Prevalence and Predictors of Chronic Organ Damage in Adults with Sickle Cell Disease.

Sickle cell disease (SCD) affects about 80,000 individuals in the US and about 1 of every 400 African Americans. Although SCD is characterized by acute painful crisis events, pain rates are a weak indicator of mortality risk. The main determinants of early mortality in adults are painless events such as sickle cell nephropathy (SCN), stroke due to cerebrovascular disease (CVD) and pulmonary hypertension (PHT). Sickle cell retinopathy (SCR) is a common cause of morbidity. There is a powerful correlation between end organ damage and early mortality. The prevalence of preclinical target organ damage has not been fully elucidated. We examined the prevalence of the full spectrum of end organ damage in a cohort at entry to our adult SCD program. We also contrasted the clinical and laboratory characteristics of patients with and without organ dysfunction.

Retrospective review of data on 118 adults (mean age 26.48±11.85 years) gathered upon entry into our program between February 2005 and October 2008. Historical presence of episodes of acute chest syndrome, pneumonia, stroke, avascular necrosis, osteomyelitis, leg ulcers, priapism, and cholecystectomy was quantitated. All patients underwent a standardized battery of tests to evaluate hematological and biochemical parameters at entry. Objective evidence of end organ damage was defined as follows: PHT, tricuspid regurgitant jet velocity (TRJV) ≥2.5 on echocardiography; SCN, glomerular filtration rate (GFR) < 90ml/min. and/or 24-hour protein>300mg and/or urine protein/creatinine ratio>0.3, all measured or calculated from 24 hour urine sample; CVD, evidence of previous ischemic and/or hemorrhagic infarct and/or aneurysmal dilatation on brain MRI or MR angiogram; SCR, background to proliferative retinopathy on fluorescent retinal angiography. Characteristics of patients were evaluated using t-test for continuous and the chi-square test for the categorical variables.

There were 58 (49%) males and 60 (51%) females (p-value 0.85). Hemoglobin genotype: 74(63%) had SS/Sβ⁰, 27(23%) had SC, 11(9%) had Sβ⁺ while 5(4%) had S/hereditary persistence of fetal hemoglobin (S/HPFH).Of the patients who were tested for individual end organ damage 26% (24/91) had PHT, 52% (48/92) had nephropathy, 40% (31/78) had CVD while 38% (26/68) had retinopathy. The relevant statistically significant correlative variables for each type of end organ damage are shown in the table: 

End organ damage was highly prevalent in this cohort of adults with SCD. Objective clinical and laboratory factors may predict the risk for end organ damage. This information can be used to develop an objective scoring system for disease severity based on early organ damage which may enable identification of patients at highest risk for severe morbidity and early mortality who might be candidates for more intensive evaluation and early management with disease-modifying interventions, beyond treatment of acute painful events.

No relevant conflicts of interest to declare.