Characteristics of Sickle Cell Disease Children Having Elevated Thrombin Potential

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4762-4762
Author(s):  
Denis F Noubouossie ◽  
Phu-Quoc Le ◽  
Laurence Rozen ◽  
Dominique Willems ◽  
Mahadeb Bhavna ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Cell Disease ◽  
Normal Children ◽  
Clotting System ◽  
Younger Age ◽  
The Mean ◽  
D Dimer ◽  
Age Category

Abstract Abstract 4762 Introduction: Abnormalities of the clotting system are often observed in sickle cell disease (SCD). In addition to activation of coagulation, increased thrombin generation (TG) has recently been demonstrated in SCD children Aim of the study: To characterize the group of SCD children with increased TG in terms of clinical and biological parameters. Material and methods: TG was performed in the platelet-poor plasma of 97 SCD children at steady-state and 80 controls aged between 2 and 20 years. TG was triggered using 1 pM tissue factor and 4μM synthetic phospholipids with thrombomodulin to activate the protein C/protein S anticoagulant pathway. The Endogenous Thrombin Potential (ETP) and the peak height were analyzed. As these parameters increase with age in normal children, controls were distributed in 4 categories of age: [2–5], [6–10], [11–15] and [16–20] years. The mean ETP and the mean peak were calculated for each age category. A ratio for ETP (r ETP) and a ratio for the peak (r Peak) were defined for each control and patient as follows: individual ETP/ mean ETP and individual peak/ mean peak according to age category. Overall mean of r ETP and r Peak was then calculated such as to eliminate bias due to age. This calculated mean was 1.00 (0.39 – 1.61) for r ETP and 0.99 (0.28 – 1.81) for r Peak in controls. TG was considered abnormal if r ETP or r Peak value was above the mean + 2SD of controls (r ETP≥ 1.62 and r Peak≥ 1.82). Clinical and laboratory parameters were compared between SCD children having normal or increased ratios using the Mann Whitney test for numbers or the Fisher's exact test for proportions. P < 0.05 was considered significant. Results and Discussion: Overall 48 (49.4 %) patients showed either high r ETP or high r Peak whereas both parameters were increased in 31 (31.9 %) patients. As shown in Tables I and II, SCD children with elevated ratios were characterized by a younger age, shorter duration of hydroxyurea (HU) treatment, lower total hemoglobin level, higher reticulocyte and monocyte counts, higher LDH and D-dimer levels and a trend to increased procoagulant microparticle level (PMP) as compared with those having normal ratios. The higher D-dimer level in the group with abnormal ratios indicates that these children also manifest a higher degree of coagulation activation than those with normal ratios. Differences observed with markers of hemolysis are consistent with other reports suggesting a link between hypercoagulability and high hemolytic rate in SCD. The borderline significance of PMP is probably due to the use of exogenous phospholipids in TG which reduces the sensitivity of the test to endogenous phospholipids at the surface of PMPs. Conclusion: According to our study, Elevated Thrombin Potential is more frequently encountered in SCD children of younger age, with a shorter duration of HU treatment and with increased rate of hemolysis. These observations together with elevated D-dimer level seem to characterize SCD children with a hypercoagulable state. Disclosures: No relevant conflicts of interest to declare.

Timing of the Initiation of Hydroxyurea and Hematologic Outcomes in Patients with Sickle Cell Disease (SCD)

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1004-1004
Author(s):  
Shaina Willen ◽  
Nirmish Shah ◽  
Courtney Thornburg ◽  
Jennifer Rothman
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Significant Relationship ◽  
Medical Center ◽  
Fetal Hemoglobin ◽  
Clinical Severity ◽  
Cell Disease ◽  
Younger Age ◽  
The Mean

