Sleep-disordered breathing and transcranial Dopplers in sickle cell disease.

OBJECTIVES: To determine the prevalence of sleep-disordered breathing in children with sickle cell disease and whether there is an association of sleep-disordered breathing with high-risk transcranial Doppler ultrasonography (TCD) velocities. Study DESIGN: Cross-sectional. SETTING: Tertiary care academic medical center. PATIENTS: Sixty-four children (aged 2-14 years) selected for eligible genotype (type SS or Sß(0)-thalassemia) and no history of stroke. INTERVENTIONS: Parents completed the Pediatric Sleep Questionnaire. Overnight polysomnography was performed for children with snoring. The TCD was performed or existing results were obtained for all children; for children who underwent transfusion therapy, readings prior to the transfusion were analyzed. Children with abnormal or conditional TCD (flow velocity ≥170 cm/s in any vessel) were considered high risk. MAIN OUTCOME MEASURES: Prevalence of sleep-disordered breathing and TCD velocity and frequency of high-risk TCD in patients with and without sleep-disordered breathing. RESULTS: The prevalence of snoring was 37.5% (95% CI, 26.7%-49.8%), the prevalence of positive polysomnography findings was 23.7% (14.6%-36.1%), and the prevalence of positive Pediatric Sleep Questionnaire scores was 21.9% (13.4%-33.6%). There was no significant difference in TCD velocity or number of patients with high-risk TCD between nonsnorers and children with snoring but negative polysomnography findings and children with snoring and positive polysomnography findings (P = .91 and P = .66, respectively) or between nonsnorers and snorers with a negative Pediatric Sleep Questionnaire score and snorers with a positive Pediatric Sleep Questionnaire score (P = .76 and P = .33, respectively). CONCLUSION: There is a high prevalence of snoring and sleep-disordered breathing among children with sickle cell disease, but our results do not support an association with cerebrovascular risk.

A short course of prednisone in the management of acute chest syndrome of sickle cell disease.

BACKGROUND: A short course of dexamethasone therapy may attenuate the course of acute chest syndrome (ACS) of sickle cell disease, but it also increases the risk of early readmission after discharge. Over several years at our institution, an "asthma regimen" of prednisone [2 mg/kg/d (max 80 mg) in 2 divided doses for 5 days] has increasingly been used to treat moderate-to-severe ACS. METHODS: Review of medical records identified 63 patients hospitalized 78 times with ACS over a 2-year period. The clinical course of patients who received prednisone was compared with that of those who did not, particularly to assess the frequency of early (within 2 weeks) readmission after discharge. RESULTS: Eight (15.1%) of the 53 children receiving prednisone and 2 (8%) of the 25 who did not were readmitted within 2 weeks (P=0.33), usually for treatment of pain. Patients with moderate-to-severe ACS were more likely to receive prednisone. There was no difference in the duration of stay or the need for blood transfusion between the 2 groups; 21.8% of all the patients received blood. CONCLUSION: A short course of prednisone did not significantly increase readmission rate after discharge. Larger prospective studies are needed to confirm safety and to establish efficacy.

Venous thrombosis and pulmonary embolism in a child with pneumonia due to Mycoplasma pneumoniae.

A 13-year-old boy with Mycoplasma pneumoniae pulmonary infection developed deep vein thrombosis and pulmonary embolism. He was found to have protein S deficiency and transient antiphospholipid antibodies. Though uncommon, it is important to consider venous thromboembolic disease in children whose clinical course is atypically severe.

A prospective appraisal of pulmonary hypertension in children with sickle cell disease.

OBJECTIVES: Pulmonary hypertension (PHT) is a life-threatening complication of sickle cell disease that occurs in 20% to 40% of adults. Measurement of maximal tricuspid regurgitant jet velocity (TRV) by echocardiography provides a noninvasive screening tool; TRV values > or =2.5 m/s are correlated with PHT and increased mortality. Our objective was to estimate the prevalence of PHT in our pediatric sickle cell population and its possible association with various clinical and laboratory findings, including obstructive sleep apnea and/or pulmonary dysfunction. STUDY DESIGN: Eligible children had measurement of the TRV. Clinical data were collected, including detailed history with a standardized sleep apnea questionnaire; those with suggestive histories had polysomonography. Pulmonary function was assessed using whole body plethysmography. RESULTS: Of 48 subjects (79% homozygous sickle cell anemia; median age 12 y; 11 receiving chronic transfusion) enrolled in the study, 4 (8.3%) had TRV >2.5 m/s; all had homozygous sickle cell anemia and 1 was receiving hydroxyurea after 3 years of transfusion for secondary stroke prevention. Subjects with elevated TRV had higher indirect bilirubin levels; we found no association between elevated TRV and obstructive apnea or pulmonary function abnormalities. CONCLUSIONS: Elevation of TRV was relatively uncommon in our pediatric patients as compared with prevalence reported in adults and may be associated with increased hemolysis. There was no association with obstructive sleep apnea or abnormal pulmonary function.

