To stress the importance of considering pulmonary complications in sickle cell disease (SCD), researchers compiled an overview on the state of research and available treatment options for patients with SCD associated with pulmonary hypertension.
Although rare, pulmonary hypertension (PH) can be a serious complication from sickle cell disease (SCD). In a recent article published in La Presse Médicale, researchers provided an overview of the pathophysiological mechanisms at work with PH in SCD, discussed available therapeutic approaches, and emphasized the importance of considering PH complications in SCD despite its infrequency.
The clinical approach of PH in SCD carries its own challenges. The physiopathology of these combined conditions is multifactorial, not fully understood, and requires the attention of both PH and SCD specialists to formulate appropriate treatment strategies. This multidisciplinary approach is often personalized to a patient and will vary depending on the specific cause of PH in that individual.
SCD is the most prevalent autosomal recessive disorder, affecting approximately 275,000 individuals globally each year. Pulmonary complications have grown increasingly frequent as the survival and management of patients with SCD has improved. At present, pulmonary issues constitute up to 30% of deaths observed in patients with SCD. PH occurs in up to 10% of cases and carries significant risks, with 6-year mortality rates at 40%.
PH associated with SCD often results from chronic, heightened, left-heart pressure contributing to veinous pulmonary vascular remodeling. Over 50% of SCD-associated PH develops into postcapillary PH resulting from elevated left atrial pressure. The remaining cases can be associated with precapillary arterial PH that can result from the obstructive remodeling of the pulmonary vascular bed. It is possible that thrombotic lesions can also develop as a consequence of PH linked with SCD.
As the authors note, patients with PH typically have reduced levels of hemoglobin and increased levels of hemolysis biomarkers. These alterations can influence endothelial dysfunction, excessive vasoconstriction, and abnormal cell proliferation of the vascular wall. Endothelial dysfunction, in particular, can encourage the expression of endothelin-1 (ET-1), a known vasoconstrictor. Patients with SCD have exhibited high levels of ET-1, and, furthermore, anemia associated with SCD can elevate cardiac output to compensate for a lowered oxygen-carrying capability. This compensation can increase endothelial activation.
There have been ongoing efforts utilizing chronic blood exchange transfusion or hydroxyurea to address the underlying disease; however, there are still insufficient data on the benefits of PAH-specific therapies for these patients, such as phosphodiesterase-5 inhibitors, endothelin receptor antagonists, soluble guanylate cyclase simulators, and prostacyclin derivatives. This represents a crucial area for improvement in the management of PH in SCD because PH development can swiftly reduce a patient’s functional capabilities and drastically increase their symptoms. Additionally, as the authors mention, a recent registry saw an approximate 60% 5-year survival rate for those with newly diagnosed SCD-associated pH.
These data underlie the significance of early detection in this population. Pinpointing the development of PH in these patients and assessing their risks can dramatically benefit the care they receive and the outcomes they experience. Diagnosing PH in SCD can be difficult, however, due to multiple confounding components: fatigue, chest pain, and worsened exertional dyspnea, all of which could be explained by anemia. At present, a right heart catheterization is necessary to confirm a PH diagnosis, as well as assessing the severity of a patient’s PH and determining whether it is post- or precapillary, or a combination of the conditions.
In their concluding remarks, the authors stress the need for advancements in the management of SCD-associated PH to improve diagnostic methods and hinder disease progression as soon as possible.
Kahf SA, Roche A, Baron A, Chantalat-Auger C, Savale L. Pulmonary hypertension in sickle cell disease. Presse Med. Published online November 14, 2023. doi:10.1016/j.lpm.2023.104209