Abstract Abstract 1004 Hydroxyurea (HU) is approved for use in adults with Sickle Cell Disease (SCD) and increases the production of fetal hemoglobin (HbF). Increased HbF is associated with decreased clinical severity in adults and children with SCD, such as decreased numbers of vaso-occlusive events, transfusions, and hospitalizations. Higher HbF at initiation of HU is predictive of HbF response, but association between age of hydroxyurea initiation and HbF response has not been investigated. We hypothesize that starting hydroxyurea at an early age may improve hematological and clinical response. In order to determine if younger age at hydroxyurea initiation affects the percentage of HbF achieved with hydroxyurea, we conducted a retrospective cohort study. We identified subjects enrolled in the Duke University Medical Center Comprehensive Sickle Cell program who initiated hydroxyurea when they were less than 17.99 years of age and were prescribed hydroxyurea for at least six months. The following data were abstracted from the medical record between December 1996 and April 2011: age, hemoglobin, percentage HbF, and mean corpuscular volume (MCV) at start of HU and at maximum tolerated dose (MTD) of HU therapy. The correlation coefficient and p-values for various parameters were calculated. Seventy-three patients (41 males and 32 females) were included in the analysis. The mean age at hydroxyurea initiation was 5.5 years (1.2–14.1). The mean hydroxyurea dose at MTD was 28.6 ± 3.2 mg/kg/day. At initiation, the mean hemoglobin was 8.2 ± 1.2 g/dL, the mean MCV was 83±7.4 fl and mean HbF was 10 ± 5.7%. At MTD, the mean hemoglobin was 9.4 ± 1.1 g/dL, the mean MCV was 99 ± 11.1 fl, and the mean HbF was 21.7 ± 9.4%. As expected, at MTD, an elevated MCV was correlated with elevated fetal hemoglobin (r2= 0.19, p= 0.0001) [Table 1]. There was a statistically significant relationship between the age at HU initiation and the HbF at MTD (r2= 0.08, p= 0.015) [Figure 1] as well as the age at HU initiation and the hemoglobin at MTD (r2= 0.19, p= 0.016). The relationship between the age at starting HU and the overall change in HbF (DHbF) was not statistically significant (r2= 0.01, p= 0.41). There was not a statistically significant relationship between age at HU initiation and the MTD of HU (r2= 0.003, p= 0.61). The 6 patients started on HU at age less than 2 years (mean 1.5 ± 0.3 years) maintained a mean elevated HbF of 19.1 ± 5% at last documented follow-up with follow-up ranging from 1.4–13 year of uninterrupted hydroxyurea use. Starting hydroxyurea therapy at a younger age appears to improve HbF response as measured at MTD, although there is variability in the level of fetal hemoglobin attained. There is not an association seen with the DHbF or dose at MTD and age at hydroxyurea initiation. In summary, starting hydroxyurea at a younger age, when HbF is >20%, leads to persistence of HbF production and overall improvement in hematological efficacy. This was not simply the result of achieving MTD at a younger age before physiologic decline of HbF. Disclosures: Off Label Use: Hydroxyurea for complications of sickle cell disease in pediatrics. Shah:Eisai: Research Funding; Adventrx: Consultancy.

Microparticles As Biomarkers Of Osteonecrosis Of The Hip In Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2226-2226
Author(s):  
Anne M Marsh ◽  
Raymond Schiffelers ◽  
Ginny Gildengorin ◽  
Frans A Kuypers ◽  
Carolyn Hoppe
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Vascular Occlusion ◽  
Predictive Biomarker ◽  
Acute Chest Syndrome ◽  
Mobility Limitations ◽  
Cell Disease ◽  
The Past ◽  
D Dimer

Abstract Introduction Sickle cell disease (SCD) is the most common cause of osteonecrosis of the femoral head (ONFH) in children. ONFH is a debilitating condition that is associated with mobility limitations, chronic pain, and an impaired quality of life. While the mechanisms that cause ONFH remain unknown, ischemia from recurrent microvascular occlusion is likely to play a role. Vascular occlusion may result directly from obstruction by sickled cells, or indirectly via complex interdependent pathways characterized by sustained endothelial activation, chronic inflammation, and coagulation. Microparticles (MP) are small, cell membrane-derived vesicles generated in response to cellular activation, injury or apoptosis. MPs have emerged as potential modulators of inflammation and thrombosis and have been found to be elevated in patients with ONFH in the general population. Objective This pilot study examined whether microparticle levels in patients with SCD who have ONFH differ from SCD patients without ONFH, as well as healthy African American (AA) controls. Methods Subjects were recruited at their baseline status and were excluded if they had been transfused within the past 30 days, hospitalized for a vaso-occlusive pain episode, acute chest syndrome, fever or surgery within the past 30 days, or had bony lesions of the femur or hip due to causes unrelated to SCD. For MP analysis, whole blood was collected in sodium citrate tubes and centrifuged for 15 minutes at 1500 x g at 20° C to generate platelet poor plasma. Aliquots of the plasma were immediately frozen and stored at -80° C until the time of MP analysis. 300 μl samples were diluted in PBS and centrifuged at 10000 x g for 1hr and the supernatant was centrifuged at 100,000 x g for 2 hr. The pellet was re-suspended in 1 mL of PBS and subjected to nanoparticle-tracking analysis to determine concentration and size. Additional laboratory biomarkers of inflammation and coagulation, including highly-sensitive C-reactive protein (hs-CRP), von Willebrand factor antigen (vWF Ag), tissue factor (TF), and D-dimer were analyzed for differences between groups. Analysis of variance was used to compare MP and biomarker levels between the three groups. The institutional review board at Children's Hospital & Research Center Oakland approved the study protocol and written informed consent was obtained from all participants. Results Characteristics of the 30 subjects enrolled are shown in Table I. Total microparticle levels in ONFH(+) patients were 2.3-fold higher than in ONFH(-) patients, and 2.5-fold higher than in AA controls (Figure 1). Mean MP levels for ONFH(+) patients, ONFH(-) patients, and AA controls were 4.55 x 1010, 1.99 x 1010, and 1.85 x 1010, respectively. Microparticle levels in ONFH(-) SCD patients did not differ from AA controls. There were no statistically significant differences in hsCRP, vWF Ag, TF, or D-dimer levels between the ONFH(-) and ONFH(+) groups. Conclusions The results of this study demonstrate significantly elevated MP levels in individuals with SCD who have ONFH. Additional studies are needed to better understand the mechanistic effects of MPs on the development of ONFH and to determine whether MP levels may be useful as a predictive biomarker for early disease detection. This publication was supported by NIH/NCRR UCSF-CTSI Grant Number UL1 RR024131. Disclosures: No relevant conflicts of interest to declare.

