Hemoglobin C trait accentuates erythrocyte dehydration in hereditary xerocytosis.

A 17-year-old male presented with acute hemolysis with stomatocytosis, elevated mean corpuscular hemoglobin concentration (MCHC), and osmotic gradient ektacytometry consistent with marked erythrocyte dehydration. Erythrocytes from both parents also demonstrated evidence of dehydration with elevated MCHC and abnormal ektacytometry, but neither to the degree of the patient. Genetic studies revealed the patient had hereditary xerocytosis (HX) due to a novel PIEZO1 mutation inherited from his mother and hemoglobin C (HbC) trait inherited from his father. HbC trait accentuated the erythrocyte dehydration of HX. Coinheritance of interrelated disorders and/or modifier alleles should be considered whenever severe erythrocyte dehydration is observed.

Hemoglobinosis C in Morocco : A report of 111 cas.

BACKGROUND: - Hemoglobin C is a hemoglobin variant encountered worldwide. The regionswith high prevalence are West Africa and South-East Asia.The objective of this study is to report cases of hemoglobin C disease brought together during these last twelve years in the Laboratory of Biochemistry and Toxicology of RabatMilitary Hospital Mohammed V (MHIMV). METHODS: - This was a retrospective study including111 cases of hemoglobin C disease collected in the Laboratory of Biochemistry of the MHIMVover the past 12 years. A questionnairewasfulfilledwith the epidemiological data,clinical data and the results of the biological explorations. The screening of the hemoglobin variant in this study included several biochemical (hemoglobin electrophoresis at acid and alkalinepH) and hematological tests. RESULTS: - Sex-ratio was equal to 1,22. The age at the time of diagnosis ranges between 4 and 80years old, with the mean of 38. North-West regions of Morocco seem most affected. The most frequent reasons for prescription of the hemoglobin's studywere: biological abnormalities, splenomegaly and anemic syndrome. Blood smear reveals frequently anisopoikilocytosis and red blood target. The biochemical tests contribute to the diagnosis and reveal various and varied etiological groups: heterozygous A/C (75%),homozygous C/C (8%), double heterozygous S/C (9%),C/ß+-thal (6%) andC/O-Arab (2%). Conclusion - The results of the present descriptive study are in line with the literature data. The importance of genetic counseling and the installation of a national card of systematic neonatal tracking seemto be unavoidable.

Blood typing profile of a school-aged population of a North Togo township.

The aim of this study was the determination of hemoglobin (Hb) variants and ABO blood groups in a school population aged 6 to 9 years in the township of Agbandé-Yaka in North Togo. A cross-sectional study was carried out on 570 children of four primary schools at Agbande-Yaka, between March and July 2010. Hemoglobin characterization was done by alkaline buffer electrophoresis and the blood types ABO-Rhesus (Rh) D by immuno-hematological methods. A Hb variant was detected in 37.0% of the schoolchildren. Among them, the AS trait accounted for 11.9% and the AC trait for 20.2%. Homozygous Hb S (HBB: c.20A>T) was not found but Hb C (HBB: c.19G>A) appeared at a frequency of 3.3%, while compound heterozygotes carrying Hb SC were seen at a frequency of 1.6%. The O, B and A blood groups accounted for 49.0, 26.8 and 21.9%, respectively. The Hb anomalies reached a high prevalence in this school population. These results are remarkable by the absence of homozygous Hb S individuals compared to homozygous Hb C individuals, which were as numerous as expected. The frequencies of the ABO blood groups are similar to what has been found in other West African populations.

Human bulbar conjunctival hemodynamics in hemoglobin SS and SC disease.

The known biophysical variations of hemoglobin (Hb) S and Hb C may result in hemodynamic differences between subjects with SS and SC disease. The purpose of this study was to measure and compare conjunctival hemodynamics between subjects with Hb SS and SC hemoglobinopathies. Image sequences of the conjunctival microcirculation were acquired in 9 healthy control subjects (Hb AA), 24 subjects with SC disease, and 18 subjects with SS disease, using a prototype imaging system. Diameter (D) and blood velocity (V) measurements were obtained in multiple venules of each subject. Data were categorized according to venule caliber by averaging V and D for venules with diameters less than (vessel size 1) or greater than (vessel size 2) 15 µm. V in vessel size 2 was significantly greater than V in vessel size 1 in the AA and SS groups (P ≥ 0.009), but not in the SC group (P = 0.1). V was significantly lower in the SC group as compared to the SS group (P = 0.03). In AA and SS groups, V correlated with D (P ≤ 0.005), but the correlation was not statistically significant in the SC group (P = 0.08). V was inversely correlated with hematocrit in the SS group for large vessels (P = 0.03); however, no significant correlation was found in the SC group (P ≥ 0.2). Quantitative assessment of conjunctival microvascular hemodynamics in SS and SC disease may advance understanding of sickle cell disease pathophysiology and thereby improve therapeutic interventions.

