thalassemia are the most common monogenetic disorders worldwide.
Pulmonary hypertension is one of the leading causes of morbidity and mortality in adult patients with
sickle cell disease and
thalassemia, and hemolytic disorders are potentially among the most common causes of
pulmonary hypertension. The pathogenesis of
pulmonary hypertension in hemolytic disorders is likely multifactorial, including
hemolysis, impaired
nitric oxide (NO) bioavailability, chronic
hypoxemia, chronic thromboembolic
disease, chronic liver disease, and asplenia. In contrast to patients with traditional forms of
pulmonary arterial hypertension, patients with hemolytic disorders have a mild-to-moderate degree of elevation in mean pulmonary pressures, with mild elevations in pulmonary vascular resistance. The hemodynamic etiology of
pulmonary hypertension in these patients is multifactorial and includes
pulmonary arterial hypertension, pulmonary venous
hypertension, and
pulmonary hypertension secondary to a hyperdynamic state. Currently, there are limited data on the effects of any specific treatment modality for
pulmonary hypertension in patients with hemolytic disorders. It is likely that maximization of treatment of the primary
hemoglobinopathy in all patients and treatment with selective pulmonary
vasodilators and antiproliferative agents in patients with
pulmonary arterial hypertension would be beneficial. However, there is still a major need for large multinational trials of novel
therapies for this patient population.