Daytime and Nocturnal Hypoxemia Are Related With Hemolysis In Adults With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2229-2229
Author(s):  
Ana Carolina Cabanas-Pedro ◽  
Sandra Satiko Matsuda, ◽  
Suely Roizenblatt ◽  
Joao Roberto Reinfelderon ◽  
Sergio Tufik ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Cell Disease ◽  
Clinical Complications ◽  
Nocturnal Hypoxemia ◽  
Previous Stroke ◽  
The Mean ◽  
De Medicina

Abstract Introduction Different studies had shown that nocturnal hypoxemia is associated with clinical complications in children with sickle cell disease (SCD), and, more recently, iron availability was related with nocturnal oxymetry in these children. However, there are few studies about this subject in adults with SCD, despite the fact that nocturnal hypoxemia occurred in 60% of the patients. We aimed to evaluate daytime and overnight hypoxia and its influence on clinical and laboratorial parameters in adults with SCD. Patients and Methods 82 steady state patients with SCD followed at Anemia Out-Patient Clinic from Escola Paulista de Medicina/UNIFESP were invited to this study. This study was approved by Ethical Committee, and all patients agreed in participate. The daytime oximetry (SpO2) utilized was the mean of at least 3 measurements by pulse oximeter during regular appointments at the out-patient clinic. The nocturnal oximetry data (basal SpO2 and mean nocturnal SpO2) were obtained during polysomnography (PSG). Besides clinical evaluation, routine laboratory tests performed near the realization of the PSG were analyzed. The data was analyzed by parametric and non-parametric tests, with α=5%. Results The median (range) age was 28 (18-69) years, and 44 (54%) were female. Moderate sleep apnea was diagnosed in 11% of the patients. The mean of SpO2 obtained for each measurement was: daytime SpO2: 95.1±4.3, basal SpO2: 94.3±3.5, and mean nocturnal SpO2: 93.3±3.6; with statistical significance between daytime and basal SpO2 (X2=17.0; p<0.001) and between daytime and mean nocturnal SpO2 (X2=10.3; p=0.001). The percentage of patients with hypoxemia (SpO2 ≤ 90%) varied according with the measurement: 14.1% at daytime SpO2, 13.7% at basal SpO2, and 20.0% at mean nocturnal SpO2. However, 55% of the patients achieved hypoxemia level during PSG. Association between daytime SpO2 and previous stroke was observed (X2=4.0; p=0.04). Patients with daytime and basal SpO2 ≤ 90% had higher lactate dehydrogenase (LDH) (634.3±114.9 and 538.0±198.3) compared to the ones with SpO2>90% (384.0±171.6 and 375.7±171.9; p<0.001 and p=0.02, respectively). Reticulocyte count was more elevated in patients with SpO2 ≤ 90% (daytime SpO2: 277,639.2±96,108.4; basal SpO2: 290,722.9±87,791.2 and mean nocturnal SpO2: 260,582.1±83,532.8) when compared to the ones with SpO2 >90% (185,537.3±90,445.7; 188,432.2±101,277.1 and 189,194.1±104,478.8; p=0.01; p=0.01 and p=0.03, respectively). No correlation was found within iron and SpO2. Conclusion Daytime and nocturnal hypoxemia showed effect on hemolytic markers in adults with SCD. Daytime SpO2 presented an association with previous stroke and considering that it was also observed an association between daytime and nocturnal SpO2, we suggest that daytime SpO2determination should be monitored in each appointment and can be used as a predictor of SCD severity Supported by CAPES/SUS and AFIP. Disclosures: No relevant conflicts of interest to declare.

