scholarly journals A Standardized Clinical Flow Adhesion Assay of Whole Blood Adhesion to VCAM-1 Predicts Severe SCD Phenotypes in a 2-Yr Prospective Observational Follow-up of the Original Elipsis Cohort

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3562-3562
Author(s):  
Patrick C. Hines ◽  
Ahmar Urooj Zaidi ◽  
Xiufeng Gao ◽  
Ke Liu ◽  
Muhammad O. Shareef ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Whole Blood ◽  
Hospital Admissions ◽  
Phenotypic Variability ◽  
Acute Chest Syndrome ◽  
Adhesion Assay ◽  
Cell Disease ◽  
Equity Ownership

Sickle cell disease (SCD) is a complex, multi-organ system condition characterized by frequent and unpredictable vaso-occlusive episodes (VOEs) and significant phenotypic variability. Red blood cell (RBC) adhesion contributes to vaso-occlusive pathology, thus we have developed and validated a standardized clinical whole blood flow adhesion assay to VCAM-1 (FA-WB-VCAM) to serve as a clinical biomarker of RBC health in sickle cell disease and other conditions1-4. Blood for the FA-WB-VCAM assay is drawn in sodium citrate tubes and can be stored at 4oC for up to 48hrs. Whole blood samples are perfused through VCAM-1-coated channels and adherent blood cells are quantified manually to generate a clinical adhesion index (cells/mm2). We previously reported longitudinal steady-state FA-WB-VCAM adhesion indices established from every 3 weeks blood sampling over 6 months (mean=368.3 ±198.4 cells/mm2, range=83.50 - 917.0), and the correlation of steady state adhesion indices to a lifetime historical SCD severity index (SCDI) (r=0.5851, p=0.0003) 5,6. The lifetime historical SCDSI was calculated by quantifying the total number of objectively, documentable, vaso-occlusive end-organ events (VEEs), including acute chest syndrome/pneumonia, stroke, priapism, splenic sequestration, hepatic sequestration, and cholelithiasis, indexed over the total years of life (# VEEs/age; range=0.0 to 0.38 in ELIPSIS). The objective of this study was to determine if the FA-WB-VCAM could predict clinical SCD severity prospectively using various metrics of disease severity, including the SCDI over a 2-year period post ELIPSIS. First, we classified study subjects as "severe" or "mild/moderate" adhesion phenotypes defined by mean steady state adhesion indices acquired from every 3 week sampling over 6 months of the ELIPSIS study (severe adhesion phenotype: > 75th percentile, 455.9 cells/mm2; mild/moderate adhesion phenotype: < 75thpercentile). VEEs were verified by retrospective review of medical records, and a SCDSI over the 2-year period following the ELIPSIS study was established. Our data show that individuals with severe adhesive SCD phenotypes experienced significantly more VEEs compared to individuals with low/moderate severe adhesive SCD phenotypes (mean=55.67 ±69.78 compared to mean=17.04 ±20.58 respectively; p=0.01). SCD patients with severe adhesive phenotypes also had more hospital admissions (mean=5.67 ±2.29 compared to mean=2.88 ±3.41, p=0.001), ER visits (mean=36.00 ±63.42 compared to mean=9.20 ±15.65, p=0.02), transfusions (mean=4.33 ±3.74 compared to mean=1.60 ±2.55, p=0.01), acute chest syndrome/pneumonia (mean=1.56 ±0.73 compared to mean=0.20 ±0.65, p<0.001), and priapism (mean=2.56 ±5.57 compared to mean=0.00 ±0.00, p=0.003) when compared to low/moderate adhesive phenotypes. These data suggest that the FA-WB-VCAM assay may serve as a predictive biomarker for impending VEEs, and a monitoring biomarker to assess response to SCD-modifying therapies. Additional studies in a larger prospective cohort are required to definitively establish the clinical utility of the FA-WB-VCAM assay. Disclosures Hines: Functional Fluidics: Equity Ownership. Gao:Functional Fluidics: Equity Ownership. Liu:Functional Fluidics: Employment. White:Functional Fluidics: Equity Ownership.

