scholarly journals Hematological and Genetic Predictors of Daytime Hemoglobin Saturation in Tanzanian Children with and without Sickle Cell Anemia

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
Sharon E. Cox ◽  
Julie Makani ◽  
Charles R. Newton ◽  
Andrew M. Prentice ◽  
Fenella J. Kirkham
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Chemistry ◽  
Pearson Correlation ◽  
Transferrin Saturation ◽  
Full Blood Count ◽  
Hemoglobin F ◽  
Hemoglobin Saturation ◽  
Highly Correlated ◽  
Glucose 6 Phosphate Dehydrogenase

Low hemoglobin oxygen saturation (SpO2) is common in Sickle Cell Anemia (SCA) and associated with complications including stroke, although determinants remain unknown. We investigated potential hematological, genetic, and nutritional predictors of daytime SpO2 in Tanzanian children with SCA and compared them with non-SCA controls. Steady-state resting pulse oximetry, full blood count, transferrin saturation, and clinical chemistry were measured. Median daytime SpO2 was 97% (IQ range 94–99%) in SCA (N = 458), lower () than non-SCA (median 99%, IQ range 98–100%; N = 394). Within SCA, associations with SpO2 were observed for hematological variables, transferrin saturation, body-mass-index z-score, hemoglobin F (HbF%), genotypes, and hemolytic markers; mean cell hemoglobin (MCH) explained most variability (, Adj ). In non-SCA only age correlated with SpO2. -thalassemia 3.7 deletion highly correlated with decreased MCH (Pearson correlation coefficient 0.60, ). In multivariable models, lower SpO2 correlated with higher MCH (-coefficient 0.32, ) or with decreased copies of -thalassemia 3.7 deletion (-coefficient 1.1, ), and independently in both models with lower HbF% (-coefficient 0.15, ) and Glucose-6-Phosphate Dehydrogenase genotype (-coefficient 1.12, ). This study provides evidence to support the hypothesis that effects on red cell rheology are important in determining SpO2 in children with SCA. Potential mechanisms and implications are discussed.

scholarly journals The -158 site 5' to the G gamma gene and G gamma expression

Blood ◽  
1985 ◽  
Vol 66 (6) ◽  
pp. 1463-1465
Author(s):  
D Labie ◽  
O Dunda-Belkhodja ◽  
F Rouabhi ◽  
J Pagnier ◽  
A Ragusa ◽  
...  
Keyword(s):  
Linkage Disequilibrium ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Beta Thalassemia ◽  
Surrounding Area ◽  
Area 5 ◽  
Highly Correlated

To test the hypothesis advanced by Gilman and Huisman that the -158 site 5′ to the G gamma gene determines the G gamma expression after the first 4 months of life, we have examined DNA from sickle cell anemia (SS) patients from Africa and beta-thalassemic homozygotes from Algeria. We find that the Xmnl site is strongly linked to the Senegal haplotype among SS patients, to haplotype IX (most probably identical to the Senegal haplotype), and to haplotype III among the Algerian thalassemics. Thalassemics with haplotypes I/I and V/V have no Xmnl site and low G gamma expression. In contrast, beta-thalassemia- associated haplotype II (also characterized by high G gamma expression) fails to exhibit the Xmnl site. We conclude that, although highly correlated, the -158 C----T substitution does not perfectly predict the presence of high G gamma expression. These findings also exclude the possibility that the Xmnl site is solely involved in the determination of high G gamma expression and suggest that either several different site substitutions in the area 5′ to the gamma gene might have the same effect or that, alternatively, the Xmnl site and its surrounding area is not involved in G gamma expression and may be only in linkage disequilibrium with a controlling sequence elsewhere.

Low Fixed Dose Hydroxyurea for the Treatment of Adults with Sickle Cell Disease in Nigeria

Blood ◽  
2017 ◽  
Vol 130 (Suppl_1) ◽  
pp. 981-981
Author(s):  
Titilola S. Akingbola ◽  
Bamidele Tayo ◽  
Santosh L. Saraf ◽  
Binal N. Shah ◽  
Chinedu A Ezekekwu ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Low Dose ◽  
Adverse Outcome ◽  
Clinical Malaria ◽  
Fixed Dose ◽  
Cell Disease ◽  
Hemoglobin F ◽  
The Us

