G6PD deficiency, absence of α-thalassemia, and hemolytic rate at baseline are significant independent risk factors for abnormally high cerebral velocities in patients with sickle cell anemia

Blood ◽  
2008 ◽  
Vol 112 (10) ◽  
pp. 4314-4317 ◽  
Author(s):  
Françoise Bernaudin ◽  
Suzanne Verlhac ◽  
Sylvie Chevret ◽  
Martine Torres ◽  
Lena Coic ◽  
...  

AbstractStroke is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). This study aimed at defining predictive factors for abnormally high velocities (≥ 2 m/sec) based on the Créteil pediatric sickle cell anemia (SCA) cohort composed of 373 stroke-free SCA children. α genes and β-globin haplotypes were determined. Biologic parameters were obtained at baseline. α-thalassemia was present in 155 of 325 and G6PD deficiency in 36 of 325 evaluated patients. TCD was abnormal in 62 of 373 patients. Multivariate logistic regression analysis showed that G6PD deficiency (odds ratio [OR] = 3.36, 95% confidence interval [CI] 1.10-10.33; P = .034), absence of alpha-thalassemia (OR = 6.45, 95% CI 2.21-18.87; P = .001), hemoglobin (OR per g/dL = 0.63, 95% CI 0.41-0.97; P = .038), and lactate dehydrogenase (LDH) levels (OR per IU/L = 1.001, 95% CI 1.000-1.002; P = .047) were independent risk factors for abnormally high velocities. This study confirms the protective effect of alpha-thalassemia and shows for the first time that G6PD deficiency and hemolysis independently increase the risk of cerebral vasculopathy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 430-430 ◽  
Author(s):  
Francoise Bernaudin ◽  
Suzanne Verlhac ◽  
Lena Coïc ◽  
Cecile Arnaud ◽  
Annie Kamdem ◽  
...  

Abstract Background Predicting the severity of sickle cell anemia (SCA) is important for providing better informed genetic counseling and for better targeting of intensive therapies. Stroke is the most severe complication in children with SCA and is predicted by abnormally high cerebral velocities by transcranial doppler (TCD). We attempted to define the risk factors associated with high velocities. Methods This study concerned the Créteil pediatric SCA cohort, composed of newborn patients, screened and followed at our Center since birth, and of patients secondarily referred to the Center because of the severity of their disease. Time-averaged mean of maximum velocities (TAMMX) higher than 200 cm/sec were considered as abnormal, resulting in initiation of a transfusion program initiated</DEL>. Cerebral MRI/MRA was done after the age of 5 years or earlier in case of abnormal TCD. Alpha </DEL>genes and beta-globin haplotypes were determined. Baseline biological parameters (G6PD activity; WBC, PMN, Reticulocytes, Platelets counts; Hemoglobin, Hematocrit, HbF, LDH levels; MCV; SpO2) were obtained a minimum of 3 months away from a transfusion, one month from a painful episode, after 18 months of age and, before intensive therapy. Results SS children (390; 189 F, 201 M) were annually explored by TCD (n=2286) since 1992, and followed for a total of 1962 patient-years. The follow-up before initiation of intensive therapy was 1032 patient-years. Nineteen patients experienced an overt stroke. TCD was abnormal in 65 of 390 patients (17%). MRI (n=850) was performed in 268 patients, was abnormal in 86 cases and showed silent infarcts in 67 of 249 patients (27%). Silent infarcts were seen in 33% of patients with abnormal TCD. Alpha genes study, available in 336 patients, demonstrated alpha-thalassemia in 158 patients (47%): 31 had a deletion of 2 genes (7.9%) and 127 of 1 gene (32.6%). G6PD deficiency was present in 26 of 228 evaluated patients (11%). Beta-globin haplotypes studied in 316 patients were Car/Car in 125 (40%), Ben/Ben in 76 (24%), Sen/Sen in 30 (9%) and, “other” in 85 (27%). Univariate analysis showed that the risk of abnormally high velocities was not related to sex, beta-globin haplotypes, pain and acute chest syndrom rates, WBC, PMN, platelets counts, HbF level and SpO2 but was significantly associated with the absence of alpha-thalassemia (p< 0.001), G6PD deficiency (p=0.012), low Hb and Ht levels (p< 0.001), high reticulocyte count (p=0.008), high MCV (p=0.004) and high LDH level (p<0.001). Multivariate logistic regression analysis showed that absence of alpha-thalassemia [OR= 14.5, 95% CI (2.6–79.7)], (p=0.002); G6PD deficiency [OR=6.7, 95% CI (1.7–26.1)], (p=0.006) and, LDH > 1200 UI/L [OR=4.5, 95% CI (1.5–13.5)], (p=0.007) were independent risk factors of abnormally high velocities. Conclusion This study confirms that the risk of high velocities in patients with SCA is significantly decreased by the presence of alpha-thalassemia. It shows for the first time that hemolysis is a more significant risk factor than the degree of anemia and that absence of alpha-thalassemia, G6PD deficiency and hemolysis are significant independent risk factors of cerebral vasculopathy in patients with SCA.


