Newborn screening for hemoglobinopathies in California

Background

Newborn screening (NBS) for hemoglobinopathies facilitates early identification of affected individuals to ensure the prompt institution of comprehensive medical care for affected newborns in California. When linked to extensive follow‐up and education, NBS has been shown to significantly reduce mortality in children with sickle cell disease. Due to changing immigration patterns from Asia and Latin America, the State of California has witnessed an increased prevalence of clinically significant hemoglobin (Hb) disorders, including those resulting from novel genotypes. In 1999, newborn screening for Hb H disorders was incorporated in the statewide hemoglobinopathy screening program.

Procedure

Primary screening for hemoglobin variants was performed using high performance liquid chromatography. Confirmatory testing on hemoglobinopathy mutations was performed by electropheresis techniques and genotyping methods.

Results

Of 530,000 newborn samples screened annually in California, 2,118 samples were referred to the Hemoglobin Reference Laboratory (HRL) for confirmatory testing between January 1, 1998 and June 30, 2006 (0.05%). Sickle cell disease was most frequently observed (1 in 6,600 births) followed by α‐thalassemia (1 in 9,000 births) and β‐thalassemia disease (1 in 55,000 births). The confirmatory analysis modified the initial screening in 5% of cases and revealed 25 rare or new genotypes. Diverse ethnicities were associated with hemoglobin mutations including Southeast Asian, Black, Indian/Asian, Middle Eastern, and Hispanic.

Conclusions

The California hemoglobinopathy screening program provides accurate diagnosis of hemoglobinopathies. Increasing incidence of diverse mutations require new strategies of laboratory screening, counseling, and patient management. Pediatr Blood Cancer 2009;52:486–490. © 2008 Wiley‐Liss, Inc.     

Fertility perspectives and priorities among male adolescents and young adults in cancer survivorship

Infertility is a common and distressing late effect of cancer treatment among male survivors. Investigators examined desire for parenthood, prioritization of fertility compared to other life goals, and reports of fertility‐related discussions among a cohort of male adolescent and young adult survivors. Eighty percent desired a biological child, yet only 31% ranked having a child among their “top 3” life goals. Only 40% reported fertility‐related discussions with their health care providers in survivorship. Given the importance of biological children among this cohort, future guidelines should encourage a more proactive approach to providing fertility counseling and offering testing, to mitigate distress and prevent unplanned pregnancies.     

Gonadal development and function after immature testicular tissue banking as part of high-risk gonadotoxic treatment

Background

Experimental fertility preservation programs have been started to safeguard the future fertility of prepubertal and pubertal males requiring high-risk gonadotoxic treatment protocols. However, long-term follow-up studies evaluating the effects on their gonadal development and function related to the testicular biopsy procedure are rather limited.

Design

This two-center follow-up study (between 2002 and 2020) evaluated the gonadal development and function of a cohort of 59 prepubertal and pubertal males who have been offered immature testicular tissue banking (TTB) prior to conventional high-risk chemo- and/or radiotherapy (HR-C/R) or conditioning therapy before hematopoietic stem cell transplantation (CT-HSCT). The aim is to investigate the long-term impact of the testicular biopsy procedure and the high-risk gonadotoxic treatment. Testicular growth and the reproductive hormones luteinizing hormone (LH), follicle-stimulating hormone (FSH), testosterone (T), and inhibin B (INHB) were analyzed after treatment completion, and compared between males accepting TTB and those refusing TTB (control) as well as between HR-C/R and CT-HSCT treatment protocols.

Results

Of the 59 prepubertal and pubertal males included, 25 were treated by HR-C/R and 34 required CT-HSCT. TTB was accepted for 39 males and refused for 20 males. Most patients were prepubertal at diagnosis (85%), at TTB (79%), and at treatment completion (76%), and pubertal or postpubertal at their last follow-up visit (66%). After 5.0 (1.0–13.0) years post treatment, most patients show normal testicular volumes (83%) and normal LH (89%), FSH (87%), T (87%), and INHB (79%) serum levels. The testicular biopsy procedure did not have an effect on testicular growth, LH, FSH, T, and INHB. Significantly more small postpubertal testicular volumes (p = .0278) and low INHB serum levels (p = .0130) were recorded after CT-HSCT, especially after myeloablative conditioning.

