Survival of transfused red blood cells from a donor with alpha-thalassemia trait in a recipient with sickle cell disease.

BACKGROUND: Post-transfusion survival of donor red blood cells (RBCs) is important for effective chronic transfusion therapy in conditions including sickle cell disease (SCD). Biotin labeling RBCs allows direct in vivo measurement of multiple donor RBC units simultaneously post-transfusion. STUDY DESIGN AND METHODS: In an observational trial of patients with SCD receiving monthly chronic transfusion therapy, aliquots of RBCs from one transfusion episode were biotin-labeled and infused along with the unlabeled RBC units. Serial blood samples were obtained to measure RBC survival. Donor units were tested for RBC indices, hemoglobin fractionation, and glucose-6-phosphate dehydrogenase (G6PD) enzyme activity. For microcytic donor RBCs (MCV < 70 fL), HBA1 and HBA2 genetic testing was performed on whole blood. RESULTS: We present one recipient, a pediatric patient with SCD and splenectomy who received two RBC units with aliquots from each unit labeled at distinct biotin densities (2 and 18 µg/mL biotin). One donor unit was identified to have microcytosis (MCV 68.5 fL after biotinylation); whole blood sample obtained at a subsequent donation showed 2-gene deletion alpha-thalassemia trait (ɑ-3.7kb/ɑ-3.7kb) and normal serum ferritin. G6PD activity was >60% of normal mean for both. The RBCs with alpha-thalassemia RBC had accelerated clearance and increased surface phosphatidylserine post-transfusion, as compared with the normocytic RBC (half life 65 vs. 86 days, respectively). DISCUSSION: Post-transfusion RBC survival may be lower for units from donors with alpha-thalassemia trait, although the impact of thalassemia trait donors on transfusion efficacy requires further study.

Post-transfusion biotin-labeled red blood cell survival studies in pediatric sickle cell disease with antibodies of uncertain significance.

BACKGROUND: Red blood cell (RBC) antibodies are common in multiply transfused patients with sickle cell disease (SCD). Unlike RBC alloantibodies, the potential of autoantibodies to cause post-transfusion hemolysis may be uncertain. Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies. Antibodies to biotinylated RBC (B-RBC) occasionally are detected after exposure, which may impact B-RBC survival in subsequent RCS studies. STUDY DESIGN AND METHODS: Pediatric patients with SCD receiving monthly chronic transfusions underwent RCS studies, receiving aliquots of allogeneic RBC labeled at distinct densities of biotin (2-18 µg/mL). B-RBC survival was followed for 4 months post-transfusion, and B-RBC antibody screening for 6 months. Patients with warm autoantibodies (WAA) or B-RBC antibodies are reported here. RESULTS: RBC antibodies were detected during RCS in four patients: one with WAA, one with WAA followed by B-RBC-specific antibodies, and two with transient B-RBC antibodies within the first 5 weeks of exposure. B-RBC half-lives (T50) ranged 37.6-61.7 days (mean 47.8 days). There was no evidence of increased hemolysis or accelerated B-RBC clearance in the presence of WAA or B-RBC antibodies. DISCUSSION: Biotinylation of allogenic RBC can be used to assess the possible effects of RBC antibodies on transfusion survival in individual cases, particularly when it is uncertain if the detected antibodies may result in hemolysis. In the cases presented here, neither WAA nor B-RBC antibodies were associated with significant shortening of B-RBC survival in individuals with SCD.

RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA.

BACKGROUND: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors. STUDY DESIGN AND METHODS: We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA. Genotyping was performed with RHD and RHCE BeadChip arrays and targeted assays. RESULTS: Prevalence of overall and Rh-specific alloimmunization varied among institutions, ranging from 5% to 41% (p = .0035) and 5%-33% (p = .0002), respectively. RH genotyping demonstrated that 33% RHD and 57% RHCE alleles were variant in this cohort. Patients with RHCE alleles encoding partial e antigens had higher rates of anti-e identified than those encoding at least one conventional e antigen (p = .0007). There was no difference in anti-D, anti-C, or anti-E formation among patients with predicted partial or altered antigen expression compared to those with conventional antigens, suggesting that variant Rh on donor cells may also stimulate alloimmunization to these antigens. DISCUSSION: These results highlight variability in alloimmunization rates and suggest that a molecular approach to Rh antigen matching may be necessary for optimal prevention of alloimmunization given the high prevalence of variant RH alleles among both patients and Black donors.