Fatal delayed transfusion reaction in a sickle cell anemia patient with Serratia marcescens sepsis.

Patients with sickle cell anemia may require repeated red cell transfusion, putting them at risk for minor blood group alloimmunization and the development of delayed hemolytic transfusion reactions. Although Streptococcus pneumoniae is the most common cause of life-threatening infection in patients with sickle cell anemia, those who have been recently hospitalized are at risk for infection with resistant hospital-associated organisms, and blood transfusion may put the patient at risk of infection with transfusion-associated organisms such as Serratia marcescens and Yersinic enterocolitica. We recently cared for an adolescent with sickle cell anemia who presented to the emergency department with a severe, delayed hemolytic transfusion reaction and Serratia marcescens infection. The patient had been discharged from the hospital five days previously, and had been transfused and treated with antibiotics while hospitalized. In addition to demonstrating the potential severity of delayed hemolytic transfusion reactions, our case illustrates the importance of providing relatively broad-spectrum antibiotic coverage to patients with sickle cell anemia and possible infection who have recently been hospitalized.

Management of a large organized intraatrial catheter-tip thrombus in a child with acquired immunodeficiency syndrome using escalating tissue plasminogen activator infusions.

OBJECTIVES: To describe the dissolution of a large organized intraatrial catheter-tip thrombus using a novel aggressive dose escalation of tissue plasminogen activator infusion. DESIGN: Case report. SETTING: A six-bed pediatric intensive care unit (ICU) at a university hospital. PATIENT: An 8-yr-old with acquired immunodeficiency syndrome with a large organized intraatrial thrombus at the tip of an indwelling central venous catheter placed for total parenteral nutrition 2 months before presentation. INTERVENTION: Escalating dose of tissue plasminogen activator infusion. MEASUREMENTS: A large intraatrial catheter-tip thrombus (2.5 x 3 cm) was an incidental finding on an echocardiogram done to assess cardiac function. The thrombus occupied almost half the right atrial cavity and hit the tricuspid valve with each heartbeat without obstruction of tricuspid inflow. The catheter had no blood return from either lumen for >1 month. Protein C, protein S, and antithrombin III were normal, and factor V Leiden and prothrombin gene mutations were absent. Blood cultures were negative. Pediatric and cardiovascular surgeons recommended open-heart surgery as the safest option for catheter removal to avoid the risk of superior vena cava occlusion, vascular rupture, or embolization. A second opinion concurred. A trial of thrombolytic therapy with tissue plasminogen activator infusions was started at 0.1 mg/kg/hr for 6 hrs daily. No change in thrombus size was seen on a followup echocardiogram after 4 days. An aggressive dose escalation (0.15, 0.2, 0.25 mg/kg/hr for 6 hrs) was done over the next 5 days in an attempt to avoid open-heart surgery. Risks regarding disseminated intravascular coagulation and bleeding were presented to the parents. MAIN RESULTS: Followup echocardiogram on day 10 showed complete resolution of the thrombus. No changes in respiratory/hemodynamic status or oxygen saturation were observed. Studies for disseminated intravascular coagulation remained stable, and no clinical bleeding was seen. The catheter was safely removed surgically; pathology examination showed no residual thrombus. CONCLUSIONS: Prolonged infusion of tissue plasminogen activator in escalating doses was safe and effective in the management of a large intracardiac catheter-tip thrombus and helped avoid open-heart surgery. In view of the potential hazards of tissue plasminogen activator, close pediatric ICU monitoring is indicated with the use of high-dose tissue plasminogen activator infusions.

Myringotomy and tympanostomy tube placement in children with sickle cell disease.

