Hospitalization Rate and Regional Differences in Comprehensive Care in Transfused Patients with Sickle Cell Disease Compared to Thalassemia: A Report from the Multi-Center Study of Iron Overload.

Abstract

Red blood cell transfusions are often used to prevent the complications of thalassaemia (Thal) and sickle cell disease (SCD), though chronic therapy frequently results in iron overload-related organ injury. The Multi-Center Study of Iron Overload is a prospective, natural history study conducted to compare the comorbidities of iron overload in Thal with SCD. This report examines differences in morbidity and comprehensive care by disease and geographic region. 584 subjects aged 12 years and over, were screened for inclusion from 30 clinical hematological centers in the US, Canada and the UK. Socioeconomic and clinical data from subjects with iron overload (LIC of ≥ 10 mg/g dry wt by biopsy) and either Thal (N=142, 54% Male) or Tx-SCD (N=199, 43% Male) were collected. A group of non-iron overloaded SCD (NonTx-SCD N=64; 50% Male) were also enrolled. Tx-SCD were hospitalized more frequently (4.1± 3.8 times/year) compared to Thal (1.8± 1.7) or NonTx-SCD (2.1± 1.7; p<0.001) subjects, though average length of stay was similar (Tx-SCD: 7.0± 5.3 days; Thal: 5.7± 4.6; NonTx-SCD: 5.3± 3.8, p=0.16). Within the Tx-SCD group, adult subjects were 2.4 times more likely to be hospitalized in the previous 12 months compared to pediatric subjects (p=0.004, 95%CI 1.3–4.4). Roughly half of the SCD hospitalizations were for pain, whereas subjects with Thal were hospitalized for a variety of reasons, most often secondary to infection. Subjects with Thal were more likely to have routine iron assessments (LIC by biopsy: 66% vs. 37%), and screening for iron related organ injury such as thyroid function (TSH: 85% vs. 33%) and cardiac function (ECHO: 75% vs. 54%; EKG: 60% vs. 41%) compared to Tx-SCD (all p<0.001). Subjects with Thal had 3.4 times higher odds of having a recent liver biopsy compared to Tx-SCD (p<0.001; 95%CI: 2.2–5.3). Pediatric Tx-SCD subjects were more likely to have a biopsy compared to adults (46.5 vs. 23.5; p <0.001), however this likelihood was not related to serum ferritin level, duration of transfusion or chelation. Combining Thal and Tx-SCD groups, liver biopsy was more commonly performed at international vs. U.S. centers, (p<0.001), however the size of the clinical center was unrelated. Whereas, both regional and center size differences were observed in ECHO and TSH testing (p<0.01). A total of 26 subjects have died or exited from the study due to significant medical events. The mortality among adult Tx-SCD subjects was 2.8 fold greater than that of Thal (p=0.017). These data suggest that despite significant morbidity and iron burden, Tx-SCD subjects are monitored on a less frequent basis for iron related organ damage compared to Thal subjects. Differences were also observed in standards of care by region and center size. This disparity in care requires attention and guidelines for the assessment and management of Tx-SCD subjects should be developed and supported until the effect of iron overload in this population is better understood.