Showing papers on "Sickle cell anemia published in 2007"

β-thalassaemia and sickle cell anaemia as paradigms of hypercoagulability

Abstract: Thalassaemia and sickle cell disease (SCD) represent the most common forms of hereditary haemolytic anaemia and result from a partial or complete lack of synthesis of one of the major alpha- or beta-globin chains of haemoglobin A or from a single amino acid mutation (beta(6Glu-->Val)) of the beta-globin chain respectively. Although they have different pathophysiologies, patients with these conditions manifest both biochemical and clinical evidence of hypercoagulability. While the frequency of various thrombotic complications may vary in beta-thalassaemia and homozygous SCD [sickle cell anaemia (SCA)], patients with both diseases manifest decreased levels of natural anticoagulant proteins, as well as increased markers of thrombin generation and platelet activation. The abnormal phospholipid membrane assymetry present in the red blood cells of beta-thalassaemia and SCA patients, with resultant phosphatidylserine exposure appears to play a significant role in the aetiology of the observed hypercoagulable state. This review presents the available data on the aetiology and clinical manifestations of the coagulation and platelet activation that exist in both beta-thalassaemia and SCA, as well as the potential therapeutic implications resulting from this hypercoagulability.

Urinary hepcidin in congenital chronic anemias.

Abstract: Background Hepcidin, a regulator for iron homeostasis, is induced by inflammation and iron burden and suppressed by anemia and hypoxia. This study was conducted to determine the hepcidin levels in patients with congenital chronic anemias. Procedure Forty-nine subjects with anemia, varying degrees of erythropoiesis and iron burden were recruited. Eight children with immune thrombocytopenia were included as approximate age-matched controls. Routine hematologic labs and urinary hepcidin (uhepcidin) levels were assessed. For thalassemia major (TM) patients, uhepcidin was obtained pre- and post-transfusion. Results In TM, uhepcidin levels increased significantly after transfusion, demonstrated wide variance, and the median did not significantly differ from controls or thalassemia intermedia (TI). In both thalassemia syndromes, the hepcidin to ferritin ratio, a marker of the appropriateness of hepcidin expression relative to the degree of iron burden, was low compared to controls. In TI and sickle cell anemia (SCA), median uhepcidin was low compared to controls, P = 0.013 and <0.001, respectively. In thalassemia subjects, uhepcidin levels were positively associated with ferritin. In subjects with SCA, uhepcidin demonstrated a negative correlation with reticulocyte count. Conclusions This study examines hepcidin levels in congenital anemias. In SCA, hepcidin was suppressed and inversely associated with erythropoietic drive. In thalassemic syndromes, hepcidin was suppressed relative to the degree of iron burden. Transfusion led to increased uhepcidin. In thalassemia, the relative influence of known hepcidin modifiers was more difficult to assess. In thalassemic syndromes where iron overload and anemia have opposing effects, the increased erythropoietic drive may positively influence hepcidin production. Pediatr Blood Cancer 2007;48:57–63. © 2005 Wiley-Liss, Inc.

Matched‐related donor transplantation for sickle cell disease: report from the Center for International Blood and Transplant Research

Abstract: We report outcomes after myeloablative haematopoietic cell transplantation (HCT) from human leucocyte antigen (HLA)-matched sibling donors in 67 patients with sickle cell disease transplanted between 1989 and 2002. The most common indications for transplantation were stroke and recurrent vaso-occlusive crisis in 38% and 37% of patients respectively. The median age at transplantation was 10 years and 67% of patients had received >10 red blood cell transfusions before HCT. Twenty-seven percent of patients had a poor performance score at transplantation. Ninety-four percent received busulfan and cyclophosphamide-containing conditioning regimens and bone marrow was the predominant source of donor cells. Most patients achieved haematopoietic recovery and no deaths occurred during the early post-transplant period. Rates of acute and chronic graft-versus-host disease were 10% and 22% respectively. Sixty-four of 67 patients are alive with 5-year probabilities of disease-free and overall survival of 85% and 97% respectively. Nine patients had graft failure with recovery of sickle erythropoiesis, eight of who had recurrent sickle-related events. This report confirms and extends earlier reports that HCT from HLA-matched related donors offers a very high survival rate, with few transplant-related complications and the elimination of sickle-related complications in the majority of patients who undergo this therapy.