Life ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 1030
Author(s):  
Abu Sadat Mohammad Sayeem Bin Shahid ◽  
Tahmina Alam ◽  
Lubaba Shahrin ◽  
K. M. Shahunja ◽  
Md. Tanveer Faruk ◽  
...  

Hospital acquired pneumonia (HAP) is common and often associated with high mortality in children aged five or less. We sought to evaluate the risk factors and outcome of HAP in such children. We compared demographic, clinical, and laboratory characteristics in children <5 years using a case control design during the period of August 2013 and December 2017, where children with HAP were constituted as cases (n = 281) and twice as many randomly selected children without HAP were constituted as controls (n = 562). HAP was defined as a child developing a new episode of pneumonia both clinically and radiologically after at least 48 h of hospitalization. A total of 4101 children were treated during the study period. The mortality was significantly higher among the cases than the controls (8% vs. 4%, p = 0.014). In multivariate logistic regression analysis, after adjusting for potential confounders, it was found that persistent diarrhea (95% CI = 1.32–5.79; p = 0.007), severe acute malnutrition (95% CI = 1.46–3.27; p < 0.001), bacteremia (95% CI = 1.16–3.49; p = 0.013), and prolonged hospitalization of >5 days (95% CI = 3.01–8.02; p < 0.001) were identified as independent risk factors for HAP. Early identification of these risk factors and their prompt management may help to reduce HAP-related fatal consequences, especially in resource limited settings.


2020 ◽  
Author(s):  
Zhongzhong Liu ◽  
Wenjuan Lin ◽  
Qingli Lu ◽  
Jing Wang ◽  
Pei Liu ◽  
...  

Abstract Background: The incidences of stroke recurrence, disability, and all-cause death of patients with minor ischemic stroke (MIS) remain problematic. The aim of the present was to identify risk factors associated with adverse outcomes at 1-year after MIS in the Xi’an region of China. Methods: The cohort of this prospective cohort study included MIS patients aged 18–97 years with a National Institutes of Health Stroke Scale (NIHSS) score of ≤ 3 who were treated in any of four hospitals in Xi’an region of China between January and December 2015. The 1-year percentage of stroke recurrence, disability, and all-cause death were evaluated. Multivariate logistic regression analysis was performed to assess the association between the identified risk factors and clinical outcomes. Results: Among the 1,121 patients included for analysis, the percentage of stroke recurrence, disability, and all-cause death at 1 year after MIS were 3.4% (38/1121), 9.3% (104/1121), and 3.3% (37/1121), respectively. Multivariate logistic regression analysis identified age, current smoking, and pneumonia as independent risk factors for stroke recurrence. Age, pneumonia, and alkaline phosphatase were independent risk factors for all-cause death. Independent risk factors for disability were age, pneumonia, NIHSS score on admission, and leukocyte count. Conclusions: The 1-year outcomes of MIS is not optimistic in the Xi’an region of China, especially high percentage of disability. In this study, we found the risk factors affecting 1-year stroke recurrence, disability and, all-cause death which need further verification in the subsequent studies.


2013 ◽  
Vol 109 (02) ◽  
pp. 207-213 ◽  
Author(s):  
Savino Sciascia ◽  
Veronica Murru ◽  
Cesar Garcia-Fernandez ◽  
Giovanni Sanna ◽  
Munther Khamashta ◽  
...  

