scholarly journals Assessment of Bone Marrow Function in Sickle Cell Anaemia Patients Using Corrected Reticulocyte Counts

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 4581-4581
Author(s):  
Titilola S. Akingbola ◽  
Chinedu Anthony Ezekekwu ◽  
Joseph Yaria ◽  
Santosh L. Saraf ◽  
Lewis L. Hsu ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Steady State ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
P Value ◽  
Production Index ◽  
Risk Of Death ◽  
Increased Risk ◽  
Reticulocyte Production

Abstract Introduction: Chronic hemolysis occurs in sickle cell anemia as a result of recurrent sickling and other abnormalities of the red blood cells including eryptosis. Exuberant reticulocytosis is anticipated to partially compensate for the resultant anemia. Sickle cell anemia patients may also have aplastic crisis, bone marrow (BM) infarction and erythropoietin deficiency which could lead to reticulocytopenia despite the anemia. High degree of reticulocytosis among asymptomatic infants with sickle cell anemia has been associated with an increased risk of death or stroke during childhood. Assessment of BM function in sickle cell anemia is important due to potential complications associated with both under-activity and hyperactivity. This study aimed at evaluating the erythropoietic function of the BM in steady state sickle cell anemia using corrected reticulocyte counts. Methods: This study was carried out at the hematology clinic in the University College Hospital, Ibadan. HbSS patients in steady state were recruited from the hematology clinic. Local ethical committee approval was obtained and all participants gave written informed consent. Patients with M. tuberculosis, Hepatitis B, HIV and P. falciparum infection were excluded. Peripheral blood samples were analyzed using Sysmex Ki-X21 for complete blood count (CBC) and standard point of care for serum electrolytes and liver function tests. The glomerular filtration rates were calculated using the Cockcroft-Gault formula. Reticulocyte counts were determined manually using fresh samples from K2 EDTA bottles and methylene blue stain. Two drops of stain were mixed with two to four volumes of anticoagulated blood and incubated at 37ºC for 15 minutes. Afterwards, the cells were re-suspended and blood films were made. Corrected reticulocyte count and reticulocyte production index were calculated. Participants were categorized according to corrected reticulocyte counts of greater than or less than 2.5%. Univariate and multivariate analyses were performed to determine variables associated with corrected reticulocyte count <2.5%. Results: 92 HbSS patients were recruited with a mean (SD) age of 19.6 (5.8) years. There was no correlation between age and eGFR (p-value: 0.227). Median (range) reticulocyte count, corrected reticulocyte count and reticulocyte production index were 5.5 (0.5 - 29.9), 3.3 (0.1 - 17.1) and 1.7 (0.2 - 8.6) respectively. 40 (43.5%) patients had corrected reticulocyte count <2.5% and 52 (56.5%) had a corrected count >2.5%. Those corrected reticulocyte count <2.5% were older (p: 0.013), taller (p: 0.041) and had higher aspartate transaminase (AST) levels (p: 0.006) than those with corrected counts >2.5% (Table 1). CBC parameters were not different when compared between both groups. Results of multivariate logistic regression analysis carried out showed that only AST was independently linked with corrected reticulocyte count <2.5% (R2: 0.172, p-value: 0.001) (Table 2). Table 1. Factors Associated with Low Reticulocyte Count Corrected count<2.5% Corrected count>2.5% p-Value Age (Mean, SD) 21.4 (6.3) 18.4 (5.0) 0.013 Gender (N, %) Male 22 (55.0) 28 (53.8) 0.912 Female 18 (45.0) 24 (46.2) Height (Mean, SD) 1.6 (0.1) 1.5 (0.1) 0.041 BMI (Mean, SD) 18.7 (3.1) 18.7 (3.0) 0.753 GFR (Mean, SD) 64.3 (37.7) 66.4 (29.3) 0.453 Bilirubin (Mean, SD) 1.7 (1.1) 1.9 (2.6) 0.674 AST (Mean, SD) 22.5 (13.5) 14.5 (6.6) 0.006 ALT (Mean, SD) 13.4 (7.7) 14.4 (11.1) 0.876 Table 2. Independent Predictors of Corrected Reticulocyte Count <2.5% or 95% CI p-Value Age 1.08 0.97 - 1.21 0.169 Height 19.8 0.11 - 366.10 0.259 AST 1.10 1.04 - 1.17 0.002 Hemoglobin 1.00 0.97 - 1.02 0.872 R2: 0.172, p: 0.001 Conclusion: Despite corrected reticulocyte count <2.5% in about half of the patients, there were similar hematological parameters and eGFR in both groups of patients. AST is a marker of hemolysis and low ALT rules out hepatic involvement. Since only 17.2% of the variability in BM response as assessed by corrected reticulocyte count could be accounted for by variables included in this study, there is a need to further evaluate the BM function of sickle cell patients to establish the causes of corrected reticulocyte count <2.5% in the setting of anemia, having ruled out erythropoietin as well as iron, folate or cobalamin deficiencies. This will aid the development of a functional algorithm for the individualized management of sickle cell disease patients with anemia. Disclosures No relevant conflicts of interest to declare.