Fetal hemoglobin in sickle cell anemia: genetic determinants of response to hydroxyurea.

Abstract: The increase in fetal hemoglobin (HbF) in response to hydroxyurea (HU) varies among patients with sickle cell anemia Twenty-nine candidate genes within loci previously reported to be linked to HbF level (6q223-q232, 8q11-q12 and Xp222-p223), involved in metabolism of HU and related to erythroid progenitor proliferation were studied in 137 sickle cell anemia patients treated with HU Three-hundred and twenty tagging single nucleotide polymorphisms (SNPs) for genotyping were selected based on HapMap data Multiple linear regression and the nonlinear regression Random Forest method were used to investigate the association between SNPs and the change in HbF level after 2 years of treatment with HU Both methods revealed that SNPs in genes within the 6q223-232 and 8q11-q12 linkage peaks, and also the ARG2, FLT1, HAO2 and NOS1 genes were associated with the HbF response to HU Polymorphisms in genes regulating HbF expression, HU metabolism and erythroid progenitor proliferation might modulate the patient response to HU

Severity of pulmonary hypertension during vaso-occlusive pain crisis and exercise in patients with sickle cell disease.

Abstract: Pulmonary hypertension is associated with sudden death and is a risk factor for mortality in adult patients with sickle cell disease. The high mortality despite only mild-to-moderate increases in pulmonary vascular resistance remains an unresolved paradox. Accordingly, little is known about the cardiovascular effects of stressors, such as vaso-occlusive pain crisis (VOC) and exercise, which may acutely increase pulmonary pressures and impair right heart function. We therefore evaluated pulmonary artery pressures by echocardiogram in 25 patients with sickle cell disease in steady-state and during VOC, and by right heart catheterisation with exercise in a second cohort of 21 patients to determine whether pulmonary hypertension worsens during acute cardiopulmonary stress. TRV increased during VOC (P < 0.001), and the increased pulmonary pressures during VOC were associated with decreases in haemoglobin levels (P < 0.001), and increases in lactate dehydrogenase (P < 0.001) and plasma haemoglobin levels (P = 0.03). During exercise stress performed during cardiac catheterisation, mean pulmonary artery pressures (P < 0.001) and pulmonary vascular resistance increased (P < 0.001) in all subjects. These data suggest that acute elevations in pulmonary pressures during VOC or exercise may contribute to morbidity and mortality in patients with sickle cell disease.

Reduction of painful vaso-occlusive crisis of sickle cell anaemia by tinzaparin in a double-blind randomized trial.

Abstract: A randomized double-blind clinical trial was performed to test the safety and efficacy of a low-molecular-weight heparin, tinzaparin (Innohep®), for the management of acute painful vasoocclusive crisis characteristic of sickle cell anemia (SCA). We studied 253 patients with acute painful crisis but with no other complications of SCA, randomized to treatment or control groups. In the treatment group, 127 patients received tinzaparin at 175 IU/kg, subcutaneous once daily, along with supportive care including morphine analgesia; in the control group, 126 patients received placebo and the same supportive care.The maxi- mal experimental treatment period was seven days. Analysis revealed a statistically significant reduction in number of days with the severest pain score, overall duration of painful crisis, and duration of hospitalization (p