Abstract Background: The vast majority of births with sickle cell anemia occur in Africa 1 and early-life mortality, generally before age five years, is as high as 90% 2,3. Hydroxyurea was approved for sickle cell anemia by the US FDA in 1998 but is not commonly used in Africa due to fear of toxicity, lack of awareness and limited availability. Hemoglobin F is a protective factor that decreases severity of sickle cell anemia, and hydroxyurea treatment leads to an increase in hemoglobin F. In the US, hydroxyurea is typically initiated at a dose of 15 mg/kg followed by dose escalations of up to 35 mg/kg if tolerated with a goal of maximal tolerated dose and maximal response in hemoglobin F. Neutropenia and thrombocytopenia are the usual limitations to achieving maximal dose. In the landmark Multicenter Study of Hydroxyurea, the clinical response to hydroxyurea correlated strongly with a reduction in the neutrophil count as well as an increase in the fetal hemoglobin concentration as reflected in percentage of F cells. A striking decrease in pain crises was observed in the first three months of therapy, before dose escalation and before maximal increase in hemoglobin F levels 4. Furthermore, hydroxyurea in the range of 10-15.9 mg/kg/day was reportedly effective in decreasing the frequency of pain episodes in children and adolescents in Oman 5, and hydroxyurea 10 mg/kg/day decreased pain episodes in children and adults with sickle cell anemia in India 6. From these perspectives, we reasoned that a fixed dose of hydroxyurea 10 mg/kg/day is reasonable to investigate in the African setting where the safety in relationship to the resources and infectious exposures is not known. Methods: We assigned 48 sickle cell anemia patients to hydroxyurea 500 mg/day for 24 weeks to determine safety and efficacy; 28 had high-risk disease based on hemoglobin F<8.6% and absence of alpha-thalassemia. We defined a clinically meaningful adverse outcome category as ≥10% of patients developing platelets <50,000/uL, granulocytes <500/uL, clinical malaria and/or active tuberculosis. Picking up refills every four weeks was the adherence metric. We analyzed the results on an intent-to-treat basis. Results: The median (interquartile range) age was 25 (22-27) years and the median hydroxyurea dose 9.8 (9.1-10.4) mg/kg per day. The patients complied with treatment for a median of 20 (16-24) weeks. Four (8.3%) developed a pre-specified adverse outcome: clinical malaria (N=2), thrombocytopenia in combination with malaria (N=1), pulmonary tuberculosis (N=1). During therapy the median hemoglobin increased by 9.0 g/L, mean corpuscular volume by 11.2 fL and body weight by 3.0 kg while median white blood cells declined by 2600 per uL and platelets by 127,000 per uL (P<0.001). The median hemoglobin F increased from 4.1% (2.3-6.3%) at baseline (N=27) to 8.5% (6.3-12.9%) during therapy (N=24) (P<0.001). Conclusion: Our results suggest that low, fixed-dose dose hydroxyurea for sickle cell anemia in Nigeria is associated with a low adverse outcome rate and with improvements in blood counts, hemoglobin F and body weight. The effects on vaso-occlusive episodes and on the risks of recrudescent tuberculosis and malaria-associated thrombocytopenia should be assessed in further studies. Acknowledgment: Supported by a grant from the Doris Duke Foundation. References 1. Williams TN, Obaro SK. Sickle cell disease and malaria morbidity: a tale with two tails. Trends Parasitol 2011;27:315-20. 2. Grosse SD, Odame I, Atrash HK, Amendah DD, Piel FB, Williams TN. Sickle cell disease in Africa: a neglected cause of early childhood mortality. Am J Prev Med 2011;41:S398-405. 3. Makani J, Cox SE, Soka D, et al. Mortality in sickle cell anemia in Africa: a prospective cohort study in Tanzania. PLoS One 2011;6:e14699. 4. Charache S, Barton FB, Moore RD, et al. Hydroxyurea and sickle cell anemia. Clinical utility of a myelosuppressive "switching" agent. The Multicenter Study of Hydroxyurea in Sickle Cell Anemia. Medicine (Baltimore) 1996;75:300-26. 5. Sharef SW, Al-Hajri M, Beshlawi I, et al. Optimizing Hydroxyurea use in children with sickle cell disease: low dose regimen is effective. Eur J Haematol 2013. 6. Patel DK, Mashon RS, Patel S, Das BS, Purohit P, Bishwal SC. Low dose hydroxyurea is effective in reducing the incidence of painful crisis and frequency of blood transfusion in sickle cell anemia patients from eastern India. Hemoglobin 2012;36:409-20. Disclosures Ezekekwu: American Society of Hematology: Other: The Visitor training program was sponsored by ASH. Hsu: AstraZeneca steering committee for HESTIA trial: Research Funding. Gordeuk: Emmaus Life Sciences: Consultancy.

