Screening children for sickle cell vasculopathy: guidelines for transcranial Doppler evaluation

Cerebral infarction is a major cause of morbidity and mortality in children with sickle cell disease. Prevention of primary stroke might be feasible with a way to identify children at greatest risk. Transcranial Doppler (TCD) has been shown to be a noninvasive, reliable, inexpensive method of identifying children at highest risk for cerebral infarction. The pros and cons of imaging and non-imaging TCD techniques are discussed. The protocol for the stroke prevention trial in sickle cell anemia (STOP), including data acquisition and interpretation, is reviewed. Providing TCD to sickle cell patients can be a valuable service that results in a significant decrease in first stroke rates.     

Expanding options to improve outcomes following hematopoietic stem cell transplantation

Allogeneic hematopoietic stem cell transplantation (HSCT) offers a curative option for children with a number of potentially lethal malignant and non-malignant conditions. Decisions regarding the appropriateness of HSCT for a given patient involve careful consideration of the risks associated with HSCT and the likelihood of cure. This is particularly important as the procedure is being used with increasing frequency for diagnoses such as high-risk sickle cell anemia where the disease is associated with shortened lifespan but death generally occurs in adulthood. Recent advances in supportive care such as improved anti-microbial agents, the use of reduced intensity conditioning regimens and high-resolution HLA typing that allows for better donor selection have all contributed to improved outcomes. However, the risk of treatment-related mortality remains approximately 5-10%, in part due to complications such as veno-occlusive disease (VOD) for which there has been less progress.     

BONE MARROW TRANSPLANTATION OR HYDROXYUREA FOR SICKLE CELL ANEMIA: Long-Term Effects on Semen Variables and Hormone Profiles

Ten male subjects affected by sickle cell anemia (SCA) were studied to evaluate the long-term effects of therapies on their fertility. Their ages ranged from 18 to 34 years (median: 32 years). Four subjects were treated by hydroxyurea (HU) and 6 by hematopoietic stem cell transplantation (HSCT). The median follow-up after HU initiation and HSCT was 10.5 years (range: 8–15 years) and 15.5 years (range: 8–21 years), respectively. Three of the 6 in the HSCT group and two of the 4 in the HU group were azoospermic. One HSCT subject had normal semen and hormone variables, showing that normal fertility can occasionally be expected after transplantation in SCA. The remaining 4 patients (2 HSCT and 2 HU) were oligozoospermic. With regard to HU, semen impairment appears to be related to the duration of treatment. To draw general conclusions, further research with a large number of patients treated since childhood with HU or HSCT is warranted.     

Successful treatment of refractory autoimmune hemolytic anemia with monthly rituximab following nonmyeloablative stem cell transplantation for sickle cell disease

Autoimmune hemolytic anemia (AIHA) can occur following hematopoietic stem cell transplantation (HSCT) and may be associated with other cytopenias. It can also occur in the context of chronic red cell transfusion in patients maintained on hypertransfusion regimens. There are an increasing number of reports on the successful treatment of autoimmune cytopenias with the monoclonal anti-CD20 antibody rituximab, including a few patients in a post-HSCT setting. The authors report the successful treatment with rituximab of refractory AIHA following allogeneic nonmyeloablative bone marrow transplantation in a child with sickle cell disease.     

Hyperreninemia and hyperaldosteronism in sickle cell anemia.

Fourteen patients with sickle cell anemia, ages 6 to 20 years, were studied while ingesting high- and low-sodium diets. Although none of the patients had excessive urinary loss of sodium, the majority had elevated plasma renin activities and aldosterone secretion rates. The PRA was higher in patients over 10 years of age; ASR in patients receiving the high-sodium diet increased with age. Patients with sickle cell anemia appeared to compensate for urinary sodium loss between crises. The mechanism of this loss could be a defect in the function of either the distal tubule or the loop of Henle.     

Bone marrow transplantation in the treatment of sickle cell anemia

The possibility of using bone marrow transplantation to treat selected patients with sickle cell anemia has recently been raised by the effectiveness of this approach in an 8-year-old girl suffering from both acute myeloblastic leukemia and sickle cell anemia. The child's sickle cell anemia was converted to the donor's sickle cell trait and she remains in complete remission from her leukemia 22 months following transplantation. This paper considers the therapeutic implications of this child's progress and discusses the major immunological complications, particularly graft-vs.-host disease, which currently limit the more widespread use of marrow transplantation in the therapy of sickle cell anemia.     