SummaryAntibodies to prothrombin in solid phase (aPT) and those to phosphatidiyserine- prothrombin complex (aPS/PT) have been suggested to strongly correlate with the presence of lupus anticoagulant (LA). As their clinical diagnostic value and true relationship with the LA remains elusive, we designed this study to evaluate the prevalence and significance of aPT and aPS/PT in a large cohort of patients with and without LA. Samples from 257 patients were included. aPT and aPS/PT were tested by ELISA. LA was tested as per the current criteria from the ISTH Subcommittee on LA-Phospholipid-dependent antibodies. aPS/PT and aPT were found in 51% and 32% of LA-positive (LA+ve) patients and in 22% and 28% of LA-negative (LA-ve) patients, respectively. Thrombosis, particularly venous thrombosis was associated with IgG aPT in the LA+ve group (p=0.0006) and in the LA-ve group (p=0.017). Antibodies to phosphatidylserine-prothrombin, either IgG and IgM were associated with thrombosis in general (p=0.0003) in particularly with venous thrombosis in the LA+ve group (p<0.0001 for IgG and p=0.025 for IgM; respectively) and the LA-ve group (p=0.028, 0.02 and 0.001, respectively). Further multivariate logistic regression analysis showed that LA and of IgG and/or IgM aPS/PT were independent risk factors for thrombosis and pregnancy loss. In conclusion, aPS/PT, but not aPT, are more frequently found in patients with LA. Their association with thrombosis seems to be independent of the presence of LA.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1651-1651 ◽  
Author(s):  
Deepika Darbari ◽  
Onyinye Onyekwere ◽  
Mehdi Nouraie ◽  
Gregory J. Kato ◽  
Caterina Minniti ◽  
...  

Abstract Abstract 1651 Background: Pain crises are the most common symptom experienced by individuals with sickle cell anemia (SCA). Frequency of pain crises varies significantly and high rate is a risk factor for higher mortality in adults with SCA. The risk factors for pain crises in children and adolescents with SCA are not completely understood. To determine factors associated with frequent severe pain crises, we analyzed the cohort of children and adolescents with SCA who were enrolled in the prospective study “The Pulmonary Hypertension and the Hypoxic Response in SCD (PUSH)”. All children were evaluated in their steady, non-crisis state. Methods: Family-reported history of number of severe pain crises in the preceding 12 months was recorded prospectively in 365 children and adolescents with SCA. Severe pain crises were defined as painful vaso-occlusive episodes requiring evaluation in Emergency Department (ED) or in-patient hospitalization. Lifetime history of red cell transfusions, echocardiography, and laboratory studies were obtained. Clinical and laboratory characteristics of study subjects who had ≥3 severe pain crises in the preceding year were compared to subjects with < 3 severe pain crises. Results: Study subject ranged in age from 3–20 years and 175 (48%) were female. Seventy two children (20 %) had ≥3 severe pain crises in the preceding year (frequent pain crisis group); 293 (80%) children had < 3 severe pain crises (infrequent pain crisis group), including 224 (61%) subjects who had no admissions/ ED visits for pain. Associated factors for frequent pain crisis included older age (odds ratio 1.2; 95% confidence interval 1.12–1.35; P <0.001) and α-thalassemia trait (odds ratio 3.22; 95% confidence interval 1.55–6.69; P =0.002) while higher steady state serum lactate dehydrogenase (LDH) was associated with infrequent pain crisis (odds ratio 0.35; 95% confidence interval 0.13–0.98; P =0.045). In a group of patients without α-thalassemia trait, older age and low LDH were linked to frequent pain crisis. Subjects in the frequent pain crisis group had higher median hemoglobin (9.0 vs. 8.5 gm/dL; p=0.003) and higher ferritin (median 455 vs. 191 ng/mL; p=0.008). Higher ferritin in the frequent pain crisis group was mirrored by the higher percentage who reported >10 lifetime transfusions (42% vs. 22%; p=0.001). Median tricuspid regurgitation jet velocity (TRV) was higher in the frequent pain crisis group (2.41 vs. 2.31; p= 0.001) but the proportion of children with TRV>2.5 was not different (19.4% vs.11.5% in infrequent crises group; p=0.09). Hydroxyurea use was not different between the groups (51% vs. 40%; p=0.08) nor was fetal hemoglobin (10% vs. 12%; p=0.2). Conclusions: The occurrence of severe pain crisis varies among children and adolescents with SCA with a large number of children experiencing no severe painful episodes. Consistent with the Cooperative Study of Sickle Cell Disease report, the risk of severe pain crisis increases with age. Individuals with α-thalassemia trait are likely to experience more frequent pain crises possibly related to higher hemoglobin concentration and viscosity. However, even after controlling for α-thalassemia trait, children and adolescents who reported more frequent severe pain crises showed evidence of less hemolysis, consistent with a hypothetical model associating the hemolytic subphenotype of SCA with less frequent vasoocclusive pain crises. Further studies are indicated to identify the molecular mechanisms of pain in sickle cell anemia. Disclosures: No relevant conflicts of interest to declare.