Elevated plasma levels and platelet-associated expression of the pro-thrombotic and pro-inflammatory protein, TNFSF14 (LIGHT), in sickle cell disease.

Chronic vascular inflammation and endothelial activation may initiate vaso-occlusion in sickle cell disease (SCD). TNFSF14 (CD258; LIGHT), a recently-identified pro-thrombotic and pro-inflammatory tumour necrosis factor (TNF)-superfamily cytokine, has a potent activating effect on endothelial cells. We evaluated whether TNFSF14 production is altered in SCD and whether platelets contribute to this production. TNFSF14 was measured in platelet-free plasma from healthy-control individuals (CON), steady-state sickle cell anaemia (SCA), SCA on hydroxycarbamide therapy (SCAHC) and haemoglobin SC (HbSC) patients. Mean plasma TNFSF14 was significantly increased in SCA, SCAHC and HbSC, compared to CON individuals. In SCA/SCAHC patients, plasma TNFSF14, showed no correlation with haematological variables, but was significantly correlated with serum lactate dehydrogenase and inflammatory markers (CD40LG , IL8 and ICAM1). Platelet-membrane TNFSF14 expression was significantly augmented on SCA platelets, and correlated with platelet activation; furthermore, measurement of platelet TNFSF14 release indicated that platelets may be a major source of circulating TNFSF14 in SCA. Interestingly, high plasma TNFSF14 was significantly associated with elevated tricuspid regurgitant velocity (≥2·5 m/s) in a population of SCA/SCAHC patients. The pro-inflammatory and atherogenic cytokine, TNFSF14, could contribute to endothelial activation and inflammation in SCA; future investigations may confirm whether this protein contributes to major clinical complications of the disease, such as pulmonary hypertension, and represents a potential therapeutic target.

Prevalence of transcranial Doppler abnormalities in Nigerian children with sickle cell disease.

Transcranial Doppler (TCD) ultrasonography helps to identify children with sickle cell disease (SCD) who are at an increased risk of stroke,making primary stroke prevention a reality. A cross-sectional study of145 Nigerian children aged ≥3 years with SCD was carried out to describe the pattern of cerebral blood flow (CBF) abnormalities. The mean time-averaged mean velocity (TAMV) was 152 ±27.0 cm/sec and122 ±22.0 cm/sec in Hb SS and Hb S1C group, respectively. Abnormal velocities were recorded in six (4.7%) of the Hb SS patients and none of the Hb S1C while conditional risk (CR) velocities were recorded in 19.7% of Hb SS (low conditional 11.0%, high conditional 8.7%) and low conditional in 5.6% of Hb S1C cases. Cerebral flow velocities showed a negative correlation with age and hematocrit. Compared with African-American children, Nigerian children with Hb SS disease have a considerably higher prevalence of CR velocities.

Variant hemoglobin phenotypes may account for differential erythropoiesis-stimulating agent dosing in African-American hemodialysis patients.

African-American patients with end-stage renal disease have historically lower hemoglobin concentrations and higher requirements of erythropoiesis-stimulating agent (ESA). While disparities in health-care access may partially explain these findings, the role of variant hemoglobin, such as sickle trait, has not been investigated. To clarify this, we evaluated 154 African-American patients receiving in-center hemodialysis with available hemoglobin phenotyping. The primary exposure was any abnormal hemoglobin variant and the primary outcome of higher-dose ESA was defined as a dose of 6500 or more units per treatment. Logistic regression assessed the association between variant hemoglobin and higher-dose ESA. Covariates included age, gender, diabetes, iron parameters, intravenous iron dose, parathyroid hormone, albumin, phosphorus, body mass index, vascular access type, hospitalization/missed treatments, smoking status, alcohol abuse, and gastrointestinal bleeding. Of 33 patients with variant hemoglobin, 24 had HbAS and 9 had HbAC. Univariate odds of higher-dose ESA among those with hemoglobin variants were twice that of those with the normal HbAA phenotype (odds ratio 2.05). In multivariate models, the likelihood of higher-dose ESA had an odds ratio of 3.31 and the nature of this relationship did not change in Poisson regression or sensitivity analyses. Hence, our findings may explain, in part, the difference in ESA dosing between Caucasians and African-Americans with end-stage renal disease but await further study.