Absolute Reticulocyte Count Is Negatively Correlated with Fetal Hemoglobin during Infancy and Early Childhood in Patients with Sickle Cell Anemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4081-4081
Author(s):  
Emily R. Meier ◽  
Colleen Byrnes ◽  
Y. Terry Lee ◽  
Maxine Weissman ◽  
Jeffery L. Miller
Keyword(s):  
Steady State ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Conflicts Of Interest ◽  
Fetal Hemoglobin ◽  
Convenience Sample ◽  
Risk Of Death ◽  
Increased Risk ◽  
F Cells ◽  
Analytical Approaches

Abstract Hemoglobin switching is largely complete in healthy infants by 6 months of age. In infants with sickle cell anemia (HbSS, SCA), reticulocytosis begins early in life as fetal hemoglobin (HbF) is replaced by sickle hemoglobin (HbS). Previous studies demonstrated that patients with an ARC greater than 200 K/uL during early infancy (60-196 days of age) were at the highest risk for SCA-associated events. 1,2 The objective of this study was to determine if ARC is related to HbF levels in a cohort of pediatric SCA patients. A convenience sample of 106 children with SCA between the ages of 1 month and 20 years who were not receiving hydroxyurea or monthly blood transfusions were enrolled in this observational study [42 (39.6%) less than 1 year of age (28-362 days old), 46 (43.4%) between the ages of 1 and 10 years, and 18 (17.0%) between 10 and 20 years old]. After consent and assent were provided, discarded peripheral blood was obtained during routine clinic visits at steady state and analyzed within 48 hours of collection and storage at 40C. Steady state was defined as a sample drawn at least 30 days following an acute event and at least 60 days following a blood transfusion. Hematologic data, including ARC and HbF levels, were measured using CLIA approved methods. F-cells were enumerated by flow cytometry following intracellular staining with a fluorescent antibody directed against HbF. Correlations were calculated to determine the relationships of ARC with HbF, F-cells, and other hematologic data, while two-tailed t tests were used to compare means. Initial studies compared groups based upon ARC greater than or equal to 200 K/uL (ARC≥200) during infancy because of the previously reported utility of this threshold as a predictive marker for SCA severity.1 Over one third of the infants less than 1 year of age (n=16) had an ARC≥200. Mean HbF and F-cell levels were significantly lower in the ARC≥200 group when compared to the ARC<200 group (HbF: 29.9±10.9% vs. 53.5±17.6%, respectively, p=2.2E-05; F-cells: 83.5±13.2% vs. 96.6±5.7%, p=6.2E-05). Mean hemoglobin levels were also lower in the ARC≥200 group [8.1±1.4 g/dL vs. 9.5±1.6 g/dL (ARC<200), p=0.005]. Of the 22 (52.4%) infants who had a HbF level greater than 40%, only 2 (9.1%) had an ARC greater than 200K/uL. Enrolled patients were also grouped according to age and comparisons were made between ARC and HbF or F-cell levels. HbF and F-cell levels were negatively correlated to ARC in the infant subgroup (r=-0.696, p=3.1E-07 and r=-0.795, p=0.000, respectively). HbF and F-cell levels from children between the ages of 1 and 10 years were inversely related to the ARC, but the correlation was less significant (r=-0.626, p=3.3E-06 and r=-0.538, p=1.2E-04, respectively). The inverse relationship was no longer present in the oldest group of patients (HbF vs. ARC r=-0.203, p=0.420 and F-cells vs. ARC, r=-0.258, p=0.302). According to both analytical approaches described here, increased ARC is associated with decreased HbF and F-cell levels in infants with SCA. Less robust negative correlations are maintained through age 10 years, but no significant correlation was identified in adolescence and young adulthood. Overall, the data suggest that increased ARC levels may identify SCA infants who manifest a more rapid or greater loss of fetal hemoglobin during the later stages of the HbF-to-HbS switching phenomenon. Meier ER, Byrnes C, Lee YT, et al. Increased reticulocytosis during infancy is associated with increased hospitalizations in sickle cell anemia patients during the first three years of life. PLoS One 2013; 8(8):e70794. doi: 10.1371/journal.pone.0070794.Meier ER, Wright EC, Miller JL. Reticulocytosis and anemia are associated with an increased risk of death and stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease. Am J Hematol 2014 May 31; doi: 10.1002/ajh.23777. [Epub ahead of print] Disclosures No relevant conflicts of interest to declare.