Pneumococcal infections in children with sickle cell disease before and after pneumococcal conjugate vaccines.

Children with sickle cell disease (SCD) are at increased risk of invasive pneumococcal disease (IPD). Over 25 years, the Georgia Emerging Infections Program/Centers for Disease Control and Prevention Active Bacterial Core Surveillance network identified 104 IPD episodes among 3707 children with hemoglobin SS (HbSS) or HbSC aged <10 years, representing 6% of IPD in Black or African American children residing in Metropolitan Atlanta (reference population). Children with IPD and HbSS/SC were older than those with IPD in the reference population (P < .001). From 1994-1999 to 2010-2018, IPD declined by 87% in children with HbSS aged 0 to 4 years, and by 80% in those aged 5 to 9 years. However, IPD incidence rate ratios when comparing children with SCD with the reference population increased from 20.2 to 29.2 over these periods. Among children with HbSS and IPD, death declined from 14% to 3% after 2002, and meningitis declined from 16% to 8%. Penicillin resistance was more prevalent in children with SCD before 7-valent pneumococcal conjugate vaccine (PCV7) licensure. After 2010, all IPD serotypes were not included in the 13-valent PCV (PCV13). Within 3 years of vaccination, the effectiveness of the 23-valent pneumococcal polysaccharide vaccine (PPSV23) against non-PCV13 serotypes included in PPSV23 plus 15A/15C was 92% (95% confidence interval, 40.8- 99.0, P = .014; indirect-cohort effect adjusted for age and hydroxyurea). PPSV23 would cover 62% of non-PCV13 serotype IPD in children with SCD, whereas PCV15, PCV20, and PCV21/V116 (in development) could cover 16%, 51%, and 92%, respectively. Although less frequent, IPD remains a life-threatening risk in children with SCD. Effective vaccines with broader coverage could benefit these children.

Novel approaches to measure transfusion effectiveness.

PURPOSE OF REVIEW: This review encompasses different considerations of transfusion effectiveness based upon clinical scenario and transfusion indication. Tissue oxygenation, cerebral metabolic oxygen use, and red blood cell (RBC) survival are important elements of transfusion effectiveness in individuals with acute and chronic transfusion requirements. RECENT FINDINGS: Noninvasive measures of tissue and cerebral oxygen extraction include near-infrared spectroscopy (NIRS) and specialized MRI sequences. RBC survival timepoints including 24 h posttransfusion recovery, 50% recovery timepoint, and mean potential lifespan may be accurately measured with biotin-labeling of RBC prior to transfusion. Labeling at different cell surface densities allows survival of multiple RBC populations to be determined. SUMMARY: Although past trials of optimal transfusion thresholds have focused on Hb as a singular marker for transfusion needs, measures of oxygenation (via NIRS or specialized MRI) and RBC survival (via biotin labeling) provide the opportunity to personalize transfusion decisions to individual patient's acute health needs or chronic transfusion goals.

Requests for Directed Blood Donations.

This Ethics Rounds presents a request for directed blood donation. Two parents feel helpless in the setting of their daughter's new leukemia diagnosis and want to directly help their child by providing their own blood for a transfusion. They express hesitancy about trusting the safety of a stranger's blood. Commentators assess this case in the setting of blood as a scarce community resource during a national blood shortage. Commentators review the child's best interest, future risks, and harm-benefit considerations. Commentators recognize the professional integrity, humility, and courage of the physician to admit his own lack of knowledge on the subject and to seek help rather than claim directed donation is not possible without further investigation into options. Shared ideals such as altruism, trust, equity, volunteerism, and solidarity are recognized as values relevant to sustainment of a community blood supply. Pediatric hematologists, a blood bank director, transfusion medicine specialists, and an ethicist conclude that directed donation is only justified by lower risks to the recipient in particular circumstances.

Influenza Vaccination Receipt in Pediatric Patients With Cancer or Sickle Cell Disease.

