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Introduction Children and adults with sickle cell disease (SCD) suffer from overt stroke, the prevalence of which has been reported to be 11% < 20 years. More commonly, they suffer from silent cerebral Infarction (SCI) that has a reported prevalence of 37.1% in children at 4 years of age1. Unlike homozygous SS disease (HbSS), the reported prevalence of overt and silent stroke in Hemoglobin SC (HbSC) is low (0% and 5.8%, respectively) in Cooperative Study of Sickle Cell Disease (CSSD)2. However, in a recent study, the prevalence of silent stroke in HbSC was found to be 13.5%3. The goal of our study was to determine the prevalence of stroke and neurovascular complications in children and adults with HbSC in the Central Missouri Cohort (MU-SCD). We also examined the demographic and laboratory factors, SCD related complications, and disease modifiers that correlated with stroke in this cohort. Methods We retrospectively analyzed charts of 131 children and adults with (SCD) who sought care at the University of Missouri between 2000 and 2018, between the ages of 1- 65 years. Clinical, laboratory, Transcranial Doppler (TCD) ultrasound, and Magnetic Resonance Imaging/Angiography (MRI/MRA) data for clinically documented overt stroke, SCI and vasculopathy were analyzed. An expert neuroradiologist analyzed all the MRI/MRAs in a blinded manner. Fisher's exact tests for categorical data and two-sided t-tests for continuous data analysis were used. P value <0.05 was considered as statistically significant. Results Of the 131 individuals analyzed, 9 were excluded from the study due to incomplete clinical information. The genotype consisted of HbSS 72 (59.0%), HbSC 39 (32.0%), and HbS/β Thal 11(9.0%) (Table 1). The overall prevalence of cerebrovascular complications were 30%, 17.7% and 22.2% in the HbSS, HbSC and HbS/β Thal (p-0.47), respectively (Table 2). Among HbSC individuals, those with stroke and cerebral vasculopathy had a marginally higher serum creatinine compared to those without complications (p-0.08) (Table 3). Prevalence of proteinuria was higher in individuals with cerebrovascular lesions (p-0.015). Of the SCD related complications, acute chest syndrome (57.7% versus 33.8%; p-0.038), gall bladder stones with cholecystectomy (53% versus 23%; p-0.006) and pulmonary hypertension (46.2% versus 7.8%, p-<0.0001) correlated with stroke (Table 4). Though not statistically significant, Hydroxyurea use was more prevalent in individuals without stroke or vasculopathy whereas, chronic transfusion was more prevalent in SCD individuals with stroke (Table 4). The neuroradiological lesions consisted of lacunae, encephalomalacia, atrophy, leukoencephalopathy and microhemorrhage in individuals with HbSC (data not shown). Conclusion We noted a higher prevalence of neurovascular complications in individuals with HbSC than previously reported by the Cooperative Study of Sickle Cell disease. The prevalence of cerebrovascular complications in comparison group of HbSS was similar to that reported previously in CSSD cohort. This study indicates that both silent stroke and vasculopathy occur in HbSC and appeared to be more prevalent than overt stroke. As TCD screenings are not routinely used in individuals with HbSC, MRI may be warranted to detect SCI and cerebral vasculopathy. Larger prospective studies are required to understand genetic and non-genetic risk factors associated with stroke in children and adults with HbSC for establishment of prevention, early detection, and treatment modalities. References 1. Blood 2011 Jan 27;117(4):1130-40 2. Blood 2002 Apr 15;99(8):3014-8 3. Blood 2015 125:416-417; Disclosures Balasa: Novartis: Honoraria, Other: Medical Advisory Board; Genetech: Honoraria, Other: Medical Advisory Board; Sanofi-Genzyme: Honoraria, Other: Medical Advisory Board; Takeda: Honoraria, Other: Medical Advisory Board; Octapharma: Honoraria, Other: Medical Advisory Board; Bayer: Honoraria, Other: Medical Advisory Board.

