ALBERT

Description: Abstract 4807 Background: Pica defined as a compulsive and persistent intake of inedible substances or atypical food combinations at least one month. Association of pica and sickle cell disease (SCD) are poorly documented. Alerted by parents, we decided to verify systematically a) the occurrence of pica in SCD children b) to determine its duration, c) to identify the substances commonly ingested and d) to determine the characteristics among children and adolescents with SCD who reported practicing pica. Methods: SCD patients were seen in the outpatient clinic at the University Children's Hospital Queen Fabiola at Brussels between May 1, 2010 and July 30, 2010 as part of their regular follow-up. Data on sex, age, weight, height, body mass index, sickle cell phenotype, G6PD deficiency as well as biological data such as hematocrit mean corpuscular volume, fetal hemoglobin, plasma iron, zinc, copper, lead levels were recorded from their medical chart. Parents and patients were interviewed for the presence of eating disorders. Children and care givers completed questionnaires assessing symptoms of pica. Patients with acute illness, pregnancy, developmental delay, cognitive impairment or age younger than 3 years were excluded. Student t-test was used for difference in mean values groups by pica presence or absence. Fisher exact test was used to compare categorical variable. Difference in means values were considered statistically significant at p 〈 0.05. Results: Fifty-Five patients (24 males and 31 females) with a median age of 8. 9 years (6. 7– 11. 3) were evaluated during the study period. Forty-five patients (81.8%) originate from Central Africa, 10.9% (6/55) from West Africa, 1.8 %(1/55) from respectively East Africa, Italy and 3.6% (2/55) have mixed origin. Fifty –two (94.5%) patients are homozygous for Hb S (Hb SS), 3 are SC and 1 has Sβ° thalassemia. Thirty-one patients (56.4%) reported an history of pica and during the study period 29.1% (16/55) reported practicing pica regularly. The mean age of patient with pica was 7. 4 years significantly lower than non-pica patients (p 0.05) (Table 1). Iron status was identical. Lead overload was absent in the entire cohort. Hemolytic phenotype assessed by LDH was identical in both group and mild zinc deficiency was present in both groups. We did not observe difference due to hydroxyurée intake (p〉0.05) Conclusion: In our study, pica appeared to have a very high prevalence in SCD children and adolescents. However, its etiology is still unknown. Except lower age and significant lower hematocrit value in pica patients when compared to non-pica ones, no differences in iron status, zinc deficiency or hematological parameters was found. The general health status evaluated by BMI was identical in both groups and the trend to more boys in the pica group is not significant. Further studies are necessary to establish the etiology of pica and its possible consequences on SCD. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4821 Background: Red cell exchange transfusion is frequently used in the management of patients with sickle cell disease either electively or therapeutically to maintain an hemoglobin S (Hb S) level 〈 30–50%. This target is often difficult to maintain. In order to assess the effects of chronic partial exchange transfusion (CPET) a) on level of Hb and Hb S, b) on iron overload c) the need for chelation, d) on risk of long term adverse events and e) clinical outcome, we analyzed the data of sickle cell disease patients treated by long term CPET in our center. Methods/subjects: In the cohort of 163 SCD patients followed at University Children's Hospital at Brussels (Belgium), 10 benefit from CPET. Main reasons for CPET were neurologic disease (4), frequent ACS (3), previous severe hepatic cholestasis (2), leg ulcer (1) and pulmonary hypertension (1). The median age at start of treatment was 13 years (range 4 –19). These patients (6 males and 4 females) account for 248 exchanges during a median follow-up of 20 months (range 6– 36). These exchanges are until now performed manually and the volume exchanged is calculated taking into account the Hb level and the last HbS percentage. It is usually between 30 and 40 ml/kg BW. Except if severe anemia occurs, the goal of these exchanges is to keep a constant hematocrit level. All patients had a full red cell phenotype performed and received blood matched for ABO, Rhesus, Kell and Duffy antigens systems. The estimation of iron balance (iron intake- iron