OCCURRENCE OF UNUSUAL HAEMOGLOBINOPATHIES IN BALOCHISTAN: HB SD AND HB SE - PRESENTATION WITH OSTEOMYELITIS.

OBJECTIVE: To describe two cases of unusual variants of sickle cell disease. CASE DESCRIPTION: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. COMMENTS: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.

Occurrence of unusual haemoglobinopathies in balochistan: hb sd and hb se - presentation with osteomyelitis / Ocorrência de hemoglobinopatias incomuns no baluchistão: hb sd e hb se - apresentação com osteomielite

ABSTRACT Objective: To describe two cases of unusual variants of sickle cell disease. Case description: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. Comments: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.

RESUMO Objetivo: Descrever dois casos de variantes raras da hemoglobinopatia falciforme. Descrição do caso: Apresentamos aqui dois casos de hemoglobinopatias variantes das células falciformes, de famílias não relacionadas, no estado do Baluchistão (Paquistão), sendo um diagnosticado como doença da hemoglobina SD na eletroforese de hemoglobina, enquanto o outro com doença da hemoglobina SE. Ambos foram diagnosticados a partir da apresentação de osteomielite. Comentários: Hemoglobina SD (Hb SD) e hemoglobina SE (Hb SE) são hemoglobinopatias raras no mundo. A escassez de literatura disponível sugere que ambas são variantes da doença falciforme (DF) com natureza heterogênea. A prevalência de hemoglobinopatia falciforme com heterozigosidade composta foi encontrada com frequência variável na população do sudeste asiático. A frequência de osteomielite na DF é de 12 a 18%, mas sua ocorrência entre as hemoglobinopatias falciformes variantes é pouco relatada. Os dois casos reportados apresentaram osteomielite como característica de apresentação da doença.

Hydroxyurea increases plasma concentrations of microparticles and reduces coagulation activation and fibrinolysis in patients with sickle cell anemia.

Microparticles (MPs) are present in healthy subjects and their concentration increases in patients at high risk of thrombosis. We evaluated 10 patients with sickle cell anemia (SCA) treated with hydroxyurea (HU) and 13 SCA patients without this treatment. MP concentrations were determined by flow cytometry. Coagulation was evaluated using the thrombin-antithrombin complex (TAT) and D-dimers. Total MP concentrations were increased in the HU-treated group (265 × 10(6)/ml vs. 67.45 × 10(6)/ml; p = 0.0026), as well as MPs derived from RBC (67.83 × 10(6)/ml vs. 26.31 × 10(6)/ml; p = 0.05), monocytes (51.31 × 10(6)/ml vs. 9.03 × 10(6)/ml; p = 0.0084), monocytes with tissue factor (TF) expression (2.27 × 10(6)/ml vs. 0.27 × 10(6)/ml; p = 0.0058), endothelium (49.42 × 10(6)/ml vs. 7.23 × 10(6)/ml; p = 0.007) and endothelium with TF (1.42 × 10(6)/ml vs. 0.26 × 10(6)/ml; p = 0.0043). Furthermore, the concentrations of TAT (7.56 vs. 10.98 µg/l; p = 0.014) and D-dimers (0.65 vs. 1.29 µg/ml; p = 0.007) were reduced with HU. The MP elevation may suggest a direct cytotoxic effect of HU. Another explanation is a cell surface increase secondary to a megaloblastic process, resulting in increased vesicle release. In our opinion, the known benefits of HU on SCA patients, along with the reduction in coagulation activation, surpass its potential detrimental effect on MPs. Future studies should elucidate the role of MPs and demonstrate their significance in different contexts.

The effect of hydroxcarbamide therapy on survival of children with sickle cell disease.

Although evidence is accumulating that hydroxycarbamide decreases mortality among adults with sickle cell disease (SCD), there are no published data regarding the effect of hydroxycarbamide on mortality among children. The Paediatric Hydroxycarbamide Program was established to treat children with SCD aged 3-18 years if they met disease severity criteria. Mortality data and clinical/laboratorial effects of hydroxycarbamide were retrospectively collected for the first 9 years of the Program. Mortality among those who received hydroxycarbamide was compared to that of untreated children. Among 1760 subjects, 267 received hydroxycarbamide at a median dose of 20·8 mg/kg/d (range 10-32) for a median of 2 years (range 0·1-6·5). Survival among hydroxycarbamide-treated children was significantly greater than that among untreated ones (99·5% vs. 94·5%, P = 0·01), due primarily to fewer deaths from acute chest syndrome and infection. Hydroxycarbamide therapy was significantly associated with increases in haemoglobin concentration, fetal haemoglobin, mean corpuscular volume, and reduction in platelet counts, reticulocytes and neutrophils. Toxicity was minimal and predominantly mild reversible neutropenia. Significantly fewer hospitalizations and emergency room visits, and shorter admissions were observed among hydroxycarbamide-treated subjects, when compared to the 12-month period prior to treatment initiation. Hydroxycarbamide therapy reduces disease severity and is probably associated with decreased mortality among children with SCD.

Hydroxyurea therapy associated with declining serum levels of magnesium in children with sickle cell anemia.

OBJECTIVE: To obtain quantitative serum levels of total and ionized magnesium (Mg(2+)) in children with homozygous sickle cell anemia (SCA) undergoing therapy with hydroxyurea. STUDY DESIGN: Five children, ages 11 to 14 years with homozygous SCA, were enrolled in a dose-escalating trial of hydroxyurea over an 18-month period. Serum levels of total and ionized magnesium together with ionized K(+), Na(+), and Ca(2+) were measured before hydroxyurea and every 6 months during hydroxyurea therapy. RESULTS: Before treatment, 4 of the 5 patients had low or below-normal serum concentrations of Mg(2+) (normal range, 0.51-0.67 mmol/L). All 5 became Mg(2+)-deficient during hydroxyurea therapy, with no indication of recovery until after 12 to 18 months of drug administration (P <.05). Similar changes were noted for total magnesium concentrations. Mean serum levels of K(+), Na(+), and Ca(2+) remained consistently within normal ranges. CONCLUSIONS: These findings warrant a controlled study of the effects of magnesium supplementation in patients with SCA receiving hydroxyurea. Potentially, such therapy could alleviate or prevent vaso-occlusive crises.

Hydroxyurea therapy in sickle cell anemia patients in Curaçao, The Netherlands Antilles.

We have treated 9 patients with sickle cell anemia (SS) with hydroxyurea (HU). All 9 patients carried 4 alpha-globin genes and the beta s-globin haplotypes 19/19 (Benin/Benin), except for 1 who had haplotype 19 together with type 3 (Benin/Senegal). Six patients received HU for 10 months and were again treated with the drug for 5 months after an interval of 1 year. One patient was given HU for 22 consecutive months. A record was kept of hematological and biochemical data, Hb F and G gamma levels, as well as possible clinical complications. Our data show that HU generally improves the hematological and biochemical values and the level of Hb F, and reduces painful crises in some patients. However, although the clinical symptoms improved in some patients during HU therapy, the older patients did not observe any changes in their general condition; the same is the case for the patient with haplotype 19/3. One patient also experienced life-threatening liver sequestration during treatment. We conclude that the selection of patients who may benefit from HU therapy needs further evaluation.