Significant pituitary siderosis is common in transfusion dependent sickle cell disease.

Chronically transfused sickle cell patients typically don't exhibit iron-mediated extrahepatic toxicity. However, we demonstrate that the pituitary gland is vulnerable to iron deposition, and it occurs regardless of other extrahepatic involvement. Severe pituitary siderosis is associated with early organ dysfunction.

A Novel Discriminating Tool for Microcytic Anemia in Childhood.

Accurate and timely interpretation of microcytic anemia can be diagnostically challenging in the primary care setting. We sought to develop a novel model for distinguishing iron-deficiency anemia from thalassemia trait in the modern pediatric population. Demographic history and red blood cell indices were retrospectively characterized for 76 children referred to our pediatric hematology clinic for evaluation of microcytic anemia. Statistically significant variables were sequentially added into a logistic regression model to develop the final model. The final discriminating model incorporates red cell distribution width, mean corpuscular hemoglobin concentration, and red blood cell values. Favorable predictive performance is seen in the initial (sensitivity 89.2%, specificity 92.3%) and external validation cohort (sensitivity 84.4%, specificity 88.9%). This novel tool may aid in determining the cause of hypochromic, microcytic anemia in the primary care setting. Finally, the study cohort reflects an underrepresented group in the development of screening tools, and thus offers generalizability.

Splenic iron decreases without change in volume or liver parameters during luspatercept therapy.

Splenic iron decreased whereas liver iron was stable during luspatercept therapy in some individuals with thalassemia. This suggests a reduction of ineffective erythropoiesis changes the organ distribution of iron and demonstrates that liver iron concentration alone may not accurately reflect total body iron content. This article describes data from subjects enrolled in BELIEVE (NCT02604433) and BEYOND (NCT03342404).

First case report of bloodstream infection by Rhizomucor pusillus in a child with hemophagocytic lymphohistiocytosis.

We describe an unusual presentation of fatal infection due to Rhizomucor pusillus bloodstream infection in a 12-year old pediatric patient recently diagnosed with hemophagocytic lymphohistiocytosis. R. pusillus was isolated from one blood culture drawn on Day 11 of hospitalization.

Ferritin trends do not predict changes in total body iron in patients with transfusional iron overload.

Ferritin levels and trends are widely used to manage iron overload and assess the efficacy of prescribed iron chelation in patients with transfusional iron loading. A retrospective cohort study was conducted in 134 patients with transfusion-dependent anemia, over a period of up to 9 years. To determine whether the trends in ferritin adequately reflect the changes in total body iron, changes in ferritin between consecutive liver iron measurements by magnetic resonance imaging (MRI) were compared to changes in liver iron concentrations (LIC), a measure of total body iron. The time period between two consecutive LIC measurements was defined as a segment. Trends in ferritin were considered to predict the change in LIC within a segment if the change in one parameter was less than twofold that of the other, and was in the same direction. Using the exclusion criteria detailed in methods, the trends in ferritin were compared to changes in LIC in 358 segments. An agreement between ferritin trends and LIC changes was found in only 38% of the 358 segments examined. Furthermore, the change in ferritin was in opposite direction to that of LIC in 26% of the segments. Trends in ferritin were a worse predictor of changes in LIC in sickle cell disease than in thalassemia (P < 0.01). While ferritin is a convenient measure of iron status; ferritin trends were unable to predict changes in LIC in individual patients. Ferritin trends need to be interpreted with caution and confirmed by direct measurement of LIC.

Tissue iron evaluation in chronically transfused children shows significant levels of iron loading at a very young age.

Chronic blood transfusions start at a very young age in subjects with transfusion-dependent anemias, the majority of whom have hereditary anemias. To understand how rapidly iron overload develops, we retrospectively reviewed 308 MRIs for evaluation of liver, pancreatic, or cardiac iron in 125 subjects less than 10 years old. Median age at first MRI evaluation was 6.0 years. Median liver iron concentrations in patients less than 3.5 years old were 14 and 13 mg/g dry weight in thalassemia major (TM) and Diamond-Blackfan anemia (DBA) patients, respectively. At time of first MRI, pancreatic iron was markedly elevated (> 100 Hz) in DBA patients, and cardiac iron ( R2* >50 Hz) was present in 5/112 subjects (4.5%), including a 2.5 years old subject with DBA. Five of 14 patients (38%) with congenital dyserythropoietic anemia (CDA) developed excess cardiac iron before their 10th birthday. Thus, clinically significant hepatic and cardiac iron accumulation occurs at an early age in patients on chronic transfusions, particularly in those with ineffective or absent erythropoiesis, such as DBA, CDA, and TM, who are at higher risk for iron cardiomyopathy. Performing MRI for iron evaluation in the liver, heart, and pancreas as early as feasible, particularly in those conditions in which there is suppressed bone marrow activity is very important in the management of iron loaded children in order to prescribe appropriate chelation to prevent long-term sequelae. .

Hemophagocytic lymphohistiocytosis in children with chronic granulomatous disease.

