Modified Delphi panel consensus recommendations for management of severe aplastic anemia.

ABSTRACT: Severe aplastic anemia (SAA) is a rare hematologic condition for which there is no clear management algorithm. A panel of 11 experts on adult and pediatric aplastic anemia was assembled and, using the RAND/University of California, Los Angeles modified Delphi panel method, evaluated >600 varying patient care scenarios to develop clinical recommendations for the initial and subsequent management of patients of all ages with SAA. Here, we present the panel's recommendations to rule out inherited bone marrow failure syndromes, on supportive care before and during first-line therapy, and on first-line (initial management) and second-line (subsequent management) therapy of acquired SAA, focusing on when transplant vs medical therapy is most appropriate. These recommendations represent the consensus of 11 experts informed by published literature and experience. They are intended only as general guidance for experienced clinicians who treat patients with SAA and are in no way intended to supersede individual physician and patient decision making. Current and future research should validate this consensus using clinical data. Once validated, we hope these expert panel recommendations will improve outcomes for patients with SAA.

Guidelines for the Standard Monitoring of Patients With Thalassemia: Report of the Thalassemia Longitudinal Cohort.

Chronic transfusion therapy has played a central role in extending life expectancy for patients with hemoglobinopathies such as thalassemia. However, this life-saving therapy is associated with numerous complications that now comprise the bulk of management considerations for patients with thalassemia. This review reports on the experience of the Thalassemia Longitudinal Cohort and reviews available literature to establish guidelines for the management of patients with thalassemia.

Effects of chronic transfusions on abdominal sonographic abnormalities in children with sickle cell anemia.

OBJECTIVE: To assess the effects of chronic erythrocyte transfusions on prevalence of sonographic incidence of organ damage in children with sickle cell anemia (SCA). STUDY DESIGN: Children (N=148; mean age, 13.0 years) with SCA, receiving chronic transfusions (average, 7 years), underwent abdominal sonography at 25 institutions. After central imaging review, spleen, liver, and kidney measurements were compared with published normal values. Potential relations between ultrasound, clinical, and laboratory data were explored via analysis of variance, Student t test, and Cochran-Mantel-Haenzel tests of non-zero correlation. RESULTS: Average spleen length was similar to normal children, but over one-third had spleen volumes >300 mL, 15 had previous splenectomy for splenomegaly, and 24 had abnormal splenic echotexture. Two-thirds had hepatobiliary disease; 37 had prior cholecystectomy, 46 had gallstones, and 16 had gallbladder sludge. Gallbladder disease correlated with older age (P=.002), longer liver length (P<.001), longer duration of transfusions (P=.034), and higher total bilirubin (P<.001). Liver (P<.001) and renal lengths (P≤.005) were larger than published norms. CONCLUSIONS: In children with SCA, long-term transfusion therapy may not prevent development or progression of abdominal organ dysfunction.

Increase in invasive Streptococcus pneumoniae infections in children with sickle cell disease since pneumococcal conjugate vaccine licensure.

Invasive pneumococcal disease (IPD) in children with sickle cell disease has decreased with prophylactic penicillin, pneumococcal polysaccharide vaccine, and pneumococcal protein-conjugate vaccine usage. We report 10 IPD cases since pneumococcal protein-conjugate vaccine licensure, including a recent surge of non-vaccine serotypes. IPD continues to be a serious risk in sickle cell disease.

Prevalence of intracardiac shunting in children with sickle cell disease and stroke.

OBJECTIVE: To determine the prevalence of potential intracardiac shunts, including patent foramen ovale (PFO), in children with sickle cell disease (SCD) and stroke. STUDY DESIGN: We performed a transthoracic echocardiogram (TTE) on 40 children with SCD (39 with hemoglobin SS and 1 with sickle-beta0 thalassemia) and earlier stroke (overt stroke in 30, silent infarction in 10). We compared 3 TTE techniques: conventional 2-dimensional imaging, color Doppler ultrasound, and intravenous agitated saline contrast injection for the detection of intracardiac shunts. We also evaluated the clinical, laboratory, and radiographic findings of the children with and without shunts. RESULTS: We identified PFO or other potential intracardiac shunts in 10 of 40 children with SCD and earlier stroke (25%; 95% CI, 11.6-38.4). With contrasted TTE, we failed to detect potential shunts in 2 children. In a comparison group of 60 children with stroke but without SCD, retrospective review of clinical echocardiograms identified PFO in 7 of 60 (11.7%; 95% CI, 3.6-19.8). Clinical features significantly associated with the presence of intracardiac shunts were stroke in the setting of vaso-occlusive crisis (P = .026) and headache at stroke onset (P = .014). CONCLUSION: One-quarter of children with SCD and stroke have potential intracardiac shunts. A combination of echocardiographic techniques is required for optimal shunt detection. Intracardiac shunting could be a risk factor for stroke in children with SCD because they are predisposed to thrombosis and elevations of right heart pressure, which could promote paradoxical embolization across an intracardiac shunt.

Vaso-occlusive episodes in older children with sickle cell disease: emergency department management and pain assessment.

OBJECTIVE: To describe emergency department (ED) management of older children with sickle cell disease (SCD) experiencing a vaso-occlusive episode (VOE) and factors associated with disposition and ED return. STUDY DESIGN: We retrospectively reviewed ED visits of children age >/=8 years with SCD over the course of 1 year. Data were collected from the electronic medical record and the SCD database. RESULTS: VOE was diagnosed 279 times in 105 patients; 45 of the patients had 1 ED visit, 25 had 2 ED visits, and 16 had >/=5 ED visits. The overall admission rate was 178/279 (64%), 166 on the first ED visit and 12 on a return visit within 72 hours. Use of home opioids, duration of VOE, and hemoglobin concentration were not associated with disposition. Discharge after 2 doses of intravenous (IV) morphine occurred in 33 patients. Pain relief after 1 dose, using a FACES scale of 1 to 5, differed significantly between the admitted patients and the discharged patients (1.1 vs 2.5; P < .0001). CONCLUSION: Suboptimal pain relief after 1 dose of IV morphine was associated with admission from the ED. Further investigation of pain relief, using validated pain assessment scales, as an outcome in VOE management is warranted.

Acquired Glanzmann's thrombasthenia as part of multiple-autoantibody syndrome in a pediatric heart transplant patient.

Although advances in immunosuppressive therapy have allowed prolonged patient survival, immune dysregulation observed in these patients has increased. We report an 11-year-old female heart transplant recipient in whom Glanzmann thrombasthenia was identified as part of a "multiple autoantibody syndrome" manifesting sequentially as autoimmune hemolytic anemia, thrombocytopenia, and neutropenia.

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.