Amelioration of clinical severity through raised fetal hemoglobin in sickle cell anaemia

In the present study, the levels of fetal hemoglobin (HbF) in sickle cell anemia patients were compared with sickle cell trait, beta thalassemia major and control. The mean HbF levels in beta thalassemia major and sickle cell anemia were 51.62 and 19.63% respectively. However, when the amount of HbF was expressed in terms of gram hemoglobin per deciliter whole blood, the mean values were 2.88 and 1.81 respectively between the two groups, suggesting that the genetic mechanism controlling the different threshold levels of increased HbF in these disorders could probably be similar. The elevated. HbF level in sickle cell anemia along with moderate hematologic profile observed in the present study is suggested to provide amelioration of the clinical severity unlike in beta thalassemia major where despite raised HbF levels, the severe clinical implications are attributed to marked imbalance in the globin chain synthesis.     

Klebsiella pneumoniae osteomyelitis in sickle cell anemia

A case ofKlebsiella pneumoniae osteomyelitis in a patient with sickle cell anemia is reported. The literature is briefly reviewed. The case is presented because of the rarity ofKlebsiella pneumonia osteomyelitis in sickle cell disease.     

CD36 immunization in a patient undergoing hematopoietic stem cell transplantation

Anti-CD36 antibodies are known to cause a platelet refractory state. We describe a previously unreported case of a 16-year-old female sickle cell disease patient with anti-CD36 antibodies, detected on routine screen prior to hematopoietic stem cell transplantation (HSCT). CD36 platelet antigen typing was negative for both the patient and her HLA-identical donor sibling. Patient plasma was compatible with 48 of 49 apheresis platelets, which were untested and presumably positive for the CD36 antigen. The patient responded adequately to transfusion of crossmatch compatible platelets and successfully underwent HSCT. The presence of anti-CD36 antibodies does not exclude potential candidates from HSCT.     

Sickle cell anemia in two White American children: essential laboratory criteria for diagnosis.

A number of hematologic disorders share diagnostic and clinical features of sickle cell anemia but have significantly different genetic implications and prognosis. Because of these differences, the establishment of a precise diagnosis is essential for the child in whom any form of sickle cell disease is identified. To illustrate the requirements for a definitive laboratory diagnosis of sickle cell anemia, this report presents the approach to establishing this diagnosis in two white American patients. From a review of the literature, these patients appear to be the only white Americans with sickle cell anemia in whom the diagnosis has been unequivocally established.     

Duodenal ulcer in sickle cell anemia

A 14-year-old black male with sickle cell anemia developed a duodenal ulcer that masqueraded as sickle cell-related abdominal pain crisis on multiple occasions. Malingering and poor therapeutic compliance aggravated the ulcer in this patient, who ultimately succumbed to a catastrophic bleed. Duodenal ulcer appears to be an infrequent but difficult to treat lesion in sickle cell disease. An in-depth review on the occurrence of duodenal ulcer in sickle cell anemia is presented. The etiological mechanisms of peptic ulcer disease in this population and the potential benefits of transfusion therapy are discussed.     

Sickle cell anemia and hematopoietic cell transplantation: When is a pound of cure worth more than an ounce of prevention?

Abstract:  Hematopoietic cell transplantation (HCT) is curative therapy for sickle cell anemia (SCA). However, its widespread use is constrained by donor availability and by concerns about its short-term and long-term toxicities. Current efforts to identify suitable candidates for HCT, to decrease the toxicity of HCT, and to broaden its availability are discussed.     

Obesity—Does It Occur in Nigerian Children with Sickle Cell Anemia

Children with sickle cell anemia are vulnerable to growth deficits; thus, it would be thought that obesity would be rare among them. The objective of the study is to examine the prevalence of obesity in a sickle cell anemia population in Lagos. A random sample of children with sickle cell anemia aged 2–15 years was interviewed and anthropometric measurements including weight and height were taken. Their body mass index (BMI) was calculated. Participants were classified as obese or not obese by their BMI or weight-for-height-for-age using World Health Organization standard definitions. The overall prevalence of obesity was 2.5% and 3.8% among hemoglobin genotype SS subjects and hemoglobin genotype AA controls, respectively. The age-specific prevalence for obesity was highest among the adolescent age category in hemoglobin genotype AA controls and the childhood age category in subjects with sickle cell anemia. All the obese subjects with sickle cell anemia were from upper socioeconomic strata, while two and one of the three subjects with hemoglobin genotype AA were from upper and middle socioeconomic strata, respectively. Obesity does exist among children with sickle cell anemia in Lagos, Nigeria. Public health programs aimed at prevention and control of obesity must include children with sickle cell anemia.     