Big Strokes in Small Persons

Abstract: Sickle cell disease (SCD) is understood on a genetic and a molecular level better than most diseases. Young children with SCD are at a very high risk of stroke. The molecular pathologic abnormalities of SCD lead to microvascular occlusion and intravascular hemolytic anemia. Microvascular occlusion is related to painful episodes and probably causes microcirculatory problems in the brain. The most commonly recognized stroke syndrome in children with SCD is large-artery infarction. These “big strokes” are the result of a vascular process involving the large arteries of the circle of Willis leading to territorial infarctions from perfusion failure or possibly artery-to-artery embolism. We can detect children who are developing cerebral vasculopathy using transcranial Doppler ultrasonography (TCD) and can provide effective intervention. Transcranial Doppler ultrasonography measures blood flow velocity in the large arteries of the circle of Willis. Velocity is generally increased by the severe anemia in these patients, and it becomes elevated in a focal manner when stenosis reduces the arterial diameter. Children with SCD who are developing high stroke risk can be detected months to years before the stroke using TCD. Healthy adults have a middle cerebral artery velocity of approximately 60 cm/s, whereas children without anemia have velocities of approximately 90 cm/s. In SCD, the mean is approximately 130 cm/s. Two independent studies have demonstrated that the risk of stroke in children with SCD increases with TCD velocity. The Stroke Prevention Trial in Sickle Cell Anemia (STOP) (1995-2000) was halted prematurely when it became evident that regular blood transfusions produced a marked (90%) reduction in first stroke. Children were selected for STOP if they had 2 TCD studies with velocities of 200 cm/s or greater. Children not undergoing transfusion had a stroke risk of 10% per year, which was reduced to less than 1% per year by regular blood transfusions. Stroke risk in all children with SCD is approximately 0.5% to 1.0% per year. On the basis of STOP, if the patient meets the high-risk TCD criteria, regular blood transfusions are recommended. A second study was performed (2000-2005) to attempt withdrawal of transfusion in selected children in a randomized controlled study. Children with initially abnormal TCD velocities (≥200 cm/s) treated with regular blood transfusion for 30 months or more, which resulted in reduction of the TCD to less than 170 cm/s, were eligible for randomization into STOP II. Half continued transfusion and half had cessation of transfusion. This trial was halted early for safety reasons. There was an unacceptably high rate of TCD reversion back to high risk (≥200 cm/s), as well as 2 strokes in children who discontinued transfusion. There are no evidence-based guidelines for the discontinuation of transfusion in children once they have been identified as having high risk based on TCD. The current situation is undesirable because of the long-term effects of transfusion, including iron overload. Iron overload has recently become easier to manage with the introduction of an oral iron chelator. The inflammatory environment known to exist in SCD and the known effect of plasma free hemoglobin, released by hemolysis, of reducing available nitric oxide may contribute to the development of cerebrovascular disease. Further research may lead to more targeted therapies. We can reduce many of the big strokes that occur in these small persons by aggressively screening patients at a young age (and periodically throughout the childhood risk period) and interrupting the process with regular blood transfusions.

Patient-controlled analgesia versus continuous infusion of morphine during vaso-occlusive crisis in sickle cell disease, a randomized controlled trial.

Abstract: Intravenous morphine is the treatment of choice for severe pain during vaso- occlusive crisis in sickle cell disease (SCD). However, side effects of morphine may hamper effective treatment, and high plasma levels of morphine are associated with severe complications such as acute chest syndrome. Furthermore, adequate dosing remains a problem since no objective measurement of pain severity exists and analgesia should be titrated upon the patient's reported pain. Patient-controlled analgesia (PCA) may therefore be an interesting alternative since patients can titrate the level of analgesia themselves. In this randomized controlled study, the efficacy of intravenous morphine administration with PCA was compared with continuous infusion (CI) of morphine in patients with SCD during vaso-occlusive crisis. Twenty five consecutive episodes of vaso-occlusive crisis in 19 patients with SCD were included in the study. Patients in the PCA-group had a markedly and significant lower mean and cumulative morphine consumption when compared with the patients in the CI-group (0.5 mg/hr versus 2.4 mg/hr (P < 0.001) and 33 mg versus 260 mg (P = 0.018, respectively). The mean daily pain scores were comparable (4.9 versus 5.3). The lower mean and cumulative morphine consumption in the PCA-group led to significant less nausea and constipation during treatment when compared with the CI-group (area under the curve, respectively, 11 versus 18 (P = 0.045) and 30 versus 45 (P = 0.021). Furthermore, a nonsignificant reduction in the duration of hospital admission of 3 days was observed in the PCA-group. PCA results in adequate pain relief at a much lower morphine consumption and should considered to be the first choice in morphine administration to sickle cell patients admitted with vaso-occlusive crisis.