BACKGROUND: Influenza causes greater morbidity in children with cancer or sickle cell disease (SCD). Literature on influenza vaccination receipt for these populations is limited in low-vaccination states. Outpatient interventions improve vaccine receipt but isolated inpatient interventions remain unstudied. PROCEDURE: We reviewed influenza vaccine receipt of children with cancer or SCD treated at Children's Healthcare of Atlanta during three influenza seasons. We implemented a clinical decision support intervention during an influenza season and compared influenza vaccine receipt preintervention and postintervention among admitted children. RESULTS: The oncology cohort (N=1548, 60% to 62%) and the SCD cohort (N=2549, 61% to 65%) had similar-to-higher vaccination receipt to the United States (58% to 64%, P =0.01 to 0.79) and Georgia (51% to 56%, P <0.01). The intervention did not significantly improve vaccination receipt for admitted children with cancer (40% vs. 56%, P =0.05 to 0.88) or SCD (44% vs. 56%, P =0.01). Regression modeling also found no significant increase in vaccine receipt (hematologic malignancy: 0.8 [0.73 to 0.98], solid tumor: 0.9 [0.80 to 1.90], central nervous system tumor: 0.9 [0.71 to 1.14], SCD: 0.9 [0.85 to 0.99]). CONCLUSIONS: Children with cancer and SCD have similar-to-greater influenza vaccination receipt compared with Georgia and the United States. An inpatient intervention did not significantly improve influenza vaccine receipt in these patient cohorts. Future studies are needed to identify alternative approaches to improving vaccine receipt in these cohorts.

Glucose-6-phosphate dehydrogenase deficiency is more prevalent in Duffy-null red blood cell transfusion in sickle cell disease.

BACKGROUND: Resistance to malaria infection may be conferred by erythrocyte genetic variations including glucose-6-phosphate dehydrogenase (G6PD) deficiency and lack of Duffy antigens. In red blood cell (RBC) transfusion, G6PD deficiency may shorten transfusion survival. Because Duffy-null units are commonly transfused in sickle cell disease (SCD) due to antigen matching protocols, we examined whether Duffy-null donor RBC units have a higher prevalence of G6PD deficiency. MATERIALS AND METHODS: Pediatric patients with SCD on chronic transfusion therapy were followed prospectively for multiple transfusions. RBC unit segments were collected to measure G6PD activity and RBC genotyping. The decline in donor hemoglobin (ΔHbA) following transfusion was assessed from immediate posttransfusion estimates and HbA measurements approximately 1 month later. RESULTS: Of 564 evaluable RBC units, 59 (10.5%) were G6PD deficient (23 severe, 36 moderate deficiency); 202 (37.6%) units were Duffy-null. G6PD deficiency occurred in 40 (19.8%) Duffy-null units versus 15 (4.5%) Duffy-positive units (p < .0001). In univariate analysis, the fraction of Duffy-null RBC units per transfusion was associated with greater decline in HbA (p = .038); however, in multivariate analysis, severe G6PD deficiency (p = .0238) but not Duffy-null RBC (p = .0139) were associated with ΔHbA. CONCLUSION: Selection of Duffy-null RBC units may result in shorter in vivo survival of transfused RBCs due to a higher likelihood of transfusing units from G6PD deficient donors.

Procedural adverse events in pediatric patients with sickle cell disease undergoing chronic automated red cell exchange.

BACKGROUND: Chronic automated red cell exchange (RCE) is increasingly employed for sickle cell disease (SCD). There is a paucity of data on the incidence of RCE adverse events (AEs) and potential patient and procedural risk factors for AEs. METHODS: A retrospective review of pediatric SCD patients receiving chronic RCE over 3 years was performed to determine the frequency of AEs and identify procedural and patient AE risk factors. AE incidence, AE rate, incidence rate ratios (IRRs), and relative risks (RRs) were calculated based on various procedural and patient characteristics by univariable (UV) and multivariable (MV) analyses. RESULTS: In 38 patients receiving 760 procedures, there were 150 (19.7%) AEs, 36 (4.7%) were symptomatic AEs. AE rates were 20.2 [95% CI 17.2, 23.6] and 4.8 [95% CI 3.49, 6.70] per 100 person months for AEs and symptomatic AEs, respectively. AE incidences were: hypocalcemia (117; 15.4%), dizziness (22; 3.0%), hypotension (15; 2.0%), and nausea (14; 1.8%). Patients with baseline Hct ≥30% experienced more total AEs and symptomatic AEs. Patients with pre-procedure systolic BP <50th percentile, severe CNS vasculopathy, and non-SCA genotype (HbSC or Sß+ thalassemia) exhibited more total AEs. IHD depletion was not associated with an increased incidence of AEs or symptomatic AEs. CONCLUSION: SCD patients with Hct ≥30%, systolic BP <50th percentile, severe CNS vasculopathy, and possibly non-SCA genotype may be at higher risk for RCE-related AEs. The effect of IHD on AE risk is likely minimal. Individualized AE risk assessment should be performed in all SCD patients undergoing chronic automated RCE.

