Sickle cell disease-associated pulmonary hypertension: an integrated framework linking pathologies, mechanisms, and clinical phenotypes - PubMed
3 hours ago
- #Pulmonary hypertension
- #Haemolysis
- #Sickle cell disease
- Sickle cell disease-associated pulmonary hypertension (SCD-PH) affects about 10% of adults with SCD and significantly increases mortality.
- An integrated framework links five axes—anaemia/high-output, haemolysis/haem/iron toxicity, hypoxia, inflammation, and thrombosis—to clinical phenotypes including post-capillary, pre-capillary, combined, CTEPH, and acute cor pulmonale.
- Chronic anaemia leads to high-output physiology and post-capillary PH, while haemolysis causes nitric oxide depletion and oxidative damage, promoting pre-capillary PH.
- Management focuses on hydroxyurea and transfusion, with PDE5 inhibitors like sildenafil shown to be harmful; emerging treatments include soluble guanylate cyclase stimulation and anti-inflammatory strategies.
- This framework supports phenotype-stratified and mechanism-guided clinical trials for SCD-PH.