Silent damage in SCD can be progressive and may occur even in patients who experience few or no vaso-occlusive crises (VOCs).1-6
Hallmarks of SCD pathophysiology include anemia, hemolysis, inflammation, vaso-occlusion, and endothelial dysfunction. These can, in turn, lead to further complications, including long-term organ damage.1-5
The degree to which SCD pathophysiology contributes to end-organ damage is not known, as multiple factors—including age, sex, genotype/genogroup, treatment status, and other patient-specific variables—may also affect its etiology.7
SCD is characterized by a mutation in HBB, the gene that encodes hemoglobin subunit β (beta-globin), leading to the expression and polymerization of hemoglobin S (HbS), which can distort RBCs into a characteristic crescent or sickled shape. Sickled RBCs can, in turn, impact hematologic and vascular function.5,8,9
References: 1. Telen MJ, Malik P, Vercellotti GM. Therapeutic strategies for sickle cell disease: towards a multi-agent approach. Nat Rev Drug Discov. 2019;18(2):139-158. 2. Kato GJ, Piel FB, Reid CD. Sickle cell disease. Nat Rev Dis Primers. 2018;4:(article 18010). doi:10.1038/nrdp.2018.10. 3. Kato GJ, McGowan V, Machado RF, et al. Lactate dehydrogenase as a biomarker of hemolysis-associated nitric oxide resistance, priapism, leg ulceration, pulmonary hypertension, and death in patients with sickle cell disease. Blood. 2006;107(6):2279-2285. 4. Damanhouri GA, Jarullah J, Marouf S, Hindawi SI, Mustaq G, Kamal MA. Clinical biomarkers in sickle cell disease. Saudi J Biol Sci. 2015;22(1):24-31. doi:10.1016/j.sjbs.2014.09.005. 5. Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750-760. 6. van Tuijn CFJ, Schimmel M, van Beers EJ, Nur E, Biemond BJ. Prospective evaluation of chronic organ damage in adult sickle cell patients: a seven-year follow-up study. Am J Hematol. 2017;92(10):E584-E590. doi:10.1002/ajh.24855. 7. Buchanan G, Vichinsky E, Krishnamurti L, Shenoy S. Severe sickle cell disease—pathophysiology and therapy. Biol Blood Marrow Transplant. 2010;16(1 suppl):S64-S67. doi:10.1016/j.bbmt.2009.10.001 8. Stuart MJ, Nagel RL. Sickle-cell disease. Lancet. 2004;364(9442):1343-1360. 9. Gordeuk VR, Castro OL, Machado RF. Pathophysiology and treatment of pulmonary hypertension in sickle cell disease. Blood. 2016;127(7):820-828.