A Multicentre Study of Environmental Factors on the Severity of Sickle Cell Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4841-4841
Author(s):  
Sanjay Tewari ◽  
Fred Piel ◽  
Valentine Brousse ◽  
Baba PD Inusa ◽  
Paul Telfer ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Environmental Factors ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
Electronic Patient Records ◽  
Cell Disease ◽  
Hospital Data ◽  
Significant Difference

Abstract Background: Sickle cell disease (SCD) is a very variable condition, with some patients being asymptomatic and others admitted frequently to hospital. Genetic factors have been extensively investigated but only explain a small amount of the variability to date. Environmental factors are undoubtedly important, but have not been studied in depth, at least in part because of the difficulty of conducting these studies. We have analysed the role of climatic, environmental and temporal factors in determining the frequency of hospital admissions in children with SCD to 4 large sickle cell centres in London and Paris. Participants and Methods: Clinical data were collected from 1st January 2007 to 31st December 2012. Inclusion criteria were children with SCD (HbSS and HbSC) between the ages of 0 and 17 years, admitted to hospital with acute pain, acute chest syndrome or fever. All children lived within 4 miles radius (London) or 10km (Paris) of the hospital. Data were collected using specific electronic patient records of SCD patients. Data were collected on the reason for admission, date and length of admission. Daily air quality records were collected from sites around Paris and London, including details of black smoke, particulate matter, nitric oxide, carbon monoxide, sulphur dioxide and ozone. Daily meteorological records were obtained from weather stations in London and Paris including wind speed, temperature, rainfall and humidity. Statistical analysis including time series studies were conducted using R software version 3.1.1. Results: There were a total of 2717 admissions over the six year study period. Overall for the London hospitals there was a mean of 0.39 admissions/patient/year, with 1406 admissions for pain, 153 for acute chest syndrome and 417 for fever. The rate of admission/patient/year by cause for HbSS and HbSC across the London hospitals is shown in table below: Table 1. Rates of admission/patient/year by cause Sickle genotype/cause of admission All London hospitals Institution A Institution B Institution C HbSS (Pain) 0.31 0.18 0.40 0.43 HbSS (Fever) 0.09 0.03 0.15 0.11 HbSS (acute chest syndrome) 0.04 0.03 0.04 0.04 HbSC (pain) 0.07 0.03 0.08 0.10 HbSC (fever) 0.03 0.01 0.04 0.05 HbSC (acute chest syndrome) 0.004 0.008 0.002 0.002 Overall admission numbers were significantly higher on Mondays and Tuesdays in London but there was no such variation in Paris (Table 2). Table 2. Mean number of admissions on days of week in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Weekday Monday 0.75** 0.35 Tuesday 0.77** 0.36 Wednesday 0.66 0.36 Thursday 0.64 0.32 Friday 0.60 0.32 Saturday 0.51 0.20 Sunday 0.57 0.27 There was no seasonal variation in admission numbers in London, but significantly higher numbers of patients admitted in Paris during autumn and winter. Table 3. Mean number of seasonal admissions in Paris (1 hospital) and London (3 hospitals). ** denotes significant difference from mean of other days (P<0.001). London Paris Season Autumn 0.70 0.35** Spring 0.60 0.31 Summer 0.64 0.25 Winter 0.62 0.34** Conclusion In London, there is a 2-3 fold variation in admission rates for the same complications between different hospitals. Similarly there is a significant difference on the effects of season and weekday between Paris and London. These results are statistically stronger than many effects which are identified in genetic and therapeutic studies, and show the importance of environmental and cultural factors, which are potentially modifiable. The effect of weather and pollution on hospital admissions is currently being analysed. Disclosures No relevant conflicts of interest to declare.

Splenectomy in Jamaican children with sickle cell disease: Outcome of selective blood transfusion

2020 ◽  
pp. 004947552097461
Author(s):  
Odayne Steele ◽  
Alfred L Duncan ◽  
Larnelle N Simms ◽  
Shani A Duncan ◽  
Simone E. Dundas Byles ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Blood Transfusion ◽  
Sickle Cell ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Operative Morbidity ◽  
Open Splenectomy ◽  
Bank Reserves ◽  
Transfusion Protocol

