Impact of Medical Approach in a Limited-resources Centre on the Pattern of Sickle Cell Disease Phenotypes and its Complication in a Nigerian Hospital: A Single-center Retrospective Study

Background: Sickle cell disease (SCD) is the commonest inherited qualitative blood disorder worldwide. Aims: To guide haematologists and other clinicians in making appropriate clinical judgement in the management of SCD patients in resource poor countries. Objective: To evaluate the demographic characteristics, clinical phenotype, laboratory parameters and complications of the enrolled patients during the period of the study. Study Design: A retrospective study. Place and Duration of the Study: Haematology and Immunology department, UNTH over 8 years period. Methodology: We enrolled 135 patients grouped into mild or severe SCD. The objective parameters were extracted from their case notes. Data analyzed using GraphPad Prism version 8. Results: Of the135 subjects, 39 (29%) had mild disease while 96 (71%) had severe disease. The mean ages in the groups were 27 and 26 years respectively (age ranged from 10 to 55years). Mean weight and frequency of crises per year between the groups were 59 and 58kg, 1.0 and 5.0 crises, respectively. Significant difference existed in the mean blood counts, F = 323.3. P < 0.0001. Renal and liver functions showed no significant derangement. Vaso-occlusive crisis (VOC) was predominant crisis. Leg ulcer (20%) was commonest complication. Significant relationship existed between frequency of crisis and number of complications, r = 0.17, P = .04, [CI = 0.003 – 0.332]. No relationship was observed between the number of blood units and frequency of crisis, r = 0.05, P = .61, [CI = -0.12 - 0.21]. Our patients were counselled at every clinic visit with proper guidance. Significant difference existed between blood pressure and proteinuria, P < .0001, [CI = 4.73 – 23.2]. Conclusion: Multidisciplinary approach improved their clinical outcome. Component blood transfusion practice is strongly advocated. We recommend further studies on the psycho-socio-economic, and environmental factors that impact on clinical phenotypes of this medical condition.

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Clinical Complications in Adult Patients with Sickle Cell Anemia and β-Thalassemia-Sickle Cell Disease

Blood ◽

10.1182/blood.v120.21.4767.4767 ◽

2012 ◽

Vol 120 (21) ◽

pp. 4767-4767

Author(s):

Giovanna Graziadei ◽

Alessia Marcon ◽

Martina Soldarini ◽

Ilaria Gandolfi ◽

Luisa Ronzoni ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Acute Chest Syndrome ◽

