Presence Of Sickle Cell Trait Research Articles

Genetic Information to Share with Parents when Newborn Screening Reveals the Presence of Sickle Cell Trait.

The primary purpose of newborn screening for sickle cell disease is to diagnose the disease before the appearance of symptoms and to initiate early treatment. To answer the question "What genetic information needs to be communicated to parents when newborn screening reveals the presence of a sickle cell trait," we conducted a survey using a self-administered online questionnaire. We received responses from 122 healthcare workers and members of sickle cell disease associations, in France and French overseas departments. Our results showed similar positions on this issue. The information conveyed is not consistent and is the result of grassroots initiatives. The negative consequences generated by this information could be reduced when this information is delivered by a multidisciplinary team, within the framework of a dedicated consultation. This information on sickle cell trait status should be given in at least three key periods: the neonatal period, early adolescence, and later adolescence, when reproductive implications become important. Neonatal screening programs should develop systems that allow referring physicians to easily access the results of neonatal screening electronically. Harmonization of practices should allow a better analysis of the consequences of this counselling on family projects.

Serum fructosamine and glycemic status in the presence of the sickle cell mutation

AimsThe glycated hemoglobin (HbA1c) test can be unreliable in the presence of hemoglobinopathies. The co-existence of type 2 diabetes (T2D) with sickle cell anemia calls for alternative tests. Therefore, we established a reference interval for serum fructosamine and evaluated its utility as a potential glycemic biomarker that is not affected by abnormal hemoglobin. MethodsThe accuracies of serum fructosamine in monitoring and diagnosing T2D were evaluated using the Area under the Receiver Operating Characteristics and other measures in 618 Nigerians with or without sickle cell trait. The estimated diagnostic cut-off for serum fructosamine was then validated in an independent multi-ethnic cohort of 634 West Africans. ResultsSerum fructosamine was similar between individuals with or without sickle cell trait (median: 287 vs 275 umol/L, p = 0·11, respectively) despite statistically different HbA1c. Fructosamine was highly correlated with both HbA1c and fasting glucose independently of sickle cell trait. The areas under the curve (AUC) of serum fructosamine in identifying individuals with uncontrolled glycemia and individuals with T2D were similar and independent of sickle cell trait: 0·92 (95% confidence interval [95% CI ], 0·88-0·95 and 0.92 (95% CI, (0.89–0.95) respectively. ConclusionsSerum fructosamine is a good alternative to HbA1c for monitoring and diagnosing T2D in the presence of sickle cell trait.

P1710MULTI-NATIONAL SURVEY AMONG NEPHROLOGISTS AND TRANSPLANT SURGEONS ABOUT THE SUITABILITY AND ACCEPTANCE OF MARGINAL LIVE KIDNEY DONORS WITH SICKLE CELL TRAIT

Abstract Background and Aims Due to organ shortage, many transplant centers may consider “marginal” kidney donors as those with sickle cell trait (SCT) for donation. Acceptance of kidney donors with SCT is in the grey zone, where there are no clear guidelines or consensus toward them. To form a consensus, we conducted a short survey about the suitability and acceptance of living kidney donors with SCT. Method This is a cross-sectional survey of nephrologists and transplant surgeons about Suitability and Acceptance of The Marginal Live Kidney Donors. The survey was sent to nephrologists in different countries and it was also distributed through AST& ERA-EDTA. Results Of a total of (n=122) respondents from 22 countries: 80.17% (N= 96) were nephrologists and 19.83% (N=23) were transplant surgeons. N= 88 of the respondents (72%) have more than 6 years in practice and they are heavily involved in pre- transplant evaluations of donors and recipients (68.5% of respondents perform donors’ evaluation on weekly or monthly basis and 60 % perform recipient evaluation on weekly basis). The majority (45%) of the respondents were from USA. The completion rate of the survey was 99%. The presence of sickle cell trait was not considered as a contraindication to donor nephrectomy by the majority of respondents (57.38%). Of those (N= 34) 27.87 % of respondents consider them fit for donor nephrectomy after explanation of the risks involved while (N= 36) 29.51 consider them for donor nephrectomy only if there is no other suitable donor available. Out of the total respondents (N= 52) 42.62% considered the presence of sickle cell trait a contraindication to donor nephrectomy. Conclusion With lack of consensus and guidelines we found that a significant pool of the transplant physicians and surgeons will consider donors with sickle cell trait for kidney donation especially if there is no other acceptable donor.