We reviewed the post-operative morbidity and mortality of open splenectomy undertaken in conjunction with selective blood transfusion in Jamaican children with sickle cell disease. Data were collected on 150 splenectomies performed between November 1994 and October 2017. Selective blood transfusion involved raising haemoglobin levels to approximately 100 g/L in patients with admission haemoglobin ≥10 g/L below steady state. There was no mortality. Mean post-operative stay was 3.2 days with a median of three days. Total morbidity was 19/150 cases (12.7%), with acute chest syndrome accounting for 11/19 (57.9%). Among the non-transfused, acute chest syndrome occurred in 10/117 cases (8.5%), while among transfused, acute chest syndrome occurred in 1/33 cases (2.9%). We recommend this selective blood transfusion protocol for patients with sickle cell disease to surgeons who undertake splenectomies in settings where blood bank reserves are perennially low.

scholarly journals Sex-based differences in the manifestations and complications of sickle cell disease: Report from the Sickle Cell Disease Implementation Consortium

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0258638
Author(s):  
Rita V. Masese ◽  
Dominique Bulgin ◽  
Mitchell R. Knisely ◽  
Liliana Preiss ◽  
Eleanor Stevenson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Pain Treatment ◽  
Multivariable Analysis ◽  
Self Report ◽  
Future Research ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Eligibility Criteria

Introduction Sex-based clinical outcome differences in sickle cell disease (SCD) remain largely unknown despite evidence that female sex is associated with an increased lifespan. To better characterize sex-based differences in SCD, we assessed pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. Methods The SCDIC consists of eight comprehensive SCD centers and one data coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Eligibility criteria included: 15 to 45 years of age and a confirmed diagnosis of SCD. Self-report surveys were completed and data were also abstracted from the participants’ medical records. Results A total of 2,124 participants were included (mean age: 27.8 years; 56% female). The majority had hemoglobin SS SCD genotype. Females had worse reports of pain severity (mean (SD) T-score 51.6 (9.6) vs 49.3 (10), p<0.001), more vaso-occlusive episodes (p = 0.01) and a higher occurrence of 3 or more hospital admissions in the past year (30.9% vs. 25.5, p = 0.03). On multivariable analysis, males had higher odds of acute chest syndrome (odds ratio (OR) 1.4, p = 0.002), cardiovascular (OR 1.70, p<0.001) and musculoskeletal (OR 1.33, p = 0.0034) complications and lower odds of depression (OR 0.77, p = 0.0381). Females had higher fetal hemoglobin levels with and without hydroxyurea use (9.6% vs 8.5%, p = 0.03 and 3% vs 2.2%, p = 0.0005, respectively). Conclusion Our data suggests that sex differences in clinical outcomes do occur among individuals with SCD. Future research needs to explore the mechanisms underlying these differences.

scholarly journals Newborn sickle cell disease screening: the Jamaican experience (1995–2006)

2007 ◽  
Vol 14 (3) ◽  
pp. 117-122 ◽  
Author(s):  
L King ◽  
R Fraser ◽  
M Forbes ◽  
M Grindley ◽  
S Ali ◽  
...  
Keyword(s):  
Cohort Study ◽  
Sickle Cell Disease ◽  
Newborn Screening ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Current System ◽  
Acute Chest Syndrome ◽  
Published Data ◽  
Cell Disease ◽  
Care Systems

Objectives: The aim of this study was to evaluate the existing newborn sickle haemoglobinopathy screening programme in Jamaica. Methods: A retrospective analysis of infants screened during the period 8 November 1995 to 22 July 2006 was performed. Patient data for analyses was restricted to patients with homozygous (Hb SS) sickle cell disease. Published data from the Jamaican Sickle Cell Cohort Study was used to make comparisons with the study sample. Results: The study sample consisted of 435 patients with Hb SS disease. Acute chest syndrome was the most common clinical (non-death) event accounting for ∼50% of all events. Acute splenic sequestration, no longer a significant cause of mortality, was responsible for ∼32% of clinical events. Seven deaths (1.8%) occurred during the study period compared with 17.6% to the same age in the Jamaican Sickle Cell Cohort Study. There was a lower proportion of hospital admissions and episodes of serious illness in the study group compared with controls. Conclusions: Survival estimates for the study sample showed improvement compared with the Jamaican Sickle Cell Cohort Study. This study continues to demonstrate the benefits of, and as such shows support for, newborn screening and early interventions in sickle cell disease. In addition, it highlights some of the areas for continued focus and research development. Although the current system is providing an essential and beneficial service, the study emphasizes the need for newborn screening programmes to be comprehensive care systems to be fully effective.