Determinants Of Heme-Oxygenase-1 Upregulation In Patients With Sickle Cell Disease

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 2235-2235 ◽  
Author(s):  
Olufolake Adisa ◽  
Benjamin Yaw Owusu ◽  
Yijuan Hu ◽  
Samit Ghosh ◽  
Fang Tan ◽  
...  
Keyword(s):  
Steady State ◽  
Sickle Cell Disease ◽  
Heme Oxygenase ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Dinucleotide Repeat ◽  
Acute Chest Syndrome ◽  
Heme Oxygenase 1 ◽  
Cell Disease ◽  
The Mean

Abstract Inflammation is a cardinal component of the pathogenesis of sickle cell disease (SCD). Increased plasma concentration of the inflammatory agonist hemin increases the odds of acute chest syndrome (ACS) in children with SCD (Adisa et al., Br. J Haematol, 2013). In addition, free hemin promotes the development of a lethal ACS-like disease in transgenic sickle mice (Ghosh et al., J Clin Invest, 2013). Hemin degradation is controlled by the rate-limiting enzyme heme oxygenase-1 (HO-1). Polymorphism of a (GT)n dinucleotide repeat in the HO-1 promoter, which enhances expression of the gene, is associated with lower rates of hospitalization for ACS in children. Over-expression of HO-1 reduces stasis in a mouse model of SCD vaso-occlusion. However, the role of plasma HO-1 in SCD patients is entirely unknown. In this study, we measured steady-state plasma HO-1 in two cohorts of patients. Cohort 1 in Atlanta (n=98) consisted of children with a mean age of 10.07±0.42 years (range 2-19 years) and cohort 2 from Accra (n=80) consisted of older patients (mean age 25.30±1.0 years, range 13-58 years). The mean plasma HO-1 of both cohorts was significantly higher compared to the mean value of age- and ethnic-matched individuals with normal adult Hb; Atlanta: 10.19±5.80 vs. 2.08± 1.16, p<0.0001 and Accra: 13.7±8.14 vs. 2.57± 0.82, p<0.0001. Plasma HO-1 varied by 25-fold in both cohorts and it correlated with the white blood cell count (Atlanta: r=0.3361, p<0.0001, Accra: r=0.25, p=0.02). Fifty-four percent (n=53) of subjects in the Atlanta cohort were on hydroxyurea. The mean plasma HO-1 of this subgroup was lower (8.1 ± 4.5) compared to the hydroxyurea naïve Accra cohort (p=<0.0001). Further studies of the Accra cohort revealed significant correlations between HO-1 and multiple markers of vascular inflammation; sICAM-1(r=0.2794, p=0.03, n=60), sE-selectin (r= 0.4209, p=0.0017, n=58) and sP-selectin (r=0.3855, p=0.0028, n=58). The number of the (GT)n dinucleotide in the HO-1 promoter ranged 17 to 45; the distribution was trimodal with peaks at 23, 30 and 41 repeats. The overwhelming majority of patients had medium and large size alleles that are generally hypo-response to induction. Plasma HO-1 level correlated with the length of the (GT)n dinucleotide repeat (p=0.003, n=80). In a multivariable regression model, WBC, sICAM-1, sE-selectin and sP-selectin accounted for 13.4% of the total variance of plasma HO-1 level, and the (GT)n polymorphism accounted for 9.8%. In conclusion, the concentration of plasma HO-1 is generally raised among SCD patients at steady-state. However, a large proportion of patients have a relatively modest level that is probably inadequate to counter the severity of inflammation typical of SCD, due in part to a hypo-responsive HO-1 promoter. Therapeutic strategies that complement induction of the endogenous HO-1 gene may be critical to ameliorate inflammation in SCD. Disclosures: No relevant conflicts of interest to declare.