Prevalence of sickle cell trait in blood donors at the regional blood transfusion center in the Haute Matsiatra Region, Madagascar

Introductionle trait drépanocytaire correspond à la forme hétérozygote de la drépanocytose. Les porteurs du trait drépanocytaire sont capables de synthétiser de l´hémoglobine A normale et de l´hémoglobine S. Cette affection est cliniquement inapparente de telle sorte que des porteurs du trait drépanocytaire, ignorant leurs statuts génétiques, peuvent se retrouver parmi les donneurs de sang. Cette situation peut avoir des conséquences sévères sur leurs propres états de santé ainsi qu´aux receveurs, particulièrement si ces derniers sont drépanocytaires. L´objectif de notre étude est de déterminer la prévalence du trait drépanocytaire chez les donneurs de sang.Méthodesnous avons réalisé une étude prospective descriptive sur 4 mois (de janvier à mai 2017) au Centre Régional de Transfusion Sanguine (CRTS) Haute Matsiatra. Tous les donneurs ont été dépistés par test d´Emmel et confirmation des cas positifs par électrophorèse de l´hémoglobine.Résultatsnous avons recruté 427 donneurs dont 332 hommes et 95 femmes avec un sex-ratio de 3,4. L´âge moyen des donneurs était de 32,72 ans allant de 18 à 64 ans. Le test d´Emmel s´est révélé positif chez 5 donneurs (1,17%), tous confirmés de génotype AS à l´électrophorèse de l´hémoglobine.Conclusionles résultats de cette étude révèlent l´existence de porteurs de trait drépanocytaire parmi les donneurs de sang du CRTS dont la plupart ignore leur statut drépanocytaire avant le don de sang. Afin d´assurer la sécurité transfusionnelle et la qualité des produits sanguins, le dépistage de la drépanocytose chez les donneurs de sang est désormais une question pertinente et d´actualité.

Risk of Venous Thrombosis in Patients with Sickle Cell Trait after Orthopedic Surgery

IntroductionSickle cell trait (SCT) is considered to confer a hypercoagulable state. Historically, venous thromboembolism (VTE, deep vein thrombosis and PE) rates for untreated patients after major orthopedic surgery (hip or knee replacement or hip fracture surgery) have been close to 4.3%, however with the introduction of post-op anticoagulation, the rates have been as low as 1.15%. Although guidelines exist regarding anticoagulation for up to 35 days after major orthopedic surgery, there are no specific recommendations for patients with SCT. The purpose of this retrospective study is to examine the rates of VTE after major orthopedic surgery in a cohort of patients with SCT. We hypothesize that rates of VTE would be higher in patients with SCT and the risk of VTE would persist beyond 35 days.MethodsA commercial database (Explorys Inc, Cleveland, OH, USA), an aggregate of electronic health record data from 26 major integrated US healthcare systems representing a sixth of the US population, was queried for data, using Systematized Nomenclature of Medicine (SNOMED) clinical terms or codes. Cases were defined as patients with SCT who underwent major knee or hip surgery. Since a majority of the US population with SCT are African American (AA) patients, controls were defined as AA patients without SCT undergoing major orthopedic surgery. For the primary end point of VTE, only adult patients (≥18 years) were selected. Those with previous history of VTE, thrombophilia, malignant disease, antiphospholipid antibody syndrome and other hemoglobinopathies such as sickle cell disease were excluded. 30 and 90-day rates of VTE were recorded for both groups. Logistic regression models were used to adjust of confounding variables (defined a priori as age > 65 or< 65, smoking, gender and presence or absence of body mass index > 30). Of note, SCT is likely under-estimated due to incomplete diagnosis. Rates or proportions were compared using Chi-squared testusing Medcalc software (2018). Logistic regression analysis was done using Statistical Package for Social Sciences (SPSS, version 21, IBM Corp, Armonk, NY). P< 0.05 was considered statistically significant.ResultsA total of 1360 major orthopedic surgeries in patients with SCT and 74040 surgeries in non-SCT patients were identified. 30 and 90-day VTE for SCT patients undergoing major orthopedic surgery was 9.7% each. 30 and 90 day VTE for non-SCT patients undergoing major hip and knee surgery were 5.9 % and 6.4 % respectively. The difference in 30-day and 90-day VTE rates between the SCT and non-SCT group was statistically significant (30 day VTE difference 3.1%, 95% CI 1.6650-4.7569, p < 0.001; 90 day VTE difference=3.6%; 95% CI 2.1658-5.2562, p= <0.001). The rates of anticoagulant dispensation (oral Xa inhibitors, enoxaparin or warfarin) after surgery were 56% and 46% in SCT and non-SCT group respectively (difference = 10%, 95% CI 7.32-12.64, p <0.001). Despite the higher proportion of patients prescribed for anticoagulants in the SCT population, there was still a higher 30 and 90-day VTE rate in that group. Compliance to anticoagulation and mortality from VTE could not be assessed in this study.Logistic regression of risk factors associated with risk of VTE revealed age over 65 years of age, female gender, active smoking status, obesity (BMI >30), and presence of sickle cell trait were all significantly associated with increased risk of both 30 and 90 day VTE post major orthopedic surgery. Please see Table 1 and 2 for further details.ConclusionOur study represents real life data outside of a clinical trial. We found that patients with SCT who underwent major hip and knee surgery had an increased 30 and 90-day VTE rates compared to non-SCT patients undergoing the same procedures. Overall, this cohort of AA patients had VTE rates higher than that were described in literature. Of note, AA patients overall are at a higher risk of VTE than are their Caucasian counterparts. The results from the study seem to suggest a role for extended prophylaxis in people with SCT who are undergoing orthopedic procedures, and warrants further study. [Display omitted] DisclosuresLittle:Doris Duke Charitable Foundations: Research Funding; NHLBI: Research Funding; PCORI: Research Funding; Hemex: Patents & Royalties: Patent, no honoraria.