Confirmation of an Association Between the TNF(−308) Promoter Polymorphism and Stroke Risk in Children With Sickle Cell Anemia

Abstract: Background and Purpose— The etiology of stroke in children with sickle cell anemia (SCA) is complex and poorly understood. Growing evidence suggests that genetic factors beyond the sickle cell mutation influence stroke risk in SCA. We previously reported risk associations with polymorphisms in several proinflammatory genes in SCA children with ischemic stroke. The aim of this replication study was to confirm our previous findings of associations between the TNF(−308) G/A, IL4R 503 S/P, and ADRB2 27 Q/E polymorphisms and large vessel stroke risk. Methods— Using previously collected MRA data, we assessed an independent population of SCA children from the multicenter Stroke Prevention Trial in Sickle Cell Anemia (STOP) for the presence or absence of large vessel stenosis. Samples were genotyped for 104 polymorphisms among 65 candidate vascular disease genes. Genotypic associations with risk of large vessel stroke were screened using univariable analysis and compared with results from our original study. Join...

Transfusion prevents acute chest syndrome predicted by elevated secretory phospholipase A2.

Abstract: Summary Acute pulmonary injury is known as acute chest syndrome (ACS) in patients with sickle cell disease (SCD). Secretory phospholipase A2 (sPLA2) was found to predict those at risk for ACS and a trial was designed to determine if red blood cell transfusion can be used to prevent ACS. Patients with an elevated sPLA2 were randomised to either receive a single transfusion or standard care. Five of the eight patients (63%) randomised to standard care developed ACS versus none of the seven patients randomised to the transfusion arm (P ¼ 0AE026, Odds ratio ¼ 23AE6, 95% confidence interval 1, 557). This study suggests that transfusion may prevent ACS.

The pathophysiology, prevention, and treatment of stroke in sickle cell disease.

Abstract: Purpose of review Stroke is one of the most devastating complications of sickle cell disease, but current research has led to improved understanding of its pathogenesis and to new approaches in the prevention of both primary and secondary stroke. This review focuses on advances reported in the past 2 years. Recent findings New concepts in the pathophysiology of central nervous system events in sickle cell disease have centered around hemolytic anemia and nitric oxide metabolism. Genetic risk factors are now being explored. Major improvement in primary stroke prevention has occurred through transcranial Doppler ultrasonography screening, but utilization of this technique is far from optimal. Hydroxyurea is now being tested as an alternative approach to chronic transfusion for secondary stroke prevention through a multicenter trial. Other studies are addressing the management of silent infarcts and nocturnal hypoxemia. Summary Increased understanding of the etiology and pathogenesis of stroke in sickle cell disease should eventually lead to improved management of all central nervous system complications. Alternative secondary stroke prevention with hydroxyurea may allow patients to avoid dependence on life-long chronic transfusion. Primary stroke prevention through transcranial Doppler ultrasonography screening may ultimately yield a dramatic reduction in the incidence of stroke in sickle cell disease.

Myocardial tissue characterization and the role of chronic anemia in sickle cell cardiomyopathy.

