In sickle cell disease (SCD),

Silent damage in SCD can be progressive and may occur even in patients who experience few or no vaso-occlusive crises (VOCs).1-6

SCD pathophysiology may lead to long-term organ damage1-5

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

Learn how SCD pathophysiology
may lead to organ damage

SCD is characterized by a mutation in HBB and polymerization of HbS1,2

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

Discover hematologic and vascular changes in SCD

Sickled red blood cell
Sickled red blood cell

See the impact that a
mutation in HBB and
polymerization of HbS
have on RBC function


Stay informed about sickle cell disease.

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.