Rheumatoid arthritis in patient with homozygous haemoglobin C disease.

To date, few cases of hemoglobinopathies in patients with rheumatoid arthritis (RA) have been reported (Marino and Mcdonald in J Rheumatol 17:970-972, 1990; Gladman and Bombardier in Arthritis Rheum 30:1065-1068, 1987; Michel et al. in Semin Arthritis Rheum 38:228-240, 2008). These haemoglobin diseases are associated with characteristics abnormalities of the skeleton. Haemoglobin C disease is a benign hemoglobinopathy rarely associated with skeletal disorders [Piéron et al. in la semaine des hôpitaux 57(1-2):22-25, 1981]. We report a case of RA in a 60-year-old woman with homozygous haemoglobin C disease. This coexistence may be a pure coincidence, although we discuss the difficulties with RA treatment in this case due to the unknown effect of anti-rheumatic drugs on the progression of haemoglobin C disease.

Differing effects of HbS and HbC traits on uncomplicated falciparum malaria, anemia, and child growth.

The high prevalence of hemoglobin S (HbS) in Africa and hemoglobin C (HbC) in parts of West Africa is caused by the strong protection against severe falciparum malaria during childhood. Much less is known about the effect of HbS and especially HbC on Plasmodium falciparum infection, uncomplicated malaria, and anemia. A total of 1070 children from the Ashanti Region, Ghana, were enrolled at the age of 3 months and visited monthly until 2 years of age. The effects of the beta-globin genotype on the age-dependent incidence of malaria, levels of parasitemia, and hemoglobin as well as physical development were analyzed by population-averaged models. Infants with HbAS were protected from uncomplicated malaria (P < .005) and anemia (P < .001), had lower age-adjusted parasite densities (P < .001), and higher age-adjusted hemoglobin levels compared with children with the HbAA genotype (P = .004). In contrast, HbAC carriers had lower hemoglobin levels (P < .033) and were not protected against malaria or anemia. Notably, infants with HbAS were also significantly protected against stunting compared with carriers of HbAA or HbAC. This indicates differing mechanisms of protection against malaria of HbAS and HbAC and might help to understand why HbC is restricted to distinct areas of West Africa.

Red blood cell aggregation, aggregate strength and oxygen transport potential of blood are abnormal in both homozygous sickle cell anemia and sickle-hemoglobin C disease.

BACKGROUND: Recent evidence suggests that red blood cell aggregation and the ratio of hematocrit to blood viscosity (HVR), an index of the oxygen transport potential of blood, might considerably modulate blood flow dynamics in the microcirculation. It thus seems likely that these factors could play a role in sickle cell disease. DESIGN AND METHODS: We compared red blood cell aggregation characteristics, blood viscosity and HVR at different shear rates between sickle cell anemia and sickle cell hemoglobin C disease (SCC) patients, sickle cell trait carriers (AS) and control individuals (AA). RESULTS: Blood viscosity determined at high shear rate was lower in sickle cell anemia (n=21) than in AA (n=52), AS (n=33) or SCC (n=21), and was markedly increased in both SCC and AS. Despite differences in blood viscosity, both sickle cell anemia and SCC had similar low HVR values compared to both AA and AS. Sickle cell anemia (n=21) and SCC (n=19) subjects had a lower red blood cell aggregation index and longer time for red blood cell aggregates formation than AA (n=16) and AS (n=15), and a 2 to 3 fold greater shear rate required to disperse red blood cell aggregates. CONCLUSIONS: The low HVR levels found in sickle cell anemia and SCC indicates a comparable low oxygen transport potential of blood in both genotypes. Red blood cell aggregation properties are likely to be involved in the pathophysiology of sickle cell disease: the increased shear forces needed to disperse red blood cell aggregates may disturb blood flow, especially at the microcirculatory level, since red blood cell are only able to pass through narrow capillaries as single cells rather than as aggregates.

Urinary cysteinyl leukotriene E4 significantly increases during pain in children and adults with sickle cell disease.

Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso-occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso-occlusion.

Genetic epidemiology of susceptibility to malaria: not only academic exercises.