Abstract: Purpose To use cardiovascular magnetic resonance (CMR) techniques to examine possible causes for the left ventricular (LV) dilatation that occurs in sickle cell disease (SCD), including the effects of chronic anemia, iron-induced cardiomyopathy, and regional fibrosis due to sludge infarcts that occur during sickle crises. Materials and Methods A total of 47 patients with sickle cell anemia were assessed for LV function and myocardial iron levels using CMR measurements; 30 of these were also assessed for regional fibrosis using late gadolinium-enhancement CMR. The LV function was compared to both normal controls and transfusion dependent non-iron-loaded (NIL) thalassemia major (TM) patients. Results Only one SCD patient had significant myocardial iron loading, and only two patients had regional fibrosis. There were significant differences in ventricular volumes of the sickle patients compared with both the normal controls and the NIL-TM population (P < 0.01). Conclusion The LV changes seen in SCD are partly the result of a chronic anemia but there appears to be another contributory factor. This extra factor is not myocardial iron loading or regional fibrosis, although a homogenous fibrotic disorder affecting the left ventricle cannot be excluded. J. Magn. Reson. Imaging 2007;26:564–568. © 2007 Wiley-Liss, Inc.

Sickle cell anemia: a review for the pediatric dentist.

Abstract: Sickle cell anemia is an inherited defect that affects the structure and synthesis of hemoglobin. In sickle cell trait, the affected individuals carry one gene for the abnormal hemoglobin (HbS). Sickle cell disease, however, is the homozygous state in which the abnormal hemoglobin is predominant in red blood cells, leading to devastating multisystem problems. Complications of the disease in children include: painful crises, stroke, pulmonary disease, delayed growth, osteomyelitis, organ damage and psychosocial dysfunction. Oral and dental manifestations include: orofacial pain, paresthesia of the mental nerve, stepladder appearance of the alveolar bone on radiographs, pulpal necrosis and enamel hypomineralization. The purpose of this manuscript was to review: (1) the pathophysiology of the disease; (2) its manifestations in the craniofacial complex; (3) contemporary medical therapy; and (4) recommendations for dental care.

Total antioxidants status and some hematological values in sickle cell disease patients in steady state.

Abstract: Congenital hemoglobin mutations may alter the delicate balance of free-radical generation and antioxidant defense systems in the red cell. Oxidative stress may thus play a role in the pathophysiology of the clinical manifestations of the disease. We assessed the total antioxidant status in steady-state sickle cell anemia (SCA) patients and related it to certain hematological parameters and their recent clinical history. Forty (25 males/15 females) adult SCA patients and 30 age-matched controls were studied. All patients and control subjects had total antioxidant status (TAS), hematocrit, white blood cells, platelets and reticulocyte count done. The results showed that TAS levels were about 50% lower in the SCA patients compared with the controls. Among the SCA patients, 57.1% of those with TAS levels 3 times in the past year, compared with 16% in those with TAS levels >1.00 mmol/L. Total leukocyte count and platelets were also significantly higher in the SCA patients than controls. Our data support the growing evidence that oxidative stress has a role to play in the pathophysiology of SCA and intervention aimed at increasing the antioxidant capacity of these patients may be beneficial.

Counterpoint: Sickle cell trait should not be considered asymptomatic and as a benign condition during physical activity

Abstract: Sickle cell trait (SCT; or AS hemoglobinopathy) is the heterozygous form of sickle cell anemia and is present in over 2.5 million African Americans. Its prevalence can reach 20–40% in some areas of sub-Saharan Africa and 10% in the French West Indies ([12][1]). SCT is usually considered a benign

The mechanisms of low birth weight in infants of mothers with homozygous sickle cell disease.