scholarly journals Effects of glucose-6-phosphate dehydrogenase deficiency upon sickle cell anemia

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 748-752 ◽  
Author(s):  
MH Steinberg ◽  
MS West ◽  
D Gallagher ◽  
W Mentzer
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
G6pd Deficiency ◽  
Electrophoretic Pattern ◽  
Hemoglobin Concentration ◽  
Wild Type ◽  
Standardized Protocol ◽  
Cellulose Acetate Membranes ◽  
Male Patients ◽  
Glucose 6 Phosphate Dehydrogenase

Abstract We studied the interactions of the A- variety of glucose-6-phosphate dehydrogenase (G6PD) deficiency and sickle cell anemia (HbSS) to see if G6PD deficiency influenced laboratory and clinical features of HbSS. A total of 801 male patients over age 2 had G6PD electrophoresis on cellulose acetate membranes. Assays of both G6PD activity and hexokinase activity were then done on all samples that had an electrophoretic pattern other than the normal wild type (GdB). The collection of clinical data used a standardized protocol. Using cluster analyses we classified 10.4% males to be G6PD deficient, while 18.4% had the functionally normal GdA+ enzyme. The prevalence of G6PD deficiency did not change significantly when age was stratified by decade, suggesting little survival advantage or disadvantage of the combination of G6PD deficiency and HbSS. Compared to patients who were not G6PD deficient, there were no significant differences in the hemoglobin concentration, mean corpuscular volume, reticulocyte count, bilirubin, or SGOT level in patients with HbSS who had G6PD deficiency. The incidence of painful episodes, sepsis, or acute anemic episodes was similar in both groups. Our results are consistent with recent studies of smaller numbers of patients that have found little influence of G6PD deficiency upon HbSS. Specifically, we found no evidence that G6PD enhanced the severity of hemolysis or increased the incidence of acute anemic episodes or sepsis in HbSS.

Hemoglobin F and Sickle-cell Anemia

1975 ◽  
Vol 63 (2) ◽  
pp. 289.2-289
Author(s):  
Ronald G. Strauss
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hemoglobin F

scholarly journals Comorbidity of Glucose-6-Phosphate Dehydrogenase Deficiency and Sickle Cell Disease Exert Significant Effect on RBC Indices

Anemia ◽  
2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Samuel Antwi-Baffour ◽  
Jonathan Kofi Adjei ◽  
Peter Owadee Forson ◽  
Stephen Akakpo ◽  
Ransford Kyeremeh ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Red Blood Cells ◽  
Sickle Cell ◽  
Blood Cells ◽  
G6pd Deficiency ◽  
Pentose Phosphate ◽  
Full Blood Count ◽  
Cell Disease ◽  
Blood Disorder ◽  
Glucose 6 Phosphate Dehydrogenase

Background. Glucose-6-phosphate dehydrogenase (G6PD) converts glucose-6-phosphate into 6-phosphogluconate in the pentose phosphate pathway and protects red blood cells (RBCs) from oxidative damage. Their deficiency therefore makes RBCs prone to haemolysis. Sickle cell disease (SCD) on the other hand is a hereditary blood disorder in which there is a single nucleotide substitution in the codon for amino acid 6 substituting glutamic acid with valine. SCD patients are prone to haemolysis due to the shape of their red blood cells and if they are deficient in G6PD, the haemolysis may escalate. Reported studies have indicated variations in the prevalence of G6PD deficiency in SCD patients and as such further work is required. The aim of this study was therefore to estimate the incidence of G-6-PD deficiency among SCD patients and to determine its impact on their RBC parameters as a measure of incidence of anaemia.Methods. A total of 120 clinically diagnosed SCD patients of genotypes HbSS and HbSC were recruited into the study. About 5ml of blood was collected via venipuncture from each patient and used to run G6PD, full blood count, and haemoglobin (Hb) electrophoresis tests. The data were analyzed using SPSS version 20 and Graphpad prism.Result. G6PD deficiency was detected in 43 (35.83%) of the participants made up of 16 (13.33%) males and 27 (22.50%) females of whom 17 (14.17%) had partial deficiency and 10 (8.33%) full deficiency. Statiscally significant differences p=0.036 and p=0.038 were established between the Hb concentration of the participants having a G6PD deficiency and those with normal G6PD activity for males and females, respectively.Conclusion. From the results obtained, it implies that G6PD deficiency may increase the severity of anaemia in SCD patients. There is therefore the need to screen all SCD patients for G6PD deficiency to ensure that their condition is not exacerbated during treatment.