Type-2 Phosphatidylserine (PS)-Positive Erythrocytes and Their Association with Markers of Hemolysis and Hemostatic Activation in Children with Sickle Cell Disease (SCD)

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 943-943
Author(s):  
Yamaja B. Setty ◽  
Suhita Gayennebetal ◽  
Nigel S. Key ◽  
Marie Stuart
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Red Cells ◽  
Red Cell ◽  
Cell Disease ◽  
Activation Markers ◽  
D Dimer

Abstract Introduction: Type-2 phosphatidylserine (PS)-positive red cells are a subpopulation of erythrocytes that are highly positive for PS, contain low levels of fetal hemoglobin, are specific for sickle cell disease (SCD) and have been identified in the dense red cell fraction. Studies have implicated PS-positive red cells in enhancing anemia due to phagocytosis and hemolysis. Shielding of red cell PS by diannexin, a synthetic homodimer of human annexin-V, has been demonstrated to provide protection against hemolysis and prevent activation of prothrombinase. Methods: Using flow cytometry, we measured the levels of type-1 (red cells with low PS positivity) and type-2 PS-positive red cells in 50 children with SCD (31 with HbSS and 19 with HbSC), and assessed their association with various markers of hemolysis and hemostatic activation. Markers of hemolysis evaluated included plasma lactate dehydrogenase (LDH), reticulocyte count, and hemoglobin. Whole blood tissue factor (WBTF), pro-thrombin fragment F1+2, and D-dimer were evaluated as markers of hemostatic activation. Results: We demonstrate that the levels of type-2 PS-positive red cells are significantly increased in HbSS patients (1.37 ± 0.97%, p<0.01) compared to children with HbSC disease (0.32 ± 0.21%) and age- and race-matched controls (0.15 ± 0.15%, n=19). WBTF and D-dimer showed significant associations with both type-1 and -2 red cells with no significant differences in the strength of their association. However, significantly greater correlations were noted between type-2 PS red cells and hemolytic markers compared to those noted with type-1 (Steiger's Z=3.05 to 4.59, p<0.01). In addition our in vitro studies demonstrate increased osmotic fragility of these red cells. Table 1. Association of PS-positive RBCs with markers of hemolysis and hemostatic activation Biomarker Type-1 PS-positive RBCs Type-2 PS-positive RBCs Markers of Hemolysis LDH r = 0.44, p<0.002 r = 0.63, p<0.00001 % Reticulocyte r = 0.43, p=0.002 r = 0.66, p<0.00001 Hemoglobin r =-0.35, p=0.014 r =-0.63, p<0.00001 Markers of Hemostatic Activation WBTF r = 0.41, p=0.008 r = 0.56, p<0.0002 F1+2 r = 0.26, p=0.07 r = 0.31, p<0.03 D-dimer r = 0.46, p<0.001 r = 0.56, p<0.0005 Conclusions: Type-2 PS-positive red cells are elevated in SCD and the number of these cells correlates significantly with both markers of hemolysis and hemostasis. These findings provide a patho-physiologic link between the intravascular hemolytic milieu of SCD and the hemostatic perturbations previously noted in this disease. Disclosures No relevant conflicts of interest to declare.

Erythrocytapheresis in Sickle Cell Disease Lead to An Elective Reduction of Erythrocytes-Derived Blood Microparticles

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 2657-2657
Author(s):  
Emna Mahfoudhi ◽  
Yann Lecluse ◽  
Françoise Driss ◽  
Claire Flaujac ◽  
Nicole Casadevall ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Red Cells ◽  
Cell Disease ◽  
Positive Effects ◽  
Significant Difference ◽  
Before And After ◽  
The Mean ◽  
Student Test

