Search

Sickle cell disease (SCD) is the most common inherited blood disorder in the United States. It is a medically and socially complex, multisystem illness that affects individuals throughout the lifespan. Given improvements in care, most children with SCD survive into adulthood. However, access to adult sickle cell care is poor in many parts of the United States, resulting in increased acute care utilization, disjointed care delivery, and early mortality for patients. A dearth of nonmalignant hematology providers, the lack of a national SCD registry, and the absence of a centralized infrastructure to facilitate comparative quality assessment compounds these issues. As part of a workshop designed to train health care professionals in the skills necessary to establish clinical centers focused on the management of adults living with SCD, we defined an SCD center, elucidated required elements of a comprehensive adult SCD center, and discussed different models of care. There are also important economic impacts of these centers at an institutional and health system level. As more clinicians are trained in providing adult-focused SCD care, center designation will enhance the ability to undertake quality improvement and compare outcomes between SCD centers. Activities will include an assessment of the clinical effectiveness of expanded access to care, the implementation of SCD guidelines, and the efficacy of newly approved targeted medications. Details of this effort are provided.

Background: The data to support chronic automated red cell exchange (RCE) in sickle cell disease (SCD) outside of stroke prevention, is limited, especially in adults. Study Design and Methods: A retrospective analysis was conducted of patients with SCD who were referred for chronic RCE at our institution over a 10‐year period. Data that were evaluated included patient demographics, referral indications, and procedural details (e.g., vascular access, adverse events, etc.). In a subanalysis, the number of annual acute care encounters during 3 years of chronic RCE was compared with that in the year preceding the first RCE. Results: A total of 164 patients were referred for chronic RCE: median age was 28 years (interquartile range [IQR] = 22–36) at referral and 60% were female. Seventy (42.6%) were naïve to chronic transfusion (simple or RCE) prior to referral. The leading indications for referral were refractory pain (73/164, 44.5%) and iron overload (57/164, 34.7%). A total of 5090 procedures occurred during the study period (median = 19, IQR = 5–45). Of the 138 patients who had central vascular access, 8 (6%) and 16 (12%) had ≥1 central‐line‐related thrombosis and/or infection, respectively. Of those who were not RBC alloimmunized at initiation of RCE, 12/105 (11.4%) developed new antibodies during chronic RCE. In those 30 patients who were adherent to therapy for 3 years, there was no significant difference in acute care encounters following initiation of RCE. Conclusion: Prospective clinical trials are needed to determine which patients are most likely to benefit from chronic RCE and refine selection accordingly. See editorial on page 1385–1387, in this issue [ABSTRACT FROM AUTHOR]

The ESCAPED (Examining Sickle Cell Acute Pain in the Emergency vs Day Hospital) trial is an ongoing prospective study comparing outcomes of people with sickle cell disease (SCD) seeking care for acute pain management in either an emergency department or specialty infusion clinic. The objective of this paper is to describe the baseline characteristics and health care utilization of patients in the trial. This is a multicenter study across 4 US cities that enrolled all adults with SCD living within 60 miles (96.6 km) of a study site who were expected to have acute care utilization over the study period. Twenty-one percent of participants had no acute care visits in the first 12 months of follow-up. Using negative binomial regression, we describe subject characteristics that predict acute care utilization. Three hundred ninety-one subjects have completed 12 months of follow-up with a mean age of 34.5 years (standard deviation, 11.4), 60% are female. Fifty-four percent of subjects with hemoglobin SS disease and 46% with hemoglobin SC disease had 3 or more acute visits over the study period. The prevalence of chronic pain in this cohort was 68%. Predictors of higher rates of acute care utilization included being unemployed, having chronic pain, being on chronic transfusion therapy, having a history of stroke, and being on disability or on Medicaid. This is the first prospective cohort in the modern era, and it demonstrates much higher rates of acute care utilization than reported in the Cooperative Study of Sickle Cell Disease.

Treatment of vaso-occlusive crises (VOC) or events in sickle cell disease (SCD) remains limited to symptom relief with opioids. Animal models support the effectiveness of the pan-selectin inhibitor GMI-1070 in reducing selectin-mediated cell adhesion and abrogating VOC. We studied GMI-1070 in a prospective multicenter, randomized, placebo-controlled, double-blind, phase 2 study of 76 SCD patients with VOC. Study drug (GMI-1070 or placebo) was given every 12 hours for up to 15 doses. Other treatment was per institutional standard of care. All subjects reached the composite primary end point of resolution of VOC. Although time to reach the composite primary end point was not statistically different between the groups, clinically meaningful reductions in mean and median times to VOC resolution of 41 and 63 hours (28% and 48%, P = .19 for both) were observed in the active treatment group vs the placebo group. As a secondary end point, GMI-1070 appeared safe in acute vaso-occlusion, and adverse events were not different in the two arms. Also in secondary analyses, mean cumulative IV opioid analgesic use was reduced by 83% with GMI-1070 vs placebo (P = .010). These results support a phase 3 study of GMI-1070 (now rivipansel) for SCD VOC. This trial was registered at www.clinicaltrials.gov as #NCT01119833.

