Early-onset indicators of a hypercoagulable state and clinical complications in a cohort of children with sickle cell trait.

Adults with sickle cell trait (SCT) have a procoagulant state with increased risk of thromboembolism, but limited data are available for children. We compared the coagulation profile of children with SCT, different sickle cell disease (SCD) genotypes, and healthy controls. Compared to controls and similarly to HbSC patients, 41 SCT children (mean age 6.85 years; 20 males; 88% Africans) had a characteristic procoagulant profile: higher levels of factor VIII, von Willebrand factor (VWF) Ag and CBA, D-dimer; lower levels of ADAMTS 13 activity, ADAMTS13 activity: VWFAg, plasminogen activator inhibitor, tissue plasminogen activator. Moreover, 13/41 had clinical complications of SCD, five requiring hospitalization.

Point-of-care testing allows successful simultaneous screening of sickle cell disease, HIV, and tuberculosis for households in rural Guinea-Bissau, West Africa.

Diagnosis of noncommunicable genetic diseases like sickle cell disease (SCD) and communicable diseases such as human immunodeficiency virus (HIV) or tuberculosis (TB) is often difficult in rural areas of Africa due to the lack of infrastructures, trained staff, or capacity to involve families living in remote areas. The availability of point-of-care (POC) tests for the above diseases offers the opportunity to build joint programs to tackle all conditions. We report successful simultaneous screening of SCD, HIV, and TB utilizing POC tests in 898 subjects in Fanhe, in rural Guinea-Bissau. Adherence was 100% and all diagnosed subjects were enrolled in care programs.

Distribution of HbS Allele and Haplotypes in a Multi-Ethnic Population of Guinea Bissau, West Africa: Implications for Public Health Screening.

Background: Sickle Cell Disease (SCD) is an inherited condition that is widespread globally and especially in malaria-endemic West African countries. Limited epidemiological data on SCD are available for Guinea Bissau, where newborn screening is not yet implemented, routine diagnosis is not available, and care is case directed. Methods: Dried blood spots were collected from children accessing two hospitals managed by Italian Non-Governmental Organizations in the capital city of Bissau and sent to Padova for Hemoglobin (Hb) quantification through HPLC and molecular analysis. Beta globin gene analysis was performed in all; and Hb haplotype of the HbSS and HbSA patients was performed in South Africa. One hundred samples belonging to the most frequent ethnic groups were randomly selected for detection of G6PD mutations. Results: Samples from 848 consecutive children (498 males and 350 females, mean age 6.8 years) accessing the two hospitals were analyzed: 6.95% AS (4.42% allelic frequency), 0.94% SS, and 0.23% AC. 376G G6PD allelic frequency was 24%; 14.8% in AS individuals. The Senegal haplotype was the most prevalent (31%), and the proposition of chromosomes with the atypical haplotype was surprisingly high (56%). Conclusion: Our study demonstrates a significant frequency of the HbS allele in the population of Guinea Bissau supporting the implementation of screening strategies. The differences among ethnic groups can help guide targeted interventions for SCD awareness campaigns and determine priority areas for public health interventions. The pilot analysis on haplotypes reveals a large proportion of the atypical haplotype, which may be indicative of a genetically heterogeneous population.

Hydroxyurea prescription, availability and use for children with sickle cell disease in Italy: Results of a National Multicenter survey.

BACKGROUND: The number of patients with sickle cell disease (SCD) has increased in Italy in the past decade due to immigration. In spite of the established efficacy of hydroxyurea (HU) in childhood, population-based data regarding its prescription and effectiveness come mainly from studies performed in adults or outside Europe. POPULATION AND METHODS: The Hydroxyurea in SCD: A Large Nation-wide Cohort Study from Italy was a retrospective cohort study of adult and pediatric patients with SCD attending 32 centers. Pediatric data are analyzed separately. RESULTS: Out of 504 children followed in 11 centers, 206 (40%) were on HU (194 SS/Sß°, 12 SC/Sß+); 74% came from Sub-Saharian Africa and 18% from Europe. HU therapy indications for SS/Sß° patients were as follows: 57% painful vaso-occlusive crisis, acute chest syndrome or both, 24% anemia, 8% anemia, and other reasons (the majority had Hb ≤ 8-8.5 g/dl, revealing scarce acceptance of low Hb values by pediatric hematologist). Mean starting dose was 15.5 mg/kg, and dose at full regimen was 17.1 mg/kg. Mean age at HU therapy was 7.68 years, although it was lower for SS/Sß° patients. Only 10% started HU before 3 years. In 92%, 500 mg capsule was used; in 6%, the galenic was used; and in 2%, 100 mg tablet was used. Significant reduction of clinical events and inpatients admissions, with improvement in hematological parameters, was observed for SS/Sß° patients and a trend toward improvement for SC/Sß+ patients was also observed. CONCLUSIONS: HU effectiveness is demonstrated in a national cohort of children with SCD living in Italy, even at a lower dose than recommended, revealing good adherence to a treatment program by a socially vulnerable group of patients such as immigrants.

Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαß and CD19 positive cells. RESULTS: All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. CONCLUSION: Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.