removed) was calculated yearly. Results: The pre-exchange Hb value was 9.5 g/dl (median; range: 7.7–10.9 g/dl) and the mean post value was 9.4/dl (range: 8.4– 11.1 g/dl). These values are not statistically different (p〉 0.05). The majority of patients (9/10) are reached an HbS 〈 50% when measured 3–5 weeks after PET (just before the next procedure) with a median HbS value of 40% (range: 30–54). At start of CPET program, the median ferritin level was 439 ng/ml (range: 80 – 1704). Five patients had already a ferritin 〉 500 ng/mL due to numerous previous transfusions. At last evaluation, the median ferritin did not change significantly and was 531 ng/ml (range 84– 3840). The two patients with ferritin higher than 1000 ng/ml start chelation with good result for one. One The mean annual net RBC load were 1.72 ml RBC/kg/yr provided approximately 1.85 mg of iron/kg/yr. Individual data are given in table 1. CPET-treated patients exchanged showed clinical improvement with disappearance of SCD crisis and related complications. The procedure was well tolerated by most patients, and adverse effects were limited to mild hypotension (3/10). No autoimmune hemolysis or allo-immunisation was documented in this cohort. All children remained negative for HIV and hepatitis C virus infections. Conclusion: Manual CPET seems to be safe to prevent middle-term iron overload and the need of elation therapy in most of patients. CPET can therefore be recommended for SCD patients who required decreased in Hb S levels either prophylactically or therapeutically. Manual are safe, effective and easy to use when mechanized exchanges are not possible for technical reasons. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 2659 Sickle cell disease (SCD) has polymorphic manifestations, it is not well known by many physicians, and patients have often a precarious status. So despite enormous improvements in the understanding of the pathogenesis of SCD, patient care remains difficult.The objectives of this work were to create a clinical data base in order to learn the characteristics of this population, to create a network between practitioners (general, emergency and specialist practitioners), to provide state-of-the art and guidelines, it could be a tool to disseminate information, for education projects and for research; it could also represent a pilot project for other chronic diseases. A practical aspect of this data base is to improve follow-up and treatment of SCD patients by “online access from everywhere”. The SCD clinical data base was a national project and was approved by each local ethic committee; informed consent of each patient was obtained. The first step was to create the electronic database with several security measures (i.e. login, password, and separate administrators). The second step was to introduce patient's data. Patients were followed in different Academic and Secondary Care Centers. Data were collected from the initial contact until December 31, 2007. The data collection included parents' origin, hemoglobin phenotype, origin of diagnosis, clinical events, biological and radiological data, hospitalizations, and types of treatment. Up to date, we introduced 280 medical records (146 diagnosed by neonatal screening). The median age and follow-up of the cohort was 9.3 year (range, 0–44) and 6.5 year (range, 0–32), respectively. The first information provided was the predominance of patients from DR Congo (67.5 %), the occurence of severe events in 84 % of patients (Table 1), the predominance of Hb SS phenotype (90 %) and its severity, the report of septicemia which remain still very worrying (8.2 %), but also that clinical and radiological neurological events are sizeable, and that there is a good response to treatment intensification, particularly to bone marrow transplantation (BMT) and hydroxyurea. Table 1: SCD related events reported in the Belgian data base SCD related events Patients,%(n) Dactilytis 24.3 (68/280) Acute Chest Syndrome 18.9 (53/280) Recurrent Vaso-occlusive Crisis 61.8 (173/280) Anemia ≤ 6 g/dl 51.8 (145/280) Septicemia 8.2 (23/280) Splenic sequestration 7.9 (22/280) Stroke/TIA 3.9 (11/280) Osteonecrosis 5.0 (14/280) Osteomyelitis 2.5 (7/280) The main pathogen remained Streptococcus pneumoniae with no resistant strain despite regular prophylaxis. The second most common germ was Salmonella. Haemophilus influenza concerned older patients and disappeared since the introduction of the vaccination. The incidence of death was 2.86% (8/280). All of them were homozygous