Malignancy in Patients with Sickle Cell Disease: A Single Center Observational Study

Abstract Introduction: Sickle cell disease (SCD) is an inherited disorder of red cells complicated by acute vaso-occlusion (VOC) and chronic organ damage in adults leading to a shortened lifespan. Improved management of SCD patients has resulted in increasing life expectancy so that the prevalence of malignancy in patients with SCD may be increasing. Patients with SCD often have comorbidities related to their disease that may limit their ability to receive cancer treatments and result in worse outcomes. Available literature describing cancer in SCD patients is limited to case reports and small retrospective reviews. This study describes a cohort of adult patients with SCD with a malignancy and the effect on their SCD. Methods: The Adult Hemoglobinopathy Resource Center at Washington University has provided care for adult SCD patients throughout the St. Louis, Missouri metropolitan area since 1990. All patients have confirmed SCD (Hgb SS, Hgb SC, Hgb Sβ+, Hgb Sβ0, Hgb SC Harlem, Hgb S Other) and have been seen at least once since 2011 or are known to have died were included in this study. A retrospective chart review of these SCD patients was conducted and medical records were reviewed for malignancies. Demographic data and SCD history included: gender, SCD genotype, baseline Hgb, and hydroxyurea use. Cancer treatment history data included: age at and date of diagnosis, cancer screening, type and stage of malignancy, date and cause of death, complications of cancer treatments, and the number of hospitalizations/emergency departments visits for VOC in the year before and after cancer diagnosis. Categorical variables were analyzed using Fisher's exact test and continuous variable analyzed using student t-test. Patients were grouped into Hgb SS and non-Hgb SS for analysis to explore differences in outcomes. Overall survival (OS) was calculated based on date of diagnosis to date of death or censored at July 7, 2016. Commonly cited oncology literature was reviewed for the median OS for each malignancy based on stage. Each patient's actual survival was compared to the expected median OS for their respective malignancy. OS was classified as better or worse if actual survival time was at least equivalent to or shorter than cited median OS, respectively. Results: From October 2011 to December 2015, 397 patients have been evaluated and 15 are known to have died. Of the surviving patients, the mean age is 35 yrs (range 18-76); 199 are female (52.1%), and 183 are male (47.9%). The hemoglobinopathies include SS-245, SC-106, Sβ+-24, Sβ0-5, SC Harlem-1, and unconfirmed-1. Overall, 85 patients have died since 1994. Eleven patients (Hgb SS-6, Hgb SC-3 and Hgb Sβ+-2) were found to have diagnoses of twelve malignancies. The diagnoses and number of patients include non-small cell lung-3, breast-2, and one each of germ cell tumor, Hodgkin lymphoma, colon, and papillary thyroid, extra-adrenal metastatic paraganglioma, tongue base squamous cell and prostate cancers. The incidence of malignancy in our cohort was 2.3% and the median age at cancer diagnosis was 41.8 yrs (range 19-68). Patients with Hgb SS trended towards having cancer diagnosed at a later age compared to non-Hgb SS patients (ages 52.3 vs 35.8 yrs respectively, p=0.1). Hgb SS patients had a lower baseline Hgb (p=0.00005) and higher frequency of hydroxyurea use (p=0.012) compared to non-Hgb SS patients at the time of cancer diagnosis. The median OS of patients was at least equivalent to expected OS in 2 out of 6 patients with Hgb SS and 4 out of 5 patients non-Hgb SS disease (p=0.16). Initial therapy consisted of surgery (5), radiation therapy (3, 1 curative and 2 palliative intent) and chemotherapy (4). Chemotherapy was indicated as standard of care but not administered to 4 patients secondary to comorbidities. There was no significant difference in VOC/year in the year before compared to the year after cancer diagnosis. Malignancy was identified by age appropriate cancer screening in 3 out of 4 applicable patients. Conclusions: In adults with SCD, malignancy occurred in 2.3% of patients over about 25yrs. There was not an observed increase in pain crises requiring in-hospital or emergency department evaluations after cancer diagnosis. Patients with SCD should complete age appropriate cancer screening for early detection. There is a modest trend towards worse outcomes for patients with Hgb SS disease compared to the general population and compared to Hgb SC/Sβ+. Disclosures Blinder: CSL Behring: Honoraria; Novartis: Honoraria; Janssen: Honoraria.