P Value ◽

Cell Disease ◽

Transfusion Therapy ◽

Clinical Complications ◽

Significant Difference ◽

The Mean

Abstract Abstract 4767 Background. Sickle-Cell Disease (SCD) is one of the most common severe monogenic inherited disorders worldwide, due to hemoglobin S (HbS), with reduced affinity for the oxygen. HbS polymerization, leading to erythrocyte rigidity, vaso-occlusion and hemolytic anemia, is central in the pathophysiology and crucial for the clinical outcome. The term SCD refers to Sickle Cell Anemia (SCA) due to homozygosis for βS allele, HbS/β-thalassemia (T-SCD) due to compound of β-thal and βS allele, and HbSC disease, owing to the coinheritance of βS and βcalleles. SCD is a multiorgan disease characterized by recurrent acute events and progressive organ damage, worsening during the life. Aims. This is a retrospective monocentric study aimed to assess and compare the clinical complications among 59 adult SCD patients, followed at the Hereditary Anemia Centre of the Foundation IRCCS “Ca Granda” Ospedale Maggiore Policlinico, in Milan, Italy. Methods. Mutation analysis of the b globin gene was established by direct DNA sequencing on the ABI Prism 310 genetic analyzer. Clinical and hematological features were evaluated by routine tests and physical examination, with special attention to the erythropoiesis stress parameters as LDH values and extramedullary erythropoietic (EE) masses. Results. Fifty-nine adult SCD patients, 16 SCA and 43 T-SCD, were evaluated. In T-SCD patients detected b-mutations were severe (b°) in 69.8%, and moderate or mild (b+-b++) in 30.2%. The mean age of SCA patients was 36±9 and 41±11 years for T-SCD patients. For both groups the mean follow-up was 20±6 years, while the mean age at the presentation in our Centre was 32±8 years in SCA patients and 31±10 years in T-SCD ones. Five out of 16 (31.2%) SCA patients and 16/43 (37.2%) T-SCD patients were male. HbF mean levels were 6.9±5.1% and 10.1±7.2%, respectively in SCA and T-SCD group; surprisingly Hb mean levels were lower in SCA (9.3±1.3 g/dl) than in T-SCD (9.9±1.4 g/dl) patients. Comparing SCA and T-SCD, there was statistically significant difference in splenic features: splenectomy was performed in 2/16 (12.5%) SCA patients vs 21/43 (48.8%) T-SCD patients (p-value < 0.01). Splenomegaly was absent in SCA, while was detected in 11/22 (50%) T-SCD (p-value < 0.0001); all SCA patients had functional asplenia, not observed in T-SCD patients; splenic infarctions were absent in SCA patients and were detected in 7/22 (31.8%) T-SCD patients, of whom 5 had splenomegaly and 2 had normal spleen size (pvalue <0.001). On the other side, there was not statistically significant difference in the prevalence of stroke, acute chest syndrome (ACS), bone pain crisis, sepsis, leg ulcers and priapism. However, we observed some clinical differences, even if not statistically significant. Cholecistectomy was performed in 4/16 (25%) SCA patients vs 17/43 (39.5%) T-SCD patients, and gallstones were detected respectively in 5/12 (41.7%) and in 14/26 (53.8%) of SCA and T-SCD patients. Thrombotic events were absent in SCA patients, compared to 4/43 (9.3%) T-SCD patients. Furthermore, we detected EE in 3/16 (18.6%) SCA and in 3/43 (7%) T-SCD, all carrying b° thal mutations. We underlie that Hb levels and LDH values were higher in SCA than in T-SCD patients (823±295 vs 689±209 U/L). About the treatment, 14/16 (87.5%) SCA and 31/43 (72%) T-SCD underwent to top-up transfusion; 5/43 (11.6%) T-SCD were regularly transfused. Seven out of 16 (43.8%) SCA and 18/43 (41.8%) T-SCD patients were treated with Hydroxycarbamide (HU). Criteria for transfusion therapy were: painful crisis not responsive to HU, major clinical complications, such as stroke or ACS, extramedullary erythropoietic masses associated with high LDH levels and low Hb values. Conclusions. These data suggest that SCA and T-SCD patients have similar clinical course. Splenomegaly is present only in T-SCD patients, probably due to the increased amount of extravascular hemolysis. Surprisingly, SCA patients showed EE and lower Hb levels with higher LDH values compared to T-SCD ones. This could be related to the prevalence of intravascular hemolysis, that can lead to erythropoietic stress in SCA, even if tissues are better oxygenated in these patients because of biochemical characteristic of HbS in terms of decreased oxygen affinity. These observations could be important to evaluate transfusion and HU treatment. Disclosures: Cappellini: Novartis: Research Funding.

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Severe Sickle Cell Disease Is Characterized by Low ADAMTS13/VWF: Ag Ratio

Blood ◽

10.1182/blood.v120.21.3235.3235 ◽

2012 ◽

Vol 120 (21) ◽

pp. 3235-3235

Author(s):

