Abstract
Introduction: Genetic counseling in sickle cell disease (SCD) allows to inform people about the genetic condition and to make informed decisions about screening and treatment opportunities. With improvement of care and follow-up of SCD and in order to provide adequate genetic counseling, the current study compared the clinical presentation of patients with hemoglobin SC disease (SC) and sickle cell anemia (SS) or SBeta°-thalassemia (Sβ°).
Methods: The Belgian SCD Registry currently includes patients followed in 8 centers. Data was retrieved retrospectively from their medical charts until 2008. From 2008 till December 2012, all data (known and new cases) was prospectively entered. Data was collected either from birth, for patients diagnosed by means of the neonatal screening program (NSP) or from diagnosis following the first contact in a center and consistently until the last follow-up (FU) visit, or death. Data included genotype, demography, method and date of diagnosis, SCD-related complications, biological parameters, radiological results, treatment and hospitalizations.
Results: Among the 469 patients recorded, 36 (8%) were SC. Their demographic and outcome data are given in Table 1, subgroups of SC patients detected at birth or not are given in Table 2. FU was 292 and 4749 patient-years (PY) for SC and SS/Sβ° groups respectively. Median age at diagnosis for SC and SS/Sβ° subgroups not detected at birth was 6.7 and 2.6 y. The first vaso-occlusive crisis (VOC) in SC patients occurred earlier in neonatal screened patients (5y vs 17y; P=0.004). Osteonecrosis was observed only in 6 patients diagnosed at birth but was significantly more frequent in SC individuals (P=0.02). Among the 6 SC patients treated with hydroxyurea (HU), indications for treatment were recurrent VOC (n=4), proteinuria (n=1) and osteonecrosis (n=1). Hospitalization days per 100 PY were 123 for the SC NSP cohort and 373 for the SS/Sβ° NSP cohort, with total hospitalization days significantly lower in SC patients (160 vs. 4059 days ; P=0.03).
Discussion: SC patients represent 8 % of the whole cohort but asymptomatic and undiagnosed patients probably exist. Overall they are much less represented than in other Western series. They are significantly less affected by VOC, acute chest syndrome (ACS), severe anemia than SS/Sβ° patients but did not differ for occurrence of retinopathy or osteonecrosis. Several published studies confirmed these data but showed also others complications such as severe infection, stroke and death.
Our data doesn’t support any impact of NSP on occurrence of major complications for SC disease. Retinopathy incidence that increases with age is as expected lower in the NSP group (younger patients at last FU when compared to no NSP group). Older age at first VOC in the no NSP group results probably from previously undiagnosed mild disease. Nevertheless several SC patients were more severely affected requiring HU treatment. Limitations of our work are linked to the small size of our SC cohort, the nature of the partial retrospective study and the unknown number of SC patients not requiring care in a specific program.
In conclusion, SC patients have a lower incidence of clinical events than SS/Sβ°, excepted for osteonecrosis and retinopathy equally observed in both groups. Our data support the need of early ophthalmological FU and special awareness to detect early osteonecrosis. These Belgian data may support a dedicated genetic counseling for SC patients and affected families.
Table 1. SC and SS/S β 0 patients: demographic and outcome SC SS/Sβ0 P Number of patients 36 (8%) 423 (90,2%) Male 14 (39%) 201 (48%) NS NSP 19 (53%) 142 (34%) Median age at diagnosis years (range) 0 (0-35) 1 (0-29) NS Median age at last FU years (range) 9,9 (1,4-44) 13 (1-53) NS Severe anemia < 60g/L 3 (8%) 208 (49%) < 0,01 ACS 1 (2,8%) 119 (28%) < 0,01 VOC 11 (31%) 253 (60%) < 0,05 Stroke 0 17 (4%) NS Severe infection 0 35 (8%) NS Osteonecrosis 4 (11%) 36 (8,5%) NS Retinopathy 4 (11%) 25 (6%) NS HU treatment 6 (17%) 179 (42%) < 0,05 Deaths 0 13 (3%) NS
Table 2. SC patients from NSP vs no NSP: demographic and outcome NSP no NSP P Number of patients 19 (53%) 17 (47%) Male 10 (53%) 4 (24%) NS Median age at last FU years (range) 6 (1-14) 14 (4-44) NS Severe anemia < 60g/L 2 (10,5%) 1 (6%) NS ACS 0 1 (6%) NS VOC 5 (26%) 6 (35%) NS Osteonecrosis 3 (16%) 1 (6%) NS Retinopathy 0 4 (23,5%) 0,04
Disclosures
No relevant conflicts of interest to declare.
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