Conclusion

The clinical follow-up data demonstrate no effect related to the biopsy procedure, but a substantial risk for impaired gonadal development after high-risk gonadotoxic treatment, in particular myeloablative CT-HSCT. Longer follow-up studies with a larger study population are needed to confirm these preliminary findings.     

Early blood transfusions protect against microalbuminuria in children with sickle cell disease

BACKGROUND: Microalbuminuria (MA) is an early indicator for glomerulopathy in sickle cell disease (SCD). PROCEDURE: We reviewed the medical records of asymptomatic patients ages 4-20 with sickle hemoglobinopathies, who were screened for MA in order to find out its prevalence and risk factors. RESULTS: Nineteen of 120 (15.8%) screened patients had MA detected by spot urine (mean albumin absolute value 6.95 +/- 0.56 mg/dl) and abnormal albumin to creatinine ratios (79.8 +/- 0.62 mg/g creatinine). Twenty four-hour urine collections confirmed 57% of MA cases by spot urine. There was no difference in hyperfiltration between positive and negative patients. From the MA-positive patients, 15 had SS (16.8% of SS group) and 4 had SC (18% of SC group). Nineteen percent of children 10 years of age or older had MA, as compared to 8% of the younger children (P = 0.018), demonstrating that increasing age is a risk factor for MA. There was a positive correlation between MA and acute chest syndrome. Young age at start of chronic transfusions was inversely related to MA and therefore renoprotective (P = 0.03). We did not see a protective effect in the group of patients taking hydroxyurea for a relatively short time, mean age at start of treatment 12 +/- 5 years; however the sample was small. CONCLUSIONS: We conclude that: (1) children with sickle cell hemoglobinopathies 10 years or older should be screened for MA and (2) chronic transfusions starting at an early age may be renoprotective.     

Utility of pediatric female fertility preservation discussions following pelvic radiation

Introduction

While many childhood cancers are curable with therapy, adverse consequences in fertility exist. We sought to assess the number of female patients with pelvic tumors receiving radiation therapy, and the proportion that undergo measures for fertility preservation (FP).

Methods

A total of 53 female patients treated with pelvic tumors from 2000 to 2016 were retrospectively identified.

Results

19 (34%) of these patients underwent pelvic radiation therapy (pXRT). Three of the patients received pXRT for palliative treatment. Of the 19 female patients receiving pXRT, six (31%) were prepubertal and 13 (68%) were postpubertal. Three patients (16%) had documentation of a discussion of FP measures prior to pXRT. One was prepubertal and the others were post-pubertal. Six patients (32%) were evaluated by endocrinology after radiation therapy, diagnosed with ovarian failure, and placed on hormone therapy. Current guidelines recommend discussion of FP in pre-and postpubertal patients with cancer. This 16-year retrospective review of female patients that underwent pXRT for pelvic tumors demonstrated?<?17% of patients have documentation of a discussion of FP measures.

Conclusion

Female pediatric patients who underwent chemotherapy and pXRT suffer a high rate of premature ovarian failure, high morbidity and mortality as well as low rates of documented FP discussions. Based on these findings we have established a multi-disciplinary fertility preservation team available for consultation and a protocol for discussing and documenting the impact of pXRT, along with other treatments, on fertility.

Level of evidence

III.

     

Adherence to hydroxyurea and clinical outcomes among children with sickle cell anemia

Objective

Hydroxyurea lowers the incidence of vaso-occlusive pain crises (VOC) and acute chest syndrome (ACS) among children with sickle cell anemia (SCA). Our objective was to assess the relationship between levels of adherence to hydroxyurea and clinical outcomes among children and adolescents with SCA.

Methods

This retrospective cohort study included Medicaid data (2005–2012) from Florida, Illinois, Louisiana, Michigan, South Carolina, and Texas. The study population consisted of children 1–17 years old with SCA enrolled in Medicaid for 3 years. Among children that initiated hydroxyurea, the medication possession ratio (MPR) was calculated as the proportion of days covered by hydroxyurea. Six months after initiation of hydroxyurea, clinical outcomes were assessed through the end of the study period: numbers of VOC-related inpatient admissions and emergency department visits, and encounters for ACS. Multivariable Poisson models were used to predict outcomes by MPR quartile adjusting for previous healthcare utilization, state, and age.