Despoina Adamidou ◽

Erasmia Rouka ◽

Despoina Kyriakou ◽

Stamatia Theodoridou ◽

E Vetsiou ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Normal Values ◽

Clinical Phenotype ◽

Severe Disease ◽

Control Group ◽

Compound Heterozygous ◽

Cell Disease ◽

Significant Difference ◽

Lower Ratio

Abstract Abstract 3235 Endothelial damage is one of the major mechanisms causing most of the manifestations in sickle cell disease (SCD). We hypothesized that a possible defect in the cleavage of large vWF multimers through the protease ADAMTS13 could add further to the well established chronic activation of the endothelium and consequently to the severity of the disease. For this purpose we measured the activity of the enzyme and looked for any correlations with regard to the clinical phenotype of patients with SCD. We studied 22 steady state patients (9 men/13 women) with a median age of 35(22–74) years. Of them, 3 were in homozygous state(HbSS) and 19 were compound heterozygous for thalassamia β(HbS/β+, HbS/β0). The clinical phenotype was mild in 12 patients, moderate in 3 and 7 were suffering from severe symptoms (history of frequent vaso-occlusive and acute chest crises and need for regular exchange transfusion). We applied FRET (fluorescence resonance energy transfer) technique to measure ADAMTS13 activity (normal values>65%). Factor VIII and vWF: Ag was measured using 1-stage clotting assay and immunoassay respectively (normal values 50–150%). We considered all relevant clinical parameters (spleen size, transfusion frequency, comorbidities, and medications with special regard to iron chelation, hydroxyurea and antiplatelet agents) together with laboratory readings (markers of haemolysis, proportion of haemoglobin fractions using high-performance liquid chromatography HPLC).We used as control group 22 healthy volunteers blood donors with their written consent matched for age, sex, body mass index and ABO blood group. All samples were taken at least 30 days post last transfusion. We found higher levels of both vWF: Ag [189(33–345)] and ADAMTS13 [164(75–310)] in the patients compared to the control group [87(44–152) και 126(55–171) (p<0.001/p<0.025)] respectively. When we analyzed the ratio ADAMTS13/vWF: Ag we found significant difference between the two groups: 1,041(0.3–4.6) vs 1.56(0.5–2.6) (p<0.020). Furthermore, patients with severe disease experienced significantly lower ratio ADAMTS/vWF 0.7(0.5–1.2) compared to both control group (p<0.001) as well as patients with milder clinical phenotype [1.30(0.3–4.6)].Of note, in patients with severe SCD despite the fact that vWF: Ag levels were found considerably higher and in significant difference with the control group [196(130–345) vs 87(44–152)p<0.001], we could not find the same pattern for ADAMTS13 [140(75–210) vs 126(55–171)].The lower ratio found in patients with SCD and in particular in those with severe disease might indicate the need for higher protease levels in comparison to healthy controls. It looks like in this group of patients ADAMTS13, although normal, is not sufficient enough to manage the reasonably high vWF levels that characterize the chronic endothelial activation. This relevant deficiency of the metaloprotease might be caused by either biggest consumption due to large and constant release of its substrate-vWF or by an acquired inhibition of its action as the free intravascular hemoglobin might exhibit an antagonistic role for the binding site of vWF. In conclusion, the low ADAMTS13/vWF: Ag ratio seems to detect patients with severe SCD and would be of interest to prospectively investigate its role both as a prognostic tool as well as a potential therapeutic target. Disclosures: No relevant conflicts of interest to declare.

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Profile of Reproductive Issues Associated with Different Sickle Cell Disease Genotypes

Revista Brasileira de Ginecologia e Obstetrícia / RBGO Gynecology and Obstetrics ◽

10.1055/s-0037-1604179 ◽

2017 ◽

Vol 39 (08) ◽

pp. 397-402

Author(s):

Flávia Carvalho ◽

Ariani Souza ◽

Ana Ferreira ◽

Simone Neto ◽

Ana Oliveira ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Contraceptive Method ◽

Severe Form ◽

Cell Disease ◽

Contraceptive Methods ◽

Cross Sectional ◽

Significant Difference ◽

The Mean ◽

Associated Variables

Purpose To describe the reproductive variables associated with different sickle cell disease (SCD) genotypes and the influence of contraceptive methods on acute painful episodes among the women with the homozygous hemoglobin S (HbSS) genotype. Methods A cross-sectional study was conducted between September of 2015 and April of 2016 on 158 women afflicted with SCD admitted to a hematology center in the Northeast of Brazil. The reproduction-associated variables of different SCD genotypes were assessed using the analysis of variance (ANOVA) test to compare means, and the Kruskal-Wallis test to compare medians. The association between the contraceptive method and the acute painful episodes was evaluated by the Chi-square test. Results The mean age of women with SCD was 28.3 years and 86.6% were mixed or of African-American ethnicity. With respect to the genotypes, 134 women (84.8%) had HbSS genotype, 12 women (7.6%) had hemoglobin SC (HbSC) disease genotype, and 12 (7.6%) were identified with hemoglobinopathy S-beta (S-β) thalassemia. The mean age of HbSS diagnosis was lower than that of HbSC disease, the less severe form of SCD (p < 0.001). The mean age of menarche was 14.8 ± 1.8 years for HbSS and 12.7 ± 1.5 years for HbSC (p < 0.001). Among women with HbSS who used progestin-only contraception, 16.6% had more than 4 acute painful episodes per year. There was no statistically significant difference when compared with other contraceptive methods. Conclusion With respect to reproduction-associated variables, only the age of the menarche showed delay in HbSS when compared with HbSC. The contraceptive method used was not associated with the frequency of acute painful episodes among the HbSS women.

