Alpha-thalassemia is related to prolonged survival in sickle cell anemia

Mears, JG; Lachman, H.; Labie, Dominique; Nagel, RL

doi:10.1182/blood.v62.2.286.bloodjournal622286

Cited by 29 publications

(9 citation statements)

References 18 publications

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“…Thus, patients with a thalassemia had less severe hemolytic anemia and lower leukocyte and platelet counts. To our knowledge, this impact on leukocytes and platelets has not been reported before and could possibly contribute to the beneficial effects of a thalassemia on patient survival 12 and frequency of crises 35 by lowering viscosity. At baseline, in the Baby-Hug trial, 36 patients with a thalassemia (75/189) had significantly lower MCV, mean corpuscular Hb, reticulocytes, and bilirubin levels, but leukocyte and platelet counts were not reported, and the presence of a thalassemia had no effect on Hb levels, probably in part because of the lower number of patients in their cohort, but the favorable impact of a thalassemia on Hb was only observed in CAR/ CAR patients and not in BEN/BEN patients in our study.…”

Section: Discussionmentioning

confidence: 63%

“…3 The presence of a thalassemia in SCA patients is known to reduce HbS polymerization and hemolysis by lowering intracellular Hb concentration [9][10][11] and improve anemia, and it has been reported to be associated with improved survival. 12 The HbS gene emerged and expanded through the selective pressure of Plasmodium falciparum malaria in separate geographic locations of Africa. 13 These distinct mutational events were identified by linked DNA polymorphic sites, located on the b-globin cluster, and defined as the Senegal (SEN), Benin (BEN), Bantu/Central African Republic (CAR), and Cameroon 14 haplotypes.…”

Section: Introductionmentioning

confidence: 99%

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Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

Bernaudin¹,

Kamdem²,

Hau

et al. 2018

Blood Advances

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Sickle cell anemia (SCA), albeit monogenic, has heterogeneous phenotypic expression, mainly related to the level of hemoglobin F (HbF). No large cohort studies have ever compared biological parameters in patients with major β-globin haplotypes; ie, Senegal (SEN), Benin (BEN), and Bantu/Central African Republic (CAR). The aim of this study was to evaluate the biological impact of α genes, β haplotypes, and glucose-6-phosphate dehydrogenase (G6PD) activity at baseline and with hydroxyurea (HU). Homozygous HbS patients from the Créteil pediatric cohort with available α-gene and β-haplotype data were included (n = 580; 301 females and 279 males) in this retrospective study. Homozygous β-haplotype patients represented 74% of cases (37.4% CAR/CAR, 24.3% BEN/BEN, and 12.1% SEN/SEN). HU was given to 168 cohort SCA children. Hematological parameters were recorded when HbF was maximal, and changes (HU-T0) were calculated. At baseline, CAR-haplotype and α-gene numbers were independently and negatively correlated with Hb and positively correlated with lactate dehydrogenase. HbF was negatively correlated with CAR-haplotype numbers and positively with BEN- and SEN-haplotype numbers. The /rs1427407 "T" allele, which is favorable for HbF expression, was positively correlated with BEN- and negatively correlated with CAR-haplotype numbers. With HU treatment, and HbF values were positively correlated with the BEN-haplotype number. BEN/BEN patients had higher HbF and Hb levels than CAR/CAR and SEN/SEN patients. In conclusion, we show that BEN/BEN patients have the best response on HU and suggest that this could be related to the higher prevalence of the favorable /rs1427407/T/allele for HbF expression in these patients.

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Section: Discussionmentioning

confidence: 63%

Section: Introductionmentioning

confidence: 99%

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

Bernaudin¹,

Kamdem²,

Hau

et al. 2018

Blood Advances

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“…[ 3 ] The oldest are now 43 years of age and the Cohort has allowed assessment of causes of death (COD) and survival to middle age in a hydroxyurea naïve population in which, for the past 30 years, interventions have included pneumococcal prophylaxis, training caregivers in splenic palpation and provision of comprehensive health care. The predictive effects of early life biomarkers of a severe clinical course (dactylitis before age 1 year or ever, a high total nucleated cell count or low hemoglobin at age one year),[ 4 ] as well as genetically determined phenotypes (alpha-thalassemia status,[ 5 ] beta-globin haplotype[ 6 ] and fetal haemoglobin[ 7 ] were assessed. Cause/s of death was assigned, where possible…”