2022 ◽  
Author(s):  
Chengcheng Sheng ◽  
Zongxu Xu ◽  
Jun Wang

Abstract Background: Acute pancreatitis in pregnancy (APIP) with persistent organ failure (POF) poses a high risk of death for mother and fetus. This study sought to create a nomogram model for early prediction of POF with APIP patients.Methods: We conducted a cross-sectional study on APIP patients with organ failure (OF) between January 2012 and March 2021 in a university hospital. 131 patients were collected. Their clinical courses and pregnancy outcomes were obtained. Risk factors for POF were identified by univariate and multivariate logistic regression analysis. Prediction models with POF were built and nomogram was plotted. The performance of the nomogram was evaluated by using a bootstrapped-concordance index and calibration plots.Results: Hypertriglyceridemia was the most common etiology in this group of APIP patients, which accounted for 50% of transient organ failure (TOF) and 72.3% of POF. All in-hospital maternal death was in the POF group (P<0.05), which also had a significantly higher perinatal mortality rate than the TOF group (P<0.05). Univariate and multivariate logistic regression analysis determined that lactate dehydrogenase, triglycerides, serum creatinine, and procalcitonin were independent risk factors for predicting POF in APIP. A nomogram for POF was created by using the four indicators. The area under the curve was 0.875 (95% confidence interval 0.80–0.95). The nomogram had a bootstrapped-concordance index of 0.85 and was well-calibrated.Conclusions: Hypertriglyceridemia was the leading cause of organ failure-related APIP. Lactate dehydrogenase, triglycerides, serum creatinine, and procalcitonin were the independent risk factors of POF in APIP. Our nomogram model showed an effective prediction of POF with the four indicators in APIP patients.


Hematology ◽  
2001 ◽  
Vol 6 (5) ◽  
pp. 347-353 ◽  
Author(s):  
Sherri A. Zimmerman ◽  
Thad A. Howard ◽  
Matthew R. Whorton ◽  
Wendell F. Rosse ◽  
Andra H. James ◽  
...  

2015 ◽  
Vol 81 (8) ◽  
pp. 820-825 ◽  
Author(s):  
Martin P. Alvarez ◽  
Andres X. Samayoa-Mendez ◽  
Mary C. Naglak ◽  
James V. Yuschak ◽  
Kenric M. Murayama

Postoperative unplanned intubation (PUI) is a significant complication and is associated with severe adverse events and mortality. By participating in the National Surgical Quality Improvement Program (NSQIP), we learned that PUI occurred more frequently than expected at our institution. The aim of this study was to identify risk factors that are predictors of PUI at our institution. We reviewed the NSQIP data from our institution and the NSQIP national database for surgery patients from 2010 through 2013. The rate of PUI at our institution was 1.54 per cent compared with the national rate of 1.03 per cent. Perioperative risk factors were analyzed by multivariate logistic regression. Analysis of the national NSQIP database identified 14 independent risk factors for PUI. Analysis of the NSQIP data at our institution demonstrated that emergent cases, preoperative ventilator status, smoking, chronic obstructive pulmonary disease, and older age were independent risk factors. In conclusion, patients at our institution with these five risk factors were at higher risk of requiring PUI. These risk factors could be used to help identify patients at high risk and possibly help prevent postoperative respiratory failure and unplanned intubation.


Antioxidants ◽  
2020 ◽  
Vol 9 (9) ◽  
pp. 863
Author(s):  
Fatou Gueye Tall ◽  
Cyril Martin ◽  
El hadji Malick Ndour ◽  
Camille Faes ◽  
Indou Déme Ly ◽  
...  

Oxidative stress would play a role in the pathophysiology of sickle cell anemia (SCA). We tested the impact of common SCA genetic modifiers (alpha-thalassemia, G6PD deficiency, HbF quantitative trait loci; QTL) and pro/antioxidant genes polymorphisms (SOD2 rs4880, XO rs207454, MPO rs2333227) on oxidative stress biomarkers (AOPP, MDA, MPO, XO, MnSOD, CAT, GPx) and clinical severity in 301 Senegalese SCA hydroxyurea-free children at steady-state (median age 9.1 years, sex ratio H/F = 1.3). Plasma oxidative stress biomarkers were compared with those of a control group (AA). CAT activity, AOPP, and MDA levels were higher in SCA than in AA individuals while XO, GPX, and MnSOD activities were lower. The presence of alpha-thalassemia decreased MDA level and MPO activity but no effect of the HbF QTL or G6PD deficiency was observed. SCA children who experienced their first hospitalized complication before 3 years old had higher MnSOD and CAT activities than the other children while those with no hospitalized VOC in the previous 2 years presented higher GPX activity. Age of the first hospitalized complication and AOPP levels were affected by the MPO rs2333227 SNP. Our results suggest that alpha-thalassemia modulates oxidative stress in SCA, presumably because of a reduction in the MPO activity.


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