Daytime Steady-State Hemoglobin Desaturation Is a Risk Factor for Overt Stroke Children with Sickle Cell Anemia.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 431-431
Author(s):  
James W. Sargent ◽  
Charles T. Quinn
Keyword(s):  
Risk Factor ◽  
Ischemic Stroke ◽  
Steady State ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
Time Interval ◽  
Increased Risk ◽  
Nested Case Control ◽  
Control Study

Abstract Stroke is a serious complication of sickle cell anemia (SS). Steady-state hemoglobin (Hgb) desaturation, which is common in SS and often thought to be benign, could contribute to the risk of stroke because it perturbs endothelial function in SS (Lancet2003;362:1450) and might limit oxygen delivery to the brain. One previous study of SS patients found an association between nocturnal oxygen desaturation and strokes, transient ischemic attacks, and seizures (Lancet2001;357:1656). Nocturnal oxygen saturation is cumbersome to measure, and the association between daytime Hgb saturation and stroke has not been reported. We hypothesized that daytime steady-state Hgb desaturation was associated with and preceded overt stroke in children with SS. We performed a nested case-control study of the Dallas Newborn Cohort (Blood2004;103:4023). Cases were defined as cohort subjects with SS or sickle-β0-thalassemia (Sβ0) who had clinically overt ischemic strokes in the preceding 12 years. Controls were cohort subjects with SS or Sβ0 but without overt stroke who were reported previously (Br J Haematol2005;131:129). We collected mean steady-state oxygen saturations by pulse oximetry (SpO2) and mean steady-state hematologic data for cases (pre-stroke) and controls. For cases we also identified one SpO2 measurement and one blood count that was recorded closest to but preceding each stroke (the proximate pre-stroke values). We further calculated a predicted SpO2 for cases using a model that includes age, sex, and mean steady-state values of Hgb and reticulocyte count (Br J Haematol2005; 131:129) and calculated odds ratios for stroke by logistic regression. We identified 22 cases (100% SS; 68% male; mean age 7.9 years) and 390 controls (98% SS; 55% male; mean age 9.5 years). The steady-state SpO2 of cases (94.2%, standard deviation [SD] 3.0) was significantly lower than controls (96.3%, SD 3.0) (P=0.0014). The proximate pre-stroke SpO2 of cases (93.7% SD 3.8) was even lower than steady-state and significantly lower than controls (P=0.0006). The predicted steady-state SpO2 for cases was 95.2% (SD 1.4), meaning that the observed SpO2 of cases (94.2%) was lower than would be expected for SS patients without stroke given age, sex, and steady-state values of Hgb and reticulocyte count. The odds ratio for stroke was 1.32 (95% confidence interval 1.15 – 1.51) for each unit (1%) decrease in SpO2 while simultaneously controlling for age, sex, and steady-state values of Hgb and reticulocyte count (P<0.0001). In summary, we found that children with SS who develop a stroke have lower pre-stroke steady-state SpO2 values than children with SS who do not develop a stroke. Moreover, in children who develop stroke, the measured SpO2 value decreases as the time interval to stroke narrows. The odds of stroke increase as the SpO2 decreases. In conclusion, steady-state Hgb desaturation is a risk factor for ischemic stroke in children with SS. Decline in steady-state SpO2 over time further increases this risk. Hgb desaturation is an easily measured, potentially modifiable risk factor that could be used to identify children with SS who have an increased risk of overt ischemic stroke. Figure Figure