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Characterization of HIV risks in a Brazilian sickle cell disease population

BMC Public Health ◽

10.1186/s12889-020-09702-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

P. F. Blatyta ◽

◽

S. Kelly ◽

T. T. Goncalez ◽

A. B. Carneiro-Proietti ◽

...

Keyword(s):

Sickle Cell Disease ◽

Risk Behaviors ◽

Sickle Cell ◽

Hiv Risk ◽

Hiv Risk Behaviors ◽

Categorical Variables ◽

Computer Assisted ◽

Fisher Exact Test ◽

Cell Disease ◽

Low Prevalence

Abstract Background A low prevalence of HIV in sickle cell disease (SCD) patients has been reported in the literature though mechanisms for this are not understood. Methods HIV risk behaviors were compared between SCD cases and non-SCD controls using a self-administered audio computer-assisted self-interview. SCD cases were recruited from a multi-center SCD cohort established in Brazil; controls were recruited from SCD social contacts. Categorical variables were analyzed using Chi-Square or Fisher exact test. Continuous variables were compared using the Mann-Whitney U test. Results There were 152 SCD cases and 154 age/location matched controls enrolled at three participating Brazilian centers during 2016–17. No significant differences in number of sexual partners (lifetime or previous 12 months), male-to-male sex partners or intravenous drug use were observed. Cases received more transfusions, surgeries, and acupuncture treatment. Conclusions Besides the risk of transfusion-transmitted HIV, which is now exceedingly rare, SCD and non-SCD participants demonstrated similar HIV risk behaviors. Causes other than risk behaviors such as factors inherent to SCD pathophysiology may explain the reported low prevalence of HIV in SCD.

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Emergency Department Management of Children with Sickle Cell Disease.

Blood ◽

10.1182/blood.v104.11.1660.1660 ◽

2004 ◽

Vol 104 (11) ◽

pp. 1660-1660

Author(s):

Melissa J. Frei-Jones ◽

Amy L. Baxter ◽

Charles T. Quinn ◽

George R. Buchanan

Keyword(s):

Emergency Department ◽

Steady State ◽

Sickle Cell Disease ◽

Hospital Admission ◽

Sickle Cell ◽

Admission Rate ◽

Categorical Variables ◽

Continuous Variables ◽

Cell Disease ◽

Ed Visits

Abstract Vaso-occlusive crises (VOC) are a common cause of emergency department (ED) visits for children with sickle cell disease (SCD). To better understand our patient population and compare with reports from other centers, we sought to describe the presentation, management, and disposition of children with VOC at our center’s ED. We also aimed to identify predictors of hospital admission. We retrospectively reviewed hospital records of all patients with SCD, age 8–19 years, who presented to our urban pediatric ED in 2003 with a chief complaint of pain. We identified all subjects diagnosed with VOC and not another cause of pain. We obtained the following data for each: SCD genotype; duration of VOC and treatment prior to ED presentation; the nature of analgesia and use of intravenous fluids (IVF) in the ED; hemoglobin (Hgb) concentration; and disposition (admitted, discharged, discharged with subsequent ED visit for same crisis). Categorical variables were evaluated by the χ2 and Fisher exact tests and continuous variables by the t-test. Odds ratios (OR) and 95% confidence intervals (CI) were calculated where appropriate. In 2003, there were 320 ED visits for patients with SCD and pain. Among these, there were 279 diagnoses of VOC in 105 individual patients: 45 had one visit, 25 two visits, and 16 ≥5 visits. Mean number of visits per patient was 2.7; 23 (22%) patients accounted for 145 (55%) visits. Homozygous sickle cell anemia (Hgb SS) was present in 73/105 patients, accounting for 222 (79%) ED visits. Overall admission rate was 179/279 (64%), with 167/179 admitted on their first visit and 12 on their return visit. Subjects with Hgb SS accounted for 147/179 (82%) admissions. Among those discharged who later returned to the ED during the same VOC, the admission rate was 86% (5 returned in 24 hours, 5 in 48 hours, 3 in 72 hours, and one 4 days later). Pre-ED home opioid use was reported in 75% of visits and was associated with increased likelihood of discharge (OR 1.63, CI 0.94–2.84, p=0.082). Duration of VOC before presentation did not significantly affect admission rate and averaged 53.2 hours for admitted patients and 49.7 hours for those discharged (p=0.689). Patients who received IVF in the ED (219/279; 79%) were less likely to be admitted (31% vs 56%, p<0.001). Hgb concentration was increased in 61%, decreased in 36% and unchanged in 3% of patients from steady-state values and was not associated with admission. After receiving 2 doses of morphine, 31 patients were discharged from the ED, while only 5 patients were discharged after receiving 3 or 4 doses of morphine. A departmental VOC protocol was followed for 25.4% of patients, with no impact on admission rate (p=0.290). In this retrospective analysis of a large series of pediatric sickle cell ED visits, patients presented later in their VOC, and admission rate was higher than previously reported. A small proportion of older patients with SCD accounted for most ED visits and hospitalizations. Hgb variation from steady-state was neither clinically significant nor predictive of admission or discharge. In contrast to previous studies, receiving IVF in the ED was associated with a greater likelihood of discharge. Home opioids prior to ED presentation seemed to decrease hospital admission. Adherence to our center’s VOC protocol did not appear to influence disposition from the ED.