Section: Introductionmentioning

confidence: 99%

Causes of death and early life determinants of survival in homozygous sickle cell disease: The Jamaican cohort study from birth

Serjeant¹,

Chin

Asnani

et al. 2018

PLoS ONE

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Globally, the majority of persons born with sickle cell disease do not have access to hydroxyurea or more expensive interventions. The objectives were to estimate the survival in homozygous sickle cell disease, unbiased by symptomatic selection and to ascertain the causes of death in a pre-hydroxyurea population. The utility of early life biomarkers and genetically determined phenotypes to predict survival was assessed. A cohort study based on neonatal diagnosis was undertaken at the Sickle Cell Unit, a specialist clinic delivering care to persons with sickle cell disease in Jamaica. Screening of 100,000 deliveries detected 315 babies with homozygous sickle cell disease of whom 311 have been followed from birth for periods up to 43 years. Pneumococcal prophylaxis and teaching mothers splenic palpation were important, inexpensive interventions. Anticipatory guidance, routine care and out-patient acute care were provided. Each participant was classified as alive, dead, or defaulted (usually emigration). Causes of death were ascertained from clinical records and/or post-mortem reports. Survival was assessed using the Kaplan-Meier function. Sex-adjusted Cox semi-parametric proportional hazards and Weibull modelling were used to assess the effects on survival of biomarkers.Survival to 40 years was 55.5% (95% CI 48.7% to 61.7%). Acute Chest Syndrome (n = 31) and septicemia (n = 14) were significant causes of death at all ages. Acute splenic sequestration (n = 12) was the most common cause of early deaths. Survival was significantly shorter in those with lower hemoglobin at 1 year, high total nucleated count at 1 year, and a history of dactylitis ever.In these hydroxyurea naïve patients, survival into midlife was common. Causes of death were often age specific and some may be preventable. Early life biomarkers predictive of decreased survival in SS disease identify a patient group likely to benefit from close clinical supervision and potentially high risk therapies.

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“…Finally, we did not evaluate our group for the presence of alpha thalassemia. Though some studies have suggested that patients with SCA and concomitant alpha thalassemia have decreased mortality rates, larger cohort studies have failed to bear out these findings [ 2 , 30 , 31 ].…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Analysis of Patient Specific Predictors for Mortality in Sickle Cell Disease

Curtis¹,

Danda

Etzion

et al. 2016

PLoS ONE

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IntroductionWhite Blood Cell (WBC) count, %HbF, and serum creatinine (Cr), have been identified as markers for increased mortality in sickle cell anemia (SCA) but no studies have examined the significance of longitudinal rate of change in these or other biomarkers for SCA individuals.MethodsClinical, demographic and laboratory data from SCA patients seen in 2002 by our hospital system were obtained. Those who were still followed in 2012 (survival cohort) were compared to those who had died in the interim (mortality cohort). Patients lost to follow-up were excluded. Age adjusted multivariable Cox proportional hazards models were constructed to assess hazard ratios of mortality risk associated with the direction and degree of change for each variable.Results359 SCA patients were identified. Baseline higher levels of WBC, serum creatinine and hospital admissions were associated with increased mortality, as were alkaline phosphatase and aspartate aminotransaminase levels. Lower baseline levels of %HbF were also associated with increased mortality. When longitudinal rates of change for individuals were assessed, increases in Hb or WBC over patient baseline values were associated with greater mortality risk (HR 1.54, p = 0.02 and HR 1.16, p = 0.01 with negative predictive values of 87.8 and 94.4 respectively), while increasing ED use was associated with decreased mortality (HR 0.84, p = 0.01). We did not detect any increased mortality risk for longitudinal changes in annual clinic visits or admissions, creatinine or %HbF.ConclusionsAlthough initial steady state observations can help predict survival in SCA, the longitudinal course of a patient may give additional prognostic information.

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Alpha-thalassemia is related to prolonged survival in sickle cell anemia

Cited by 29 publications

References 18 publications

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

Biological impact of α genes, β haplotypes, and G6PD activity in sickle cell anemia at baseline and with hydroxyurea

Causes of death and early life determinants of survival in homozygous sickle cell disease: The Jamaican cohort study from birth

Longitudinal Analysis of Patient Specific Predictors for Mortality in Sickle Cell Disease

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