Abstract Abstract 2657 Introduction: Erythocytapheresis is a highly effective procedure used in the management of both acute and chronic complications of sickle cell disease (SCD). Indeed, exchange transfusion is recommended as a part of the initial treatment of vaso-occlusive stroke in children. Red cells exchange can also be proposed in primary and secondary stroke prevention in order to maintain a low level of HbS. Microparticles (MPs) are small vesicles released from cells after activation or apoptosis. Microparticles number is increased in SCD both at the steady state and during crisis. The majority of these microparticles are originated from erythrocytes and platelets. In SCD, erythrocytes MPs are strongly correlated with hemolysis and activation of coagulation. In this study, we aimed to measure the level of total, platelets-derived and erythrocytes-derived MPs in patients with SCD undergoing erythrocytapheresis; we compared the level of MPs before and after red cells exchange in order to evaluate if the reduction of stroke observed in patients undergoing erythrocytapheresis could be due to a specific decrease in erythrocytes-derived MPs known to be implicated in coagulation activation in this disease. Materials and Methods: After informed consent, 24 samples were harvested on a tube containing buffered sodium citrate from 22 patients with SCD undergoing erythrocytapheresis. For each patient, a sample was collected before and just after the exchange. 20 samples from donor with neither anemia nor coagulation disorders were used as controls. Each sample was centrifugated at 1500g during 15 mn, the supernatant was collected and centrifugated 2mn at 13000g at 20°C and then frozen at -80°C until analysis. For MPs detection, 38mL of the thawed supernatant was labelled with 5mL of 10X Annexine V buffer, 1mL of Annexine V-FITC, 1 mL of anti-GPA-PE and 5 mL of anti-CD41-APC. 5mL of calibrated beads at known concentration were added to 345 mL of 1X Annexine buffer just before analysis on the MoFlow cytometer (Beckman Coulter). The Megamix beads system was used in order to delimitate the FSC/SSC gate of MPs. Results: Total number of plasma MPs (1755/mL vs 273), erythrocytes-derived MPs (174/mL vs 8) and platelets-derived MPs (1520/mL vs 236) were significantly increased in SCD patients in comparison with controls. For SCD patients undergoing erythrocytapheresis, the mean HbS level was respectively 52% and 24% before and after red cells exchange. No significant difference in the total hemoglobin concentration was noted. The mean number of MPs did not differ before and after the exchange (1755/mL versus 1940/mL respectively, student test p>0.05). The mean number of platelets-derived MPs remained stable before and after the exchange (1520/mL versus 1250mL, student test, p>0.05). In sharp contrast, we observed a significant clearance of the erythrocytes-derived MPs in the plasma of SCD patients after red cells exchange (mean number of GPA+-MPs: 174/mL before exchange versus 77mL after, student test, p<0.05). However, we could also observe a great variation of the number of erythrocytes and platelets-derived MPs between the different patients. Conclusion: The number of erythrocytes-derived MPs decreased specifically after red cells exchange, in contrast with the total and the platelets-derived MPs which remained stable; this selective decrease in the GPA+-MPs of SCD patients could be due to a reduction in the total number of red cells containing a high HbS content in the circulation, because of their replacement by normal erythrocytes that have a far lower capacity to produce MPs. It has been recently shown that in SCD, GPA+-MPs are specifically correlated with coagulation and fibrinolysis activation, underlying the fact that a direct link exists between hemolysis, erythrocytes- derived MPs liberation and procoagulant state. The specific clearance of the GPA+-MPs after red cells exchange could partially explain the positive effects of this procedure in primary and secondary prevention of stroke in SCD. However, that GPA+-MPs remained statistically increased after red cells exchange in comparison with controls; whether a low number of post-exchange MPs could be correlated with a better outcome is actually under investigation. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Prevalence and Predisposing Factors of Atrial Fibrillation in a Multi-Ethnic Society: The Impact of Racial Differences in Bahrain

2011 ◽  
Vol 4 ◽  
pp. OJCS.S8032 ◽  
Author(s):  
Taysir Garadah ◽  
Saleh Gabani ◽  
Mohamed Al Alawi ◽  
Ahmed Abu-Taleb
Keyword(s):  
Atrial Fibrillation ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Middle Eastern ◽  
Predisposing Factors ◽  
Cell Disease ◽  
Clinical Events ◽  
History Of ◽  
The Mean ◽  
One Year

Background The prevalence and epidemiological data of atrial fibrillation (AF) among multi-ethnic populations is less well studied worldwide. Aim Evaluation of the prevalence and predisposing factors of AF in patients who were admitted to acute medical emergencies (ER) in Bahrain over the period of one year. Methods Two hundred and fifty three patients with onset of AF were studied. The mean difference of biochemical data and clinical characteristics between Middle Eastern (ME) and sub continental (SC) patients was evaluated. The odds ratio of different predisposing factors for the development of clinical events in AF patients was assessed using multiple logistic regression analysis. Results Out of 7,450 patients that were admitted to ER over one year, 253 had AF based on twelve leads Electrocardiogram (ECG), with prevalence of 3.4%. In the whole study, the mean age was 59.45 ± 18.27 years, with 164 (65%) male. There were 150 ME patients (59%), and 107 (41%) SC, 55 (22%) were Indian (IND) and 48 (19%) were South Asian (SA). In the whole study clinical presentation was of 48% for palpitation, pulmonary edema was of 14%, angina pectoris on rest of 12%, 10% had embolic phenomena, 6% had dizziness, and 7% were asymptomatic. The odds ratio of different variables for occurrence of clinical events in the study was positive of 2.2 for history of hypertension, 1.8 for sickle cell disease, 1.2 for high body mass index (BMI) >30, 1.1 for mitral valve disease. The ME patients, compared with SC, were older, had significantly higher body mass index, higher history of rheumatic valve disease, sickle cell disease with high level of uric acid and lower hemoglobin. The history of hypertension, DM and smoking was higher among the SC patients. The rate of thyroid disease was equal in both groups. Conclusion The prevalence of atrial fibrillation was 3.4% with male predominance of 65%. Patients of sub continental origin were younger with a significantly high history of hypertension and ischemic heart disease. The patients of Middle Eastern origin had significantly high rate of rheumatic heart disease, and sickle cell disease. The history of hypertension was the most important independent clinical predictor of adverse events in patients presented with AF.