Description of criteria for near miss in high-complexity obstetric population with sickle cell anemia: an observational study

Introduction: Sickle cell disease (SCD) is one of the most common monogenic diseases worldwide, affecting approximately 30 million people across the globe. It is one of the most common hemoglobinopathies affecting pregnancy, particularly in the black population. Pregnant women with SCD, in conjunction with the physiological changes of pregnancy, have an increased risk of developing severe maternal and fetal complications.Materials and methods: A descriptive, observational study was conducted retrospectively to determine the maternal and neonatal disease burden of pregnant women with SCD between 2011 and 2016. The study included pregnant patients with SCD admitted to the hospital, with confirmed diagnosis through hemoglobin electrophoresis. Patients having no confirmatory testing of the disease were excluded.Results: In all, 54% (34 patients) had no previous diagnosis of sickle cell anemia or presence of sickle cell trait, and so an in-hospital diagnosis was carried out through hemoglobin gel electrophoresis, whereas the remaining 46% (28 patients) had already a peripheral diagnosis. In total, the following profiles were obtained: Hb AS 62.9% (39 patients), Hb SC 17.7% (11 patients), Hb SS 16.1% (10 patients), Hb AC 3.2% (2 patients), and Hb CC 0% (0 patients). Vaso-occlusive pain crises constituted the most common cause of hospital admission antepartum (54.8% of the general population), occurring in 100% of the patients with Hb SS and Hb AC, in 45% of the Hb SC group and in 43% of those with the Hb AS trait. The second cause of hospital admission encompassed infectious processes, which affected 45% of the general population, 30% of the Hb AS group, 60% of the Hb SS group, 77% of the Hb SC group, and 100% of the Hb AC group. The method of termination of pregnancy of 44% (27 patients) was C-section. The most common perinatal complication was preterm birth, occurring in 26% (16 patients), with the highest incidence in the Hb AC group. The second most common complication was the intrauterine growth restriction, reported in 6% (4 patients) of all patients, being most frequently in the Hb SS group.Conclusion: Pregnant women having SCD should be assessed and managed by a multidisciplinary team composed of hematology, perinatology, and intensive care. Management should be conducted preferably in high-quality centers experienced in treating this entity, thereby decreasing the great impact of morbidity and mortality associated with SCD in the pregnant population.

Updated Recommendations on the Diagnosis, Management, and Clinical Trial Eligibility Criteria for Patients With Renal Medullary Carcinoma.

Renal medullary carcinoma (RMC) is one of the most aggressive renal cell carcinomas. It predominantly afflicts young adults and adolescents with sickle cell trait and other sickle hemoglobinopathies, and is refractory to targeted and antiangiogenic therapies used in patients with clear-cell renal cell carcinoma. Platinum-based cytotoxic chemotherapy is the mainstay for RMC treatment. On the basis of recent advances in the diagnosis, management, and clinical trial development for RMC, a panel of experts met in October 2017 and developed updated consensus recommendations to inform clinicians, researchers, and patients. Because RMC often aggressively recurs while patients are still recovering from nephrectomy, upfront chemotherapy should be considered for most patients, including those with localized disease. After safety and dosing information has been established in adults, phase II and III trials enrolling patients with RMC should allow patients aged 12 years and older to be accrued. Patients with the very rare unclassified renal cell carcinoma with medullary phenotype variant should be included in RMC trials. Medical providers should be aware that RMC can afflict subjects of all races, and not only those of African descent, and that the presence of sickle cell trait, or of other sickle hemoglobinopathies, can affect drug responses and toxicity.

Sickle Cell Trait, Hemoglobin Levels and Anemia among Black Patients with Predialysis Chronic Kidney Disease: A Post Hoc Analysis

Objective: To assess the relationship between SCT, hemoglobin levels and anemia in CKD black patients. Method: A post-hoc analysis of data from 188 patients, enrolled in a cross-sectional study of sickle cell trait (SCT) and chronic kidney disease (CKD), was performed to assess the relationship between SCT, hemoglobin (Hb) levels and anemia defined as Hb < 12 g/dl in men and <11 g/dl in women. Student t test, Mann Whitney and Chi square test were used as appropriate for different comparisons. P < 0.05 defined the level of statistical significance. Results: SCT (HbAS) and normal hemoglobin (HbAA) were present in 39 (21%) and 149 (79%) CKD patients, respectively. Despite similar estimated GFR (eGFR) and age, HbAS patients had significantly lower Hb levels (8.8 ± 1.8 vs 10 ± 2.2 g/dl; p = 0.001) and a higher proportion of anemia (95% vs 72%, p = 0.001). In multiple linear regression analysis, eGFR, BMI, SBP and SCT emerged as independent determinants of Hb levels. The presence of SCT was associated with 1.185 g/dl decrease in Hb levels. Conclusion: In the present case series, SCT was associated with lower Hb levels suggesting its potential contribution to the pathogenesis of CKD-associated anemia.

Association of sickle cell trait with chronic kidney disease and albuminuria in African Americans.

