Bacteremia in sickle hemoglobinopathies

We analyzed 178 episodes of bacteremia that occurred during 13,771 patient-years of follow-up of 3451 patients with sickle hemoglobinopathies. Age-specific incidence rates of bacteremia were calculated for patients with sickle cell anemia (SS) and sickle cell-hemoglobin C (SC) disease. The incidence rate was highest among children with SS and SC younger than age 2 years. Children with SC showed an abrupt decrease after age 2 years, whereas children with SS had a gradual decline in rate from 2 to 6 years of age. The predominant pathogen in patients younger than 6 years was Streptococcus pneumoniae (66%); gram-negative organisms were responsible for 50% of bacteremias in patients 6 years and older. Urinary tract infection was present during 73% of Escherichia coli bacteremias, and 77% of Salmonella bacteremias were associated with osteomyelitis. In contrast, no focus of infection was present in 52% of pneumococcal bacteremias. The incidence of pneumococcal bacteremia in children with SS younger than age 3 years was 6.1 events/100 patient-years; the case fatality rate for pneumococcal sepsis in this age group was 24%. No hematologic or demographic variables were associated with occurrence of pneumococcal bacteremia in young children. Retrospective analysis of pneumococcal bacteremia suggests that the prophylactic use of penicillin may decrease the incidence in children younger than 3 years of age.     

Pneumococcal septicemia despite pneumococcal vaccine and prescription of penicillin prophylaxis in children with sickle cell anemia

Although polyvalent pneumococcal vaccine and prophylactic penicillin are used to prevent overwhelming Streptococcus pneumoniae septicemia in infants and young children with sickle cell anemia, infection rates remain high. We have reviewed our seven-year experience with a regimen of twice daily oral penicillin V potassium prophylaxis in 88 affected children. The median age at the start of prophylaxis was 10 months, and the median duration of prophylaxis was 29 months (range, three months to seven years). The total period of observation of patients who were prescribed penicillin was 248 person-years. Most patients also received one or two doses of polyvalent pneumococcal vaccine. Despite penicillin prophylaxis and pneumococcal vaccine, eight episodes of S pneumoniae septicemia have occurred and three have been fatal. Four episodes were in children older than 3 years. Suboptimal compliance with the prescribed oral penicillin regimen was usually apparent. With one possible exception, the infections occurred when penicillin had not been taken during the previous 24 hours. The S pneumoniae septicemia rate in this patient population, 3.2 per 100 person-years, is somewhat less than that described in previous reports of children not receiving penicillin but is still unacceptably high. Vigorous advocacy of a penicillin prophylaxis regimen does not eliminate the risk of pneumococcal septicema in this patient population.     

Invasive pneumococcal infections in children with sickle cell disease in the era of penicillin prophylaxis, antibiotic resistance, and 23-valent pneumococcal polysaccharide vaccination

Rates and severity of pneumococcal infections in children with sickle cell disease were examined before licensure of pneumococcal-conjugated vaccine (PVC). Rates of peak invasive infection rates in 1-year-old children with hemoglobin SS and mortality in those 0 to 10 years of age were 36.5 to 63.4 and 1.4 to 2.8 per 1000 person-years, respectively (>10 and 100 times as frequent as in the general population). Overall, 71% of serotyped isolates (n=80) were PVC serotypes and 71% of nonvaccine serotype strains were penicillin-sensitive. Clinical presentation in children with hemoglobin SS (n=71; more with hypotension) and hemoglobin SC (n=18; more with acute chest syndrome, otitis media) differed. Penicillin nonsusceptibility (38% of isolates) varied between geographic study sites. Penicillin prophylaxis appeared less effective against intermediate and resistant strains. Of all infected children, meningitis developed in 20% and 15% died (hemoglobin SS, n=15 and 11; hemoglobin SC, n=1 each). Factors associated with death included age >4 years (58%), serotype 19F, and not being followed by a hematologist (42% each). The pneumococcal-polysaccharide vaccine was 80.4% effective within 3 years after vaccination (95% CI, 39.7, 93.6). Children with sickle cell disease of all ages may benefit from PVC boosted with polysaccharide vaccination.     