scholarly journals The Senegal DNA haplotype is associated with the amelioration of anemia in African-American sickle cell anemia patients

Blood ◽  
1991 ◽  
Vol 77 (6) ◽  
pp. 1371-1375 ◽  
Author(s):  
RL Nagel ◽  
S Erlingsson ◽  
ME Fabry ◽  
H Croizat ◽  
SM Susuka ◽  
...  
Keyword(s):  
New York ◽  
Gene Cluster ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Globin Gene ◽  
Inhibitory Effect ◽  
Hemoglobin F ◽  
Globin Gene Cluster ◽  
Alpha Gene ◽  
Hbf Level

Abstract We have previously determined that in African sickle cell anemia (SS) patients three different beta-like globin gene cluster haplotypes are associated with different percent G gamma (one of the two types of non- alpha chains comprising hemoglobin F [HbF]), mean percent HbF, and percent dense cells. We report now that in adult New York SS patients, the presence of at least one chromosome with the Senegal haplotype is associated with higher Hb levels (1.2 g/dL higher) than is found for any other non-Senegal haplotype (P less than .004). The percent reticulocytes and the serum bilirubin levels were lower in these patients. When the effect of alpha-gene number was analyzed by examining a sample of SS patients with concomitant alpha-thalassemia, the same results were obtained. Because the HbF level is significantly higher among the Senegal haplotype carriers in this sample, the inhibitory effect on sickling of this Hb variant may be one of the reasons for the haplotype effect. We conclude that the Senegal beta- like globin gene cluster haplotype is associated with an amelioration of the hemolytic anemia that characterizes sickle cell disease.

Red Blood Cell Deformability Demonstrated with the Oxygenscan: Exploring the Association with Hydroxyurea Treatment, Co-Inherited α-Thalassemia, and Frequency of Pain in Children with Sickle Cell Anemia

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4834-4834
Author(s):  
Amina Nardo-Marino ◽  
Jesper Petersen ◽  
Andreas Glenthoej ◽  
John N. Brewin ◽  
Joergen Kurtzhals ◽  
...  
Keyword(s):  
Blood Cell ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Red Blood Cell ◽  
Hemoglobin F ◽  
Positive Correlation ◽  
King's College ◽  
Hydroxyurea Treatment ◽  
Pain Frequency ◽  
Rbc Deformability

