A stepwise diagnostic approach for undiagnosed Anemia in children: A model for low-middle income country.

BACKGROUND: Reaching a precise diagnosis in rare inherited anemia is extremely difficult and challenging, especially in areas with limited use of genetic studies, which makes undiagnosed anemia a unique clinical entity in tertiary hematology centers. In this study, we aim at plotting a stepwise diagnostic approach in children with undiagnosed anemia while identifying indications for genetic testing. PATIENTS AND METHODS: A one-year cross-sectional study involved 44 children and adolescents with undiagnosed anemia after undergoing an initial routine panel of investigations. They were classified based on mean corpuscular volume (MCV) into 3 groups: microcytic (n = 19), normocytic (n = 14) and macrocytic (n = 11). An algorithm that included four levels of investigations was devised for each category. RESULTS: After applying a systematic diagnostic approach, 33 patients (75 %) were diagnosed of whom 7 (15 %) had combined diagnoses, while 11 (25 %) patients remained undiagnosed. Based on the first, second, third and fourth levels of investigations, patients were diagnosed, respectively, as follows: of the 11 patients, 7 were microcytic, 3 normocytic and 1 macrocytic; of the 7 patients, 2 were microcytic, 2 normocytic, and 3 macrocytic; of 10 patients, 5 were microcytic, 4 normocytic and 1 macrocytic; finally, of the 16 patients, 8 were microcytic, 6 normocytic and 2 macrocytic. Numbers recorded appear higher than the actual number of the patients because some of them were diagnosed by more than one level of investigation. The diagnoses obtained in the microcytic group showed hemoglobinopathies, iron refractory iron deficiency anemia (IRIDA), membrane defects, sideroblastic anemia, hypo-transferrinemia, a combined diagnosis of sickle cell trait and pyropoikilocytosis. The diagnoses also showed a combined diagnosis of hereditary spherocytosis (HS) and alpha thalassemia minor, and a combined diagnosis of iron deficiency anemia and beta thalassemia minor, while 15 % remained undiagnosed. In the normocytic group, the diagnosis revealed autosomal recessive (AR) HS, vitamin B12 deficiency, pyruvate kinase deficiency (PKD), congenital dyserythropoietic anemia (CDA) type I, Diamond Blackfan anemia and beta thalassemia major. In addition, it showed a combined diagnosis of AR HS and CDA type II, a combined diagnosis of AR HS and PKD, and a combined diagnosis of dehydrated stomatocytosis (DHS) and G6PD carrier, meanwhile 20 % remained undiagnosed. Finally, the macrocytic group was diagnosed by vitamin B12 deficiency, sideroblastic anemia, PKD, a combined diagnosis of PKD and G6PD deficiency carrier, while 45 % remained undiagnosed. CONCLUSION: Conducting a stepwise approach with different levels of investigations may help reach the diagnosis of difficult anemia without having to resort to unnecessary investigations. Combined diagnosis is an important cause of undiagnosed anemia, especially in countries with high frequency of consanguinity. The remaining 25 % of the patients continued to be undiagnosed, requiring more sophisticated investigations.

Evaluation of Sickle Cell Module for Quality of Life in Egyptian Children and Adolescents Patients: Impact of Psychiatric and Disease Specific Variables.

Sickle cell disease (SCD) impacts the physical, emotional, and psychological aspects of life. We aimed to study the quality of life (QoL) in Egyptian children and adolescents with SCD using the sickle cell module in relations to social, psychological and disease variables. A cross sectional study included 40 patients with SCD between 5 and 18 years. Details of diagnosis, SCD related complications, socioeconomic status were revised. Psychological assessment was done using children depression inventory, revised Children's Manifest anxiety scale and Health related QoL for both patients and parents using a validated Arabic age specific version of sickle cell module. Significant better scores for communication problems in mothers with college degree was found compared with other academic levels with no significant difference in QoL in relation to father education and significant higher communication problems with high rate of hospitalization (P = .021). Pain score was higher in 8-13 years compared with 13-18 years age groups. Significant worse scores for worrying was found in females, P = 0.033; Depression was found in 90% of studied patients. The main determinants of QoL in patients with SCD were maternal education and frequency of hospitalization. Depression is of alarming frequency for intervention.

Posterior Mediastinal and Cutaneous Back Hemangiomas in Infants: A New Association.

