Damage in Sickle Cell Disease

LDH is a marker of hemolysis that shows a link between the extent of hemolysis, organ damage, and mortality1-3

Elevated lactate dehydrogenase (LDH) levels have been associated with increased complications and mortality.

Complications by LDH range3

Bar chart showing association between LDH levels and history of leg ulcers, priapism, and pulmonary hypertension in SCDBar chart showing association between LDH levels and history of leg ulcers, priapism, and pulmonary hypertension in SCD

LDH=lactate dehydrogenase; SCD=sickle cell disease.

Bilirubin level is a marker of hemolysis that shows a link between the extent of hemolysis, organ damage, and mortality1,2,5

Bilirubin levels are widely used to assess severity of hemolysis. Elevated levels lead to clinical manifestations like jaundice, and have been associated with increased risk of organ damage and mortality.1,2,5

Jaundice impacts a large percentage of SCD patients. In a 2012 published cross-sectional survey of 100 SCD patients, 79% reported experiencing jaundice.6

Bilirubin association with complications & mortality7*

Total bilirubin levels >6 mg/dL (>103 μmol/L)†

Complications

~2× risk Leg ulcer risk
~2× risk Elevated RVSP‡

Mortality risk

~9×Higher mortality risk

†Normal total bilirubin levels for adults range from 0.2–1.3 mg/dL.8

‡Elevated RVSP can be indicative of pulmonary hypertension, which represents one of the major vasculopathic complications of SCD.9,10

IQR=interquartile range; RVSP=right ventricular systolic pressure.

Elevated reticulocyte counts in SCD are reflective of ongoing hemolysis and are associated with increased organ damage11,12

Stroke-free survival over time based
on reticulocyte count13

Line graph showing probability of stroke-free survival over time based on reticulocyte count in patients with SCD

Figure adapted from de Oliveira Taques et al.

*A reticulocyte count is a percentage of the total number of red blood cells in a sample. Normal range is from 0.5% to 2.5% in adults and 2% to 6% in infants.14

All 3 markers of hemolysis (LDH, bilirubin, reticulocytes) have been linked to organ damage and/or mortality1,3,11

References:

1. Kato GJ, Steinberg MH, Gladwin MT. Intravascular hemolysis and the pathophysiology of sickle cell disease. J Clin Invest. 2017;127(3):750-760. doi:10.1172/JCI89741 2. Ataga KI, Gordeuk VR, Agodoa I, Colby JA, Gittings K, Allen IE. Low hemoglobin increases risk for cerebrovascular disease, kidney disease, pulmonary vasculopathy, and mortality in sickle cell disease: a systematic literature review and meta-analysis. PLoS One. 2020;15(4):e0229959. doi:10.1371/journal.pone.0229959 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. doi:10.1182/blood-2005-06-2373 4. Dey T, Mukherjee A, Chakraborty S. A practical overview and reporting strategies for statistical analysis of survival studies. Chest. 2020;158(1S):S39-S48. doi:10.1016/j.chest.2020.03.015 5. Joseph A, Samant H. Hyperbilirubinemia. National Library of Medicine. National Institutes of Health. Accessed July 27, 2026. https://www.ncbi.nlm.nih.gov/books/NBK544252/ 6. Nero AC, McCavit TL, Adix LM, et al. Impact of jaundice on adults with sickle cell anemia. Blood. 2012;120(21):4753. doi:10.1182/blood.V120.21.4753.4753 7. Deeb M, Leung KK, Ward R, Feld JJ, Kuo KHM, Hirschfeld GM. Hepatobiliary complications in patients with sickle cell disease: a 30-year review of 1009 patients. Hepatol Commun. 2025;9(5):e0712. doi:10.1097/HC9.0000000000000712 8. Bilirubin test. Cleveland Clinic. Accessed July 1, 2026. https://my.clevelandclinic.org/health/diagnostics/17845-bilirubin 9. Kotrri G, Youngson E, Fine NM, et al. Right Ventricular Systolic Pressure Trajectory as a Predictor of Hospitalization and Mortality in Patients With Chronic Heart Failure. CJC Open. 2023;5(9):671-679. doi:10.1016/j.cjco.2023.05.011 10. Gladwin MT, Sachdev V. Cardiovascular abnormalities in sickle cell disease. J Am Coll Cardiol. 2012;59(13):1123-1133. doi:10.1016/j.jacc.2011.10.900 11. Belisàrio AR, Sales RR, Toledo NE, et al. Reticulocyte count is the most important predictor of acute cerebral ischemia and high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia. Ann Hematol. 2016;95(11):1869-1880. doi:10.1007/s00277-016-2789-5 12. Xu JZ, Thein SL. Revisiting anemia in sickle cell disease and finding the balance with therapeutic approaches. Blood. 2022;139(20):3030-3039. doi:10.1182/blood.2021013873 13. de Oliveira Taques W, Bett GC, de Moraes BLB, Medeiros I, Fontes CJF, Godinho de Oliveira R. Factors associated with overt stroke in children and adolescents with sickle cell disease: a retrospective cohort study. Hemoglobin. 2024;48(1):39-46. doi:10.1080/03630269.2023.2301490 14. Reticulocyte count. Cleveland Clinic. Updated April 18, 2022. Accessed August 7, 2026. https://my.clevelandclinic.org/health/diagnostics/22787-reticulocyte-count