Results

Hydroxyurea was initiated by 515 children. The median MPR was 0.53 (interquartile range = 0.3–0.8). The annual median number of visits was 0.0 for ACS, 1.3 for VOC-related emergency department, and 1.4 for VOC-related inpatient admissions. For each outcome, the highest quartile of MPR had the lowest predicted count; this difference was significant for ACS visits when compared with the lowest quartile of MPR.

Conclusion

This study demonstrated a high level of adherence (>75%) was essential to achieve a lower incidence of common negative clinical outcomes. Further, moderate and severe hydroxyurea nonadherence may be more common than previously appreciated among children, emphasizing the importance of developing and testing innovative strategies to increase adherence.     

Efficacy of hydroxyurea (HU) in reduction of pack red cell (PRC) transfusion requirement among children having beta-thalassemia major: Karachi HU trial (KHUT)

BACKGROUND: Packed red blood cell (PRC) transfusion with iron chelation is the mainstay of treatment for patients with beta-thalassemia major. Hemoglobin F augmentation is another approach to treat this hemoglobinopathy. This study evaluates the efficacy and safety of hydroxyurea (HU) in minimizing PRC transfusions in patients with beta-thalassemia major. METHOD: Twenty-three patients with beta-thalassemia major received HU at a mean dose of 16 mg/kg/d. The results were analyzed at the end of 24 months. Transfusion requirement during the 6 months preceding the study was considered as the control. RESULT: Twenty patients were evaluable after 24 months. The mean volume of PRC transfused was reduced from 2126.45 mL to 1489.59 mL (P<0.001). The interval between transfusions was increased by 68.7%. Grade I myelosuppression was observed in 4 patients and diarrhea in 2 patients. CONCLUSIONS: HU was found to be safe in patients with beta-thalassemia major, and resulted in reduction in the transfusion requirements and in increase of the intervals between transfusions.     

Efficacy of fixed low dose hydroxyurea in Indian children with sickle cell anemia: A single centre experience

Introduction

Data on the efficacy of hydroxyurea (HU) in Indian children with sickle cell anaemia (SCA) is limited. Hence, we have evaluated the efficacy of fixed low dose HU in Indian children.

Methods

The study cohort consisted of 144 children (<18 years of age) with SCA having severe manifestations (≥3 episodes of vasocclusive crisis or blood transfusions, or having ≥1 episode of acute chest syndrome or cerebrovascular stroke or sequestration crisis) who were started on fixed low dose HU (10 mg/kg/day). They were followed up for two years and monitored for the hematological and clinical efficacy and safety.

Results

There was significant increase in the fetal hemoglobin level (HbF%), total hemoglobin and mean corpuscular volume. Vasoocclusive crises, blood transfusions, acute chest syndrome, sequestration crises and hospitalizations decreased significantly. Baseline HbF% had significant positive correlation with HbF% at 24 months. There was significant negative correlation between baseline HbF% and change in HbF% from baseline to 24 months. No significant correlation was found between HbF% at baseline and clinical event rates per year after HU. No major adverse events occurred during the study period.

Conclusion

Fixed low dose HU is effective and safe in Indian children with SCA.     

Fertility preservation in pediatric leukemia and lymphoma: A report from the Children's Oncology Group

Certain chemotherapy agents, radiation, and surgery can all negatively impact future fertility. Consults regarding treatment-related risk for infertility and gonadal late effects of these agents should occur at the time of diagnosis as well as during survivorship. Counseling on fertility risk has traditionally varied significantly across providers and institutions. We aim to provide a guide to standardize the assignment of gonadotoxic risk, which can be used in counseling patients both at the time of diagnosis and in survivorship. Gonadotoxic therapies were abstracted from 26 frontline Children's Oncology Group (COG) phase III protocols for leukemia/lymphoma, in use from 2000–2022. A stratification system based on gonadotoxic therapies, sex, and pubertal status was used to assign treatments into minimal, significant, and high level of increased risk for gonadal dysfunction/infertility. Risk levels were assigned to protocols and different treatment arms to aid oncologists and survivor care providers in counseling patients regarding treatment-related gonadotoxicity. Males were most commonly at high risk, with at least one high-risk arm in 14/26 protocols (54%), followed by pubertal females (23% of protocols) and prepubertal females (15% of protocols). All patients who received direct gonadal radiation or hematopoietic stem cell transplant (HSCT) were considered at high risk. Partnering with patients and their oncology/survivorship team is imperative for effective fertility counseling both prior to and post treatment, and this comprehensive guide can be used as a tool to standardize and improve reproductive health counseling in patients undergoing COG-based leukemia/lymphoma care.     