Prevalence and Predictors of Steady-State Hypoxemia in Sickle Cell Disease.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1662-1662
Author(s):  
Charles T. Quinn ◽  
Naveed Ahmad
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Arterial Oxygen ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Chronic Anemia ◽  
Independent Variables ◽  
Hemoglobin C ◽  
Age And Sex

Abstract Individuals with sickle cell disease (SCD) may have arterial oxygen desaturation during the steady-state that is mainly due to a right shift of the oxyhemoglobin dissociation curve. This right shift has both non-specific causes (increased concentration of 2,3-DPG due to chronic anemia) and SCD-related causes (an effect of the intracellular concentration of hemoglobin (Hgb) S and an enhanced Bohr effect). Another possible cause is chronic cardiopulmonary disease that may be related to past acute chest syndrome (ACS). We aimed to describe the distribution of steady-state peripheral oxygen saturation (SpO2) in a large population of children with SCD and to determine whether any simple laboratory or clinical features were predictive of SpO2. We hypothesized that most of the variation in SpO2 was not explained by steady-state Hgb alone, and that a history of ACS could explain some of this variability. Using our center’s comprehensive database we identified all subjects with sickle cell anemia (SS), sickle-hemoglobin C disease (SC), sickle-β+-thalassemia (Sβ+), or sickle-β0-thalassemia (Sβ0) who had been evaluated within the past 5 years for whom steady-state Hgb concentration, reticulocyte count (retic), and SpO2 were available. All steady-state values are rolling averages calculated at routine well clinic visits. SpO2 was determined by pulse oximetry in room air. Individuals receiving chronic transfusions were excluded. Lifetime rates of ACS were known for a subset of subjects with SS and Sβ0. A standard multiple regression analysis was performed between steady-state SpO2 as the dependent variable, and steady-state Hgb and retic, age, and sex as independent variables. 585 subjects were analyzed (390 SS/Sβ0, 195 SC/ Sβ+; 47% female, 53% male). Mean age was 9.4 years (SD 5.6, range 0.2 – 19.7). Mean SpO2 was 96.3% (SD 3.0) for SS/Sβ0 and 98.7% (SD 1.7) for SC/ Sβ+ subjects. The percentage of subjects with SpO2 <96% and <90% was 33.1 and 2.8 for SS/Sβ0 and 3.6 and 0.5 for SC/ Sβ+. Bivariate analyses showed no correlation between Hgb and SpO2 for SC/ Sβ+ subjects (N=195, Pearson R=0.024, P=0.74) and no correlation between ACS rate and SpO2 in those with SS/Sβ0 (N=183, Pearson R=−0.043, P=0.56). Thus, only the 390 subjects with SS/Sβ0 were included in the multivariate analysis, and ACS rate was not included in the model as an idependent variable. All 4 independent variables (Hgb, retic, age, and sex) contributed significantly to prediction of SpO2. Altogether, about 45% (adjusted 44%) of the variability in SpO2 was explained by the model. Multiple correlation coefficient (R = 0.67) showed a significant linear relationship between independent variables and SpO2 (F = 78.07, p < 0.001). The estimated model can be given as: SpO2 = 94.24 + (0.58 * Hgb) − (0.16 * Age in years) + (0.64 * Female sex) − (0.20 * Retic in %). In summary, steady-state hypoxemia is common among individuals with SS and Sβ0, in whom decreased steady-state SpO2 is related to decreased steady-state Hgb, increased steady-state retic, increased age, and male sex. This relationship was not found for individuals with SC and Sβ+. Only 5% of the variation in SpO2 was explained by Hgb while controlling for other variables, and ACS rate was not associated with SpO2. We conclude that most steady-state hypoxemia in individuals with SCD is explained by factors other than chronic anemia, and that hypoxemia appears to be unrelated to prior episodes of ACS.