Infantile hemangiomas (IHs) are common vascular tumors. In most cases, a benign course with favorable outcome can be anticipated. IH typically present as cutaneous lesions either with a localized or diffuse segmental distribution. Segmental hemangiomas in the face may be associated with brain and cardiac anomalies (PHACES syndrome), whereas airway involvement has been reported to be associated with hemangiomas in the "beard" area. Multiple cutaneous hemangiomas may be associated with visceral hemangiomas (commonly in the liver). In this report, we present a new association where deep paravertebral hemangiomatous lesions were observed to be associated with cutaneous back hemangiomas in two consecutive cases.

Sirolimus: A Rescue Drug to Control Complications of Extensive Venous Malformation.

Venous malformations represent a major sector of vascular anomalies. Most cases are asymptomatic or subclinical; however, large extensive lesions can cause severe disability and sometimes mortality. In this report, we present a successful case of sirolimus treatment in managing an extensive venous malformation in the pelvis of a 21-month-old boy who presented with life-threatening complications. With a history dating since the day 2 of life, the patient suffered from chronic bleeding due to scrotal skin ulcerations, in addition to recurrent attacks of severe bleeding per rectum necessitating hospital admission and blood transfusion (three attacks since the age of 7 months). Pelvic magnetic resonance image showed the typical findings of extensive venous malformation involving the pelvis, perineum, scrotum, and extending to the gluteal region. The lesion was seen totally encasing the anorectum with marked thickening of their walls almost occluding their lumen. Oral sirolimus (2 mg/m 2 ) was started with a target blood trough level of 5 to 10 ng/mL. Over a follow-up period of 5 months, there was obvious clinical improvement that included healing of skin lesions (scrotal ulcer) with complete re-epithelialization, absence of bleeding per rectum with improvement of constipation, and rise of hemoglobin level from 7.5 to 11.5 g/dL.

Study of alpha hemoglobin stabilizing protein expression in patients with ß thalassemia and sickle cell anemia and its impact on clinical severity.

UNLABELLED: The α hemoglobin stabilizing protein (AHSP) binds α-Hb and prevents its precipitation limiting free α-Hb toxicities. Our aim was to study AHSP expression in ß thalassemia syndromes in relation to their clinical severity and to compare it with its level in sickle cell anemia. We compared patients with ß-thalassemia (n=37) (ß-thalassemia major (BTM) (n=19) and ß-thalassemia intermedia (BTI) (n=18)) with 12 patients with sickle cell anemia as regards clinical severity, age at presentation, transfusion dependency, mean pre-transfusion hemoglobin level, use of hydroxyurea and AHSP expression by real time quantitative PCR. Median (and IQR) AHSP expression was significantly higher in patients with sickle cell anemia 2275 (3898) compared to thalassemia 283 (718), P=0.001, with no significant difference between BTM and BTI (P=0.346). It was also significantly higher in non-transfusion dependent patients with ß thalassemia (NTDT) compared to transfusion dependent ones (P=0.019), and in patients on hydroxyurea therapy (P<0.001). However, there was no significant difference in its level according to clinical severity score (P=0.946) or splenectomy status (P=0.145). CONCLUSION: AHSP expression was higher in patients with sickle cell anemia versus thalassemia, with no significant difference between BTM and BTI. Expression was higher in patients with NTDT and on hydroxyurea therapy.

Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia.

