Pathways to pulmonary hypertension in sickle cell disease: the search for prevention and early intervention
- 21 August 2017
- journal article
- research article
- Published by Taylor & Francis Ltd in Expert Review of Hematology
- Vol. 10 (10), 875-890
- https://doi.org/10.1080/17474086.2017.1364989
Abstract
Pulmonary hypertension (PH) develops in a significant number of patients with sickle cell disease (SCD), resulting in increased morbidity and mortality. This review focuses on PH pathophysiology, risk stratification, and new recommendations for screening and treatment for patients with SCD. Areas covered: An extensive PubMed literature search was performed. While the pathophysiology of PH in SCD is yet to be fully deciphered, it is known that the etiology is multifactorial; hemolysis, hypercoagulability, hypoxemia, ischemic-reperfusion injury, oxidative stress, and genetic susceptibility all contribute in varying degrees to endothelial dysfunction. Hemolysis, in particular, seems to play a key role by inciting an imbalance in the regulatory axis of nitric oxide and arginine metabolism. Systematic risk stratification starting in childhood based on clinical features and biomarkers that enable early detection is necessary. Multi-faceted, targeted interventions, before irreversible vasculopathy develops, will allow for improved patient outcomes and life expectancy. Expert commentary: Despite progress in our understanding of PH in SCD, clinically proven therapies remain elusive and additional controlled clinical trials are needed. Prevention of disease starts in childhood, a critical window for intervention. Given the complex and multifactorial nature of SCD, patients will ultimately benefit from combination therapies that simultaneously targets multiple mechanisms.Keywords
This publication has 100 references indexed in Scilit:
- Mortality in Adults With Sickle Cell Disease and Pulmonary HypertensionJAMA, 2012
- N-acetylcysteine reduces oxidative stress in sickle cell patientsAnnals of Hematology, 2012
- Nitric Oxide for Inhalation in the Acute Treatment of Sickle Cell Pain CrisisJAMA, 2011
- Diminished Global Arginine Bioavailability and Increased Arginine Catabolism as Metabolic Profile of Increased Cardiovascular RiskJournal of Invasive Cardiology, 2009
- Improvement in hemolysis and pulmonary arterial systolic pressure in adult patients with sickle cell disease during treatment with hydroxyureaAmerican Journal of Hematology, 2009
- Cardiac iron across different transfusion-dependent diseasesBlood Reviews, 2008
- Evolution of Novel Small-Molecule Therapeutics Targeting Sickle Cell VasculopathyJAMA, 2008
- Physician‐diagnosed asthma and acute chest syndrome: Associations with NOS PolymorphismsPediatric Pulmonology, 2007
- Deconstructing sickle cell disease: Reappraisal of the role of hemolysis in the development of clinical subphenotypesBlood Reviews, 2007
- PULMONARY HYPERTENSION IN SICKLE CELL DISEASE: Relevance to ChildrenPediatric Hematology and Oncology, 2007