Report on the International Co-Operative Study of the Effects of L-Selectin Gene Polymorphisms on the Development of Complications in Sickle Cell Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3775-3775
Author(s):  
Iheanyi Okpala ◽  
Cynthia C. Ugochukwu ◽  
Panagiotis Pantelidis ◽  
Baba Inusa ◽  
Obike Ibegbulam ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Surface Expression ◽  
Control Individual ◽  
Acute Chest Syndrome ◽  
Nucleotide Polymorphisms ◽  
Cell Disease ◽  
Increased Risk ◽  
Significant Difference

Abstract Our previous study showed that patients with sickle cell disease (SCD) and high steady-state expression of the adhesion molecules L-selectin and αMβ2 integrin on leukocytes developed complications [Blood. 2002;100(suppl):11a. Eur J. Haematol. 2002; 69:135–144]. The aim of this study was to find out if L-selectin protein expression by leukocytes and the development of complications in SCD are affected by previously described single nucleotide polymorphisms within the coding regions of the gene. To detect F206L, T49S and P213S polymorphisms we determined the L-selectin genotype in 142 HbSS patients (64M, 78F, age 2 – 62 yr, mean 27 yr ±12); and 102 racially-matched HbAA controls with similar age and sex distribution. The T49S and P213S amino acid changes in L-selectin are respectively associated with increased risk of vasculopathy and nephropathy; important features of SCD. [Hum Genet. 1996; 97:15–20. Am. J. Hum. Genet.2002; 70: 781–786]. All HbSS patients were evaluated for disease complications. Steady-state expression of L-selectin on neutrophils, lymphocytes and monocytes was measured by flow cytometry in 44 HbSS patients. With respect to F206L polymorphism, 100/142 (70%) patients and 73/102 (72%) controls were FF homozygous, 42 patients and 28 controls were heterozygous FL, and 1 control individual was LL homozygous. There was no significant difference in distribution of the polymorphic variants between patients and controls [Chi-squared (X2) = 0.1, p&gt;0.05]. In codon 213, 48 (33.8%) patients and 42 (41.2%) controls were PP homozygous, 91 patients and 55 controls PS heterozygous, 1 patient and 5 controls SS homozygous [X2 =1.9, p&gt;0.05]. With regard to the T49S polymorphism, 100% of the patients and controls were TT homozygous. At least one complication of SCD was observed in 110 SCD patients; 32 had uncomplicated disease. The most common complications observed were avascular joint necrosis (n=39), sickle nephropathy (n=31), stroke (n=25) and acute chest syndrome (n=20). The observed frequencies of FF genotype in codon 206 among patients with complications (74), and without complication (26) were not significantly different from the expected values [X2 = 2.37, p&gt;0.05]. Similarly, none of the other genotypes (FL, PP, PS) was significantly associated with complications of SCD. Of the 44 patients in who leukocyte L-selectin expression was measured, 31 turned out to be FF homozygous in codon 206, and 13 FL. No significant differences were observed between FF and FL patients in the mean levels of L-selectin expression by neutrophils (FF: 4.00+ 4.56 vs FL: 3.24+ 3.4), monocytes (FF: 4.30+ 5.6 vs FL: 2.56+ 3.39) or lymphocytes (FF: 2.61+ 3.02 vs FL: 2.11+ 2.0); p&gt;0.05. Similarly, the P213S polymorphism had no effect on the level of L-selectin expression. The findings suggest that neither F206L nor P213S L-selectin gene polymorphism predisposes to high leukocyte surface expression of this adhesion molecule, or the development of complications in SCD.

Antecedent Transfusion and Primary Hemorrhagic Stroke in Adults with Sickle Cell Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1437-1437
Author(s):  
John J. Strouse ◽  
Joshua Field ◽  
Regina D. Crawford ◽  
Sophie Lanzkron
Keyword(s):  
Risk Factors ◽  
Ischemic Stroke ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hemorrhagic Stroke ◽  
Neurological Deficits ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Elevated Systolic Blood Pressure