The association between sickle cell trait (SCT) and chronic kidney disease (CKD) is uncertain. To describe the relationship between SCT and CKD and albuminuria in self-identified African Americans. Using 5 large, prospective, US population-based studies (the Atherosclerosis Risk in Communities Study [ARIC, 1987-2013; n = 3402], Jackson Heart Study [JHS, 2000-2012; n = 2105], Coronary Artery Risk Development in Young Adults [CARDIA, 1985-2006; n = 848], Multi-Ethnic Study of Atherosclerosis [MESA, 2000-2012; n = 1620], and Women's Health Initiative [WHI, 1993-2012; n = 8000]), we evaluated 15,975 self-identified African Americans (1248 participants with SCT [SCT carriers] and 14,727 participants without SCT [noncarriers]). Primary outcomes were CKD (defined as an estimated glomerular filtration rate [eGFR] of <60 mL/min/1.73 m2 at baseline or follow-up), incident CKD, albuminuria (defined as a spot urine albumin:creatinine ratio of >30 mg/g or albumin excretion rate >30 mg/24 hours), and decline in eGFR (defined as a decrease of >3 mL/min/1.73 m2 per year). Effect sizes were calculated separately for each cohort and were subsequently meta-analyzed using a random-effects model. A total of 2233 individuals (239 of 1247 SCT carriers [19.2%] vs 1994 of 14,722 noncarriers [13.5%]) had CKD, 1298 (140 of 675 SCT carriers [20.7%] vs 1158 of 8481 noncarriers [13.7%]) experienced incident CKD, 1719 (150 of 665 SCT carriers [22.6%] vs 1569 of 8249 noncarriers [19.0%]) experienced decline in eGFR, and 1322 (154 of 485 SCT carriers [31.8%] vs 1168 of 5947 noncarriers [19.6%]) had albuminuria during the study period. Individuals with SCT had an increased risk of CKD (odds ratio [OR], 1.57 [95% CI, 1.34-1.84]; absolute risk difference [ARD], 7.6% [95% CI, 4.7%-10.8%]), incident CKD (OR, 1.79 [95% CI, 1.45-2.20]; ARD, 8.5% [95% CI, 5.1%-12.3%]), and decline in eGFR (OR, 1.32 [95% CI, 1.07-1.61]; ARD, 6.1% [95% CI, 1.4%-13.0%]) compared with noncarriers. Sickle cell trait was also associated with albuminuria (OR, 1.86 [95% CI, 1.49-2.31]; ARD, 12.6% [95% CI, 7.7%-17.7%]). Among African Americans in these cohorts, the presence of SCT was associated with an increased risk of CKD, decline in eGFR, and albuminuria, compared with noncarriers. These findings suggest that SCT may be associated with the higher risk of kidney disease in African Americans.

Sickle Trait in African-American Hemodialysis Patients and Higher Erythropoiesis-Stimulating Agent Dose

African Americans require higher doses of erythropoiesis-stimulating agents (ESAs) during dialysis to manage anemia, but the influence of sickle cell trait and other hemoglobinopathy traits on anemia in dialysis patients has not been adequately evaluated. We performed a cross-sectional study of a large cohort of adult African-American hemodialysis patients in the United States to determine the prevalence of hemoglobinopathy traits and quantify their influence on ESA dosing. Laboratory and clinical data were obtained over 6 months in 2011. Among 5319 African-American patients, 542 (10.2%) patients had sickle cell trait, and 129 (2.4%) patients had hemoglobin C trait; no other hemoglobinopathy traits were present. Sickle cell trait was more common in this cohort than the general African-American population (10.2% versus 6.5%-8.7%, respectively, P<0.05). Among 5002 patients (10.3% sickle cell trait and 2.4% hemoglobin C trait) receiving ESAs, demographic and clinical variables were similar across groups, with achieved hemoglobin levels being nearly identical. Patients with hemoglobinopathy traits received higher median doses of ESA than patients with normal hemoglobin (4737.4 versus 4364.1 units/treatment, respectively, P=0.02). In multivariable analyses, hemoglobinopathy traits associated with 13.2% more ESA per treatment (P=0.001). Within subgroups, sickle cell trait patients received 13.2% (P=0.003) higher dose and hemoglobin C trait patients exhibited a similar difference (12.9%, P=0.12). Sensitivity analyses using weight-based dosing definitions and separate logistic regression models showed comparable associations. Our findings suggest that the presence of sickle cell trait and hemoglobin C trait may explain, at least in part, prior observations of greater ESA doses administered to African-American dialysis patients relative to Caucasian patients.

Hematopoietic Progenitor Cell Mobilization In Response To G-CSF Is More Robust In Healthy African American Compared To Caucasian Donors