<b><i>Introduction:</i></b> Unlike homozygous hemoglobin SS (HbSS) disease, stroke is a rare complication in hemoglobin SC (HbSC) disease. However, recent studies have demonstrated a high prevalence of silent stroke in HbSC disease. The factors associated with stroke and cerebral vasculopathy in the HbSC population are unknown. <b><i>Methods:</i></b> We conducted a retrospective study of all patients with sickle cell disease treated at the University of Missouri, Columbia, over an 18-year period (2000–2018). The goal of the study was to characterize the silent, overt stroke, and cerebral vasculopathy in HbSC patients and compare them to patients with HbSS and HbS/β thalassemia1 (thal) in this cohort. We also analyzed the laboratory and clinical factors associated with stroke and cerebral vasculopathy in the HbSC population. <b><i>Results:</i></b> Of the 34 HbSC individuals, we found that the overall prevalence of stroke and cerebral vasculopathy was 17.7%. Only females had evidence of stroke or cerebral vasculopathy in our HbSC cohort (33.3%, <i>p</i> = 0.019). Time-averaged means of maximum velocities were lower in the HbSC group than the HbSS group and did not correlate with stroke outcome. Among HbSC individuals, those with stroke and cerebral vasculopathy had a marginally higher serum creatinine than those without these complications (0.77 mg/dL vs. 0.88 mg/dL, <i>p</i> = 0.08). Stroke outcome was associated with recurrent vaso-occlusive pain crises (Rec VOCs) (75 vs. 25%, <i>p</i> = 0.003) in HbSC patients. The predominant cerebrovascular lesions in HbSC included microhemorrhages and leukoencephalopathy. <b><i>Conclusion:</i></b> There is a distinct subset of individuals with HbSC who developed overt, silent stroke, and cerebral vasculopathy. A female predominance and association with Rec VOCs were identified in our cohort; however, larger clinical trials are needed to identify and confirm specific clinical and laboratory markers associated with stroke and vasculopathy in HbSC disease.

Cardiac failure is one of the leading causes of death in sickle cell disease (SCD) and transfusion-dependent thalassemia (TDT). For this reason, early detection of silent cardiac dysfunction is crucial for treatment and prevention of heart failure. Speckle-tracking echocardiography (STE) is an easily accessible tool for analyzing myocardial function and this modality has increased sensitivity in detecting asymptomatic disease. Attenuation in cardiac strain has been correlated to early systolic dysfunction among patients with cardiomyopathies. This technique has not been consistently evaluated in children with SCD and TDT. Due to the role of anemia and siderosis in the pathology of cardiac dysfunction, we hypothesized that early myocardial dysfunction correlates with the degree of anemia and hyperferritinemia in SCD. We analyzed the clinical, echocardiographic, STE and laboratory parameters in SCD and compared them to children with TDT and normal controls. We retrospectively analyzed date from consecutive patients with SCD and TDT who received treatment at our institution from 2008 to 2018. Echocardiographic data from children with benign murmurs served as normal controls (NC). Data was independently verified by a pediatric cardiologist. Descriptive and correlation analysis were used; a p-value &lt; 0.05 was considered significant. Echocardiographic data were available for 77 SCD (HbSS and HbS/ ß 0 Thal), 25 TDT (ß 0/ ß 0 and ß +/ ß + Thal)and 138 NC. Mean hemoglobin (Hg) and ferritin values were 9.8 g/dl (6.8-14.6 g/dl); 392 ng/ml (19.3-8,3437.67 ng/ml), respectively for SCD patients and 9.3 g/dl (7-17.03 ng/dl); 2,960 ng/ml (13-13,831 ng/ml), respectively for TDT. Standard echocardiographic parameters left ventricular ejection fraction (LVEF), right VEF and LV shortening fraction (LVSF) were within the normal limits in SCD, TDT, and NC children. Significant differences were observed in the steady-state global circumferential strain (GCS) between the three groups SCD, TDT and NC [-26.5 (mean), 3.6 (SD); -27.6 (mean), 4.8(SD); -25.0 (mean), 3.6 (SD), respectively; p = 0.002] (Table 1). Subset analysis based on ferritin levels (&gt; or &lt; 1000 ng/ml), revealed no significant difference in GCS between the SCD or TDT groups (Table 2). However, global longitudinal strain (GLS) was significantly lower among SCD compared to TDT with ferritin levels greater than 1,000 ng/ml (Table 2). A positive correlation (r = 0.25, p = 0.046) was found between GLS and Hg in SCD patients (n=63) (Figure 1). No significant correlation was found between Hg and GLS in the TDT group (Figure 2). No significant correlation was found between GCS and Hg (r = 0.1, p = 0.42); GLS and GCS and ferritin in the SCD group. LVEF was found to be normal in patients with abnormal strain indices. Cardiac strain indices are abnormal in children with SCD and TDT compared to normal children. Significantly abnormal GLS was noted in hyperferritinemic SCD patients compared to TDT patients. A positive correlation between severity of anemia and GLS was observed in this study in SCD children. Based on these results, we speculate that therapies aimed at ameliorating anemia can potentially improve GLS and thus, early cardiac dysfunction in SCD patients. However, further studies are warranted to understand the contributory role of anemia and hyperferritinemia and its therapeutic implications on early myocardial dysfunction in SCD. Figure 1 Figure 1. Disclosures Sathi: Vertex Pharmaceuticals: Consultancy.