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Examination of IQ in 7 to 14 years old children with sickle cell disease compared with healthy children

Journal of Preventive Epidemiology ◽

10.34172/jpe.2020.13 ◽

2020 ◽

Vol 5 (1) ◽

pp. e13-e13

Author(s):

Arash Alghasi ◽

Zohreh Hassanpour ◽

Mohammad Bahadoram ◽

Somayeh Ashrafi ◽

Seyed Mohammad Kazem Nourbakhsh

Keyword(s):

Standard Deviation ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Healthy Subjects ◽

Healthy Children ◽

Brain Circulation ◽

Cell Disease ◽

Significant Difference ◽

The Mean ◽

Iq Scores

Introduction: Sickle cell disease (SCD) is a genetic disorder that can be diagnosed by early onset screening tests. In embryos and newborns with sickle cell syndrome, the anatomic development and brain circulation is less than the normal people, and brain circulation plays an important role in brain development. Objectives: The purpose of this study was to evaluate the level of IQ in children with SCD. Patients and Patients and Methods: The study was a descriptive-epidemiologic. The population of the present study was all children aged 7-14 years old with SCD in Ahvaz. The sample of this study was 50 children with SCD. They were selected from among clients referring to the hepatitis clinic of Shafa hospital in Ahvaz. About 50 healthy children were selected from the first or second-degree family members of the patients with SCD as the control group. The data was collected using Raven’s Progressive Matrices (RPM) and demographic information questionnaire. Results: The mean and standard deviation of IQ scores of the patients with SCD was 94.52 ± 14.41, and the mean and standard deviation of IQ scores of healthy subjects was 105.86 ± 11.38. The results showed a significant difference between the two groups in terms of IQ score (P<0.05). Moreover, the results showed that IQ level in patients with SCD was significant regarding their place of residence (P<0.05), however IQ level was not significant in patients with SCD regarding gender and race (P>0.05). Conclusion: The results showed that IQ in children with SCD is lower than that of the healthy subjects. Thus, the present study showed the importance of SCD on children’s IQ.

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Prevalence of Vaso-Occlusive Crises in Patients with Sickle Cell Disease: A Retrospective US Claims Database Analysis

Blood ◽

10.1182/blood-2020-140756 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 8-9

Author(s):

Abiola Oladapo ◽

Elyse Swallow ◽

Allison Briggs ◽

Miriam L. Zichlin ◽

Bjorn L Mellgard

Keyword(s):

Health Care ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Clinical Characteristics ◽

Cell Disease ◽

Publicly Traded ◽

Database Analysis ◽

Claims Database ◽

Blood Disorder ◽

The Mean

Introduction: Sickle cell disease (SCD) is an inherited blood disorder affecting ~100,000 individuals in the US. SCD is considered a chronic, lifelong condition that requires comprehensive management. Vaso-occlusive crises (VOCs) are the most common complications of SCD, resulting in intense pain and potential irreversible organ damage. The objective of this study was to characterize the demographic and clinical characteristics of patients with SCD. Methods: A retrospective database analysis was conducted using data from the IBM MarketScan Commercial Claims and Medicare-Supplemental Claims database (July 1, 2013 to June 30, 2018). Patients were included if they met the following criteria: ≥2 diagnoses of SCD on different claims between July 1, 2013 and January 1, 2017, ≥6 years of age on January 1, 2017, and continuous enrollment throughout the 1-year study period (January 1, 2017 to December 31, 2017). Descriptive statistics were used to assess patient demographics (age and sex) and clinical characteristics (Charlson Comorbidity Index [CCI] and other selected comorbidities). In addition, the following outcomes were assessed: the proportion of patients who experienced ≥1 VOC, the frequency of VOCs by care setting, the duration of inpatient VOCs, the monthly VOC risk, and the time between subsequent VOCs. Results: A total of 8174 patients met the inclusion criteria. The mean (± standard deviation [SD]) age was 40.8 (±19.5) years and 63.5% of the patients were female. The mean (±SD) CCI was 0.6 (±1.3), with chronic pulmonary disease, diabetes, renal disease, cerebrovascular disease, and stroke identified as the most common comorbidities. Approximately 20% (n=1659) of patients experienced ≥1 VOC and the mean monthly VOC risk was 0.07 (±0.19). Among patients with ≥1 VOC, the mean (±SD) number of VOCs was 5.2 (±7.7) and the median (interquartile range) time from first to second VOC was 2.4 (0.5-8.2) months. Approximately 18% (n=1461) of patients experienced ≥1 VOC managed in an outpatient setting and 10% (n=844) of patients experienced ≥1 VOC managed in an inpatient setting. Approximately 8% (n=646) of patients experienced ≥1 inpatient and ≥1 outpatient VOC during the study period. Among patients with ≥1 outpatient VOC, the mean (±SD) number of outpatient VOCs was 4.6 (±6.9); among patients with ≥1 inpatient VOC, the mean (±SD) number of inpatient VOCs was 2.2 (±2.3) and the mean (±SD) inpatient VOC duration was 6.6 (±6.4) days. Conclusions: VOCs are common complications of SCD, affecting a subset of patients who often experience recurrent VOC episodes requiring professional health care. VOCs are associated with a significant disease burden on the patient and, potentially, the health care system. Disclosures Oladapo: Takeda:Current Employment, Current equity holder in publicly-traded company.Swallow:Analysis Group, Inc.:Current Employment.Briggs:Analysis Group, Inc.:Current Employment.Zichlin:BMS:Other: Employee of Analysis Group Inc., which received consulting fees.Mellgard:Baxalta US Inc., a Takeda company:Current Employment, Current equity holder in publicly-traded company.