Reticulocytosis and Anemia in Early Infancy Is Associated with Abnormal and Conditional Transcranial Doppler Velocities in Pediatric Sickle Cell Anemia Patients

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4080-4080
Author(s):  
Emily R. Meier ◽  
Ross M. Fasano ◽  
Monica Estrada ◽  
Jianping He ◽  
Robert Mccarter ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Steady State ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Transcranial Doppler ◽  
Cox Regression ◽  
Early Infancy ◽  
Cox Regression Analysis ◽  
Risk Of Death ◽  
Increased Risk

Abstract All sickle cell anemia patients (HbSS, SCA) have the same genetic mutation, but the clinical phenotype is highly variable and difficult to predict prior to the onset of complications. Transcranial Doppler (TCD) is the only validated predictive indicator of severe SCA currently available, identifying SCA patients age 2 years or older with the greatest stroke risk. Preliminary studies have identified that elevated absolute reticulocyte count (ARC) between 2 and 6 months of age is associated with an increased risk of hospitalization for SCA complications, stroke and death.1,2 To determine if early reticulocyte levels in SCA patients are useful in classifying children at highest risk of developing an abnormal (abTCD) or conditional (cdTCD) TCD, 121 consecutive patients with SCA who had TCD screening were identified after IRB review granted a waiver of consent. Retrospective chart review was then performed to collect the steady state ARC between 2 and 6 months of age; patients were excluded if this value was not available in the medical record. Steady state was defined as a sample collected at least 30 days from an acute illness and at least 60 days since the patient received a blood transfusion. ARC and hematologic data were analyzed using Cox regression analysis to determine the relationship between ARC levels and time to cdTCD/abTCD. TCDs were considered normal (nlTCD) if the Time Average Mean Maximum Velocity (TAMMV) in the middle cerebral artery or distal internal carotid artery was <170 cm/sec, cdTCD if TAMMV was 170-199 cm/sec and abTCD if TAMMV was 200 cm/sec or greater. To evaluate the utility of ARC or hemoglobin in risk stratification, patients were divided into groups: ARC less than 200K/uL (ARC<200) and ARC greater than or equal to 200K/uL (ARC≥200), or hemoglobin less than 8.5 g/dL (Hb<8.5) and hemoglobin greater than or equal to 8.5 g/dL (Hb≥8.5). Twenty of the 121 (16.5%) patients had abTCD, while 36/121 (29.8%) had cdTCD; the remaining 65/121 (53.7%) had nlTCDs. Mean ARC between 2 and 6 months of age was highest in those children with abTCDs (264±149 K/uL) and cdTCDs (175±76 K/uL) while those who had nlTCDs had the lowest values (mean ARC 140±100K/uL, p<0.001 across groups). Mean hemoglobin was lower in the abTCD (8.1±1.2 g/dL) and cdTCD groups (8.9±1.1 g/dL) compared to the nlTCD group (9.5±1.5 g/dL, p<0.001). The three groups did not differ in age at time of ARC measurement [mean age in months: 3.6±1.2 (nlTCD) vs. 3.8±1.3 (cdTCD) vs. 3.4±1.0 (abTCD), p=0.86]. Kaplan Meier analysis revealed that those children with higher ARC had an increased rate of cdTCD/abTCD (p<0.001 by the log-rank test). Lower hemoglobin was also associated with an increased rate of cdTCD/abTCD (p=0.002). Cox regression analysis revealed that those subjects with an ARC≥200 between the ages of 2 and 6 months had 2.9 times the risk of having an abTCD or cdTCD than the group with an ARC<200 (HR 2.92, 95% CI 1.68-5.08, p=0.0004). In separate analyses, patients with a hemoglobin less than 8.5 g/dL had 2.4 [95%CI 1.38-4.06 (p=0.002)] times the risk of having an abTCD/cdTCD than patients with a hemoglobin level of 8.5 g/dL or greater. These data suggest that both elevated ARC and low baseline hemoglobin during early infancy are associated with an increased risk of developing a cdTCD or abTCD later in childhood. ARC and hemoglobin at this early age should be prospectively studied as standard screening tests to assist with treatment decisions in young children with SCA. Meier ER, Byrnes C, Lee YT, et al. Increased reticulocytosis during infancy is associated with increased hospitalizations in sickle cell anemia patients during the first three years of life. PLoS One 2013; 8(8):e70794. doi: 10.1371/journal.pone.0070794.Meier ER, Wright EC, Miller JL. Reticulocytosis and anemia are associated with an increased risk of death and stroke in the newborn cohort of the Cooperative Study of Sickle Cell Disease. Am J Hematol 2014 May 31; doi: 10.1002/ajh.23777. [Epub ahead of print] Disclosures No relevant conflicts of interest to declare.