Infections and sickle cell disease in Eastern Saudi Arabian children

The rate and pattern of infections in 144 Saudi Arabian children with sickle cell disease (SCD) and matched normal control subjects are reported. All diagnoses of SCD were made at birth by means of screening blood from the umbilical cord. The children were prospectively followed up from birth to 4 years of age. Severe bacterial infections occurred in none of the children with SCD; one of the control children developed pneumococcal meningitis. Acute gastroenteritis was significantly more common among patients with SCD. For the first year of life, patients with SCD had significantly more infections than did the control children; but the reverse was true in the group that was 37 to 48 months of age. Considering all types of infections for all age groups, no difference was noted between patients with SCD and control subjects in terms of infection rate or related hospital admission. There were no deaths caused by infection in this series. We conclude that Saudi Arabian infants and young children of oasis origin with SCD are not at increased risk of infections compared with healthy children of the same age.     

Is there an increased risk of Haemophilus influenzae septicemia in children with sickle cell anemia?

The risk of Haemophilus influenzae septicemia/meningitis to children who have sickle cell anemia (SS) has been determined to be greater than that seen among normal infants. Of ten bacteriologically proven cases, eight episodes of infection were observed among 234 children with sickle cell anemia (645 person-years), who were less than 5 years of age. There was one case per 69 infants with sickle cell anemia who were less than 18 months old and one case per 36 children with sickle cell anemia between 19 and 59 months of age. Unexpectedly, two infections occurred among 224 children (824 person-years), aged 5 to 9 years; both died. Contrary to the rapid clinical course of pneumococcal infections in children with sickle cell anemia H influenzae septicemia was regularly heralded by a greater than 24-hour prodrome of upper respiratory tract infection, low-grade fever, and otitis media. Three (30%) preventable deaths occurred. Antibiotic therapy for the febrile child with sickle cell anemia must be predicated on the known 400-fold increased risk of pneumococcal septicemia in those less than 5 years old and the fourfold risk of H influenzae septicemia in those less than 9 years of age.     

Sickle cell disease in children in Dakar, Senegal]

AIM OF THE STUDY: To determine the socioeconomic, clinical and biological aspects of sickle cell disease (SCD) in Senegalese children and adolescents, we retrospectively analysed all records of follow-up attending patients in the Albert Royer Children Hospital of Dakar (Senegal). RESULTS: Homozygous sickle cell (SS) was the most frequent genotype (307 cases). Sickle cell hemoglobin C (13 cases) and sickle cell beta-thalassemia (three cases) were uncommon. Patients were aged from five months to 22 years (mean age: eight years). Most of them came from poor families. The mean number of children was five in patients' families, with at least two cases of SCD in 60% of them. Immunization against hepatitis B virus (10.2%), Haemophilus influenzae b (8.4%), Salmonella (8.7%) and Streptococcus pneumoniae (21.4%) was insufficiently performed, because of its relatively high cost. Only 30% of the patients had received a blood transfusion. Painful crises occurred less than three times a year in 74% of the cases. Complications such as acute chest syndrome (1%), stroke (1%), cholelithiasis (9%), meningitis (0.4%), septicemia (2%) and osteomyelitis (6%) were rare. Mean steady state hemoglobin (Hb) and hemoglobin F(HbF) levels were 8.27 +/- 1.36 g/dL and 6.8 +/- 5.9% respectively among SS patients. No correlations were found neither between Hb and HbF nor between these parameters and the frequency of complications. Eleven patients (1.1% per year of follow-up) died, and infection was the main cause of death (73%). CONCLUSION: In comparison with published data, SCD seems to have mild severity in Senegalese children and adolescents in spite of poor follow-up conditions. In addition to genetic factors, environmental factors might have an important role in disease tolerance.     

