Transient neonatal hemolytic anemia due to the novel gamma globin gene mutation HBG2:C.290T>C, p.Leu97Pro (hemoglobin Wareham).

Unstable gamma globin variants can cause transient neonatal hemolytic anemia. We have identified a novel variant in a newborn who presented with jaundice and anemia requiring phototherapy and red blood cell transfusion. The patient was found to be heterozygous for the mutation HGB2:c.290T>C, p.Leu97Pro, which we have termed hemoglobin (Hb) Wareham. This substitution is expected to generate an unstable hemoglobin with increased oxygen affinity based on the homologous mutation previously described in the beta globin gene, which is termed as Hb Debrousse. The patient fully recovered by 9 months of age as expected with the transition from fetal to adult hemoglobin.

Transcranial Doppler velocity and brain MRI/MRA changes in children with sickle cell anemia on chronic transfusions to prevent primary stroke.

BACKGROUND: Chronic transfusions help prevent primary stroke in children with sickle cell anemia (SCA) and abnormal transcranial Doppler (TCD) velocities. However, the effects of transfusions on TCD velocities and brain MRI/MRA findings are incompletely described. PROCEDURE: We reviewed TCD and brain MRI/MRA results in 27 children with SCA and abnormal TCD velocities receiving transfusions to prevent primary stroke. All TCDs were performed by a single examiner, immediately prior to a scheduled transfusion. We also examined the effects of laboratory and clinical parameters on TCD responses to transfusion therapy. RESULTS: For the whole cohort, the average pre-transfusion HbS on transfusions was 31.7 ± 12.3%. The most significant decline in TCD velocities occurred within 10 months of starting transfusions. Follow-up TCD values trended upward with increasing pre-transfusion %HbS levels while on treatment. Half of the children had persistent conditional/abnormal TCD velocities despite transfusions and 28% had new/progressive stenosis on MRA, but none had primary stroke during 73 patient-years of follow-up. CONCLUSIONS: For children with SCA and abnormal TCD velocities, transfusions lower TCD velocities and help prevent stroke, but do not always result in normal velocities or protect against progression of cerebral vasculopathy. Improved adherence to transfusion goals may improve on-treatment TCD velocities.

Increasing COVID-19 Vaccination Rates for Children With Sickle Cell Disease.

BACKGROUND: The COVID-19 vaccine is important for children with sickle cell disease (SCD). This quality improvement project's objective was to increase the proportion of children with SCD receiving ≥2 COVID-19 vaccine doses to ≥70% by June 2022. METHODS: We used the Model for Improvement framework. We assessed COVID-19 vaccination rates biweekly. Three plan-do-study-act cycles focusing on patient education, provider awareness, and access were performed. Process measures included the outcome of outreach calls and educational video views. Missed clinic appointments was our balancing measure. Line graphs and statistical process control charts were used to track changes. Interrupted time series was used to model implementation rates while accounting for preexisting trends. RESULTS: A total of 243 patients were included. During the preintervention (September 2021-January 2022) and intervention periods (February 2022-June 2022), overall vaccination rates increased from 33% to 41% and 41% to 64%, respectively. Mean vaccination rate in eligible children in each 2-week period increased from 2.1% to 7.2%. The achieved vaccination rate was 11% greater than predicted for patients with SCD. For the general population the achieved vaccination rate was 23% lower than predicted. The proportion of missed visits did not change (9.0% vs. 9.6%). During outreach calls, 10 patients (13.5%) booked a vaccine. Forty percent of patients watched the promotional video. CONCLUSIONS: A significant number of patients with SCD are not vaccinated against COVID-19. Targeting misinformation and improving vaccine access aided in increasing vaccination. Additional interventions are needed as a large number of patients remain unvaccinated.

Bone marrow transplant options and preferences in a sickle cell anemia cohort on chronic transfusions.

BACKGROUND: Bone marrow transplantation (BMT) using human leukocyte antigen (HLA)-matched sibling donors can be curative for children with sickle cell anemia (SCA). However, minimal data exist regarding availability of HLA-identical matched siblings for transplant-eligible children, and family interest in pursuing transplantation. METHODS: We retrospectively analyzed a pediatric SCA cohort receiving chronic transfusions between July 2004 and January 2011. Data were analyzed regarding the number of full siblings and half-siblings, availability, and family interest in HLA testing the full siblings, and interest in proceeding with HLAmatched transplantation. RESULTS: Among 113 patients, 46 (41%) had at least 1 full sibling and 40 (35%) had an unaffected full sibling who could serve as a BMT donor. The families of 23 of these patients (58%) agreed to HLA-type sibling, 8 of whom (35%) were matched. Transfusion indications for families agreeing to HLA typing included stroke (46%) abnormal TCD (29%), acute chest syndrome (21%), and other CNS reasons (4%). Common reasons to decline HLA typing or transplantation included fear of the process, toxicities of the procedure, and comfort with current quality of life on transfusions. Only 8 of 113 (7%) were eligible for matched BMT, and only 3 (3%) underwent HLA-matched transplantation. Two unmatched children received haploidentical transplantation. CONCLUSIONS: Most families of children with SCA on chronic transfusions choose to proceed with HLA typing. However, when a matched sibling was identified, most families declined to proceed with matched-sibling transplantation. Discussing BMT as a treatment option, offering HLA typing and identifying barriers may improve acceptance of this treatment modality.

The impact of preparation and support procedures for children with sickle cell disease undergoing MRI.

BACKGROUND: Children with sickle cell disease (SCD) often undergo MRI studies to assess brain injury or to quantify hepatic iron. MRI requires the child to lie motionless for 30-60 min, thus sedation/anesthesia might be used to facilitate successful completion of exams, but this poses additional risks for SCD patients. To improve children's ability to cope with MRI examinations and avoid sedation, our institution established preparation and support procedures (PSP). OBJECTIVE: To investigate the impact of PSP in reducing the need for sedation during MRI exams among children with SCD. MATERIALS AND METHODS: Data on successful completion of MRI testing were compared among 5- to 12-year-olds who underwent brain MRI or liver R2*MRI with or without receiving PSP. RESULTS: Seventy-one children with SCD (median age 9.85 years, range 5.57-12.99 years) underwent a brain MRI (n = 60) or liver R2*MRI (n = 11). Children who received PSP were more likely to complete an interpretable MRI exam than those who did not (30 of 33; 91% vs. 27 of 38; 71%, unadjusted OR = 4.1 (P = 0.04) and OR = 8.5 (P < 0.01) when adjusting for age. CONCLUSION: PSP can help young children with SCD complete clinically interpretable, nonsedated MRI exams, avoiding the risks of sedation/anesthesia.