ImportanceThe association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain.ObjectiveTo describe the relationship between SCT and CKD and albuminuria in self-identified African Americans.Design, setting, and participantsUsing 5 large, prospective, US population-based studies (the Atherosclerosis Risk in Communities Study [ARIC, 1987-2013; n = 3402], Jackson Heart Study [JHS, 2000-2012; n = 2105], Coronary Artery Risk Development in Young Adults [CARDIA, 1985-2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA, 2000-2012; n = 1620], and Women's Health Initiative [WHI, 1993-2012; n = 8000]), we evaluated 15,975 self-identified African Americans (1248 participants with SCT [SCT carriers] and 14,727 participants without SCT [noncarriers]).Main outcomes and measuresPrimary outcomes were CKD (defined as an estimated glomerular filtration rate [eGFR] of 30 mg/g or albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately for each cohort and were subsequently meta-analyzed using a random-effects model.ResultsA total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of 14,722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs 1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers [19.6%]) had albuminuria during the study period. Individuals with SCT had an increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34-1.84]; absolute risk difference [ARD], 7.6% [95% CI, 4.7%-10.8%]), incident CKD (OR, 1.79 [95% CI, 1.45-2.20]; ARD, 8.5% [95% CI, 5.1%-12.3%]), and decline in eGFR (OR, 1.32 [95% CI, 1.07-1.61]; ARD, 6.1% [95% CI, 1.4%-13.0%]) compared with noncarriers. Sickle cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49-2.31]; ARD, 12.6% [95% CI, 7.7%-17.7%]).Conclusions and relevanceAmong African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These findings suggest that SCT may be associated with the higher risk of kidney disease in African Americans.

Summary: In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD‐related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared the characteristics of subjects with new or worsening proteinuria (NWP) during pregnancy to those without. We then constructed receiver operating characteristic (ROC) curves to determine the blood pressure (BP) that best identifies those with NWP. The SBP or DBP thresholds which maximized sensitivity and specificity were 120 mmHg SBP (sensitivity: 55.2%, specificity: 73.5%) and 70 mmHg DBP (sensitivity: 27.6%, specificity: 67.7%). The existing BP threshold of 140/90 mmHg lacked sensitivity in both genotype groups (HbSS/HbSβ0: SBP = 21% sensitive, DBP = 5.3% sensitive; HbSS/HbSβ+: SBP = 10% sensitive, DBP = 0% sensitive). Finally, percent change in SBP, DBP and MAP were all poor tests for identifying NWP. Existing BP thresholds used to diagnose hypertensive disorders of pregnancy (HDP) are not sensitive for pregnant people with SCD. For this population, lowering the BP threshold that defines HDP may improve identification of those who need increased observation, consideration of early delivery and eclampsia prophylaxis. [ABSTRACT FROM AUTHOR]

Summary: In this retrospective cohort study of singleton pregnancies in people with sickle cell disease (SCD) delivered at two academic centres between 1990 and 2021, we collected demographic and SCD‐related data, pregnancy outcomes, and the highest systolic and diastolic blood pressure (SBP and DBP) at seven time periods. We compared blood pressure values and trajectories in the composite cohort and in each genotype group to control values in a non‐SCD pregnancy dataset. There were 290 pregnancies among 197 patients with SCD. Sixteen per cent (n = 47) of pregnancies had a hypertensive disorder of pregnancy (HDP); the rates did not differ by genotype. The mean SBP and DBP were lower in the HbSS/HbSβ0 group than in the non‐SCD control group at all timepoints. Mean SBP and DBP trajectories were similar between the HbSS/HbSβ0 group and non‐SCD controls, whereas the mean SBP and DBP in the HbSC/HbSβ+ group decreased between the first and second trimesters and plateaued between the second and third trimesters. There were no differences in blood pressure trajectory by haemoglobin >/< 10 gm/dL or by chronic transfusion status. Overall, pregnant people with SCD have lower blood pressure than unaffected pregnant people, raising the possibility that HDP are underdiagnosed, particularly in people with HbSS/HbSβ0. [ABSTRACT FROM AUTHOR]

Background: Red blood cell (RBC) transfusion remains a major treatment for sickle cell disease (SCD). Patients with SCD have a high prevalence of renal impairment and cardiorespiratory disease, conferring risk of transfusion‐associated circulatory overload (TACO). Study Design and Methods: We describe an approach, titled euvolemic automated transfusion (EAT), to transfuse SCD patients with severe anemia who are at risk of TACO. In EAT, plasmapheresis is performed using donor RBCs, rather than albumin or plasma, as replacement fluid. Euvolemia is maintained. A retrospective analysis was conducted of patients with SCD who underwent EAT at our institution over a 10‐year period, to evaluate the efficacy and safety of EAT. Results: Eleven SCD patients underwent 109 EAT procedures (1–59 procedures per patient). The median age was 42 years (IQR = [30–49]) and 82% (n = 9) were female. Most (82%; n = 9) patients had severe chronic kidney disease and 55% (n = 6) had heart failure. One (9%) patient had a history of life‐threatening TACO. Mean pre‐ and post‐procedure Hct values were 19.8% (SD ± 1.6%) and 29.1% (SD ± 1.4%), respectively. The average Hct increment was 3.2% per RBC unit. Only two EAT‐related complications were recorded during the 109 procedures: central line‐associated infection and citrate toxicity (muscle cramping). EAT used an average of two RBC units less than that projected for standard automated RBC exchange. Conclusion: Our findings suggest that EAT is safe and effective to treat patients with SCD and severe anemia, who are at risk for TACO. EAT requires fewer RBC units compared to automated RBC exchange. [ABSTRACT FROM AUTHOR]