Developmental pattern of splenic dysfunction in sickle cell disorders

Splenic function in sickle hemoglobinopathy syndromes was assessed to determine the developmental pattern of splenic dysfunction. Nonvisualization of the spleen using technetium-99 metastable (99mTc) spleen scans correlated strongly with pocked (vesiculated) RBCs greater than or equal to 3.5%. Cross-sectional analysis of pocked RBC data from 2,086 patients showed differences in the developmental pattern of splenic dysfunction between several disorders. In hemoglobin SS disease (sickle cell anemia) and hemoglobin S beta(0) thalassemia, splenic dysfunction (greater than or equal to 3.5% pocked RBCs) often occurred in the first 6 to 12 months of life. In hemoglobin S beta(+) thalassemia, splenic dysfunction occurred less frequently and later. Splenic dysfunction in hemoglobin SC disease (sickle cell-hemoglobin C) was intermediate. The level of pocked RBCs was inversely associated with fetal hemoglobin (P less than .007) and directly associated with age (P less than or equal to .001). These patterns of splenic dysfunction reflect the known severity of hemolysis and intravascular sickling and are consistent with the epidemiology of severe bacterial meningitis and sepsis in these diseases. Serial measurement of pocked RBCs permits determination of the onset of splenic dysfunction and the time of increased susceptibility to severe bacterial infections.     

Treatment of sickle cell disease in early childhood in Jamaica

The Jamaican sickle cell cohort study, based on neonatal diagnosis of all cases of sickle cell disease among 100,000 consecutive births, has identified acute splenic sequestration (ASS) and pneumococcal disease as the most important complications in early life. The etiology of ASS is unknown and prophylaxis is therefore not possible. For first attacks, attention has been directed to parental education to achieve earlier diagnosis. Recurrent attacks may be prevented by prophylactic splenectomy. A controlled trial on the prevention of pneumococcal disease has indicated many pneumococcal septicemias in children given the 14 valent pneumococcal vaccine between the ages of 6 months and 3 years. No pneumococcal isolations occurred during the same period in children given monthly long-acting prophylactic penicillin. A controlled trial of folate supplementation for 1 year in children aged 6 months to 4 years indicated no difference between control and treatment groups in hemoglobin levels or weight and height velocity. The MCV was 4 fl less in the supplemented group. A controlled trial of feeder vessel photocoagulation in the therapy of proliferative retinopathy indicated significantly less vitreous hemorrhage in treated patients, but choroidal neovascularisation was a common complication of xenon arc therapy, and retinal tears commonly followed the use of the Argon laser. A new trial of scatter therapy is in progress.     

Acute splenic sequestration in homozygous sickle cell disease: natural history and management

Of a cohort of 308 children with homozygous sickle cell disease diagnosed at birth, 89 experienced 132 clinically significant attacks of acute splenic sequestration (ASS) over a 10-year period. The age at first attack ranged from 3 months to 6 years. Survival curve analysis of the interval until first attack indicated a cumulative probability of 0.225 by 2 years, and 0.265 by 3 years, and 0.297 by 5 years of age. Thirteen events were fatal, 11 during the first attack, and all before transfusion could be instituted. Recurrences occurred in 49% of survivors of the first attacks, and there were diminishing intervals between subsequent events. Respiratory symptoms were associated with 52 of 132 events, but bacterial isolates on blood culture were less frequent, and ASS was not prevented by pneumococcal vaccine or penicillin prophylaxis. A high fetal hemoglobin level protected against attacks of ASS. A parental education program aimed at early diagnosis of ASS was followed by an increase in the incidence rate for ASS from a mean of 4.6 per 100 patient-years to 11.3 per 100 patient-years, probably reflecting increased awareness of the complication. During the same periods, the fatality rate fell from 29.4 per 100 events to 3.1 per 100 events. The improvement in outcome is likely to have resulted from improvement in medical management and earlier detection of ASS.     

Cholelithiasis in children with sickle cell disease

Abdominal ultrasonography was performed on 305 children with sickle cell disease (SCD) (285 SS and 20 S-beta-thalassemia) to establish the prevalence of cholelithiasis in Saudi children with SCD. Their ages ranged from 1 to 18 years (mean 10.45 years). Gallstones were demonstrated in 60 children, giving a prevalence of 19.7%. An additional 50 patients (16.4%) had only biliary sludge. The youngest patient with gallstones was 3 years old. There was a correlation between the presence of gallstones and increasing age. Patients with gallstones were also found to have higher serum bilirubin levels, but their hemoglobin, hematocrit, reticulocyte count, hemoglobin S, and hemoglobin F levels were not significantly different from those of patients without gallstones.     