The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question.

Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count >10 × 103/µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

Bloodstream Infections in Children With Sickle Cell Disease: 2010-2019.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bloodstream infections (BSIs), mainly because of functional asplenia. Immunizations and antibiotic prophylaxis have reduced the prevalence of invasive bacterial infections, but contemporary analysis of BSI in children with SCD is limited. METHODS: We conducted a retrospective cohort study of children aged <18 years with SCD who had blood cultures collected at our institution from 2010 to 2019 to identify BSI. Probable contaminant organisms were identified and not included as BSI. We calculated the annual incidence of BSI at our institution with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: There were 2694 eligible patients with 19 902 blood cultures. Excluding repeated cultures and contaminant cultures, there were 156 BSI episodes in 144 patients. The median age at BSI was 7.5 years. The average incidence rate of BSI was 0.89 per 100 person-years (95% CI 0.45-1.32). The most common pathogens were Streptococcus pneumoniae (16.0%), Streptococcus viridans group (9.0%), Escherichia coli (9.0%), Staphylococcus aureus (7.7%), Bordetella holmesii (7.7%), Haemophilus influenzae (7.1%), and Salmonella species (6.4%). Odds of BSI were higher with sickle cell anemia genotypes (odds ratio [OR] 1.88; 95% CI 1.20-2.94) and chronic transfusions (OR 2.66; 95% CI 1.51-4.69) and lower with hydroxyurea (OR 0.57; 95% CI 0.39-0.84). CONCLUSIONS: BSI remains a risk for children with SCD. Overall incidence, risk factors, and spectrum of pathogens are important considerations to guide prevention and empirical treatment of suspected infection in SCD.

The ASH-ASPHO Choosing Wisely Campaign: 5 hematologic tests and treatments to question.

Choosing Wisely is a medical stewardship and quality-improvement initiative led by the American Board of Internal Medicine Foundation in collaboration with leading medical societies in the United States. The American Society of Hematology (ASH) has been an active participant in the Choosing Wisely project. In 2019, ASH and the American Society of Pediatric Hematology/Oncology (ASPHO) formed a joint task force to solicit, evaluate, and select items for a pediatric-focused Choosing Wisely list. By using an iterative process and an evidence-based method, the ASH-ASPHO Task Force identified 5 hematologic tests and treatments that health care providers and patients should question because they are not supported by evidence, and/or they involve risks of medical and financial costs with low likelihood of benefit. The ASH-ASPHO Choosing Wisely recommendations are as follows: (1) avoid routine preoperative hemostatic testing in an otherwise healthy child with no previous personal or family history of bleeding, (2) avoid platelet transfusion in asymptomatic children with a platelet count 10 × 103 /µL unless an invasive procedure is planned, (3) avoid thrombophilia testing in children with venous access-associated thrombosis and no positive family history, (4) avoid packed red blood cells transfusion for asymptomatic children with iron deficiency anemia and no active bleeding, and (5) avoid routine administration of granulocyte colony-stimulating factor for prophylaxis of children with asymptomatic autoimmune neutropenia and no history of recurrent or severe infections. We recommend that health care providers carefully consider the anticipated risks and benefits of these identified tests and treatments before performing them.

Thrombocytosis with acquired von Willebrand disease in an adolescent with sickle cell disease.

Thrombocytosis is common in sickle cell disease and may contribute to vaso-occlusion. Hydroxyurea treats extreme thrombocytosis. Acquired von Willebrand disease should be considered prior to aspirin therapy.

The burden of respiratory syncytial virus infections among children with sickle cell disease.