Background Sickle hemoglobin (hemoglobin S, HbS) is a structural variant of adult hemoglobin. HbS polymerizes when oxygen tensions are low, leading to red blood cell (RBC) deformation, so-called "sickling". In sickle cell anemia (SCA), loss of RBC deformability is considered to be a primary factor responsible for vaso-occlusion and hemolysis. Until recently no laboratory tests to measure RBC deformability in SCA have been readily available. Study Aims In this study we examine RBC deformability, measured with the oxygenscan module of the Laser Optical Rotational Red Cell Analyzer (Lorrca) ektacytometer, in children with SCA treated with or without hydroxyurea (HU). Furthermore, we investigate the relationship between RBC deformability and pain frequency, as well as genetic and laboratory measures known to be associated with disease severity in SCA. Methods We included children aged 0-16 years with a confirmed diagnosis of SCA (HbSS) from the pediatric sickle cell clinic at King's College Hospital in London. Children were excluded if they had received any blood transfusions within 3 months of study inclusion. Children on HU were only included if treatment had been initiated >3 months prior to recruitment and the dose was stable. Children and their parents or guardians reported frequency of pain as: daily, weekly, monthly, yearly, or never. Laboratory measurements, including total hemoglobin (hb), hemoglobin F (HbF), and reticulocyte percentage, were performed on the same day as a sample was taken for oxygenscan analysis. Data on co-inheritance of α-thalassemia was recorded if available. EDTA blood samples were kept at approximately 4°C and transported from King's College London to Copenhagen University Hospital (Herlev and Gentofte Hospital), where they were analyzed within 48 hours of sampling using the Lorrca oxygenscan (RR Mechatronics, the Netherlands). The oxygenscan measures RBC deformability expressed as an elongation index (EI) during deoxygenation and reoxygenation, with EImax expressing RBC deformability at normal oxygen concentrations, EImin expressing RBC deformability after deoxygenation, and the point of sickling (POS) expressing the point at which >5% decrease in EI is observed, representing the pO2 at which sickling begins. All statistical analyses were performed in Stata V16.0 (StataCorp. 2019, USA), using the two-sided t-test, one-way ANOVA, and Pearson's correlation when appropriate. Results We included 47 children aged 0-16 years (mean age 7.9 years) in the study, 24 (51%) receiving HU. Children in the HU group presented with significantly higher HbF percentage compared to the non-HU group (15.6% and 10.9%, p=0.03). Children receiving HU had higher EImax and EImin, and lower POS values, compared to children in the non-HU group, although results were not significant (Table 1). There was a positive correlation between HbF and EImax (r= 0.57, p=0.0001) and HbF and EImin (r= 0.56, p=0.0001), and a negative correlation between HbF and POS (r=-0.37, p=0.01), as well as a positive correlation between total hb and EImax (r=0.35, p=0.02). There was no significant correlation between any oxygenscan parameters and reticulocyte percentage. Data on α-thalassemia was available for 23 children. EImax and EImin values were higher in heterozygous children compared to children without co-inherited α-thalassemia, and POS values were lower, but results were not significant (Table 2). We found no significant association between any oxygenscan parameters and pain frequency (Table 3). Conclusion In this study we identified a strong correlation between all oxygenscan parameters and HbF percentage, as has been reported previously. We found higher EImax and EImin and lower POS values in children receiving HU treatment and children with co-inherited heterozygous α-thalassemia, suggesting increased RBC deformability in these children. These results were not significant, however, which may in part be due to lack of power in the study. Also, it is possible that children in the HU group would have presented with lower EImax and EImin and higher POS values prior to HU initiation, with treatment response leading to results similar to those found in the non-HU group. Finally, our results suggest that there is no association between oxygenscan parameters and self-reported frequency of pain in children with SCA. Disclosures No relevant conflicts of interest to declare.

Elevated Systolic Blood Pressure and Low Fetal Hemoglobin Are Risk Factors for Silent Cerebral Infarcts in Children with Sickle Cell Anemia.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 262-262
Author(s):  
Sharada A. Sarnaik ◽  
James F. Casella ◽  
Bruce A Barton ◽  
Michele Afif ◽  
Gladstone Airewele ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Systolic Blood Pressure ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Beta Thalassemia ◽  
Cerebral Infarcts ◽  
Hemoglobin F ◽  
Elevated Systolic Blood Pressure

Abstract Abstract 262 Introduction: The most common cause of neurological injury in sickle cell anemia is silent cerebral infarcts (SCI). In the Silent Cerebral Infarct Multi-Center Clinical Trial (SIT Trial) cohort, we sought to identify risk factors associated with SCI. Patients and Methods: In this cross-sectional study, we evaluated the clinical history, baseline laboratory values and performed magnetic resonance imaging of the brain. For those children with SCI-like lesions, a pediatric neurologist examined the child and neuroradiology and neurology committees adjudicated the presence of SCI. Children between the ages of 5 and 15 years with hemoglobin SS or S-beta° thalassemia and no history of overt strokes or seizure were evaluated. Results: A total of 542 children were evaluated; 173 (31.9%) had SCI. The mean age of the children was 9.3 years, with 280 males (51.7%). In a multivariate logistic analysis, two covariates were significant: a single systolic blood pressure (SBP) obtained during a baseline well-visit, p = 0.015 and hemoglobin F (Hgb F) level obtained after three years of age, p = 0.038. Higher values of SBP and lower values of Hgb F increased the odds of SCI; Figure. Baseline values of white blood cell count, hemoglobin level, oxygen saturation, reticulocytes, pain, or ACS event rates were not associated with SCI. Conclusion: SBP and Hgb F level are two previously unidentified risk factors for SCI in children with sickle cell disease. Modulation of SBP and Hgb F levels might decrease the risk of SCI. Disclosures: No relevant conflicts of interest to declare.