Rapid assessment of platelet production would distinguish between thrombocytopenia due to decreased platelet production or increased peripheral platelet destruction. We evaluated the value of immature platelet fraction (IPF) in differentiating immune thrombocytopenia (ITP) from thrombocytopenia secondary to bone marrow failure and its potential use as a prognostic marker. Forty-one young patients with ITP were compared with 14 patients with hematological malignancies under chemotherapy, representing a control group with thrombocytopenia due to bone marrow suppression and 30 age- and sex-matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Complete blood count including IPF was performed using Sysmex XE-2100. ITP patients were classified into two subgroups: acute ITP with spontaneous resolution within 3 months from diagnosis and chronic ITP that lasted ≥ 1 year from diagnosis. Median IPF was 11.8% in patients with ITP, 7% in those with hematological malignancy and 3% in the control group (p < 0.001). ITP patients had significantly higher mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and IPF compared with patients with malignancy or healthy controls, while plateletcrit (PCT) was significantly lower in ITP patients than other groups (p < 0.001). IPF was increased in patients with chronic ITP compared with acute ITP group (p < 0.001). Patients with active ITP had the highest IPF followed by those in partial remission, while ITP patients in remission had the lowest IPF. IPF was positively correlated to the number of lines of treatment used, MPV, PDW and P-LCR, while negatively correlated to platelet count and PCT among ITP patients (p < 0.001). Multiple regression analysis showed that platelet count and P-LCR were independently related to IPF. ROC curve analysis revealed that the cut-off value of IPF at 9.4% could be diagnostic for ITP patients with a sensitivity of 88% and a specificity of 85.7%. We suggest that IPF may be a rapid and inexpensive automated marker for etiology of thrombocytopenia and can be integrated as a standard parameter to evaluate the thrombopoietic state of the bone marrow. It may be considered as a potential prognostic marker for the development of chronic ITP.

Effect of using bedside leukocyte filter on pulmonary functions in patients with thalassemia major.

UNLABELLED: In settings of limited health resources, using leukocyte-filtered blood is limited to patients with leukocyte-mediated complications. The aim of this study was to determine the patterns of lung dysfunction among patients with ß-thalassemia major (BTM) after the application of the leukostop filter during transfusion for a period of 6 months. The study included 30 patients with transfusion-dependent BTM divided into two groups according to the use of leukocyte filter. Group I included 15 patients with BTM allocated to use the leukocyte filter before each blood transfusion for 6 months and group II included 15 patients with BTM using nonleukocyte-filtered blood. Patients with history of airway disease and smokers were excluded. Chest X-ray and pulmonary function tests (PFT) using spirometry were done for each patient at baseline and after the use of the leukocyte filter for 6 months. No significant difference was found at baseline PFTs in both groups, the distribution of obstructive pulmonary disease significantly improved in group I in the postfilter evaluation, P < 0.05, however no change in pulmonary disease distribution in group II. A statistical significance improvement in forced vital capacity (FVC), forced expiratory volume in 1st second (FEV1) and FEV1/FVC in postfilter evaluation, while in group II a decline in FEV1, FVC, and no significant change in FEV1/FVC ratio. There was no correlation between serum ferritin and PFT results. CONCLUSION: Pulmonary function abnormalities, although subclinical is not an infrequent finding in patients with BTM; leukofiltred blood may improve PFT.

Pathogenesis and prognosis of neutropenia in infants and children admitted in a university children hospital in Egypt.

This study aimed to assess the prevalence, severity, and etiology of neutropenia in infants and children admitted to a children's hospital in Egypt. A total of 200 patients with neutropenia were recruited from April 1, 2010 to September 30, 2010. Patients with a known hematological or immunological disease were excluded. Patients were followed till recovery or an underlying cause was uncovered. Viral serological analysis was done for patients with moderate/severe neutropenia, including cytomegalovirus (CMV); Epstein-Barr virus (EBV); hepatitis A, B, and C viruses; and HIV. Antineutrophil cytoplasmic antibody (ANCA) tested by enzyme immunoassay and bone marrow aspirate were done for prolonged neutropenia. The results revealed that neutropenia was mild in 90 (45%), moderate in 56 (28%), and severe in 54 (27%). Clinical diagnosis at admission was bronchopneumonia (38%), pyrexia of undetermined etiology (17%), bronchiolitis (13%), urinary tract infection (9%), acute gastroenteritis (8%), hepatitis (6.5%), and septicemia (5%). Patients with mild neutropenia recovered within 1 week. Among 110 patients with moderate/severe neutropenia, 80 (73%) recovered in <3 weeks. Predictors of prolonged neutropenia were age younger than 18 months (P < .01), absolute neutrophils count (ANC) < 500/mm(3) (P < .05), hemoglobin < 10 gm/dL (P < .05), and positive CMV serology (P < .01). CMV and EBV serology were positive in 34.5% and 7.3% of patients, respectively. ANCA was positive in 42.8% of patients with prolonged severe neutropenia. In conclusion, neutropenia is a frequent finding in Egyptian infants and children, usually mild and transient, and mainly associated with infection. CMV and EBV are associated with prolonged neutropenia. Immune neutropenia is a common cause of moderate/severe neutropenia in the first two years of life.