Oral-steroid sparing effect of inhaled fluticasone propionate in children with steroid-dependent asthma

OBJECTIVE:

To evaluate the oral steroid-sparing effect of inhaled fluticasone propionate (FP) in eight children with steroid-dependent asthma.

DESIGN AND SETTING :

Treatment protocol study at a tertiary pulmonary care centre at a children’s hospital.

PATIENTS:

Eight children with severe persistent steroid dependent asthma (mean age 11.6 years [range 10 to 13 years], mean duration of asthma 8.37 years [range three to 11 years]) were enrolled in the study.

MEASUREMENTS:

Inhaled FP 880 μg/day (two puffs of 220 μg/puff, two times a day) was added to the children’s asthma treatment, and attempts were made to reduce the dose of oral steroids by 20% every two weeks over a six-month period. After this six-month period, in the patients responding to inhaled FP, the dose of inhaled FP was reduced to 440 μg/day (two puffs of 110 μg/puff, two times a day) for the next six months. The mean percentage predicted values for forced expiratory volume in 1 s (FEV₁) and maximal mid-expiratory flow rate (FEF_25%–75%) were compared during the first month, at two to six months, and at seven to 12 month intervals before and after starting FP. The number of asthma exacerbations, emergency room visits, hospital admissions and number of school days lost were also compared.

RESULTS:

Within three months of starting inhaled FP, the mean alternate-day oral steroid dose decreased from 38 mg to 2.5 mg. In addition, six patients (66%) were able to discontinue the use of oral steroids. There was significant improvement in the number of mean emergency room visits per patient (P=0.016), mean asthma exacerbations per patient (P=0.016), mean hospital admissions per patient (P=0.016) and mean number of school days lost per patient (P=0.004) while patients were receiving high dose inhaled FP compared with oral steroids. There was no deterioration of any of the above mentioned parameters during the six month period when the dose of inhaled FP was reduced. The mean FEV₁ and FEF_25%–75% during the two- to six-month and seven- to 12-month periods showed significant improvement, while the patients were receiving FP compared with oral steroids (P<0.05 for both parameters for both time periods).

CONCLUSIONS:

High dose inhaled FP 880 μg/day has an important oral steroid-sparing effect. After oral steroids are tapered, patients maintain adequate control of asthma with low dose inhaled FP. These findings suggest that FP may control asthma better than oral steroids.     

Sperm banking in adolescent cancer patients

Background

Semen cryopreservation is a widely available method of maintaining fertility in male cancer patients. However this facility is not always used.

Aims

To identify the barriers to successful sperm banking in a group of adolescent and young adult patients.

Methods

Questionnaires were administered to 55 patients aged 13–21 years who had received potentially gonadotoxic therapy between 1997 and 2001 and had been offered sperm banking.

Results

Forty five questionnaires were completed; 67% of respondents were able to bank sperm. Those who had been unsuccessful were younger and described higher levels of anxiety at diagnosis and greater difficulty in talking about fertility. They also described less understanding of sperm banking at the time of diagnosis.

Conclusion

Most adolescent cancer patients who have been offered fertility preservation are able to bank sperm. Younger patients may be helped by the provision of high quality information and more open discussion of the technique.     

Barriers to medication adherence in sickle cell disease: A comprehensive theory-based evaluation using the COM-B model

Background

Sickle cell disease (SCD) affects more than 100,000 Americans, with complications such as pain episodes and acute chest syndrome. Despite the efficacy of hydroxyurea in reducing these complications, adherence remains low. Study objectives were to examine barriers to hydroxyurea adherence, and to evaluate the relationship between barriers and their impact on adherence.