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Elevated Tricuspid Regurgitant Jet Velocity In Lebanese Patients With Sickle Cell Disease Is Associated With Severe Disease and Is Clustered In Families

Blood ◽

10.1182/blood.v122.21.4684.4684 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4684-4684

Author(s):

Rouba Abdennour ◽

Mariam Arabi ◽

Paul Nietert ◽

Sarah Keyrouz ◽

Ruby Khoury ◽

...

Keyword(s):

Young Adults ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Rate Ratio ◽

Reticulocyte Count ◽

Severe Disease ◽

P Value ◽

Cell Disease ◽

Familial Clustering ◽

The Mean

Introduction Pulmonary hypertension (PHT) is a known complication of sickle cell disease (SCD), and it is indirectly assessed by measurement of the tricuspid regurgitant jet velocity (TRV). Despite the fact that PHT was found to be associated with early mortality in adults SCD patients, the association between elevated TRV and SCD severity and mortality is still controversial particularly in children and adolescents. The objective of this study was to investigate the relationship between elevated TRV and parameters of disease severity in children, adolescents and young adults with SCD. Methods The study is a retrospective review of medical records of patients with SCD followed at the comprehensive sickle cell clinic at the American University of Beirut Medical Center between April 2002 and January 2012. These include 115 patients with homozygous hemoglobin S disease, 8 with sickle β0-thalassemia, and 24 with sickle β+-thalassemia who have had at least one echocardiogram done as part of their routine medical care. All echocardiograms were done at steady state, at least four weeks after the last vasoocclusive crisis (VOC) or acute chest syndrome (ACS). Elevated TRV was defined as peak TRV of 2.5 meters per second or higher. Disease severity was assessed by comparing hemolysis biomarkers, rate of transfusions, VOCs and ACS and other SCD complications. In patients with sequential echocardiograms, changes in hydroxyurea (HU) doses were examined against TRV variation. Results 147 patients were studied over a mean number of 3.77 ± 1.96 years. The mean age was 15.07 ± 8.62 years, ranging from 18 to 43.4 years, with 66% being below 18 years of age. Elevated TRV was found in 57 patients (38.8%). T-tests and chi-square tests did not show any statistically significant differences between the patients with normal and elevated TRV with respect to age, gender, SCD subtype, time of follow-up, presence of stroke, AVN, ulcers and splenectomy. In addition, hemoglobin (mean=9.43±1.46 in normal TRV group versus 9.20±1.19 in high TRV, p=0.309) mean corpuscular volume (MCV, mean=93.04±16.96 vs. 96.56±15.03, p=0.203), reticulocyte count (mean= 9.51 ± 4.81 vs 9.97±5.55, p=0.596), bilirubin (indirect bilirubin mean=1.40±1.28 vs. 1.44±1.04, p=0.883) and lactate dehydrogenase (LDH, mean=423.20±192.00 vs. 451.40±399.40, p=0.398) did not show any significant differences between the two groups. Among patients with elevated TRV, 71.9% were on HU at a mean dose of 16.27 mg/kg/day compared to 70% of patients with low TRV who were on a mean HU dose of 15.13 mg/kg/day. HU was started in both groups for indications including pain crises, ACS and low hemoglobin but not TRV alone. Initially markers of hemolysis including MCV, reticulocyte count, bilirubin and LDH were significantly higher and hemoglobin lower in patients with elevated TRV, but these differences between the two groups were no longer evident after the dose of HU was optimized. In the 99 patients with 2 or more echocardiograms, no trend in TRV variation was observed after HU dose adjustment and sequential TRV readings. The mean transfusion rate per patient did not differ between the two groups. However, RBC alloimmunization was found in 6.2% of patients with normal TRV compared to 15% of patients with elevated TRV. Results of the Poisson models demonstrated that the VOC rate was 1.4 times higher among subjects with TRV ≥ 2.5 compared to subjects with TRV < 2.5 (rate ratio = 1.4; 95% CI = 1.04 to 2.02; p=0.029). Additionally, ACS rate was almost 3 times higher among subjects with high TRV (rate ratio = 2.8; 95% CI = 1.3 to 6.2; p=0.01). No deaths were reported in either study groups. Fisher's exact test and the generalized linear mixed model (GLMM) both indicated the presence of familial clustering of elevated TRV (Fisher's p-value: 0.009; GLMM p-value: 0.026). Conclusion The overall prevalence of elevated TRV in our study population was 38.8%. Despite improvement in hemolyis after introducing and optimizing hydroxyurea doses, patients with elevated TRV still had more severe disease as defined by higher rates of VOC, ACS and alloimmunization. Familial clustering of elevated TRV was observed in our highly consanguineous population. These findings suggest that elevated TRV is a marker that defines patients with more severe SCD even among children and young adults. Disclosures: No relevant conflicts of interest to declare.