The Hyperhemolysis Phenotype in Sickle Cell Anemia: Increased Risk of Leg Ulcers, Priapism, Pulmonary Hypertension and Death with Decreased Risk of Vasoocclusive Events.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 787-787 ◽  
Author(s):  
James G. Taylor ◽  
Vikki G. Nolan ◽  
Gregory J. Kato ◽  
Mark Gladwin ◽  
Martin H. Steinberg
Keyword(s):  
Pulmonary Hypertension ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Phenotypic Expression ◽  
Vascular Complications ◽  
Clinical Variable ◽  
Leg Ulcers ◽  
Risk Of Death ◽  
Arginase 1 ◽  
Increased Risk

Abstract Polymerization of hemoglobin in sickle cell anemia (HbSS) results in red blood cell damage, vasoocclusive disease and hemolytic anemia. Plasma hemoglobin and arginase released during hemolysis produce endothelial dysfunction and lead to vascular complications such as leg ulceration, priapism, pulmonary hypertension and increased risk of death. Examination of 2 independent patient groups from the NIH and CSSCD revealed considerable heterogeneity in the rates of hemolysis as estimated by LDH. We therefore hypothesized that inter-individual variation in hemolytic rate influences the phenotypic expression of HbSS. To test this hypothesis, we have defined a hemolysis phenotype as a clinical variable in our 2 HbSS groups. At NIH, LDH was analyzed as a quantitative trait in 166 adults to define a subgroup above the 75th percentile suggestive of exaggerated hemolysis (n= 42, mean LDH 645). When compared with 42 cases in the lowest LDH quartile (mean 230), the hyperhemolysis group had significantly lower hemoglobin and higher AST, bilirubin, and absolute reticulocyte levels supporting this phenotypic classification. HbF, arginine:ornithine ratios and arginase 1 activity were also significantly different. Clinically, the hyperhemolysis group had an increased prevalence of leg ulcers (OR 5.10; P=0.007), priapism (OR 3.67; P=0.16), and pulmonary hypertension (TRV &gt; 3.0 m/s; OR 12.00; P&lt;0.001). In addition, these patients have fewer severe vasoocclusive pain crises (3.1 ER visits/yr. with high LDH vs. 9.1/yr. with low LDH; P=0.004), supported by a lower prescription rate for hydroxyurea (37% with high LDH vs. 61% with low LDH; P=0.06). To validate these findings, we repeated the LDH phenotypic assignment analysis using 451 comparable CSSCD adults greater than 30 years of age. An identical pattern of laboratory results was seen when comparing high and low LDH quartiles. Hyperhemolysis was defined by anemia, elevated total bilirubin and AST and lower HbF. The most striking observations for this group were the significantly higher proportion of males (55% vs. 27% with low LDH; P&lt;0.001), occurrence of leg ulcers (OR 3.44; P&lt;0.001), and frequent death (33% vs. 16% with low LDH; P=0.003). There were also trends towards more prevalent priapism and stroke in the hemolysis group. After adjustment for HbF and gender, the associations between hyperhemolysis and risk of leg ulceration and risk of death remained significant in the CSSCD. Together, these findings suggest that excessive hemolysis results in a vascular HbSS phenotype characterized by leg ulcers, priapism, pulmonary hypertension, possibly stroke, and death. The lack of an association between excess hemolysis and pain/ACS suggests this phenotype is distinct from vasoocclusion/hyperviscosity. The consistent association of hyperhemolysis with this spectrum of symptoms, even after HbF correction, indicates the existence of unknown determinants for hemolysis. Future environmental and genetic studies of hyperhemolysis may provide novel mechanistic insights into the pathogenesis and treatment of HbSS vascular complications. From a clinical standpoint, these data further support the use of LDH as a simple biomarker for identifying a sub-set of HbSS patients at high risk for hemolysis-driven complications and death, who may otherwise be overlooked by clinicians because of infrequent vasoocclusive pain events.

scholarly journals Erythroid Adhesion Molecule Expression Profile in Sickle Cell Anemia Infants

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1368-1368
Author(s):  
Valentine Brousse ◽  
Yves Colin ◽  
Catia Pereira ◽  
Arnaud Cecile ◽  
Marie-Helene Odievre ◽  
...  
Keyword(s):  
Adhesion Molecules ◽  
Disease Severity ◽  
Sickle Cell ◽  
Expression Profile ◽  
Adhesion Molecule ◽  
Sickle Cell Anemia ◽  
Reticulocyte Count ◽  
Adhesion Molecule Expression ◽  
Risk Of Death ◽  
Hbf Level