Methods

In this cross-sectional study, patients with SCD and their caregivers were enrolled if they were taking hydroxyurea. Study measures included demographics, self-report of adherence using visual analog scale (VAS), and the Disease Management and Barriers Interview (DMI)-SCD. The DMI-SCD was mapped to the Capability, Opportunity, Motivation, and Behavior (COM-B) model.

Results

Forty-eight caregivers (females 83%, median age 38 [34–43]) and 19 patients (male 53%, median age 15 [13.5–18]) participated. Using VAS, many patients (63%) reported low hydroxyurea adherence, while most caregivers (75%) reported high adherence. Caregivers endorsed barriers across multiple COM-B components, with physical opportunity (e.g., cost) and reflective motivation (e.g., SCD perceptions) being the most identified categories (48% and 42%), respectively. Patients’ most identified barriers included psychological capability (e.g., forgetfulness) and reflective motivation (84% and 68%), respectively. Patients’ and caregivers’ VAS scores negatively correlated with the number of barriers (r_s = –.53, p = .01; r_s = –.28, p = .05) and COM-B categories (r_s = –.51, p = .02; r_s = –.35, p = .01), respectively, suggesting lower adherence with more endorsed barriers.

Conclusions

Fewer barriers to hydroxyurea adherence were associated with higher adherence. Understanding barriers to adherence is essential to develop tailored interventions aimed at improving adherence.     

Hydroxyurea therapy in UK children with sickle cell anaemia: A single‐centre experience

1 Introduction

Despite the demonstrated efficacy of hydroxyurea therapy, children with sickle cell anaemia in the UK are preferentially managed with supportive care or transfusion. Hydroxyurea is reserved for children with severe disease phenotype. This is in contrast to North America and other countries where hydroxyurea is widely used for children of all clinical phenotypes. The conservative UK practice may in part be due to concerns about toxicity, in particular marrow suppression with high doses, and growth in children.

2 Methods and results

We monitored 37 paediatric patients with sickle cell anaemia who were treated with hydroxyurea at a single UK treatment centre. Therapy was well tolerated and mild transient cytopenias were the only toxicity observed. Comparative analysis of patients receiving ≥26 mg/kg/day versus <26 mg/kg/day demonstrates increasing dose has a significant positive effect on foetal haemoglobin (Hb; 29.2% vs. 20.4%, P = 0.0151), mean cell volume (94.4 vs. 86.5, P = 0.0183) and reticulocyte count (99.66 × 10⁹/l vs. 164.3 × 10⁹/l, P = 0.0059). Marrow suppression was not a clinical problem with high‐dose treatment, Hb 92.25 g/l versus 91.81 g/l (ns), neutrophil count 3.3 × 10⁹/l versus 4.8 × 10⁹/l (ns) and platelet count 232.4 × 10⁹/l versus 302.2 × 10⁹/l (ns). Normal growth rates were maintained in all children. Good adherence to therapy was a significant factor in reducing hospitalisations.

3 Conclusion

This study demonstrates the effectiveness and safety in practice of high‐dose hydroxyurea as a disease‐modifying therapy, which we advocate for all children with sickle cell anaemia.     

Prehospital blood transfusions in pediatric trauma and nontrauma patients: a single-center review of safety and outcomes

Purpose

Prehospital transfusions are a novel yet increasingly accepted intervention in the adult population as part of remote damage control resuscitation, but prehospital transfusions remain controversial in children. Our purpose was to review our pediatric prehospital transfusion experience over 12 years to describe the safety of prehospital transfusion in appropriately triaged trauma and nontrauma patients.

Methods

Children (<18 years) transfused with packed red blood cells (pRBC) or plasma during transport to a single regional academic medical center between 2002 and 2014 were identified. Admission details, in-hospital clinical course, and outcomes were analyzed.

Results

28 children were transfused during transport; median age was 8.9 ± 7 years and 15 patients were male (54%). Most patients required at least one additional unit of blood products during their hospitalization (79%), and/or required operative intervention (53%), endoscopy (7%), or died during their hospitalization (14%). Comparison of trauma patients (n = 16) and nontrauma patients (n = 12) revealed that nontrauma patients were younger, more anemic, more coagulopathy on admission, and required more ongoing transfusion in the hospital. Trauma patients were more likely to need operative intervention. No patient had a transfusion reaction.