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The Effect Of Microalbuminuria On Duration Of Hospitalization In Adult Sickle Cell Disease Patients With Pain Crisis

Blood ◽

10.1182/blood.v122.21.4694.4694 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4694-4694

Author(s):

Mohammed Shaik ◽

Borys Hrinczenko

Keyword(s):

Sickle Cell Disease ◽

Length Of Stay ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Categorical Variables ◽

Cell Disease ◽

Exact Test ◽

Blood Disorder ◽

Significant Difference ◽

Pain Crisis

Introduction Sickle cell disease (SCD) is a genetic blood disorder of hemoglobin resulting in severe morbidity and early mortality. The prevalence of microalbuminuria and/or proteinuria in children with SCD varies from 18 to 28% and increases with age. However, the exact prevalence in adults in not known. In the general population, the presence of albuminuria has been shown to be associated with all cause mortality. The urine microalbumin to creatinine ratio (MA) is considered to be an early sign of impending sickle cell nephropathy. We sought to investigate the association of MA with various SCD genotypes (HbSS, HbSC, HbS/β-thalassemia) in our clinic and also the length of stay (LOS) in hospitalized SCD patients with acute pain crisis. Methods Twenty-eight consecutive SCD patients diagnosed in our clinic by hemoglobin electrophoresis were included in our study. The patients (pts) age, gender, hemoglobin electrophoresis, and baseline MA were obtained. Based on their MA level they were divided into two groups, abnormal MA (MA ≥ 30 mg/g creatinine) or normal MA (< 30 mg/g creatinine). Eleven of these 28 patients were eventually hospitalized for a sickle cell related pain crisis. Their MA level was obtained within 24-hours of hospital admission and their hospitalization length of stay (LOS) was also recorded. We analyzed the association between the two groups of patients, those with normal or abnormal MA, with the different genetic variants of SCD in both our clinic and hospitalized pts. Furthermore, for hospitalized pts we also assessed an association of MA with their mean LOS. The Chi-square test/Fisher’s exact test was used for categorical variables and the T-test/Mann-Whitney test was used for numerical variables. Results All twenty-eight patients were African American without significant renal impairment, with 11, 10, and 7 pts with SS, SC and S β-thalassemia (Sβ), respectively. Fifteen of these pts had abnormal MA, 12 pts were female. The median age was 35.5 yrs (range, 19 - 59), median LOS was 3.5 days (range, 2-8). The SS pts had higher abnormal MA levels followed by SC and then Sβ (p=0.03) (Table 1). There was no significant difference in gender between the two groups (p=0.2). SCD pts admitted to the hospital for pain crisis with an abnormal MA within 24-hours of admission had a significantly higher mean LOS when compared to pts with normal MA (p=0.0089) (Table 1). Conclusion Microalbuminuria is more prevalent in the severe genotypes of SCD disease such as SS and SC vs. Sβ pts. Thereby, MA might be a useful biomarker of generalized SCD vasculopathy, in addition to a known marker of progressive nephropathy. Furthermore, MA has a significant impact on length of hospitalization. An abnormal MA obtained within the first 24-hrs of hospitalization of a SCD pt in pain crisis was predictive of prolonged hospital duration. Early and more aggressive supportive care symptom management for those patients might be a reasonable option but requires more study. Further large prospective clinical trials are needed to validate our findings. Disclosures: No relevant conflicts of interest to declare.

