Pulmonary hypertension in hemolytic disorders: pulmonary vascular disease: the global perspective

Abstract

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.

Figure 1.

Global distribution of hemoglobin disorders. Republished with permission from the World Health Organization.

Figure 2.

Pulmonary arteriopathy in hemolysis-associated pulmonary hypertension. Autopsy findings of a patient with sickle cell disease and pulmonary hypertension who died suddenly during an episode of vasoocclusive crisis. A right-sided heart catheterization performed approximately 1 year earlier demonstrated the following findings: right arterial pressure, 12 mm Hg; mean pulmonary artery pressure, 40 mm Hg; pulmonary capillary wedge pressure, 13 mm Hg, cardiac output, 7.7 L/min; and pulmonary vascular resistance, 281 dyne/s/cm⁵. Low-power photomicrographs demonstrate pulmonary arterial smooth muscle hypertrophy (hematoxylin and eosin stain; original magnification ×10) (A), a plexogenic lesion (hematoxylin and eosin stain; original magnification ×40) (B), and smooth muscle cell hyperplasia (Mason trichrome stain; original magnification ×40) (C).

Figure 3.

Prevalence of elevated pulmonary artery systolic pressure and pulmonary hypertension in sickle cell disease. Approximately 30% of patients with sickle cell disease have an elevated estimated pulmonary artery systolic pressure (> SD above mean reference value for patients aged < 40 years). Right-sided heart catheterization-confirmed pulmonary hypertension occurs in 6% of patients. Pulmonary arterial hypertension occurs in 2% of patients. Data are based on 213 patients from Gladwin et al and Anthi et al. mPAP = mean pulmonary artery pressure; PAH = pulmonary arterial hypertension; PCWP = pulmonary capillary wedge pressure; PH = pulmonary hypertension; PVH = pulmonary venous hypertension; PVR = pulmonary vascular resistance; RHC = right-sided heart catheterization; TRV = tricuspid regurgitant jet velocity.