BACKGROUND: Although respiratory syncytial virus (RSV) is the leading cause of pediatric lower respiratory tract infections, the burden of RSV in children with sickle cell disease (SCD) is unknown. METHODS: We conducted a retrospective, nested, case-control study of children with SCD <18 years who had respiratory viral panels (RVPs) performed at Children's Healthcare of Atlanta from 2012 to 2019. We abstracted the medical records to describe the demographics, clinical features, and outcomes of children who tested positive for RSV (cases) versus children who tested negative (controls). We calculated the annual incidence of RSV and related hospitalization rates with 95% confidence intervals (CIs) and used multivariate logistic regression to evaluate associations. RESULTS: We identified 3676 RVP tests performed on 2636 patients over seven respiratory seasons resulting in 219/3676 (6.0%) RSV-positive tests among 160/2636 (6.1%) patients. The average annual incidence of laboratory-confirmed RSV infection among children with SCD was 34.3 (95% CI 18.7-49.8) and 3.8 (95% CI 0.5-7.0) cases per 1000 person-years for those <5 years and 5-18 years, respectively. The RSV-related hospitalization rate for children <5 years was 20.7 (95% CI 8.5-32.8) per 1000 person-years. RSV-positive cases were significantly younger than RSV-negative patients (3.8 years vs 7.6 years, P < .001). Of RSV-positive cases, 22 (13.8%) developed acute chest syndrome and nine (5.6%) required intensive care, which was not significantly different from RSV-negative children with SCD. CONCLUSION: RSV infections are common in children with SCD with higher burden in younger patients. RSV is associated with considerable morbidity, including higher rates of hospitalization compared to the general population.

Microbiology and radiographic features of osteomyelitis in children and adolescents with sickle cell disease.

BACKGROUND: Children with sickle cell disease (SCD) are at increased risk for bacterial infections including osteomyelitis (OM). Fever and bone pain, key presenting symptoms of OM, are common in SCD, thus complicating diagnosis. We reviewed presentation, imaging features, and microbiologic etiologies of children with SCD treated for OM. METHODS: The comprehensive SCD clinical database of children and adolescents with SCD followed at a single, large tertiary pediatric center were searched to identify all diagnostic coding for potential cases of osteomyelitis in children ages 6 months to 21 years from 2010 to 2019. Medical charts were reviewed to determine OM diagnostic probability based on radiographic and microbiologic findings and the duration of prescribed antibiotic treatment for OM. RESULTS: Review of 3553 patients (18 039 person-years) identified 20 episodes of probable OM in 19 children. Magnetic resonance imaging (MRI) findings to support OM were definitive in 4/19 (21%), probable in 10/19 (53%), suspected in 5/19 (26%), based on blinded radiologist review. Blood and/or operative cultures from bone and tissue debridement isolated Salmonella species in seven (35%) cases and methicillin-susceptible Staphylococcus aureus (MSSA) in two (10%). Six patients received antibiotic treatment prior to obtainment of cultures. Of culture-positive cases, MRI findings for OM were definitive or probable in six of nine (67%), suspected in three of nine (33%). CONCLUSIONS: Distinction between OM and sickle-related bone infarct or vasoocclusion is difficult based on imaging findings alone. Early attainment of blood and operative cultures increases the likelihood of identifying and adequately treating OM.

Influenza vaccine effectiveness and disease burden in children and adolescents with sickle cell disease: 2012-2017.

BACKGROUND: Data are limited on the burden of influenza and seasonal influenza vaccine effectiveness (VE) in children with sickle cell disease (SCD). METHODS: We used a prospectively collected clinical registry of SCD patients 6 months to 21 years of age to determine the influenza cases per 100 patient-years, vaccination rates, and a test-negative case-control study design to estimate influenza VE against medically attended laboratory-confirmed influenza infection. Influenza-positive cases were randomly matched to test-negative controls on age and influenza season in 1:1 ratio. We used adjusted logistic regression models to compare odds ratio (OR) of vaccination in cases to controls. We calculated VE as [100% × (1 - adjusted OR)] and computed 95% confidence intervals (CIs) around the estimate. RESULTS: There were 1037 children with SCD who were tested for influenza, 307 children (29.6%) had at least one influenza infection (338 infections, incidence rate 3.7 per 100 person-years; 95% CI, 3.4-4.1) and 56.2% of those tested received annual influenza vaccine. Overall VE pooled over five seasons was 22.3% (95% CI, -7.3% to 43.7%). Adjusted VE estimates ranged from 39.7% (95% CI, -70.1% to 78.6%) in 2015/2016 to -5.9% (95% CI, -88.4% to 40.4%) in the 2016/17 seasons. Influenza VE varied by age and was highest in children 1-5 years of age (66.6%; 95% CI, 30.3-84.0). Adjusted VE against acute chest syndrome during influenza infection was 39.4% (95% CI, -113.0 to 82.8%). CONCLUSIONS: Influenza VE in patients with SCD varies by season and age. Multicenter prospective studies are needed to better establish and monitor influenza VE among children with SCD.