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Fetal hemoglobin in sickle cell anemia: a glass half full?

Blood ◽

10.1182/blood-2013-09-528067 ◽

2014 ◽

Vol 123 (4) ◽

pp. 481-485 ◽

Cited By ~ 102

Author(s):

Martin H. Steinberg ◽

David H. K. Chui ◽

George J. Dover ◽

Paola Sebastiani ◽

Abdulrahman Alsultan

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Anemia ◽

Severe Disease ◽

Fetal Hemoglobin ◽

Cell Disease ◽

Sickle Hemoglobin ◽

F Cells ◽

The Mean ◽

Number Of Cells

Abstract Fetal hemoglobin (HbF) modulates the phenotype of sickle cell anemia by inhibiting deoxy sickle hemoglobin (HbS) polymerization. The blood concentration of HbF, or the number of cells with detectable HbF (F-cells), does not measure the amount of HbF/F-cell. Even patients with high HbF can have severe disease because HbF is unevenly distributed among F-cells, and some cells might have insufficient concentrations to inhibit HbS polymerization. With mean HbF levels of 5%, 10%, 20%, and 30%, the distribution of HbF/F-cell can greatly vary, even if the mean is constant. For example, with 20% HbF, as few as 1% and as many as 24% of cells can have polymer-inhibiting, or protective, levels of HbF of ∼10 pg; with lower HbF, few or no protected cells can be present. Only when the total HbF concentration is near 30% is it possible for the number of protected cells to approach 70%. Rather than the total number of F-cells or the concentration of HbF in the hemolysate, HbF/F-cell and the proportion of F-cells that have enough HbF to thwart HbS polymerization is the most critical predictor of the likelihood of severe sickle cell disease.

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Intra-Patient Variability in Fetal Hemoglobin Measurements over Time in Sickle Cell Disease Patients Not on Fetal Hemoglobin Inducing Agents

Blood ◽

10.1182/blood.v124.21.4096.4096 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4096-4096

Author(s):

Esther E Knapp ◽

Deepa Manwani ◽

Abdullah Kutlar ◽

Hillel W Cohen ◽

Richard G. Ghalie

Keyword(s):

Standard Deviation ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Fetal Hemoglobin ◽