for Hb S. Two deaths occurred in the very early childhood due to the no compliance to antibio-prophylaxis in the first patient and poor follow-up in the second one. One death was very sudden after meningeal hemorrhage. Two other deaths happened in the adulthood, one after cerebral hemorrhage and the other one of unknown cause after going back to native country. The last three deaths were due to BMT complications (Table 2). Table 2: Causes of death reported in the national data base Patient Sex Phenotype Age at event Origin 1 F SS 18 m Cardiopulmonary arrest - Severe anemia 2 M SS 26 m Septic shock on St pmeumococcus septicaemia 3 M SS 7 y Secondary Leukemia after BMT 4 F SS 11 y 9 m Obliterans bronchiolitis/MOF* post BMT 5 M SS 14 y 3 m Meningeal hemorrhage 6 F SS 14 y 9 m Hemorrhage diathesis/MOF post BMT 7 F SS 18 y 9 m Cerebral aneurysm rupture 8 M SS 24 y 3 m Return to native country * Multiple Organ Failure In conclusion, the preliminary results confirmed the still high morbidity and mortality of SCD. It is not only a precious practical tool, but it also helps to improve clinical management of patients with SCD, it is a tool to identify risk factors and to tailor treatments. In this perspective, it constitutes a basis for prospective studies in view to validate criteria of disease severity and to adopt guidelines for adequate treatment. Disclosures: No relevant conflicts of interest to declare.

Description: Abstract 4762 Introduction: Abnormalities of the clotting system are often observed in sickle cell disease (SCD). In addition to activation of coagulation, increased thrombin generation (TG) has recently been demonstrated in SCD children Aim of the study: To characterize the group of SCD children with increased TG in terms of clinical and biological parameters. Material and methods: TG was performed in the platelet-poor plasma of 97 SCD children at steady-state and 80 controls aged between 2 and 20 years. TG was triggered using 1 pM tissue factor and 4μM synthetic phospholipids with thrombomodulin to activate the protein C/protein S anticoagulant pathway. The Endogenous Thrombin Potential (ETP) and the peak height were analyzed. As these parameters increase with age in normal children, controls were distributed in 4 categories of age: [2–5], [6–10], [11–15] and [16–20] years. The mean ETP and the mean peak were calculated for each age category. A ratio for ETP (r ETP) and a ratio for the peak (r Peak) were defined for each control and patient as follows: individual ETP/ mean ETP and individual peak/ mean peak according to age category. Overall mean of r ETP and r Peak was then calculated such as to eliminate bias due to age. This calculated mean was 1.00 (0.39 – 1.61) for r ETP and 0.99 (0.28 – 1.81) for r Peak in controls. TG was considered abnormal if r ETP or r Peak value was above the mean + 2SD of controls (r ETP≥ 1.62 and r Peak≥ 1.82). Clinical and laboratory parameters were compared between SCD children having normal or increased ratios using the Mann Whitney test for numbers or the Fisher's exact test for proportions. P 〈 0.05 was considered significant. Results and Discussion: Overall 48 (49.4 %) patients showed either high r ETP or high r Peak whereas both parameters were increased in 31 (31.9 %) patients. As shown in Tables I and II, SCD children with elevated ratios were characterized by a younger age, shorter duration of hydroxyurea (HU) treatment, lower total hemoglobin level, higher reticulocyte and monocyte counts, higher LDH and D-dimer levels and a trend to increased procoagulant microparticle level (PMP) as compared with those having normal ratios. The higher D-dimer level in the group with abnormal ratios indicates that these children also manifest a higher degree of coagulation activation than those with normal ratios. Differences observed with markers of hemolysis are consistent with other reports suggesting a link between hypercoagulability and high hemolytic rate in SCD. The borderline significance of PMP is probably due to the use of exogenous phospholipids in TG which reduces the sensitivity of the test to endogenous phospholipids at the surface of PMPs. Conclusion: According to our study, Elevated Thrombin Potential is more frequently encountered in SCD children of younger age, with a shorter duration of HU treatment and with increased rate of hemolysis. These observations together with elevated D-dimer level seem to characterize SCD children with a hypercoagulable state. Disclosures: No relevant conflicts of interest to declare.