Descriptive genetic epidemiology represents the initial step of a logical procedure of linked and consequential phases spanning from the identification of genes involved in the resistance/susceptibility to diseases, to the determination of the underlying mechanisms and finally to the possible translation of the acquired knowledge in new control tools. In malaria, the rational development and potential of this pathway is based on complementary interactions of heterogeneus disciplines going from epidemiology (the transmission, the infection, the disease) to vaccinology passing through genetics, pathogenesis, and immunology. Several epidemiological approaches can be applied in the study of the genetic susceptibility to Plasmodium falciparum malaria: intra-ethnic case-control studies comparing genetic candidates of resistance/susceptibility between subjects with different presentation of malaria (from severe disease to asymptomatic infection) and the general healthy population is the classic approach; inter-ethnic comparative analyses among populations with different genetic backgrounds, exposed to the same epidemiological context and showing different susceptibility to the disease is a further, complementary, strategy.

Case report of HbC/beta(0)-thalassemia from India.

This 22-year-old women presented to the ante-natal clinic of this hospital for prenatal screening for beta-thalassemia. Cation exchange high performance liquid chromatography (HPLC) using 'Beta Thalassemia Short Program' on Bio-Rad 'Variant' system revealed HbC value of 81.6%. The CBC showed microcytic hypochromic anemia. The HPLC and CBC suggested the possibility of compound heterozygote state for HbC/beta-thalassemia. The alkali and acid electrophoresis findings were consistent with the above diagnosis. The DNA analysis confirmed compound heterozygote state for HbC/beta(0)-thalassemia (Fr 8/9 mutation). The studies on the parents showed that mother was a compound heterozygote for HbD(Punjab) and HbC while father had beta-thalassemia trait. To the best of our knowledge, this is the first confirmed report of HbC from India. The paper discusses the hematological findings in this subject and her mother (a compound heterozygote for HbD(Punjab) and HbC).

[Hemoglobin C disease: report of 16 Tunisian cases]. / L'hemoglobinose C: a propos de 16 cas Tunisiens.

AIM: was to provide the clinical and biological patterns hemoglobine disease in Tunisia. METHODS: This retrospective study collected to 16 cases of hemoglobin C disease : 6 homozygotic Hb C and 10 heterozygotic Hb C/beta-thalassemia. RESULTS: The clinical profile is characterized by mild hemolytic anemia (Hb = 11.7 g/dl) associated with splenomegaly and hypersplenism. Contrary to homozygous state, the Hb C/beta-thalassemia is associated with microcytosis and pseudopolycythemia. The diagnosis is based on target cells, specific intraerythrocytic Hb C crystals in blood smear and Hb C level at 100%. CONCLUSION: The Hb C disease must be considered as a benign hemoglobinopathy which is associated with a long survival without major complications.

Association between haemoglobin variants S and C and Mycobacterium ulcerans disease (Buruli ulcer): a case-control study in Benin.

Risk factors for Buruli ulcer (BU) are poorly understood. We conducted a case-control study in southern Benin to investigate the association between haemoglobin variants S or C and BU, and particularly the association between haemoglobinopathies HbSS/SC and BU osteomyelitis. We compared the haemoglobin genotype of 179 patients with BU and 44 with BU osteomyelitis to that of 242 community controls. We found no evidence of an increased risk of BU according to the presence of haemoglobin variants S and/or C [odds ratio adjusted for sex, age, region of residence and ethnicity: 1.24 (95% CI: 0.80-1.93), P = 0.34]. Haemoglobin variants S and C are unlikely to play a role in the BU burden. However, haemoglobinopathies HbSS/SC were more frequent among BU osteomyelitis patients than among controls (6.8% vs. 1.0%, Fisher's exact P-value = 0.045), which may suggest that those disorders facilitate growth of Mycobacterium ulcerans in the bone matrix.

Incidence of haemoglobinopathies detected through neonatal screening in the United Arab Emirates.

In January 2002, a pilot programme of neonatal screening for sickle cell disease was launched in the United Arab Emirates (UAE) in 3 districts of Abu Dhabi emirate. This paper reports the incidence of sickle cell diseases, other haemoglobinopathies and haemoglobinopathy carriers over a 12-month period using high performance liquid chromatography as a primary screening method. The overall incidence of sickle cell disease among 22 200 screened neonates was 0.04% (0.07% for UAE citizens and 0.02% for non-UAE citizens). The incidence of sickle cell trait was 1.1% overall (1.5% for UAE citizens and 0.8% for non-UAE citizens). Universal neonatal screening for sickle cell haemoglobin at the national level should be considered.