Health Science ◽

Reference Laboratory ◽

Cell Disease ◽

Significant Difference ◽

The Mean ◽

Over Time

Abstract Introduction: We previously reported results of the placebo-controlled phase II study of the short-chain fatty acid derivative 2,2-dimethylbutyrate in inducing fetal hemoglobin (Hb F) in 76 patients with sickle cell disease (SCD). The primary endpoint was a comparison of Hb F levels in the treatment versus the placebo arms. Week 24 interim analyses revealed no statistically significant difference in change in Hb F levels between the 2 groups. We examined the placebo arm in order to assess untreated, intra-patient variability of Hb F%. Methods: Only Hb F values performed by HPLC at the central reference laboratory (Georgia Health Science University) were included. Any Hb F values determined within a 3 month period after a blood transfusion were excluded. Baseline and at least one subsequent Hb F levels were available in 37 of the 38 patients randomized to the placebo arm, which were included in the analysis. Serial determinations were performed at 4 week intervals, resulting in a total of 348 determinations and a median of 9 values per patient (range 2 - 15). Mean and standard deviation of repeat measures of Hb F% in each individual patient were calculated. A mean ± SD of the individual coefficients of variation (SD/mean of repeat measures for each individual) was calculated. Peak-to-trough (maximum - minimum) ranges of repeated measures were also calculated per individual and quartiles for the group determined. To assess the potential for regression to the mean from baseline, we calculated the median peak-to-trough within quartiles of baseline Hb F. We assessed the difference between maximum and minimum values as a percentage of the maximum or percentage deviation from personal best Hb F%, and finally we examined the association of baseline Hb F, age, gender and race with the degree of variability. Results: Patient median (range) age was 25.9 years (12 – 46), 24 (63%) were female, the genotype was Hb SS in 30 patients (79%) and Hb S/β0 thalassemia in 8 (21%), and no patient was treated with hydroxycarbamide at enrollment. Median (range) values of Hb F percentage at baseline were 7.5% (0.5 – 23.4). The mean coefficient of variation of all Hb F values was 13%, with a peak to trough median (range) of 1.8 (0.1 - 9.8). The mean percentage Hb F % variability over time was 31.8% (S.D +/- 18) and median (range) value of 26.1 (7.2-80) with quartiles depicted in Table 1. Baseline Hb F% negatively correlated with the percentage variability and this association was highly statistically significant (Spearman rho –0.34, p = 0.04). Table I: Intra-patient variability in successive Hb F% levels expressed as a percentage deviation from peak values Quartiles Range of Values (% difference between maximum and minimum HbF) n < 25th 7.2-20.6 9 25-49 20.7-26.1 10 50-74 26.2- 39.2 9 75-100 39.3-80 9 Discussion: There is substantial Hb F variability among patients not on any Hb F inducer. This variability has not been previously reported and influences both the standard deviation and standard error, and would likely lower the statistical power of any comparative analysis in a clinical trial. Thus, sample sizes should be larger to be able to detect a sizeable difference between experimental and control groups. Variability among treated patients is harder to assess because it is difficult to separate out intrinsic variability from treatment effects and medication adherence. We have not attempted to assess the intra-patient variability in Hb F among patients given study drug in this study. However, it seems reasonable to assume that the variability seen in untreated patients would also be seen, to some degree, within treated patients. Thus, using Hb F percentage alone as a measure of medication compliance (with a Hb F inducing agent) may not be reliable. Possible explanations for this variability over time include artifacts of laboratory technique, increased hemolysis with increased erythropoietic drive, worsening renal function (and subsequent decrease in erythropoietin production), and bone marrow infarction, leading to disrupted hematopoiesis. Disclosures Kutlar: NIH/NIMHD: Research Funding. Ghalie:HemaQuest Pharmaceuticals, Inc.: Employment.

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Study of Prevalance of Nephropathy among Sickle Cell Disease Patients in Waghodia Region, Vadodara, Gujarat

Journal of Pharmaceutical Research International ◽

10.9734/jpri/2021/v33i60a34524 ◽

2021 ◽

pp. 607-613

Author(s):

Charmi C. Thakkar ◽

Inampudi Sailaja

Keyword(s):

Renal Failure ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Sickle Cell Trait ◽

Mean Value ◽

Cell Disease ◽

Protein Loss ◽

Cross Sectional ◽

Blood Disorder ◽

The Mean

Introduction: Sickle-cell disease (or drepanocytosis) is a life-long blood disorder Characterized by red blood cells that assume an abnormal, rigid, sickle shape. Sickle cell disease (SCD) has several complications, including chronic renal failure, manifesting with hypertension (high blood pressure) proteinuria (protein loss in the urine), hematuria (redblood cells in urine) and worsening anaemia. Progression to end-stage renal failure confers a poor prognosis. Objective: The objective of the study was to determine the Prevalence of Nephropathy among sickle cell disease patients. Materials and Methods: This cross sectional study includes a total 150 participants who suffering from sickle cell anemia and attending our Institute. Renal function test and Urine examination of all participants was done. Estimated Glomerular Filtration Rate (eGFR) calculated using the Cockroft Gault formula. Comparison of results was done between Sickle cell trait and Sickle cell disease Group. Results: The mean age of the SCA patients were 25.54±10 years. Maximum participants are found to be from age group 25-30 yr(n=35) followed by 20-25 yr(n=30). Of the 150 SCA patients, 89 (59.33%), and 61 (40.66%) were males and females, respectively. The Mean value of S.Creatinine of SCT group is 0.73±0.46 mg/dl and SCD is 1.0±0.35 mg/dl, while the Mean value of eGFR is 134.19±87.21 ml/min and 124.20 ±58.25 ml/min in SCT and SCD Group respectively. Conclusions: From our study we conclude that the Derangement of Kidney function in sickle cell disease is frequent in our setting especially among young adult. It concerns SCD as well as SCT patients. Albuminuria is more frequent in homozygote patients and its prevalence increase with age. Age ≥ 25 years is associated with high risk of CKD in SCA group and albuminuria in SCD.

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