Pulmonary Hypertension Among Individuals Living With Hemoglobinopathies: A Systematic Review

Hemoglobinopathy has a diverse clinical presentation and complications, and is severe among individuals with the homozygous form. It is the most common cause of chronic anemia among affected individuals. Hemoglobinopathy is an inherited blood disorder arising from mutations in globin genes and is broadly categorized into those involving structural changes that produce abnormal hemoglobin variants or defects in globin chain production. This review aims to evaluate the risk factors and outcomes of pulmonary hypertension among individuals with hemoglobinopathies. A search was conducted on PubMed and Google Scholar databases from inception to April 30, 2025. In total, 1,825 articles were synthesized, of which 13 were included in the final qualitative analysis and data extraction. We included English-language original articles published in peer-reviewed journals that reported the risk factors and outcomes of pulmonary hypertension in patients of any age and gender diagnosed with any type of hemoglobinopathy. This review synthesized 13 articles from 10 countries. A total of 2,873 individuals were diagnosed with hemoglobinopathy (1,031 (36%) with sickle cell disease and 1,842 (64%) with β-thalassemia), and 472 were diagnosed with pulmonary hypertension. Among those with pulmonary hypertension, 289 (61%) had sickle cell disease, while 183 (39%) had β-thalassemia. Older age (>40 years), a history of splenectomy, a hemoglobin level of <8 g/dL, frequent blood transfusions, frequent hospitalization for vaso-occlusive crisis, and β-thalassemia were associated with pulmonary hypertension. Some laboratory parameters (serum creatinine, reticulocyte, albumin, nucleated red blood cells, globulin, cell-free hemoglobin, N-terminal pro-B-type natriuretic peptide, high-sensitivity C-reactive protein, soluble vascular cell adhesion molecule, platelet, lactate dehydrogenase) were associated with pulmonary hypertension. Overall, the mortality rate was 27 (10%), with respiratory failure, sudden death, and cor pulmonale as the common causes of mortality. Early recognition and risk stratification for pulmonary hypertension must become integral components of hemoglobinopathy care, particularly in adult patients and those with high-risk profiles. Establishment of a standardized treatment guideline and optimizing the use of disease-modifying therapies, such as hydroxyurea and iron chelators, and exploring novel pharmacologic strategies (endothelin receptor antagonist, phosphodiesterase type 5 inhibitors), may hold promise for altering the trajectory of pulmonary hypertension in this vulnerable group. Our findings confirm that pulmonary hypertension is not only a prevalent complication but also a serious prognostic marker associated with increased morbidity and mortality in this population.