▪Hematopoietic progenitor cells (HPCs) collected by apheresis of G-CSF-stimulated donors have surpassed bone marrow as the predominant graft source for hematopoietic stem cell transplantation in adults. Among healthy allogeneic donors, demographic characteristics (age, sex, and BMI) and baseline hematologic parameters have been shown to affect HPC mobilization, leading to significant variability in peak levels of CD34 cell egress into the blood and in quantity of CD34 cells harvested by apheresis. Racial differences in G-CSF-mediated HPC mobilization are less well characterized. Benign physiologic neutropenia is common among healthy African Americans (AAs), and may be due to decreased stem cell reserve, fewer G-CSF receptors, or Duffy (null) blood group antigen-mediated decrease in leukocyte trafficking into the circulation. However, preliminary studies have shown relatively robust CD34+ cell mobilization among non-Caucasians given G-CSF (Vasu et al., Blood 2006).We retrospectively analyzed 1,096 consecutive healthy allogeneic related and unrelated first-time donors who self-characterized their race as AA or Caucasian. They underwent G-CSF (filgrastim, Neupogen, Amgen) stimulated HPC collection by leukapheresis from April 1999 to May 2013. G-CSF dose ranged from 10-16 mcg/kg, given daily for 5 days. An unstimulated leukapheresis procedure for lymphocyte collection was performed in the 7 days preceding G-CSF in 336 subjects. Apheresis procedures were performed on the CS-3000 Plus or COBE Spectra device. Baseline lab data included CBC, serologic blood group antigen typing, and Hb electrophoresis in AA donors. CD34+ cell counts were performed on peripheral blood immediately pre-apheresis (2 hours after the 5th dose of G-CSF) and on the apheresis product. Values are given as mean ± SD.All AA (n=215) and Caucasian donors (n=881) with complete data sets were included. Sex ratio was similar among the groups (45 vs 52% male; p=0.09). AAs were younger (39 vs 43 yrs, p=0.001) and had greater weight (86 vs 81 kg, p=0.001) and BMI (30 vs 27; p<0.0001) than Caucasians. G-CSF dose/kg was similar in the 2 groups, but total daily dose of G-CSF was greater in AAs than Caucasians (920 vs 850 mcg, p<0.0001). After adjusting for age, sex, height, weight, and total daily G-CSF dose, peak CD34+ cell mobilization immediately pre-apheresis was higher among AAs than Caucasians (123 ± 87 vs 75 ± 47 cells/uL; p<0.0001) (Figure). When laboratory parameters such as baseline WBC, MNC, and platelet counts were included in the stepwise regression model, AA race remained a significant predictor of higher peak CD34 cell counts. At higher G-CSF doses (16 mcg/kg/d), the difference in mobilization responses between the 2 groups was less apparent (peak CD34 counts 123 vs 93 cells/uL, AA (n=33) vs Caucasian (n=73), p=0.07) than at lower doses (10 mcg/kg/d), where peak CD34 counts were 123 vs 74 cells/uL, AA (n=182) vs Caucasian (n=808), p<0.0001. AAs had lower baseline ANC (3.4 vs 4.0 x 103 cells/uL, p<0.001) than Caucasians, but demonstrated significantly higher peak WBC and MNC counts after G-CSF. In AA donors with known HbS status, presence of sickle cell trait had no effect on CD34 mobilization (peak CD34 counts 123 ± 91 vs 107 ± 72 cells/uL, HbAS (n=41) vs HbAA (n=84), p=0.34). Similarly, in AA donors with known Duffy phenotype, Duffy expression did not affect CD34 mobilization (peak CD34 counts 114 ± 81 vs 134 ± 85 cells/uL, Fya-b- (n=49) vs Fya+ &/Fyb+ (n=20), p=0.4). Lymph-apheresis prior to starting G-CSF was associated with significantly improved CD34+ cell mobilization; however the effect did not differ by race. CD34 apheresis yield was also greater in AAs than Caucasians (51 ± 35 vs 32 ± 21 x 106 cells per liter processed, p <0.0001), consistent with higher pre-apheresis counts.African Americans demonstrated significantly more robust CD34 mobilization responses to G-CSF than Caucasians. The effect was independent of age, BMI, HbS and other variables, and occurred despite physiologically lower neutrophil counts among AAs. A ceiling effect in response to increased doses of G-CSF (>10 mcg/kg) was seen in AAs but not in Caucasians, suggesting that dose titration based on race might be used to optimize HPC yields. Further evaluation of race-associated genetic polymorphisms in relation to G-CSF pharmacokinetics may help improve G-CSF dosing strategies. [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Sickle Cell Trait: Is There an Increased VTE Risk in Pregnancy and the Postpartum?

Blacks are purported to have a higher venous thromboembolism (VTE) risk than whites. We hypothesized that this might be due, in part, to the greater presence of sickle cell trait (SCT) among blacks. We investigated whether the presence of SCT resulted in a higher VTE incidence in a population predisposed to VTE, the pregnant/postpartum women. Methods: Using a mirrored clinical database that prospectively gathered in- and out-patient information for the years 1998–2008, we collected demographic data, including hemoglobin electrophoreses, on all pregnant/postpartum non-Hispanic women who delivered at a large, diverse, urban hospital. We identified those women who developed VTE either while pregnant or postpartum during those 11 years. Charts initially identified as potential VTE cases were subjected to review to ensure accuracy of VTE coding. Results: Of 12,429 women, 679 non-Hispanic SCT black women, 5,465 non-Hispanic Hemoglobin AA (women with HbA as the only hemoglobin present on electrophoresis, with normal amounts of the minor hemoglobins) black women and 1,162 non-Hispanic HbAA white women were included in the analysis. SCT prevalence was high (11.1%) within this black population as compared to 8.3% in the general non-white population. Proportions with VTE were similar for black SCT and black HbAA groups: 0.44% for the SCT group, 0.49% for non-Hispanic black HbAA women. Black HbAA women had a non-significantly higher proportion of VTE than white HbAA women 0.49% vs 0.26% (RR 1.9, 95%CI:0.6,6.3, p = 0.28). Women with VTE were older than those without VTE (32.2 vs. 27.6 years, p = 0.0002) and the majority of VTE occurred postpartum in all groups, and significantly in the HbAA groups. There was no increase in the incidence of pulmonary emboli in the SCT group. Conclusion: In the largest analysis to date, we could not detect a meaningful difference in peripartum VTE incidence between women with and without sickle cell trait.