scholarly journals Ischemic Stroke in Children and Young Adults with Sickle Cell Disease (SCD) in the Post-STOP Era

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 68-68 ◽  
Author(s):  
Janet L. Kwiatkowski ◽  
Julie Kanter ◽  
Heather J. Fullerton ◽  
Jenifer Voeks ◽  
Ellen Debenham ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Stroke Prevention ◽  
Cell Disease ◽  
Clinical Series ◽  
The Mean

Abstract Background: The Stroke Prevention Trial in Sickle Cell Anemia (STOP) and Optimizing Primary Stroke Prevention in Sickle Cell Anemia (STOP 2) established routine transcranial Doppler ultrasound (TCD) screening with indefinite chronic red cell transfusions (CRCT) for children with abnormal TCD as standard of care. To identify children at high-risk of stroke, annual TCD screening is recommended from ages 2 to 16 years, with more frequent monitoring if the result is not normal. A reduction in stroke incidence in children with SCD has been reported in several clinical series and analyses utilizing large hospital databases when comparing rates before and after the publication of the STOP study in 1998. We sought to determine the rate of first ischemic stroke in a multicenter cohort of children who had previously participated in the STOP and/or STOP 2 trials and to determine whether these strokes were screening or treatment failures. Subjects and Methods: Between 1995 and 2005, STOP and STOP 2 (STOP/2) were conducted at 26 sites in the US and Canada. These studies included 3,835 children, ages 2 to 16 y with SCD type SS or S-beta-0-thalassemia. Participation in STOP/2 ranged from a single screening TCD to randomization. STOP 2 also had an observational arm for children on CRCT for abnormal TCD whose TCD had not reverted to normal. The Post-STOP study was designed to follow-up the outcomes of children who participated in one or both trials. 19 of the 26 original study sites participated in Post-STOP, contributing a total of 3,539 (92%) of the STOP/2 subjects. After exit from STOP/2, these children received TCD screening and treatment according to local practices. Data abstractors visited each clinical site and obtained retrospective data from STOP/2 study exit to 2012-2014 (depending on site) including follow-up TCD and brain imaging results, clinical information, and laboratory results. Two vascular neurologists, blinded to STOP/2 status and prior TCD and neuroimaging results, reviewed source records to confirm all ischemic strokes, defined as a symptomatic cerebral infarction; discordant opinions were resolved through discussion. For the first Post-STOP ischemic stroke, prior TCD result and treatment history subsequently were analyzed. Results: Of the 3,539 subjects, follow-up data were available for 2,850 (81%). Twelve children who had a stroke during STOP or STOP2 were excluded from these analyses resulting in data on 2,838 subjects. The mean age at the start of Post-STOP was 10.5 y and mean duration of follow-up after exiting STOP/2 was 9.1 y. A total of 69 first ischemic strokes occurred in the Post-STOP observation period (incidence 0.27 per 100 pt years). The mean age at time of stroke was 14.4±6.2 (median 13.8, range 3.5-28.9) y. Twenty-five of the 69 patients (36%) had documented abnormal TCD (STOP/2 or Post-STOP) prior to the stroke; 15 (60%) were receiving CRCT and 9 (36%) were not (treatment data not available for 1 subject). Among the 44 subjects without documented abnormal TCD, 29 (66%) had not had TCD re-screen in the Post-STOP period prior to the event; 7 of these 29 (24%) were 16 y or older at the start of Post-STOP, which is beyond the recommended screening age. Four of the 44 (9%) patients had inadequate TCD in Post-STOP (1 to 10.7 y prior to event). Six (14%) had normal TCD more than a year before the event (1.2 - 4 y); all but one of these children were younger than 16 y at the time of that TCD. Only 5 (11%) had a documented normal TCD less than 1 year prior to the event. Conclusions: In the Post-STOP era, the rate of first ischemic stroke was substantially lower than that reported in the Cooperative Study of Sickle Cell Disease, prior to implementation of TCD screening. Many (39%) of the Post-STOP ischemic strokes were associated with a failure to re-screen according to current guidelines, while only 11% occurred in children who had had recent low-risk TCD. Among those known to be at high risk prior to stroke, treatment refusal or inadequate treatment may have contributed. While TCD screening and treatment are effective at reducing ischemic stroke in clinical practice, significant gaps in screening and treatment, even at sites experienced in the STOP protocol, remain to be addressed. Closing these gaps should provide yet further reduction of ischemic stroke in SCD. Disclosures No relevant conflicts of interest to declare.