Conclusion

Remote damage control prehospital transfusions of blood products were safe in this small group of appropriately triaged pediatric patients. Further studies are needed to determine if outcomes are improved and to devise a rigorous protocol for this prehospital intervention for critically ill pediatric patients.

     

Prevalence of GB virus C/hepatitis G virus infection in pediatric patients receiving multiple transfusions in Southern Turkey

The aim of this study was to determine the prevalence of GB virus C (GBV-C) infection in pediatric patients receiving multiple blood transfusions in Turkey where HBV and HCV infections are common. Sera of a total of 148 children, of whom 85 had cancer and 63 hemoglobinopathies, were tested for GBV-C RNA and HCV RNA by RT-PCR and for antibodies to HBV and HCV. Demographic and clinical information as well as laboratory results were recorded for the patients (81 boys, 67 girls, aged 1-19 years). HBsAg positivity was found in 23 (15.5%) patients, HBV DNA positivity in 12 (8.1%), HCV RNA positivity in 9 (6.7%), and GBV-C RNA positivity in 4 (2.7%). There was no significant difference in the GBV-C RNA positivity between patients with cancer (3.2%) and patients with hemoglobinopathies (2.4%) (p > 0.05). GBV-C RNA was found in 4 (3.1%) out of 127 patients who had received transfusions, but it was not found in any of 21 patients who had not received transfusions. However, there was no relationship between GBV-C RNA positivity and the number of transfusions. Two of the patients with GBV-C RNA had high levels of ALT (ALT > 40 IU). In these two patients, neither HBV DNA nor HCV RNA were detected by PCR, and serological tests were also negative for these agents. We concluded that pediatric patients who had multiple transfusions in Turkey are at risk of being infected with GBV-C, in addition to HBV and HCV. Investigation of GBV-C RNA in patients with high ALT levels in the absence of other viral markers may be useful.     

Gonadal function and parenthood 20 years after treatment for childhood lymphoma: a cross-sectional study

Background

Gonadal function decades after treatment for childhood lymphoma (CL) is not well described. This cross‐sectional study had two aims: (1) describe long‐term gonadal function and fertility in childhood lymphoma survivors (CLSs), and (2) explore anti‐Mullerian hormone (AMH) as a measure of ovarian function in CLSs.

Procedure

Seventy‐four male and 62 female CLSs participated in a survey consisting of a questionnaire, clinical examination, and blood/semen analysis. Prior treatment was categorized according to gonadotoxicity. Hypogonadism was determined by levels of gonadal hormones based on luteinizing hormone, follicle‐stimulating hormone, testosterone (males), AMH (females <40 years), and menstrual status. Fertility was explored according to pregnancies achieved, semen analysis, and AMH.

Results

Hypogonadism was observed in 7 of 66 males (11%). Seven of 64 males (11%) were categorized as infertile. Nine of 45 females <40 years (20%) were at risk to develop premature ovarian failure (POF). Twenty of 45 females (44%) showed low‐AMH levels indicating decreased fertility. Four “critically low” females reported pregnancies within the preceding 2 years. Sixty‐four percent of the males and 93% of the females attempting parenthood had been successful (P = 0.01). Hypogonadism and low‐AMH were related to treatment burden.

Conclusion

Twenty years after treatment of CL, female CLSs' attempts of pregnancy initiation are mostly successful, while males seem at higher risk of infertility. Hypogonadism is a problem in 10% of the male CLSs. Based on AMH levels, POF is a risk in 20% of the female CLSs. The clinical significance of AMH reflecting true probability of fertility needs further research in cancer survivors. Pediatr Blood Cancer 2012;59:271–277. © 2011 Wiley Periodicals, Inc.     

High birth prevalence of sickle cell disease in Northwestern Tanzania

1 Background

Worldwide, hemoglobinopathies affect millions of children. Identification of hemoglobin disorders in most sub‐Saharan African countries is delayed until clinical signs of the disease are present. Limited studies have been conducted to understand their prevalence and clinical presentation among newborns in resource‐limited settings.