Erythrocyte Adhesion in Hemodialysis Patients – A Novel Potential Contributor to Inflammation in End-Stage Renal Disease.

AbstractAbstract 2092 Background:Widespread adhesion of erythrocytes in the vasculature would be incompatible with life. However, in illnesses such as sickle cell disease, malaria and diabetes, adhesive RBCs have been documented and are likely contributors to disease severity, inflammation and coagulation activation. End-stage renal disease is characterized by profound, global inflammation and relative thrombophilia. While we, and others, have reported the extensive exposure of RBC phosphatidylserine in patients on hemodialysis, the role of RBC adhesion in inflammation has never been examined in this condition. We performed an analysis of RBCs from hemodialysis patients to characterize their ability to adhere to other cells, elucidate the potential mechanisms of adhesion, and to relate RBC adhesion to the inflammatory state of hemodialysis. Methods:This study was conducted in a cohort of 20 African American patients receiving in-center hemodialysis at 2 separate dialysis clinics as part of a study of sickle cell trait in hemodialysis. There were 9 of 20 patients with documented sickle cell trait. Blood samples were drawn immediately pre-dialysis and prior to administration of heparin. Plasma samples were processed to minimize platelet activation, aliquoted, and frozen for batch analysis. Plasma factors (RANTES, CRP & CD40L) were analyzed via ELISA. Adhesion events in whole blood were detected via two color flow cytometry. Cause of renal failure, mode of venous access and relevant clinical data were obtained from patient charts. All adhesion assays with washed blood cells were conducted under static conditions using microvascular endothelial cells. All studies were compared to those results of healthy control patients (n =11). Spearman’s regression analysis was performed to analyze the correlation between continuous variables. Mann-Whitney U and Kruskal Wallis tests were used to compare continuous variables between groups. A p<0.05 was considered significant. Results:We found that RBCs from patients on hemodialysis were significantly more adhesive than those from healthy controls. In whole blood, we detected marked RBC adhesion to T-cells (median % of T-cells bound to RBCs: 67.9 [hemodialysis] vs. 10.55 [healthy control]) and platelets (median % of platelets bound to RBCs: 33.0 vs. 1.1%). We also noted significant RBC adhesion to neutrophils (median % of neutrophils bound to RBCs: 11.0% vs. 0.1%). Incubation of healthy RBCs with plasma from hemodialysis patients, but not healthy control plasma, was sufficient to induce RBC adhesion to cultured endothelial cells (median RBCs/mm2: 8.0 vs. 0.5) and to T-cells (median % T-cells bound to RBCs: 30.0 vs. 5.0). Plasma from hemodialysis patients also induced phosphatidylserine exposure on healthy RBCs. Phosphatidylserine exposure on the RBC appeared to mediate RBC adhesion to endothelial cells as annexin V significantly reduced RBC adherence (8.0 vs 3.8 RBC/mm2). The extent to which RBCs in hemodialysis patients adhered to T-cells directly correlated with both plasma RANTES (rspearman = 0.65, 95% CI: 0.247–0.864) and CD40L levels (rspearman= 0.60, 95% CI: 0.1645 – 0.847), but not plasma CRP levels. There was also no significant difference in adhesion of RBCs due to cause of renal failure (diabetes, hypertension, or glomerulonephritis) or presence of sickle cell trait. Conclusions:We describe for the first time a novel adhesion of RBCs in patients receiving hemodialysis and how this adhesion may relate to inflammation in these patients. Our findings also suggest that factors in uremic plasma are sufficient to induce phosphatidylserine exposure on RBCs. This exposure, in addition to providing a site for thrombin generation, also serves as an adhesive moiety on RBCs for endothelial cells. These data may describe an unrecognized etiology of inflammation in hemodialysis and end-stage renal disease. Disclosures:No relevant conflicts of interest to declare.

Sickle cell trait is not independently associated with susceptibility to end-stage renal disease in African Americans

Conflicting reports exist as to whether sickle cell trait is a risk factor for the progression of nephropathy. In order to determine whether African Americans with sickle cell trait are at increased risk for kidney disease, we assessed the genetic association between sickle cell trait and end-stage renal disease (ESRD). Hemoglobin S, non-muscle myosin heavy chain 9 (MYH9), and apolipoprotein L1 (APOL1) risk variants were genotyped in 3258 unrelated African Americans: 1085 with non-diabetic ESRD, 996 with type 2 diabetes-associated ESRD, and 1177 controls. Since APOL1 is strongly associated with ESRD in African Americans, interactions between APOL1 and MYH9 risk variants and hemoglobin S were assessed using case-only and case-control centered two-way logistic regression interaction analyses. The sickle cell trait genotype frequencies were 8.7% in non-diabetic ESRD, 7.1% in type 2 diabetes-ESRD, and 7.2% in controls. There was no age-, gender-, and admixture-adjusted significance for sickle cell trait association with non-diabetic ESRD (odds ratio 1.16); type 2 diabetes-ESRD (odds ratio 1.01); or all-cause ESRD (combined non-diabetic and type 2 diabetic-ESRD patients compared to the controls; odds ratio 1.05) in dominant models. In addition, no evidence of APOL1 or MYH9 interactions with sickle cell trait was detected. Hence, sickle cell trait is not associated with diabetic or non-diabetic ESRD in a large sample of African Americans.