Abstract: OBJECTIVE. A low mean birth weight is a constant finding in pregnancies of women with homozygous sickle cell disease. The factors responsible are largely unknown and have now been investigated in an 11-year retrospective analysis. METHODS. Records for 126 pregnancies of mothers with homozygous sickle cell disease and 126 pregnancies of control women with an AA phenotype, matched according to age and date of delivery, were examined. Events during pregnancy and outcomes of pregnancy were recorded. RESULTS. Pregnancy outcomes for mothers with homozygous sickle cell disease confirmed the lower birth weight, gestational age, and placental weight. A low birth weight in infants of mothers with homozygous sickle cell disease was strongly related to gestational age and placental weight and weakly related to reticulocyte counts and a history of preeclampsia in univariate analyses, but only gestational age and placental weight remained significant in multivariate analyses. No relationships were seen with maternal age, parity, anthropometric features, other hematologic features (hemoglobin levels, fetal hemoglobin levels, mean cell volume, and α-thalassemia), pregnancy-induced hypertension, or prepartum hospital admissions (expressed as number or total days). Compared with Jamaican standards, birth weight was affected more than head circumference or length in infants of mothers with homozygous sickle cell disease, indicating asymmetric growth retardation, which occurred for 27% of boys and 38% of girls (compared with 4% and 9%, respectively, among infants of control mothers). CONCLUSIONS. A chronic condition such as homozygous sickle cell disease might have been expected to cause symmetric growth retardation throughout pregnancy. The finding of asymmetric retardation might indicate adverse factors emerging late in pregnancy and might have relevance for the poor pregnancy outcomes in such mothers.

Estimated glomerular filtration rate in sickle cell anemia is associated with polymorphisms of bone morphogenetic protein receptor 1B.

Abstract: Renal disease is common in sickle cell anemia. In this exploratory work, we used data from a longitudinal study of the natural history of sickle cell disease to examine the hypothesis that polymorphisms (SNPs) in selected candidate genes are associated with glomerular filtration rate (GFR). DNA samples and clinical and laboratory data were available for 1,140 patients with sickle cell anemia. GFR was estimated using the Cockcroft-Gault and Schwartz formulas for adults and children, respectively. We examined approximately 175 haplotype tagging (ht) SNPs in about 70 genes of the TGFbeta/BMP pathway for their association with GFR using linear regression. Four SNPs in BMPR1B, a bone morphogenetic protein (BMP) receptor gene, yielded statistically significant associations (P values ranging from 0.015 to 0.046). Three haplotypes in this gene were also associated with GFR. The TGF-beta/BMP pathway has been associated with the development of diabetic nephropathy, which has some features in common with sickle cell nephropathy. Our results suggest that, as with other subphenotypes of sickle cell disease, renal function may be genetically modulated.

Blood transfusion rate in congolese patients with sickle cell anemia

Abstract: Objective The main objective of this study was to evaluate the rate of blood transfusion in African Sickle Cell Patients and the risks related to the use of total blood.

Effect of myeloablative bone marrow transplantation on growth in children with sickle cell anaemia: results of the multicenter study of haematopoietic cell transplantation for sickle cell anaemia.

Abstract: Although haematopoietic cell transplantation (HCT) is curative for sickle cell anaemia (SCA), concerns about its short- and long-term toxicities limit its application. A potential toxicity is an adverse effect on growth. To identify an HCT growth effect, serial height and weight measurements from 53 children and adolescents with SCA after receiving a transplant were compared to historical controls. Hierarchical Linear Models for longitudinal data were used for analysis. In general growth was not impaired by HCT for SCA in young children; however, diminished growth may occur if HCT is carried out near or during the adolescent growth spurt.

Preventing stroke among children with sickle cell anemia: an analysis of strategies that involve transcranial Doppler testing and chronic transfusion.