Hemophagocytic lymphohistiocytosis (HLH) is characterized by fever, cytopenias, splenomegaly, and hemophagocytosis by macrophages activated by high cytokine levels. Chronic granulomatous disease (CGD) is characterized by recurrent infections, hyperinflammation, and excessive cytokine release. This may predispose patients with CGD to developing HLH during an infection. We conducted a retrospective review of patients with CGD, treated at our institution between 1999 and 2008. Three out of 17 patients developed HLH. Patients with CGD may be at increased risk for developing HLH. Remission of HLH was achieved after treatment with antimicrobials, steroids, and intravenous immunoglobulin This approach to treatment appears to be effective.

Nutritional deficiencies in iron overloaded patients with hemoglobinopathies.

One of the hallmarks of both sickle cell disease (SCD) and thalassemia major (TM) is accelerated oxidative damage. Decreased antioxidant levels and increased oxidant stress biomarkers are found in both diseases. Although isolated vitamin deficiencies have been reported in TM and nontransfused SCD patients, a comprehensive evaluation of vitamin and trace mineral levels has never been performed in chronically transfused SCD or TM patients. As vitamins and trace minerals may be consumed as a result of chronic oxidative stress; we hypothesized that levels of these compounds would correlate with surrogates of iron overload, hemolysis, and inflammation in chronically transfused patients. Using a convenience sample of our group of chronically transfused patients we studied 43 patients with SCD (17 male, 26 female) and 24 patients with TM (13 male and 11 female). The age range for our patients varied from 1.5 to 31.4 years. Levels of vitamins A, thiamin, B6, B12, C, D, E as well as selenium, zinc, copper, and ceruloplasmin were measured. We found that 40-75% of the patients were deficient in A, C, D and selenium and 28-38% of the patients had low levels of B vitamins and folate. There was little association with iron overload, hemolysis, or inflammation. Although the precise mechanism of these deficiencies is unclear, they may contribute to the morbidity of chronically transfused hemoglobinopathy patients.

Vitamin D deficiency, cardiac iron and cardiac function in thalassaemia major.

Vitamin D25-OH and D1-25OH levels were compared with cardiac R2* (1/T2*), left ventricular ejection fraction (LVEF), age, ferritin and liver iron in 24 thalassaemia major patients. Vitamin D25-OH levels were reduced in 13/24 patients while vitamin D1-25OH levels were often elevated. Vitamin D25-OH levels decreased with age (r(2) = 0.48) and with liver iron (r(2) = 0.20). Cardiac R2* was inversely related with the ratio of D25-OH to D1-25OH levels (r(2) = 0.42). LVEF was also proportional to the D25-OH/D1-25OH ratio (r(2) = 0.49). Vitamin D deficiency may be associated with cardiac iron uptake and ventricular dysfunction in thalassaemia major patients.

Successful anti-CD20 monoclonal antibody treatment of severe autoimmune hemolytic anemia due to warm reactive IgM autoantibody in a child with common variable immunodeficiency.

Autoimmune hemolytic anemia due to warm reactive IgM autoantibodies is unusual, severe, and often fails to respond to standard immunosuppressive therapies in both adults and children. A 6-year-old girl with common variable immunodeficiency had longstanding steroid dependent, splenectomy-unresponsive, warm IgM autoantibody-mediated autoimmune hemolytic anemia. Rituximab, a monoclonal antibody directed against CD20 antigen, was used to deplete B lymphocytes and reduce autoantibody production. She received a total of six doses of rituximab (375 mg/m2). Therapy was well tolerated, and B-lymphocytes were effectively depleted from the peripheral blood. The patient was completely tapered off glucocorticoids. The patient has remained off immunosuppressive agents for 16 months despite the return of B lymphocytes to the peripheral circulation. She continues to require IVIG. Early treatment with rituximab might be an option for patients with warm reactive IgM autoantibody-mediated autoimmune hemolytic anemia not responding to other treatments or experiencing untoward side effects from those treatments.

Pharmacokinetic analysis of plasma-derived and recombinant F IX concentrates in previously treated patients with moderate or severe hemophilia B.

BACKGROUND: Hemophilia B is an X-linked bleeding disorder that affects approximately 1 in 25,000 males. Therapy for acute bleeding episodes consists of transfusions of plasma-derived (pd-F IX) or recombinant (r-F IX) concentrates. STUDY DESIGN AND METHODS: A double-blind, two-period crossover study was initiated to assess the pharmacokinetics of pd-F IX and r-F IX and to address patient-specific variables that might influence in vivo recovery. Study product was administered by a single bolus infusion (50 IU/kg) to 43 previously treated patients in the nonbleeding state, and F IX:C levels were measured over a period of 48 hours after infusion. RESULTS: The mean in vivo recovery in the pd-F IX group was 1.71 +/- 0.73 IU per dL per IU per kg compared with 0.86 +/- 0.31 IU per dL per IU per kg with r-F IX (p