Abstract Introduction: In normal conditions, circulating red blood cells (RBCs) are not supposed to adhere. Some erythroid adhesion molecules expressed on young reticulocytes are therefore lost upon maturation. Conversely, abnormal RBC adhesiveness in sickle cell anemia (SCA) through activation, sustained or increased expression of adhesion molecules are considered central in vaso occlusive crisis (VOC), the hallmark of SCA. SCA is seldom symptomatic in the first six months of life. One main explanation lies in the sustained level of fetal hemoglobin (HbF) and F cells during this period preventing HbS polymerization. However, infra clinical vaso occlusion, particularly in the spleen, has been demonstrated to be present and the absolute reticulocyte count is paradoxically elevated in the first semester of life, evidencing the very early onset of hemolysis. Our objectives were to analyze the profile of erythroid adhesion molecules in SCA and non-SCA infants in combination with HbF level, in order to evidence significant differences specifically attributable to SCA, informative on very early pathophysiology and disease severity. Patients and methods: Infants were enrolled in a longitudinal multi center prospective study on prognostic factors in SCA between September 2010 and March 2013. Blood sampling was performed at enrolment (3-6 months) at steady state, in asymptomatic infants. In parallel, blood samples from infants with no hemoglobinopathy were collected. Flow cytometer analysis (BD FACSCanto II) was performed using murine monoclonal antibodies against CD36, CD44, CD47, CD49d, CD58, CD99, CD147, CD239 and CD242. Statistical analysis was performed with Graphpad software, Prism 6. Differences in the percentage of positive cells and the level of expression of molecules between groups were calculated with Mann Whitney test. Results were considered statistically significant at an a-risk level of 5%. Results: Fifty-four SCA infants were included and compared to 17 non-SCA infants. Median age in the two groups was not statistically different (144 days, range 81-196 versus 128, range 68-621, p=0,84). Mean HbF level was, as previously described, statistically increased in SCA compared to non-SCA infants (41.2% +/-11.2 versus 10,4 % +/- 1,8; p<0,0001). Median reticulocyte count tended to be more elevated in SCA infants (2.6 % range 0,5-10) compared to non-SCA infants (2 range 1-3,1) without reaching statistical significance (p=0,052). Reticulocytes from SCA infants display a distinct surface molecule expression profile, with a statistically increased percentage of reticulocytes expressing the following adhesion molecules: CD239 (Lu/BCAM), CD242 (ICAM-4), CD47, CD99, CD58, CD147 and CD44 (Figure 1). Furthermore the mean intensity of fluorescence is statistically increased concerning CD239, CD58 and CD242 (data not shown). Surprisingly, known adhesion markers demonstrated to play an important role in SCA pathogeny i.e. CD36 and CD49d (α4β1/Very Late Antigen-4) are not significantly increased in SCA infants (Figure 1) No significant difference of expression profile was found on mature or total RBCs between SCA and non-SCA infants (data not shown). Figure 1 