Abstract: BACKGROUND. Transcranial Doppler ultrasonography can identify children with sickle cell anemia who are at elevated risk of stroke and may benefit from chronic transfusions. Uncertainty about the risk/benefit trade-offs of chronic transfusion has led some clinicians to decide not to offer transcranial Doppler ultrasonography screening. OBJECTIVES. Our goals were to (1) compare the projected benefits and risks of 6 primary stroke-prevention strategies, (2) estimate the optimal frequency of screening, and (3) identify key assumptions that influence the risk/benefit relationship. METHODS. We designed a decision model to compare 6 primary stroke-prevention strategies: (1) annual transcranial Doppler ultrasonography screening until age 16 with children at high risk of stroke receiving monthly transfusion for life; (2) annual transcranial Doppler ultrasonography until age 16 with transfusions until age 18; (3) biannual transcranial Doppler ultrasonography until age 16 with transfusions until age 18; (4) annual transcranial Doppler ultrasonography until age 10 with transfusion until age 18; (5) 1-time screening at age 2 with transfusion until age 18; and (6) no intervention. Assumptions were derived from the published literature. RESULTS. For a hypothetical cohort of 2-year-old children, the optimal strategy was transcranial Doppler ultrasonography screening annually until age 10 with children at high risk receiving monthly transfusions until age 18. The optimal strategy would prevent 32% of strokes predicted to occur without intervention. The optimal strategy led to benefits similar to more intensive screening and transfusion strategies but resulted in fewer adverse events. All the intervention strategies resulted in net losses in life expectancy, because the projected mortality averted by stroke prevention was outweighed by the projected increase in mortality from transfusion. Results were sensitive to adherence rates to iron-chelation therapy. CONCLUSIONS. The optimal stroke-prevention strategy was projected to be annual transcranial Doppler ultrasonography screening until age 10 with transfusion for children at high risk until age 18. Better adherence to chelation therapy would improve life expectancy in all intervention strategies.

Prevalence of beta-thalassemia and sickle cell anemia trait in premarital screening in Konya urban area, Turkey.

Abstract: Thalassemias and sickle cell anemia (SCA) are common disease in Turkey. To determine the prevalence of beta-thalassemia and SCA traits in Konya urban area of Turkey, all couples applied for marriage procedures were screened. Screening tests included complete blood count and quantitation of hemoglobin for both partners. The subjects were considered to have the beta-thalassemia trait if they had a mean corpuscular volume of less than 80 fL and/or a mean corpuscular hemoglobin level of less than 27 pg and a hemoglobin A2 level of more than 3.2% or a hemoglobin F level of more than 2%. Subjects were considered to have an SCA trait if they were positive for sickle hemoglobin. During the study, premarital screening of hemoglobinopathies was evaluated retrospectively in 72,918 subjects; the thalassemia trait was detected in 1465 subjects (2%), and the SCA trait was detected in 37 subjects (0.05%). Of the carriers of the beta-thalassemia trait, 820 (56%) people had high hemoglobin A2, 513 (35%) people had high hemoglobin F, and 132 (9%) people had both high hemoglobin F and hemoglobin A2. Our results are very similar to Turkey's beta-thalassemia and SCA trait averages.

The pediatric spleen.

Abstract: Many pathological processes affect the spleen in children. As a basis for recognizing pathology, knowledge of the normal imaging appearance of the pediatric spleen is needed. In addition to congenital anomalies and trauma, pathology of the pediatric spleen includes enlargement (splenomegaly), cysts, neoplasms, infection and infarction. Specific diseases processes, including sickle cell anemia and Gaucher disease, may have specific affects on the spleen.

Circulating DNA: a potential marker of sickle cell crisis.

Abstract: Free circulating DNA is present in the plasma of healthy subjects, and is elevated in conditions characterized by increased cell death, such as cancer and physical trauma. Analysis of circulating DNA in plasma could provide a useful biomarker in sickle cell disease (SCD) in view of the increased cell turnover through chronic ongoing haemolysis, recurrent vaso-occlusion and inflammation. Plasma DNA was determined by real-time quantitative polymerase chain reaction (PCR) amplification of the beta-globin gene (HBB) in 154 patients with SCD [105 haemoglobin (Hb)SS, 46 HbSC and three HbS/beta(0) thalassaemia] and 53 ethnically matched controls. Blood samples were obtained from all patients in steady state; 21 of the 154 patients were also sampled during admission to hospital for acute pain. Median concentration of circulating plasma DNA in acute pain was more than 10-fold that in steady state and in controls - 10070 vs. 841 and 10070 vs. 933 genome equivalents/ml respectively (P < 0.0001, in both cases). During steady state, patients had plasma DNA levels similar to controls. Plasma DNA levels in SCD correlated with C-reactive protein levels (P < 0.005) and total white cell counts (P < 0.05) in steady state. The study shows that plasma DNA concentration may have potential as a biomarker in sickle cell patients.