Progression of albuminuria in patients with sickle cell anemia: a multicenter, longitudinal study.

Sickle cell nephropathy results in chronic kidney disease (CKD), which is associated with significant morbidity and mortality in sickle cell anemia (SCA). Albuminuria is an early manifestation of sickle nephropathy; however, little is known about progression of albuminuria or its correlation with glomerular filtration rate (GFR) decline or CKD. We studied nephropathy progression in 303 SCA participants in a prospective, multicenter, longitudinal study. We collected steady-state urine and serum samples yearly and assessed albumin/creatinine ratio (ACR), estimated GFR (eGFR), and SCA and nephropathy biomarkers. Participants with albuminuria (ACR ≥30 mg/g) for ≥2 annual measurements were classified as having persistent albuminuria (PA). At baseline (mean age, 21 years; range, 2-64 years), 32% had albuminuria. In longitudinal multivariate analysis, ACR was associated with sex, anemia, older age, and higher bilirubin and kidney injury molecule-1 levels. Albuminuria increased with age by 3.5 mg/g per year (P < .0001). Of 175 participants with ≥3 annual samples, 81% with baseline albuminuria ≥100 mg/g developed PA. Decreased eGFR and adult CKD were associated with PA (P = .002 and P = .02, respectively), but not with baseline albuminuria. Rate of eGFR decline was steeper among adults (but not children) with albuminuria, compared with those without (P = .02). Participants with PA were more likely to have rapid eGFR decline compared with those without (P = .03). In this longitudinal study, albuminuria progressed with age, and adults with albuminuria had worse eGFR decline than those without. Albuminuria ≥100 mg/g predicted PA, which was associated with rapid eGFR decline and CKD development in adults with SCA. This trial was registered at www.clinicaltrials.gov as #NCT02239016.

Patient and family experience with chronic transfusion therapy for sickle cell disease: A qualitative study.

BACKGROUND: There is a limited understanding of the patient and family experience of Chronic Transfusion Therapy (CTT) for prevention of complications of Sickle Cell Disease (SCD). We sought to understand patient and family experience with CTT using qualitative methods. METHODS: Fifteen parents of children < 18 years old and nine children 12-18 years old with SCD who were receiving CTT for > 1 year were interviewed using a semi-structured interview format, and interviews were analyzed using open coding methods. RESULTS: Four themes created a narrative of the patient and family experience of CTT: 1) Burden of CTT, 2) Coping with CTT, 3) Perceived benefits and risks of CTT, and 4) Decision making regarding CTT. Participants reported substantial burden of CTT, including the impact of CTT on daily life and family, distress about venous access, burden of chelation therapy, and anxiety about CTT complications. Participants described how they coped with CTT. Participants reported increased energy, decreased pain, fewer hospitalizations, and stroke prevention with CTT, but also recognized complications of CTT, though awareness was limited in adolescents. Parents described sharing in the informed decision-making process with their healthcare provider about CTT, but adolescent patient participants reported that they were not involved in this process. CONCLUSIONS: CTT is associated with significant patient and family burden. Support from family, healthcare providers and school may help individuals cope with some of this burden. These findings provide the basis for future studies to identify strategies to mitigate the burden of CTT and improve the patient experience with this therapy. Future studies should also systematically assess patient knowledge about the key components of CTT and chelation using quantitative assessments.

Examining the Role of Complement in Predicting, Preventing, and Treating Hemolytic Transfusion Reactions.

Red blood cell (RBC) transfusion is a critical component of optimal management for a broad range of conditions. Regardless of the indication, pretransfusion testing is required to appropriately match RBC donors and recipients to provide immunologically compatible blood. Although this approach is effective in the vast majority of situations, occasionally, patients will inadvertently receive an incompatible RBC transfusion, which can result in a hemolytic transfusion reaction (HTR). In addition, patients with life-threatening anemia and a complex alloantibody profile, which precludes rapid procurement of compatible RBCs, may also receive incompatible RBCs, placing them at risk for an HTR. Despite the rarity of these clinical situations, when incompatible blood transfusion results in an HTR, the consequences can be devastating. In this review, we will explore the challenges associated with actively preventing and treating acute HTRs following incompatible RBC transfusion. In doing so, we will focus primarily on the role of complement, not only as a key player in HTRs, but also as a potential target for the prevention and treatment of HTRs.