Transcranial Doppler Peak Systolic Velocities Overestimate The Risk Of Stroke In Sickle Cell Anemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2240-2240 ◽  
Author(s):  
Titilope Ishola ◽  
Charles T. Quinn
Keyword(s):  
Clinical Practice ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Clinical Care ◽  
Pearson Correlation ◽  
Systematic Bias ◽  
Anatomic Site ◽  
The Right

Abstract Background Children with sickle cell anemia (SCA) have a high risk of stroke that can be estimated by transcranial Doppler ultrasonography (TCD). The gold standard TCD measurement to determine the risk of primary stroke is the time-averaged mean of the maximum velocity (TAMMV) in specific intracranial arteries. Peak systolic velocity (PSV), a different TCD measurement, has been proposed as an alternative method for risk stratification, especially for imaging TCD (TCDi) techniques (Jones et al. 2005). Although PSV has been little studied for this purpose, some centers use PSV in addition to TAMMV for the classification of risk of stroke by TCD for clinical care. A systematic bias in the classification of risk of stroke by PSV (higher or lower compared to TAMMV) would substantially affect medical resources and patient outcomes. Objective Describe the test performance characteristics of PSV compared to TAMMV for the classification of risk of stroke in children with SCA and determine the suitability of PSV for classification of TCDs in clinical practice. Methods We studied all patients in our center with homozygous HbSS, sickle-β0-thalassemia, or sickle-Hb D disease (all genotypes referred to here as SCA) who were ≥2 years of age and had a clinical TCD (all by TCDi technique) between 1998-2013. For each patient, the single most recent TCD performed >30 days from a transfusion was used, except for patients receiving chronic transfusions for whom the TCD before the initiation of chronic transfusions was used. Patients were included only once in this analysis. The highest TAMMV and PSV were recorded for the distal internal carotid artery (DICA), bifurcation and middle cerebral artery on the right and left sides of the brain. The TAMMV in each vessel was classified using modified STOP velocity criteria for TCDi: <155, normal; 155-184, conditional; ≥185 abnormal. The PSV in each vessel was classified using criteria proposed by Jones et al.: <200, normal; 200-249, conditional; ≥250 abnormal. Two overall TCD classifications, using either TAMMV or PSV, were made according to standard STOP methods by considering the worst (most abnormal) classification of any vessel as the overall classification. The primary outcome was the multi-level agreement between overall TCD classification based on TAMMV and PSV as measured by the kappa statistic. Kappa was also calculated for individual vessels to determine if agreement differed by anatomic site. Coefficients of determination (r2) were calculated using Pearson correlation. Results We studied 120 patients with SCA [mean age 12.0 years ± 6.0 (S.D.); 51.1% male]. Fifty-nine (49%) had at least one prior transfusion that was given a mean of 588 (median 387) days before the TCD (none ≤40 days). The distribution of overall TCD classification by simultaneous TAMMV and PSV is shown in the Figure (Panel A). The distribution of classifications by TAMMV, compared to PSV, better approximates the expected distribution in a screening population. Classifications by PSV were skewed higher, giving more conditional and abnormal results, when compared to classification by TAMMV (P<0.0001). Kappa was 0.488 (P<0.001) for overall TCD classification, indicating only moderate agreement between the TAMMV and PSV methods. Agreement between TAMMV and PSV classification was highest (“substantial”) in the right and left DICA (k: 0.657–0.717, P<0.001). Agreement was only moderate in all other vessels (k: 0.428–0.539, P<0.001). Compared to TAMMV, use of PSV resulted in misclassification of 28% of overall TCD interpretations (Figure, Panel B); 32 studies (27%) were up-coded (27 normal to conditional; 5 conditional to abnormal). Only 1 study was down-coded (abnormal to conditional). Considering TAMMV and PSV as continuous variables, TAMMV accounted for 84.2-90.2% (r2) of the variation in PSV across different vessels; so, approximately 10-15% of the variability in PSV is not explained by TAMMV. Conclusions The use of PSV (rather than TAMMV) to classify TCDs overestimates the risk of stroke for almost one-third of children with SCA. This systematic bias will unnecessarily increase anxiety, the frequency of follow-up testing, and use of chronic transfusions for primary stroke prophylaxis. PSV should not be used for primary classification of TCDs in clinical practice. Jones A et al. Can peak systolic velocities be used for prediction of stroke in sickle cell anemia? Pediatr Radiol. 2005;35:66-72. Disclosures: No relevant conflicts of interest to declare.

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