Invasive pneumococcal infections in children with asplenia

BACKGROUND: Asplenia is associated with an increased risk of infections caused by Streptococcus pneumoniae. Overwhelming infection can be fulminate and lead to a fatal outcome. OBJECTIVE: To review the epidemiology and clinical course of invasive S. pneumoniae infections in children with asplenia before the release of the conjugate pneumococcal vaccine. METHODS: Children with S. pneumoniae infections from eight children's hospitals in the US were identified prospectively from September, 1993, to August, 1999. Further demographic, medical and microbiologic information was gathered retrospectively from the charts of patients with asplenia. RESULTS: Twenty-two asplenic patients with 26 episodes of invasive S. pneumoniae were identified. This represents 1% of the 2,581 episodes of invasive S. pneumoniae infections identified in our study. Twelve had congenital asplenia (CA), and 10 had undergone surgical splenectomy. Nine of the patients with CA had associated complex congenital heart disease. The median age at first infection was 12.5 months for CA patients as compared with 69 months in children with surgical splenectomy (P < 0.001). Seventy-five percent of those eligible had received the polysaccharide pneumococcal vaccine. The most common serotypes isolated were 6B (8), 23F (7), 18C (2) and 19A (2). Antimicrobial prophylaxis had been prescribed for 82% of the study cohort. Clinical presentations of the 26 episodes included fever (22), shock (7), petechiae or purpura (7), disseminated intravascular coagulation (5) and respiratory distress (5). Clinical illness included bacteremia alone (12), meningitis alone (8), bacteremia with otitis media-sinusitis (3), bacteremia with pneumonia (2) and meningitis with osteomyelitis (1). Five of the 6 patients who died had meningitis. Three of the survivors (19%) had significant morbidity, and all of them had meningitis. Two patients had 2 episodes each, and 1 patient had 3 episodes. All but 1 of the multiple episodes was with a different serotype. Forty-six percent of isolates were nonsusceptible to penicillin, and 19% were nonsusceptible to ceftriaxone. There was no association between antimicrobial resistance and mortality. CONCLUSIONS: Invasive pneumococcal disease in patients with asplenia has a high mortality, especially in those with meningitis. Even though the new conjugate vaccine might increase protection, 19% of patients had disease caused by serotypes not included in the current heptavalent vaccine. Clinicians should continue to be aggressive in evaluating asplenic patients with unexplained fevers.     

Prophylaxis of pneumococcal infection in sickle-cell disease by the combined use of vaccination and penicillin

Forty children homozygotes for sickle-cell disease (SCD) aged 2-5 years were enrolled in a study to assess the efficacy of pneumococcal vaccine combined with penicillin prophylaxis in preventing pneumococcal infection. The vaccine was given initially and then every 2 years as a booster. In addition to pneumococcal vaccine, 24 children were prescribed penicillin-V orally twice daily while the remaining 16 were given benzathine penicillin intramuscularly every 4 weeks in the clinic. The study period lasted for 4 years during which the clinic attendance rate of both groups was 90% and 92% respectively. The compliance with oral penicillin intake was checked by random urine testing for penicillin. The test was positive in 128 out of 320 urine samples (40%). The parenteral penicillin was given at every clinic visit and the rate of compliance was 92%. Twelve episodes of bacterial sepsis were documented: 10 of them were caused by Gram-negative organisms. The pneumococcus caused a fatal episode of septicaemia and meningitis in a child who did not comply with penicillin prophylaxis. In a retrospective search, 15 episodes of bacterial sepsis have been documented in 22 children receiving no prophylaxis for 2 years. Eight of those episodes were caused by the pneumococcus. The combination of pneumococcal vaccine with penicillin prophylaxis was effective in preventing pneumococcal sepsis in children with SCD followed up for 153 patients years.     

Sickle cell haemoglobinopathies in England.