2 Methodology

This was a prospective cohort study. Newborns (aged 0–7 days) at two hospitals in Northwestern Tanzania were enrolled and followed prospectively for 6 months. Clinical and laboratory information were collected at baseline. Participants were screened for hemoglobinopathies using high‐performance liquid chromatography. Clinical and laboratory follow‐up was performed at 3 and 6 months for those with hemoglobinopathies as well as a comparison group of participants without hemoglobinopathies.

3 Results

A total of 919 newborns were enrolled. Among these, 1.4% (13/919) had sickle cell anemia or Hb S/β⁰‐thalassemia (Hb FS), and 19.7% (181/919) had sickle cell trait or Hb S/β⁺ thalassemia (Hb FAS). Furthermore, 0.2% (two of 919) had β⁺‐thalassemia. Red cell indices compared between Hb FS, Hb FAS, and Hb FA were similar at baseline, but hemoglobin was lower and red cell distribution width was higher in children with Hb FS at 3‐ and 6‐month follow‐up. Febrile episodes were more common for children with Hb FS at 3‐ and 6‐month follow‐up.

4 Conclusion

The prevalence of sickle cell disease among neonates born in Northwestern Tanzania is one of the highest in the world. Newborn screening is needed early in life to identify neonates with hemoglobinopathies so that clinical management may commence and morbidity and mortality related to hemoglobinopathies be reduced.     

Impact of hydroxyurea on perioperative management and outcomes in children with sickle cell anemia

Hydroxyurea has enhanced the treatment for children with sickle cell anemia. The objectives of this study were to compare perioperative transfusions and outcomes for children taking hydroxyurea versus those not taking hydroxyurea. We retrospectively reviewed perioperative management and outcomes for 51 children with sickle cell anemia (HbSS genotype) who underwent surgery in our center between January 2003 and April 2008. Of the 51 patients, 30 (59%) were taking hydroxyurea and 21 (41%) were not taking hydroxyurea. Eight of 30 (27%) in the hydroxyurea group were not transfused preoperatively, 12 of 30 (40%) received a single transfusion and 10 of 30 (33%) received serial transfusions, compared with 1 of 21 (5%) children in the nonhydroxyurea group who was not transfused, 2 of 21 (10%) who received a single transfusion and 18 of 21 (85%) who received serial transfusions or pheresis (P=0.004; for comparison across groups). One patient not taking hydroxyurea developed a delayed hyperhemolytic transfusion reaction, and 2 children taking hydroxyurea developed acute chest syndrome. Overall, children taking hydroxyurea had substantially fewer transfusions compared with children not taking hydroxyurea. Both groups of children had a low complication rate. Further research should be done to optimize perioperative management of children taking hydroxyurea.     

Prevention of secondary stroke and resolution of transfusional iron overload in children with sickle cell anemia using hydroxyurea and phlebotomy

OBJECTIVE: Transfusions prevent secondary stroke in children with sickle cell anemia (SCA) but also cause iron overload. Alternatives for stroke prophylaxis with effective therapy to reduce iron burden are needed. STUDY DESIGN: For 35 children with SCA and stroke, transfusions were prospectively discontinued. Hydroxyurea was prescribed for stroke prophylaxis, and phlebotomy removed excess iron. Initial patients discontinued transfusions before hydroxyurea therapy, but later patients overlapped transfusions with hydroxyurea until tolerating full-dose therapy. RESULTS: Children received hydroxyurea for 42 +/- 30 months (range, 3-104 months). Hydroxyurea (26.7 +/- 4.8 mg/kg per day) led to mild neutropenia (3.9 +/- 2.3 x 10(9)/L) with significant increases in hemoglobin concentration, mean corpuscular volume, and fetal hemoglobin. Stroke recurrence rate was 5.7 events per 100 patient-years, but children receiving overlapping hydroxyurea therapy had only 3.6 events per 100 patient-years. For 26 children with >6 months of phlebotomy, 14,311 +/- 12,459 mL blood (315 +/- 214 mL/kg) was removed, with serum ferritin decreasing from a median of 2722 to 298 ng/mL. Among patients completing phlebotomy, liver biopsy documented normal histology and no excess iron deposition. CONCLUSIONS: For children with SCA and stroke, hydroxyurea effectively prevents secondary stroke and serial phlebotomy leads to complete resolution of transfusional iron overload.