Figure 1. Discussion: Recent publications have pointed to the significance of reticulocytosis associated with an increased risk of death or stroke during childhood. Our results further demonstrate that this early rise of reticulocyte count in SCA infants, despite elevated HbF level, include reticulocytes with a specific adhesion molecule expression profile. This numerically small subpopulation of red cells may play in fact a major role in this complex disease. An interesting hypothesis may be that the spleen, as long as its function is preserved, prevents VOC by trapping this subpopulation in very young infants. As spleen function decreases, proadhesive reticulocytes remain in the circulation, which may, in combination with the decline of HbF, subsequently favor extra splenic VOC. Ongoing analysis will confirm if this idiosyncratic erythroid adhesion molecule profile in infants indeed correlates with HbF level and, importantly, correlates with functional activation, in order to serve as a readily available biomarker of disease severity. Disclosures De Montalembert: Novartis: Speakers Bureau. Le Van Kim:SHIRE: Research Funding.

scholarly journals Determination of Coagulation Profile among Children with Sickle Cell: Anemia in Steady-State and Crisis

2021 ◽  
pp. 179-185
Author(s):  
Maysaa Ali Hassan Ali ◽  
Elharam Ibrahim Abdallah ◽  
Alaa Eltayeb Omer ◽  
Lienda Bashier Eltayeb
Keyword(s):  
Platelet Count ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Venous Blood ◽  
P Value ◽  
Cell Disease ◽  
Coagulation Profile ◽  
The Mean

Background: Patients with Sickle Cell Disease (SCD) have been found to have an aberrant coagulation profile. One of the primary elements hypothesized to contribute to the vaso-occlusive crisis that characterizes sickle cell disease is coagulopathy (SCD) Material and Methods: A total of 150 children were enrolled as follows, 50 children with Sickle Cell Anemia (SCA) in steady-state, 50 in crisis, and 50 with Hb AA genotype as control. 5 ml of Venous blood was collected. The platelets count was performed using Sysmex KX21N, the electrical impedance principle. The Mean Platelet Volume (MPV) is derived from the impedance platelet size distribution curve. STAGO PT31039352) semi-automated machine was used for estimation of PT, and APTT. Result: children with SCA have significantly a prolonged PT, and APTT compared with children with normal hemoglobin genotype (P. value < 0.001) the mean of PT was (16.64, and 12.6) respectively, and APTT (41.45 and 37.94) consequently. A significant increase in platelet count between patients with SCA when compared with control (p. value 0.02), however a significant prolonged in APTT when compared to steady-state (P. value 0.005). MPV among children with crises when compared with steady-state revealed a significant result (p. value 0.006) the mean of MPV in steady-state = 6.79 while the mean of MPV in crisis = 7.09. Conclusion: children with sickle cell anemia had a longer coagulation profile and marked variation in platelet count, which may increase the risk of thrombosis or bleeding.

scholarly journals Is there a role for selective vasodilation in the management of sickle cell disease?