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Venous Thromboembolism In Pregnant Women With Sickle Cell Disease

Blood ◽

10.1182/blood.v122.21.2217.2217 ◽

2013 ◽

Vol 122 (21) ◽

pp. 2217-2217

Author(s):

Craig D. Seaman ◽

Margaret V. Ragni ◽

Charity G. Moore ◽

Jie Li ◽

Jonathan Yabes

Keyword(s):

Venous Thromboembolism ◽

Sickle Cell Disease ◽

Length Of Stay ◽

Pregnant Women ◽

Sickle Cell ◽

Pregnancy Complications ◽

Categorical Variables ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Discharge Data

Abstract Background The risk of venous thromboembolism (VTE) is increased in pregnancy and sickle cell disease (SCD), yet the rates of pregnancy-related VTE are not firmly established in SCD, nor are other SCD-related complications, including pneumonia, vasooclusive crisis (VOC), and acute chest syndrome (ACS), which may be clinically indistinguishable from VTE. Moreover, the American College of Chest Physicians has made no recommendations regarding thromboprophylaxis in pregnant women with SCD. Methods Inpatient hospital discharge data for PE for the most recent 5-year period available, 2007-2011, were obtained from the Pennsylvania Health Care Cost Containment Council (PHC4). We compared VTE, pregnancy complications, medical co-morbidities, and mortality among pregnant women with and without SCD. Among pregnant SCD women with and without VTE, we also compared rates of pneumonia, vasooclusive crisis (VOC), and acute chest syndrome (ACS). All patient identifiers were removed. Diagnostic categories and co-morbidities were obtained using ICD-9 codes. Data from categorical variables were analyzed by chi-square or Fisher's exact test; and from continuous variables by two-sample Student t-test. Results The prevalence of VTE was 2.8% among pregnant women with SCD. Among pregnant women with SCD and VTE, the rate of pneumonia, 28.6% vs. 4.4%, p=0.043, was significantly higher than in those without VTE. While somewhat higher, the rates of VOC, 57.1% vs. 24.7%, p=0.073, and ACS, 14.3% vs. 2.4%, p=0.177, were not significantly different between pregnant SCD VTE and non-VTE groups. Comparing VTE and non-VTE pregnant SCD women, the rate of pregnancy complications did not differ, p=0.999; nor did the rates of medical co-morbidity, other than diabetes, 28.6% vs. 3.6%, p=0.031. Among the subset of pregnant SCD with pneumonia, the prevalence of VOC, 80.0% vs. 36.1%, p=0.001; ACS, 35.0% vs. 2.9%, p<0.001; and length of stay, 12.5 vs. 4.6 days, p=0.030, were significantly greater than in those without pneumonia. Among the subset of SCD pregnancies with VOC, the prevalence of preeclampsia, 28.4% vs. 13.5%, p=0.003; pneumonia, 15.7% vs. 2.6%, p=0.001; ACS, 12.8% vs. 0.6%, p<0.001; and length of stay, 7.7 vs. 3.6 days, p<0.001, were significantly more common than in those without VOC. Among the subset of SCD pregnancies with ACS, the rates of intrauterine fetal death, 14.3% vs. 1.6%, p=0.036; postpartum infection, 28.6% vs. 6.6%, p=0.016; pneumonia, 50.0% vs. 5.3%, p<0.001; and VOC, 92.9% vs. 36.5%, p<0.001, were significantly higher than in those without ACS. Overall, the rate of VTE, among SCD women with pneumonia, VOC, and/or ACS, 6.6%, was significantly higher than among those without these conditions, 2.2%, p<0.001. Discussion The prevalence of pregnancy-related VTE in women with SCD, while low, 2.8%, appears to be at least 10-fold greater than the general 0.2% incidence of pregnancy-related VTE in the unaffected population. Further, the higher rates of VTE we observed among pregnant women with SCD-related complications, including pneumonia, VOC, or ACS, and the well-recognized potential clinical overlap with VTE, suggest that VTE may be missed in such women, and that VTE rates in pregnant women with SCD may be higher than herein reported or previously recognized. The presence of pneumonia, VOC, or ACS appears to be associated with VTE and may be a potential marker(s) of its occurrence. Prospective studies, however, are needed to determine the incidence of VTE in pregnant women with SCD with and without complicating pneumonia, VOC, and/or ACS. We conclude that pregnancy-related VTE may be more common than previously recognized in pregnant women with SCD and, if confirmed, such women might be candidates for thromboprophylaxis. Disclosures: No relevant conflicts of interest to declare.