Ninety-six Birmingham children with sickle cell disease were studied prospectively between 1969 and 1979. Thirty-five were homozygotes for HbS (SS), 12 had sickle thalassaemia (S thal), and 23 were double heterozygotes for HbS and C (SC). Twenty-six whose family studies were incomplete were classified as SS or S thal although most were thought to be SS. The average length of follow-up was 5.1 years. Four SS children and 1 SC child died, the annual mortality rates being 1.3% for SS and presumed SS, 0% for S thal, and 0.9% for SC children. The incidence of pulmonary illnesses and anaemic crises was greater than reported from Jamaica, while leg ulceration described there and in New York was not observed in Birmingham. Severe infections were less common than in the series reported from New York and no case of salmonella osteomyelitis was observed in Birmingham. In general the S thal and SC children had milder illnesses than the SS, and the SS children often showed impairment of growth and sexual maturation.     

Renal kallikrein: a risk marker for nephropathy in children with sickle cell disease

OBJECTIVE: Although improvements in the management of sickle cell disease (SCD) have increased patient survival into adulthood, morbidity and mortality from end-organ damage remain major concerns. One of the most serious complications of SCD is renal failure, affecting about 20% of patients. The clinical manifestations of sickle cell nephropathy (SCN) involve changes in glomerular ultrastructure, albuminuria, and a progressive decline in glomerular hemodynamics. The mechanisms or factors that promote SCN are not fully elucidated. In the present study, the role of renal kallikrein as a risk marker for promoting SCN was explored in a cross-sectional study. METHODS AND RESULTS: We measured the urinary excretion rate of active kallikrein in 73 children with sickle cell anemia (hemoglobin SS, SC, or S thalassemia) and in 30 control healthy African American children. The findings demonstrated that a significant difference in the excretion rate of log kallikrein in male versus female patients with SCD, P<0.0078 was observed. In children with SCD, cross-sectional analysis revealed a positive and significant correlation between the excretion rate of active kallikrein and log albumin excretion rate (AER), P<0.0088. Regression analysis also determined that the excretion rate of active kallikrein negatively correlates with hemoglobin in children with SCD, P<0.0096. In addition, an inverse relationship between log AER and hemoglobin was observed in male patients with SCD, P<0.0143. In children with SCD, cross-sectional analysis revealed a positive and significant correlation between log AER and age, suggesting age as a risk marker for AER in SCD. In multivariate regression analysis, our findings demonstrate a strong association between log AER and age and log kallikrein in children with SCD. About 20% of the variability in log AER in SCD patients is influenced by age and 6% is influenced by log kallikrein, P<0.0001 and P<0.02, respectively. CONCLUSIONS: These findings provide the first evidence that the excretion rate of active kallikrein is positively and independently correlated with log AER in children with SCD, and suggest that kallikrein could be a marker for progressive nephropathy. Longitudinal studies are essential to address this issue.     

Invasive pneumococcal disease in children with sickle cell disease in the pneumococcal conjugate vaccine era

Invasive pneumococcal disease (IPD) in children with sickle cell disease (SCD) can be devastating. We sought to assess the impact of IPD in children with SCD since licensure of the pneumococcal conjugate vaccines (PCVs). We found 11 cases of IPD giving an incidence of 417 per 100,000 person‐years, much higher than that reported in children without SCD. Although all isolates were sensitive to penicillin, 89% of isolates were nonvaccine serotypes. Further study is needed to characterize the incidence of and risk factors for the development of IPD in SCD in the PCV era to help drive better prevention strategies.     

Prevalence of Pneumococcal Bacteremia in Children with Sickle Cell Disease

We performed a retrospective chart review of children with sickle cell disease hospitalized for fever at our local institution. We reviewed 456 hospitalizations in 133 patients between January 2006 and June 2012. The prevalence of true bacteremia was 4%. The mean C-reactive protein values and temperatures were nonsignificantly higher in patients with positive blood cultures. The mean time to detection was 22.5 hours in bacteremia compared to 32.6 hours in blood cultures that grew contaminants (p = .034). Only two (0.4%) cases of pneumococcal bacteremia were reported and both occurred before May 2010, which marks the introduction of 13-valent pneumococcal vaccine (PCV13). Both patients with pneumococcal bacteremia had discontinued penicillin prophylaxis after the age of 5 years. The first patient was immunized but contracted a nonvaccine serotype (23B). The second patient was partially vaccinated and acquired a vaccine-preventable serotype (23F). Both serotypes were sensitive to ceftriaxone and vancomycin; one was resistant to penicillin. This is the first study reporting the prevalence of pneumococcal bacteremia since the introduction of PCV13.     