scholarly journals Sexual Maturity in Adolescents Suffering from Sickle Cell Disease: A Cross-sectional Study

2021 ◽  
Author(s):  
Vijay Shah ◽  
Akash Patel ◽  
Praful Bambharoliya ◽  
Jigisha Patadia
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sexual Maturity ◽  
Tanner Stage ◽  
Cross Sectional Study ◽  
Reproductive Capacity ◽  
Sectional Study ◽  
Cell Disease ◽  
Cross Sectional ◽  
The Mean

Introduction: Sickle Cell Disease (SCD) is an inherited chronic haemolytic anaemia. The diseased person suffers from various complications such as anaemia, frequent infection, fever, hand-foot syndrome, stroke, etc. Puberty changes includes the appearance of the secondary sexual characteristics, increase in height, change in body composition and development of reproductive capacity. Aim: To study the sexual maturity and effect of multiple blood transfusions in adolescents suffering from SCD. Materials and Methods: It was a cross-sectional study conducted on 35 adolescents of age group 11 to 15 years, suffering from SCD. Study was conducted over a period of six months from March 2018 to September 2018 at Department of Paediatrics. SCD was diagnosed by Haemoglobin (Hb) electrophoresis. Weight and height were measured of all the participants. For assessing the sexual maturity, Tanners staging was used. Unpaired t-test was done for data analysis. Results: The mean age of the patients was 13.03±1.7 years. There were 25 males and 10 females. The mean age of male patients between Tanner stage 2(14.63±0.52 years) and Tanner stage 3 (14.75±0.5 years) was significantly higher than the Indian data for males (11.3 and 12.8 years, respectively). The mean age of female patients between Tanner stages 2 (13.5±2.12 years) and Tanner stage 3 (14.33±1.16 years) was higher than the Indian reference data for girls (10.2 and 11.6 years respectively). Conclusion: This study concluded that adolescents with SCD were significantly shorter in height and weight than the standard reference population. Sexual maturity is delayed in adolescents with sickle cell anaemia.

scholarly journals Case Report: Acute Stroke in Young Adult Patient with Moyamoya Syndrome Secondary to Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 13-13
Author(s):  
Oladipo Cole ◽  
Asia Filatov ◽  
Javed Khanni ◽  
Patricio Espinosa
Keyword(s):  
Case Report ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Moyamoya Disease ◽  
Conflicts Of Interest ◽  
Acute Chest Syndrome ◽  
African American Female ◽  
Moyamoya Syndrome ◽  
Cell Disease ◽  
Radiographic Findings

Moyamoya disease, well described in literature, is a chronic cerebrovascular occlusive disorder. It is characterized by progressive stenosis/occlusion of the terminal portions of the internal carotid arteries (ICA) and the proximal portions of the middle cerebral arteries (MCA). Less frequently described is Moyamoya syndrome, the name given to radiographic findings consistent with Moyamoya disease, but with an identifiable cause. The diseases associated with Moyamoya Syndrome include Sickle Cell Disease (SCD), Thalassemias, and Down's Syndrome to name a few. Common complications of Moyamoya include both ischemic and hemorrhagic strokes. Upon literature review, Moyamoya syndrome caused by SCD is not well described. When it is, the discussion is centered around the pediatric patient population and surgical management. Our case report describes a 22-year-old African American female with SCD who initially presented with Acute Chest Syndrome. Her hospital course was complicated by development of overt debilitating neurologic deficits. Subsequently, she was found to have Moyamoya Syndrome on neuroimaging. She was successfully treated with medical management without any surgical intervention. This case highlights the necessity of thorough examination, differential diagnosis, imaging findings, and consideration of predisposing syndromes in the work-up for Moyamoya syndrome; especially individuals with Sickle Cell Disease. Disclosures No relevant conflicts of interest to declare.

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