Glucose-6-phosphate dehydrogenase status and severity of malarial anaemia in Nigerian children

Glucose-6-phosphate dehydrogenase (G6PD) deficiency (Gd-) contributes to morbidity and mortality in sub-Saharan Africa but recent data on the interaction between Gd- and malaria among children is scarce. We hypothesised that, being a haemolytic factor, Gd- makes severe malarial anaemia (SMA) more common and even more severe. We selected 930 children aged 0.5-12 years attending a reference hospital with microscopically proven falciparum malaria. G6PD and haemoglobin were typed by the fluorescent spot test and electrophoresis, respectively. Molecular typing by PCR and restriction enzyme digestion was also performed on 15% of randomly selected samples. Haematocrit (PCV) values, haemoglobin type, blood group, presence of sickle cell trait (HbAS), and parasite counts were compared between G6PD-normal and deficient children. Prevalence of Gd- was 16.4% and 8.1% among boys and girls with malaria, respectively. Mean PCV was 22.8% in deficient children compared with 21.0% in normal children (p = 0.041). In boys, 2.7% of Gd- had PCV ≤ 10%, as compared to 13.6% in Gd+ (p = 0.005). Similarly, 21.3% of Gd- had PCV ≤ 15% compared with 39.4% in Gd+ (p = 0.003). No such difference was found among girls. Overall, HbAS was typed in 7.6% and was more common in Gd- (13.0%) than in Gd+ (6.8%), but the difference was not statistically significant (p = 0.058). The mean parasite counts were significantly lower in Gd- (15477.5/µl) than in Gd+ (19784.4/µl; p = 0.013), and it was independent from HbAS. Gd- males but not females were significantly less likely to develop severe malarial anaemia.

Presence of the Sickle Cell Trait and Preterm Delivery in African-American Women

To estimate the association between presence of the sickle cell trait and preterm delivery among African-American women. A retrospective cohort study was conducted to study all deliveries by African-American women at one institution between 1976 and 2001. The primary predictor of interest was the presence of the sickle cell trait, and the primary outcome was preterm delivery. Post hoc analyses were conducted to explore the relationship between presence of sickle cell trait and multiple gestations, an apparent modifier of the relationship between sickle cell trait and preterm delivery. Of the 5,028 African-American women eligible for inclusion, 6.5% carried the sickle cell trait. In adjusted analyses, the presence of sickle cell trait was associated with a lower risk of preterm delivery at less than 32 weeks (adjusted odds ratio 0.15, 95% confidence interval 0.05-0.49), and was found to be associated with an increased odds of multiple gestations (adjusted odds ratio 1.94, 95% confidence interval 1.22-2.09). A significant interaction exists between the presence of multiple gestation and sickle cell trait and the odds of preterm delivery, such that the protective effect of sickle cell trait on preterm delivery risk is greater among those with multiple gestations than those with singletons. Among African-American women, the presence of the sickle cell trait was associated with lower odds of early preterm delivery despite adjustment for potential confounders. An increased odds of multiple gestations was also noted among these women, possibly suggesting a persistence of selection for the hemoglobin S trait in nonmalarial settings. II.