OBJECTIVE: To assess the event rate of myringotomy and tube placement (M&T) in the pediatric patient population with sickle cell disease (SCD). METHODS: Four hundred and forty-nine children with confirmed SCD have been followed over a period of 11.5 years at two hospital-based pediatric hematology and otolaryngology offices, and three tertiary care hospitals. Children with SCD who had undergone M&T were identified via computer search of International Classification of Diseases codes by the medical records departments of the three hospitals, and from two databases of the hematology offices. The inpatient and outpatient medical records of all children identified were reviewed. RESULTS: For the 449 patients, mean duration of SCD follow-up was 6.13 +/- 3.36 years. Of these, eight patients (four boys, four girls, mean age 9 +/- 3.5 years; four patients had hemoglobin SC disease, and four patients had sickle cell anemia type SS) underwent M&T. Two children met criteria for severe SCD. The event rate for M&T insertion was 0.29/100 person-years, 95% CI (0.15, 0.58). CONCLUSIONS: The event rate for M&T in children with SCD, compared to a historical control group, is lower than that of the general population. Type and severity of SCD were not predictive of the need for tube insertion. Children with sickle cell disease do not have an increased rate of M&T insertion.

Elevated plasma sVCAM-1 levels in children with sickle cell disease: impact of chronic transfusion therapy.

Vascular cell adhesion molecule-1 (VCAM-1) has been implicated as being important in the pathophysiology of acute pain episodes (APE) and acute chest syndrome (ACS) of sickle cell disease (SCD). The frequency of these episodes is reduced by chronic transfusion therapy. The impact of chronic transfusion therapy on VCAM-1 expression is unknown. Soluble VCAM-1 (sVCAM-1) levels were measured in plasma using an ELISA assay (R&D Systems) in 61 patients with SCD (age range 1.5-20 years) and 12 normal controls (2.5-14 years). SCD patients included 20 with ACS, 14 with APE, 12 at well-child visits, and 15 receiving chronic transfusion therapy. Asymptomatic SCD patients had higher sVCAM-1 levels compared to normal subjects (P < 0.001). Levels of sVCAM-1 were further elevated during ACS (P < 0.001) and APE (P = 0.072) and returned to the asymptomatic range on resolution. Levels were significantly lower in transfused patients (P = 0.003) compared to asymptomatic SCD patients. Our findings of increased VCAM-1 expression during ACS and perhaps APE offer a rationale for therapeutic use of cytokine and other VCAM-1 modulators. The reduction of sVCAM-1 levels observed in our transfused SCD patients offers insight into the mechanism of the protective effect of transfusion against ACS and APE and possibly stroke.

Identification of a 4-base deletion in the gene in inherited intrinsic factor deficiency.

A 4-base deletion has been identified in the coding region of the gene for gastric intrinsic factor (IF) in an 11-year-old girl with severe anemia and cobalamin (Cbl) deficiency. The bone marrow showed frank megaloblastic morphology, and the Schilling test indicated a failure to absorb Cbl that was corrected by coadministration of IF. Pentagastrin administration induced acid secretion, but the gastric juice lacked IF as determined by CbI binding, by fractionation of protein-bound CbI, and by immunoprecipitation with anti-IF antiserum. Individual exons were amplified by the polymerase chain reaction by using primers to the flanking intronic regions, and the nucleotide sequence analysis identified a 4-base deletion (c183_186delGAAT) spanning positions 104 to 107 in exon 2, resulting in premature termination of translation. This mutation also eliminates a site for Bst XI endonuclease and introduces a site for BsaBI for identifying this deletion in hereditary IF deficiency.

Systemic lupus erythematosus in children with sickle cell disease.

Coexistence of sickle cell disease (SCD) and systemic lupus erythematosus (SLE) has been reported in 11 patients. The authors describe five additional patients with SCD and symptoms initially attributable to SCD who were later found to have SLE. Patients were identified over a 10-year period (1991-2001) in a pediatric sickle cell population numbering approximately 350. All patients are African-American. Age at diagnosis of SLE was 9 to 17 years (median 11 years), and follow-up after diagnosis ranged from 6 months to 10 years (median 3 years). SLE cerebritis (n = 3), serositis (n = 4), and nephritis (n = 2) were common findings. Physicians should be alerted to the possible development of SLE in patients with SCD.

Familial transient erythroblastopenia of childhood is associated with the chromosome 19q13.2 region but not caused by mutations in coding sequences of the ribosomal protein S19 (RPS19) gene.

Transient erythroblastopenia of childhood (TEC) is a rare condition, which at onset may be difficult to distinguish from Diamond-Blackfan anaemia (DBA). We have previously shown that mutations in the ribosomal protein S19 gene (RPS19) cause DBA. In order to clarify whether TEC and DBA are allelic, we investigated the segregation of markers spanning the RPS19 gene region on chromosome 19q13.2 and performed sequence analysis of all exons in the RPS19 gene in seven TEC sibling pairs. Linkage analysis supported allelism for TEC and DBA at the RPS19 gene locus and implies molecular mechanisms other than structural mutations in the RPS19 gene.