Abstract Primary hemorrhagic stroke is an uncommon but serious complication of sickle cell disease (SCD) with mortality from 20 to 65%. Proposed risk factors include previous ischemic stroke, aneurysms, low steady-state hemoglobin, high steady-state leukocyte count, acute chest syndrome, and transfusion. We performed a retrospective case-control study to evaluate risk factors for primary hemorrhagic stroke in adults (age &gt;18 years) with SCD from Johns Hopkins and Barnes- Jewish Hospitals and Duke University Medical Center from January 1989 to April 2008. Cases had SCD and intraparenchymal (IPH), subarachnoid (SAH), or intraventricular (IVH) hemorrhage confirmed by neuroimaging or analysis of cerebrospinal fluid; traumatic hemorrhages and hemorrhagic conversion of ischemic strokes were excluded. Controls had SCD and ischemic stroke (focal neurological deficits with corresponding cerebral infarcts by neuroimaging). Both were identified by searching the hospital discharge database using ICD-9 codes for acute stroke and SCD and reviewing divisional records. We compared continuous variables by Student’s t-test and calculated odds ratios with exact methods. We identified 19 cases (mean age 29 years, range 18 – 66, 42% male) and 18 controls (mean age 34 years, range 19 – 61, 39% male). Most cases (14/18) had sickle cell anemia (HbSS) and 22% had a prior overt stroke; controls had HbSS (9/17), HbSB0thalassemia (1), or HbSC (7) and 41% had a history of overt stroke. Cases presented with headache (89%) and seizure (37%) and less frequently hemiparesis (27%). Controls presented with hemiparesis (78%), headache (57%), and rarely seizure (11%). Twelve cases had IPH including those with extension to the ventricles (1), subarachnoid (2) or both (2); six had SAH including ventricular extension (1). Potential causes of hemorrhagic stroke included moyamoya (4), aneurysms (3), anticoagulation (1) and ateriovenous malformation (1). Four cases (21%) and no controls died during the initial hospitalization. More cases (82%) than controls (44%, P&lt;0.05) had elevated systolic blood pressure at the time of stroke. At steady-state, cases had lower hemoglobin (mean ± SEM 8.5 ± 0.6 g/dl vs. 9.7 ± 0.6 g/dl), lower blood pressures (systolic 121 ± 4 vs. 127 ± 6 mm Hg, diastolic 71 ± 4 vs. 72 ± 9 mm Hg) and higher platelet counts (399,231 ± 74,024/ul vs. 362,200/ul ± 39,927/ul) than controls, but these differences were not statistically significant. Mean hemoglobin concentration at the time of stroke increased 1.3 g/dl (19%) from steady-state in cases and 0.01 g/dl (2%) in controls (p&lt;0.05). Seven cases had simple transfusions (between 1 and 11 days before their primary hemorrhagic stroke) in preparation for surgery (3), and for aplastic crisis (1), bacteremia (1), acute renal failure (1), or suspected acute chest syndrome (1). Only 1 control was transfused; and 1 with HbSS had a hemoglobin of 14.5 g/dl at the time of stroke (from excessive erythropoietin administration). In this group of adults with SCD, primary hemorrhagic stroke was associated with antecedent transfusion. Identifiable causes include moyamoya from obstructive cerebral vasculopathy, aneurysms and other vascular malformations, and rarely coagulopathy. Mortality was similar to that previously described. The association of recent transfusion and cerebral vasculopathy with hemorrhagic stroke suggests caution in the use of simple transfusion in adults with SCD and moyamoya or cerebral aneurysms. Table 1: Associations with Primary Hemorrhagic Stroke Variable Odds Ratio (95% CI) P-value Genotype (HbSS vs. other) 3 (0.6 – 17) NS Moyamoya 5 (0.4 – 260) NS Transfusion in the last 14 days 13 (1.3 – 630) &lt;0.02 NSAID in the last 14 days 2.9 (0.3 – 36) NS

Sickle Cell Disease in Central India: High Prevalence of Sickle/Beta Thalassemia and Severe Dsiease Phenotype

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4588-4588 ◽  
Author(s):  
Dipty Jain ◽  
Vinit Warthe ◽  
Roshan Colah ◽  
Graham Roger Serjeant
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Conflicts Of Interest ◽  
Central India ◽  
Beta Thalassemia ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Beta Thalassaemia ◽  
Alpha Thalassaemia