Obesity--does it occur in Nigerian children with sickle cell anemia

Children with sickle cell anemia are vulnerable to growth deficits; thus, it would be thought that obesity would be rare among them. The objective of the study is to examine the prevalence of obesity in a sickle cell anemia population in Lagos. A random sample of children with sickle cell anemia aged 2-15 years was interviewed and anthropometric measurements including weight and height were taken. Their body mass index (BMI) was calculated. Participants were classified as obese or not obese by their BMI or weight-for-height-for-age using World Health Organization standard definitions. The overall prevalence of obesity was 2.5% and 3.8% among hemoglobin genotype SS subjects and hemoglobin genotype AA controls, respectively. The age-specific prevalence for obesity was highest among the adolescent age category in hemoglobin genotype AA controls and the childhood age category in subjects with sickle cell anemia. All the obese subjects with sickle cell anemia were from upper socioeconomic strata, while two and one of the three subjects with hemoglobin genotype AA were from upper and middle socioeconomic strata, respectively. Obesity does exist among children with sickle cell anemia in Lagos, Nigeria. Public health programs aimed at prevention and control of obesity must include children with sickle cell anemia.     

Sickle cell trait/hereditary persistence of fetal hemoglobin trait. Misdiagnosis as sickle cell anemia by newborn screening

A black female infant, reported as a result of mandatory newborn screening to have sickle cell anemia, was found at 8 months of age to have instead the entirely benign disorder sickle cell trait/hereditary persistence of fetal hemoglobin trait. The finding of hemoglobin S without Hb A does not suffice for the diagnosis of homozygous Hb S. Screening programs that diagnose sickle cell aneimia without first demonstrating sickle hemoglobin in both parents will consistently misdiagnose several more benign hemoglobin states as sickle cell anemia.     

On the road to gene therapy for beta-thalassemia and sickle cell anemia

Human globin gene therapy is a potential cure for sickle cell disease and β-thalassemia (Cooley anemia). A clinical trial of this treatment is currently under way in Paris using lentiglobin vectors.     

Adenotonsillar hypertrophy: a precipitating factor of cerebrovascular accident in a child with sickle cell anemia

Cerebrovascular accident is one of the most serious complications of sickle cell anemia. The specific factors that predispose patients with sickle cell anemia to stroke are increased disease severity, higher baseline white blood cell count and lower baseline hematocrits. Likewise the presence of a co-existent alpha thalassemia trait and/or high fetal hemoglobin (HbF%) may reduce the risk. We report a child with sickle cell anemia and marked adenotonsillar hypertrophy resulting in obstructive sleep apnea syndrome. There was no other known risk factor for developing cerebrovascular accident in this child during her hospitalization for adenotonsillectomy.     

Sickle cell intrahepatic cholestasis with cholelithiasis

Sickle cell intrahepatic cholestasis (SCIC) is a rare complication seen in sickle cell patients who present with sudden onset of RUQ pain, progressive hepatomegaly, mild elevation of transaminases, coagulopathy, and extreme hyperbilirubinemia. Early recognition of this entity is essential to avoid life-threatening complications. Diagnosis can be challenging given the overlap in clinical presentation with other conditions affecting the hepatobiliary biliary system in sickle cell anemia such as hepatitis, cholecystitis, and hepatic crisis. Treatment is currently limited to exchange transfusion. The authors present two patients with SCIC and cholelithiasis; the clinical picture of one is complicated by choledocholithiasis.     

Lack of mortality in 22 children with sickle cell anemia and severe malarial anemia

Retrospective studies suggest that there is high mortality in children with sickle cell anemia (SCA) and severe malaria. We assessed mortality in Ugandan children with severe malarial anemia (SMA, n = 232) or cerebral malaria (CM, n = 267) by sickle cell hemoglobin genotype. Admission and 2‐year follow‐up mortality did not differ among children with SMA who had homozygous form of sickle cell hemoglobin (HbSS) versus normal form of adult hemoglobin (admission, 0/22, 0%, vs. 1/208, 0.5%; follow‐up, 1/22, 4.5%; 7/207, 3.4%, respectively; all P > 0.6). The single child with CM and HbSS survived. The study findings highlight the need for large prospective studies of malaria‐related mortality in children with SCA.     

Successful early intervention for hyperacute transplant‐associated thrombotic microangiopathy following pediatric hematopoietic stem cell transplantation

Jodele S, Bleesing JJ, Mehta PA, Filipovich AH, Laskin BL, Goebel J, Pinkard SL, Davies SM. Successful early intervention for hyperacute transplant‐associated thrombotic microangiopathy following pediatric hematopietic stem cell transplantation.
Pediatr Transplantation 2012: 16: E39–E42. © 2010 John Wiley & Sons A/S. Abstract: TA‐TMA is a serious complication of hematopoietic stem cell transplantation, presenting as microangiopathic hemolytic anemia with severe renal injury and mortality as high as 60%. Diagnosis and treatment of TA‐TMA is very challenging after HSCT because anemia, thrombocytopenia, hypertension, and renal impairment are multifactorial, leading to delayed recognition and management of this complication. We report a successful outcome following early intervention for hyperacute TA‐TMA after allogeneic HSCT.