The spleen in the sickling disorders: an update

In early life, patients with sickle cell disease (SCD) can have acute, life-threatening emergencies related to splenic hypofunction (overwhelming bacterial sepsis), as well as anemic crises from acute splenic sequestration because of sudden pooling of blood in the spleen. The landmark penicillin prophylaxis study in 1985 showed a remarkable decrease in mortality from sepsis in young children with SCD who were treated with oral penicillin prophylaxis compared to placebo. Since that study, newborns are screened for SCD and placed on oral penicillin prophylaxis in nearly all of the United States, as well as in other countries where the disease is highly prevalent. The previously described permanent, complete and nearly universal “autosplenectomy” emerging by late childhood or early adulthood is now challenged by recent findings of reversibility of splenic dysfunction by the antisickling drug hydroxyurea or by successful allogeneic stem cell transplantation, even in older patients. Imaging techniques for hypofunction of the spleen are the most commonly used modalities to guide the clinician in decisions regarding medical or surgical management.     

Serotype distribution and antimicrobial susceptibility of <Emphasis Type="Italic"> Streptococcus pneumoniae </Emphasis>causing invasive infections and acute otitis media in children

A prospective study was conducted to determine the serotypes and antibiotic resistance patterns of pneumococcal isolates from children with invasive pneumococcal disease (IPD) and acute otitis media (AOM). From October 2001 to May 2002, 65 children with IPD (28 bacteraemic pneumonia, 24 bacteraemia without focus, 7 meningitis, 6 other infections) and 78 with AOM were identified. The most common serotypes causing IPD were 14 (32.3%), 6B (20.0%), 1 (18.5%) and 19F (7.7%) whereas the predominant serotypes causing AOM were 19F (35.9%), 14 (16.7%) and 23F (9.1%). Sixty-nine percent of IPD and 70.5% of AOM were caused by vaccine serotypes. The vaccine serotypes were more commonly encountered in meningitis cases and in children younger than 2 years of age. Intermediate resistance to penicillin was observed in 6 of 65 (9.2%) IPD isolates, one of which was intermediately resistant to cefotaxime (1.6%), whereas none exhibited high-level resistance to penicillin or other beta-lactam antibiotics. A higher proportion of antimicrobial resistance was noted in AOM isolates; 29 of 78 (37.4%) exhibited intermediate resistance and 8 (10.2%) high level resistance to penicillin, four of which had intermediate resistance to cefotaxime. Significant resistance was also noted to erythromycin; 38.5% of IPD and 48.7% of AOM isolates were resistant. Multidrug resistance was observed in one IPD and in eight AOM isolates. Conclusion:these findings have implications in the potential use of 7-valent conjugate vaccine in our region.Abbreviations AOM acute otitis media - IPD invasive pneumococcal disease - MIC minimal inhibitory concentration     

Value of pneumococcal vaccination in infants and young children]

Streptococcus pneumoniae is a common cause of meningitis, sepsis, pneumonia, acute otitis media, and sinusitis in children. Children younger than 24 months have the highest rates of invasive pneumococcal infections (Germany 1997-1999: 19.5/100,000/year). Pneumococcal infections cause in Germany 220-250 cases of meningitis, about 50,000 of pneumonia (children younger than 5 years) and more than 1 million cases of otitis media (children) annually. The case-fatality rate for invasive pneumococcal diseases is high (1997-1999 5.5%, meningitis 8.3%). 20-30% of survivors from meningitis suffer from CNS-related sequelea. In children up to 2 years vaccination with the heptavalent pneumococcal conjugate vaccine can reduce invasive pneumococcal diseases by about 80% and otitis media and recurrent otitis media by 6% and 9-16%, respectively. Due to the increased risk of pneumococcal infections in the first two years of live all children of this age group should be vaccinated. The high rate of resistance of pneumococci against macrolides in Germany, the high rate of non-licensed antibiotics in infants and the inefficacy of the 23-valent vaccine in children younger than 2 years makes the new vaccine to a necessary alternative.     

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.