Abstract Objectives: To assess the clinical, haematological and molecular features of sickle cell disease in central India where the disease has been reported to be more severe than the mild clinical course usually observed in the Asian haplotype of homozygous sickle cell (SS) disease. Methods: A cross-sectional assessment of 91 consecutive patients with sickle cell disease attending clinics at the Akola Government Medical College, Akola, Maharastra State, India. Results: Of the 91 patients, who were predominantly of the scheduled caste community, 49 had SS disease, 6 had sickle cell-HbD Punjab, and 36 had sickle cell-beta thalassaemia. Of the patients with sickle cell-beta thalassaemia, the beta thalassemia mutation was IVS1-5 G>C mutation in 25 patients (69%) while the rest had one of seven other molecular mutations identified (Table1). Contrary to commonly held beliefs, alpha thalassaemia occurred in only 9/90 (10%) of subjects but fetal haemoglobin (HbF) levels were markedly elevated with mean and median levels of 24.4%. All except 3 SS disease patients had the Xmn1(+/+) polymorphism. These patients exhibited many of the severe manifestations of sickle cell disease. Comparison of SS disease and sickle cell-beta thalassaemia showed no differences in the prevalence of dactylitis, bone pain crisis, acute chest syndrome, haemoglobin level, reticulocyte counts or hydroxyurea usage but patients with sickle cell-beta thalassaemia had significantly more hospital admissions, blood transfusions, and greater frequencies of splenomegaly and hepatomegaly. Conclusions: Many of the patients with sickle cell disease in central India appear to have relatively severe manifestations. This appears to be due to much lower frequencies of alpha thalassaemia and more frequent sickle cell-beta thalassaemia. There is a need for assessment of the indications and policies for blood transfusion and for hydroxyurea. Table 1. Beta Thalassemia mutations associated with HbS/Beta Thalassemia in Akola Mutation Expression Number IVS 1-5 (G>C) severe b+ 22 IVS 1-1 (G>A) bo 3 Cd 15 (-T) bo 2 Cd 30 (G>C) bo 2 Cd 15 (G>A) bo 1 Cd 39 (C>T) bo 1 Cd 41/42 (-CTTT) bo 1 619 bp deletion bo 1 Total 36 Disclosures No relevant conflicts of interest to declare.

scholarly journals Phospholipase A2 levels in acute chest syndrome of sickle cell disease

Blood ◽  
1996 ◽  
Vol 87 (6) ◽  
pp. 2573-2578 ◽  
Author(s):  
LA Styles ◽  
CG Schalkwijk ◽  
AJ Aarsman ◽  
EP Vichinsky ◽  
BH Lubin ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Phospholipase A2 ◽  
Sickle Cell ◽  
Fat Embolism ◽  
Clinical Severity ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Marrow Fat ◽  
Embolism Syndrome

Acute chest syndrome (ACS) is associated with significant morbidity and is the leading cause of death in patients with sickle cell disease (SCD). Recent reports suggest that bone marrow fat embolism can be detected in many cases of severe ACS. Secretory phospholipase A2 (sPLA2) is an important inflammatory mediator and liberates free fatty acids, which are felt to be responsible for the acute lung injury of the fat embolism syndrome. We measured SPLA2 levels in 35 SCD patients during 20 admissions for ACS, 10 admissions for vaso-occlusive crisis, and during 12 clinic visits when patients were at the steady state. Eleven non-SCD patients with pneumonia were also evaluated. To determine if there was a relationship between sPLA2 and the severity of ACS we correlated SPLA2 levels with the clinical course of the patient. In comparison with normal controls (mean = 3.1 +/- 1.1 ng/mL), the non- SCD patients with pneumonia (mean = 68.6 +/- 82.9 ng/mL) and all three SCD patient groups had an elevation of SPLA2 (steady state mean = 10.0 +/- 8.4 ng/mL; vaso-occlusive crisis mean = 23.7 +/- 40.5 ng/mL; ACS mean = 336 +/- 209 ng/mL). In patients with ACS sPLA2 levels were 100- fold greater than normal control values, 35 times greater than values in SCD patients at baseline, and five times greater than non-SCD patients with pneumonia. The degree of SPLA2 elevation in ACS correlated with three different measures of clinical severity and, in patients followed sequentially, the rise in SPLA2 coincided with the onset of ACS. The dramatic elevation of SPLA2 in patients with ACS but not in patients with vaso-occlusive crisis or non-SCD patients with pneumonia and the correlation between levels of SPLA2 and clinical severity suggest a role for SPLA2 in the diagnosis and, perhaps, in the pathophysiology of patients with ACS.

Sign in / Sign up

Export Citation Format

Share Document