From the Guidelines
All of the listed conditions—pulmonary hypertension, heart failure with reduced ejection fraction, retinopathy, and hypersplenism—are chronic complications of sickle cell disease. According to the American Thoracic Society clinical practice guideline 1, pulmonary hypertension is a well-established risk factor for mortality in sickle cell disease, and its diagnosis can be made through noninvasive measurement of tricuspid regurgitant jet velocity via Doppler echocardiography or serum N-terminal pro–brain natriuretic peptide level measurement. The American Society of Hematology 2019 guidelines for sickle cell disease also highlight the association between pulmonary hypertension confirmed by right-heart catheterization and increased mortality among adults with sickle cell disease 1.
Some key points to consider about these complications include:
- Pulmonary hypertension develops in approximately 10% of sickle cell patients due to chronic hemolysis, which releases free hemoglobin that depletes nitric oxide, causing vasoconstriction and vascular damage.
- Heart failure with reduced ejection fraction occurs as a result of chronic anemia leading to high-output cardiac states and eventual myocardial dysfunction.
- Sickle cell retinopathy develops when sickling red blood cells occlude retinal vessels, causing ischemia and neovascularization that can lead to vision loss.
- Hypersplenism results from repeated splenic infarctions and subsequent fibrosis, initially causing splenomegaly and eventually leading to autosplenectomy in many patients.
These complications highlight how the chronic sickling process affects multiple organ systems over time, causing progressive damage through recurrent vaso-occlusion, ischemia, and tissue infarction, as noted in the guidelines 1.
From the Research
Chronic Complications of Sickle Cell Disease
- Pulmonary hypertension is a recognized complication of sickle cell disease, with a prevalence of approximately 30% in adult patients 2.
- It is characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, and confers a high risk of death, with 2-year mortality rates of 40-50% 2.
- The pathogenesis of pulmonary hypertension in sickle cell disease is heterogeneous, including hemolysis, asplenia, thrombosis, chronic lung disease, and iron overload 2, 3.
- Other chronic complications of sickle cell disease include:
- Heart failure with reduced ejection fraction, which can be related to pulmonary hypertension 3.
- Retinopathy, although not directly mentioned in the provided studies as a complication of sickle cell disease.
- Hypersplenism, which is not mentioned in the provided studies as a complication of sickle cell disease, but asplenia is mentioned as a potential factor in the pathogenesis of pulmonary hypertension 2.
Diagnosis and Management
- Doppler echocardiography is recommended for screening for pulmonary hypertension in sickle cell patients, using tricuspid regurgitant jet velocity to estimate pulmonary artery systolic pressure 2, 4.
- Management of pulmonary hypertension in sickle cell disease includes intensification of sickle cell-directed therapies, treatment of causal factors or associated diseases, general supportive measures, and use of PH-specific pharmacologic agents 2, 3, 4.