LEFT ARM PAIN AND SWELLING IN A COLLEGE FOOTBALL PLAYER

HISTORY An 18 year old African American male presented with left arm swelling after starting summer football camp. He had been weightlifting the day prior to developing swelling, stiffness and arm pain confined to his left forearm and mid-biceps. He noted that the intensity of the weightlifting, which was primarily bicep and shoulder work, was greater than normal for him. He denied any previous episodes of arm pain and had been working out alone during the summer. He denied any dizziness, numbness or tingling or recent viral illness. He denied chest pain, SOB, nausea or vomiting, fever, chills or rash. He denied any hematuria but his urine may have been a bit darker than normal. He denied using any supplements, illegal drugs or alcohol. PMHX: exertional heat cramps in the past; NKDA, MEDS: none, FHX: significant for sickle cell trait in his father and mother. His review of systems was negative. PHYSICAL EXAMINATION general: WDWN African American male in NAD, height 68 inches, weight 167 lbs. vitals: stable, BP 110/60, afebrile. HEENT: unremarkable. neck: FROM, no nodules or LAN chest: CTA. heart: RRR, normal S1 and S2, no MRG. abdomen: benign. extremities: Left arm; ecchymosis or erythema, mid bicep circumference was 36 cm, right mid bicep circumference was 34 cm, tenderness to palpation over left biceps and brachialis muscles. Limited left elbow extension to 150 degrees, flexion WNL neuro: Left bicep strength 4+/5 limited by pain, otherwise was 5/5 in all major muscles of upper and lower extremities; no sensory deficit was noted; 2+ radial and brachial pulses bilaterally, no cyanosis, cap refill < 2 seconds. DIFFERENTIAL DIAGNOSIS Musculoskeletal: delayed-onset muscle soreness (DOMS), compartment syndrome, exertional rhabdomyolysis. Infection: cellulitis. Vascular: venous or arterial thrombosis. Bone: fracture, tumor. TEST AND RESULTS WBC 12.8, Hgb 39.1, MCV 79.9, CPK 63,880 U/L, BUN 15.0, creatinine 1.5, Urinalysis: negative, no blood or RBCs. Hgb A 59%, Hgb F 0%, Hgb S 38%, HgC 0%, HgA2 3%, postive for sickle cell trait; repeat testing 1 week later confirmed sickle cell trait and CPK had decreased to 2001 U/L. FINAL/WORKING DIAGNOSIS Exertional in the presence of sickle cell trait. TREATMENT AND OUTCOMES Pain and swelling subsided with rest and aggressive hydration. He was placed on relative rest and restricted to activities of daily living. Two weeks after presentation, he had no swelling, pain or stiffness in his left arm. His CPK returned to normal. He was permitted to return to football but limited to sprints less than 400 yards. He was advised to modify his exercise regimen to avoid excessive muscle injury. The genetics and potential complications of sickle cell trait were discussed with him.

Lactate Exchange and Removal Abilities in Sickle Cell Trait Carriers During and After Incremental Exercise

Arterial blood lactate concentrations and pH were measured on seven black male sickle cell trait (SCT) carriers before, during and after incremental exhaustive bicycle exercise (25 W increments per minute) and compared with those of six control individuals of the same ethnic origin having a similar physical fitness level. The object of the experiment was to determine if SCT has an effect on lactate kinetics. At volitional exhaustion which was reached at a comparable overall mean absolute work rate for both groups, oxygen consumption expressed per kilogram body mass was significantly lower for the SCT carriers than for the control volunteers. Lactate concentrations were higher for the SCT carriers after the 150 W exercise step but differences reached statistical significance only at exhaustion. Concentrations were distinctly higher for the SCT group during the following 40 minutes of recovery. While there were no observable differences in blood pH between the SCT and control subjects during the exercise, this variable became significantly lower for the SCT than for the control group 8 minutes after the end of exercise. Lactate recovery curves were fitted by a biexponential time function where the two velocity constants inform on the body's overall ability to exchange and remove lactate. The ability to remove lactate was comparable for the two groups. The present results do not warrant drawing a definite conclusion on impairment of the ability to exchange lactate in the presence of SCT. However, SCT carriers are likely to produce more lactate than control subjects reaching exhaustion at similar mean absolute work rate during exhaustive incremental bicycle exercise.

Chloroquine treatment of falciparum malaria in an area of Kenya of intermediate chloroquine resistance

106 children aged 1–10 years who had pure Plasmodium falciparum infections and temperatures ⩾38 °C were treated with chloroquine base, 25 mg/kg body weight. 29% of the infections were sensitive in vivo, 41% recurred within 4 weeks (RI), 26% were RII resistant, and 4% were RIII resistant. Rieckmann micro in vitro tests were successful in 64% of isolates obtained from these children; 63% were resistant to chloroquine. In 58 paired isolates obtained before and after treatment, the level of chloroquine sensitivity was lower in the parasites persisting or recurring after treatment. All children except 2 of the 4 with RIII resistance became afebrile an average of 1–4 d after starting treatment and their other symptoms resolved in an average of 1·8 d. By day 28, 57% of the children with RI resistance and 78% of those with RII resistance had recurrence of fever and other symptoms, compared with 19% of children with sensitive infections. No relationship was observed between the clinical or parasitological response and age, nutritional status, haematocrit, splenomegaly, presence of sickle-cell trait, or seropositivity to malaria by enzyme-linked immunosorbent assay. The study demonstrates that, in most children with malaria in an area of intermediate chloroquine resistance, fever and other symptoms resolve at least temporarily when treated with chloroquine.

Reduced frequency of iron deficiency anaemia in sickle cell trait.

The prevalence and causes of anaemia among the inhabitants of a Southern Lebanese village were studied. Of the 317 patients examined 75, or 24% were found to be heterozygotes for Hb S. There was a reciprocal relation between the presence of sickle cell trait and of iron deficiency anaemia. The prevalence of iron deficiency anaemia defined as the coexistence of Hb below 13 g/dl in adult males and below 12 in adult females and children with two laboratory indicators of iron deficiency, was 10.3% in the normal population as against 1.3% in the sickle cell trait group (P less than 0.008). The reduced frequency of iron deficiency anaemia in sickle cell trait may be explained by increased iron absorption, or alternatively by reduced iron requirements and a lower risk of discrepancy between iron supply and demand. Because of the central role of iron in the function of a great number of enzymes and proteins, it is possible that protection against iron deficiency anaemia by the sickle cell trait may result in improved working capacity and a lower incidence of infections.