Clinical profile of sickle cell disease in Yemeni children.

Abstract: The clinical spectrum of sickle cell disease (SCD) in the Arabian Peninsula varies widely. This is the first report in Yemeni children. Methods: A hospital-based, cross-sectional study was undertaken in Al-Wahada Teaching Hospital in Aden of children under 16 years with homozygous (SS) SCD. Results: Fifty-six (55%) were males. There were clinical manifestations in 20% by the age of 6 months and in 67%, 88% and 92% by 1, 2 and 3 years, respectively. Dactylitis (hand-foot syndrome) was the most common presenting symptom and occurred in 54% of cases, followed by acute respiratory infections and other acute febrile illnesses. The main causes of hospitalisation were painful crisis (36%), anaemic crisis (16%) and acute chest syndrome (11%). Hepatomegaly was detected in 72% and splenomegaly in 40%. Cerebrovascular accident, cholelithiasis, hepatic crisis and leg ulcers each occurred in about 5% of patients. There was first-and second-degree consanguinity in 31% and 16%, respectively, of patients' families. Conclusion: SCD is a serious problem, affecting children in Yemen from an early age. Disease course and severity were similar to that in Africans and American blacks and some reports from western Saudi Arabia. A screening programme linked to comprehensive medical care and genetic counselling is required to improve management and quality of life.

Sickle cell disease: the Lebanese experience

Abstract: Sickle cell disease (SCD), the commonest single gene disorder worldwide, is an inherited disease that has different clinical and hematological manifestations in different populations. The objective of this study is to describe the characteristics of the Lebanese SCD population. This was a retrospective study that included information on 387 patients with either sickle cell anemia (SS) or sickle beta-thalassemia (ST). The mean (+/-SD) age was 17.9 years (+/-12.5), and the mean (+/-SD) follow-up was 9.3 +/- 6.9 years. Fifty percent of the patients were males and SS/ST distribution was 3 : 1. The disease was clustered in two geographic areas in North and South Lebanon. Nearly, all patients were Muslims and 56% were the offspring of consanguineous parents. The prevalence of splenomegaly beyond 6 years of age among SS patients was 28.9%. The prevalence rates of stroke, leg ulcers and priapism were 4.1%, 1.4%, and 0.8%, respectively. Comparing the SS and the ST patients, there were no statistically significant differences in the prevalence of all clinical manifestations except for splenomegaly (SS: 28.9%, ST: 54.9%, P-value < 0.001) and splenectomy (SS: 16.1%, ST: 35.7%, P-value < 0.001). In contrast to Northern American populations and similar to some Mediterranean populations, Lebanese SCD patients have a higher prevalence of persistent splenomegaly. The relatively low incidence of thrombotic complications deserves further investigation. The study's limitations include those of any other retrospective study and the fact that not all Lebanese centers caring for inherited hemoglobin disorders were included. However, the results of this first large scale national survey indicate that preventive efforts should target the Northern and Southern regions of Lebanon to decrease the number of new off springs afflicted with this disease similar to what has been successfully achieved with Thalassemia, another hemoglobinopathy that is highly prevalent in the country.

Sickle Cell Anemia: Targeting the Role of Fetal Hemoglobin in Therapy:

Abstract: Sickle cell anemia results from the single amino acid substitution of valine for glutamic acid in the beta-chain owing to a nucleotide defect that causes the production of abnormal beta-chains in hemoglobin S. Abnormal hemoglobin chains form polymers in the deoxygenated state, leading to the characteristic sickle cells. The polymerization of deoxygenated hemoglobin S accounts for the pathologic changes in sickle cell disease. The main-stay of therapy in sickle cell disease aims to reduce the amount of sickled hemoglobin present through the prevention of polymerization and reversal of this process. One way of discouraging polymerization is to increase the level of fetal hemoglobin, which because of its high oxygen affinity, does not participate in the polymerization process. Fetal hemoglobin production may be induced pharmacologically or by the use of gene therapy and genetic engineering techniques.