Blood ◽  
1988 ◽  
Vol 71 (3) ◽  
pp. 597-602 ◽  
Author(s):  
GP Rodgers ◽  
MS Roy ◽  
CT Noguchi ◽  
AN Schechter
Keyword(s):  
Blood Flow ◽  
Steady State ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Microvascular Obstruction ◽  
Controlled Study ◽  
Control Group ◽  
Cell Disease ◽  
Retinal Arteriolar

Abstract To test the hypothesis that microvascular obstruction to blood flow at the level of the arteriole may be significant in individuals with sickle cell anemia, the ophthalmologic effects of orally administered nifedipine were monitored in 11 steady-state patients. Three patients with evidence of acute peripheral retinal arteriolar occlusion displayed a prompt reperfusion of the involved segment. Two other patients showed fading of retroequatorial red retinal lesions. Color vision performance was improved in six of the nine patients tested. The majority of patients also demonstrated a significant decrease in the amount of blanching of the conjunctiva which reflects improved blood flow to this frequently involved area. Such improvements were not observable in a control group of untreated stable sickle cell subjects. These findings support the hypothesis that inappropriate vasoconstriction or frank vasospasm may be a significant factor in the pathogenesis of the microvascular lesions of sickle cell disease and, further, that selective microvascular entrapment inhibition may offer an additional strategy to the management of this disorder. We believe a larger, placebo-controlled study with nifedipine and similar agents is warranted.

Study of Platelet Function in Patients with Sickle Cell Anemia during Steady State and Vaso-Occlusive Crisis

1993 ◽  
Vol 89 (4) ◽  
pp. 180-183 ◽  
Author(s):  
Christos A. Papadimitriou ◽  
Anthi Travlou ◽  
Alexander Kalos ◽  
Dimitrios Douratsos ◽  
Polyxene Lalï
Keyword(s):  
Steady State ◽  
Sickle Cell ◽  
Platelet Function ◽  
Sickle Cell Anemia

Is There an Increased Risk of Haemophilus influenzae Septicemia in Children with Sickle Cell Anemia?

PEDIATRICS ◽  
1983 ◽  
Vol 71 (6) ◽  
pp. 927-931
Author(s):  
Darleen Powars ◽  
Gary Overturf ◽  
Ernest Turner
Keyword(s):  
Haemophilus Influenzae ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Clinical Course ◽  
Febrile Child ◽  
Low Grade ◽  
Upper Respiratory Tract ◽  
Pneumococcal Infections ◽  
Increased Risk ◽  
Upper Respiratory

The risk of Haemophilus influenzae septicemia/meningitis to children who have sickle cell anemia (SS) has been determined to be greater than that seen among normal infants. Of ten bacteriologically proven cases, eight episodes of infection were observed among 234 children with sickle cell anemia (645 person-years), who were less than 5 years of age. There was one case per 69 infants with sickle cell anemia who were less than 18 months old and one case per 36 children with sickle cell anemia between 19 and 59 months of age. Unexpectedly, two infections occurred among 224 children (824 person-years), aged 5 to 9 years; both died. Contrary to the rapid clinical course of pneumococcal infections in children with sickle cell anemia H influenzae septicemia was regularly heralded by a greater than 24-hour prodrome of upper respiratory tract infection, low-grade fever, and otitis media. Three (30%) preventable deaths occurred. Antibiotic therapy for the febrile child with sickle cell anemia must be predicated on the known 400-fold increased risk of pneumococcal septicemia in those less than 5 years old and the fourfold risk of H influenzae septicemia in those less than 9 years of age.

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