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Sex Based Differences in Sickle Cell Disease

Blood ◽

10.1182/blood-2020-140896 ◽

2020 ◽

Vol 136 (Supplement 1) ◽

pp. 37-37

Author(s):

Rita V Masese ◽

Dominique Bulgin ◽

Mitchell Knisely ◽

Liliana Preiss ◽

Eleanor Stevenson ◽

...

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Research Funding ◽

Categorical Variables ◽

Continuous Variables ◽

Cell Disease ◽

Advisory Committees ◽

Blood Institute ◽

National Heart Lung

Introduction Sickle cell disease (SCD) is the most common inherited blood disorders in the United States. The disease predominantly affects African Americans with 1 out of every 365 individuals born with SCD. The disease is characterized by vascular inflammation and vaso-occlusion leading to numerous complications and multi-organ dysfunction. Previous studies have shown women with SCD tend to outlive their male counterparts. Other than the increased life expectancy, sex-based clinical outcome differences in SCD remain largely unknown. To better characterize sex-based differences in SCD, we assessed sociodemographic characteristics, pain, treatment characteristics, laboratory measures and complications among males and females currently enrolled in the Sickle Cell Disease Implementation Consortium (SCDIC) registry. Methods The SCDIC consists of eight academic and comprehensive SCD centers, and one data-coordinating center that received funding from the National Heart Lung and Blood Institute to improve outcomes for individuals with SCD. Participants were eligible for the enrollment in the SCDIC registry if they were 15 to 45 years of age and had a confirmed diagnosis of SCD. Participants were excluded if they had sickle cell trait or had a successful bone marrow transplant. Enrolled participants completed surveys. Data were also abstracted from the participants' medical records. Data were entered into a REDCap database and analyzed using SAS version 9.4 (SAS Institute; Cary, NC). Categorical variables were presented as frequencies and percentages, continuous variables were presented as medians and interquartile ranges (IQR) or means and standard deviations. Categorical variables were analyzed using Chi-Square or Fisher exact tests when appropriate. Continuous variables were compared using the Mann-Whitney U test or independent sample t-tests depending on the distribution. A two-sided p-value less than 0.05 was deemed significant. Results A total of 2,124 participants were included in the study. The mean (SD) age of our participants was 27.8 (7.9) years. Almost all (95.6%) were Africa American, female (56%) and had hemoglobin SS (68.2%) SCD genotype. More males (55.4 % vs. 44.6%, p <0.0001) were taking hydroxyurea. Females had significantly worse reports of pain frequency and severity (p=0.0002 and <0.0001 respectively), more vaso-occlusive episodes (p=0.01) and a higher occurrence of 3 or more hospital admissions in the past year (30.9 % vs. 25.5, p= 0.03). Males had significantly more skin ulcers and respiratory, musculoskeletal, genitourinary and cardiovascular complications while females had more anxiety, depression and autoimmune conditions. Males also had significantly higher creatinine, blood urea nitrogen, albumin and liver enzymes (alkaline phosphatase, aspartate and alanine aminotransferases). Females had higher fetal hemoglobin levels with and without hydroxyurea use. There were no statistical differences in ethnicity, marital and employment status. Conclusion Key differences in SCD presentation and occurrence of complications exist among males and females. Females had higher rates of depression and anxiety while males had more chronic end-organ complications that are life threatening. Our findings emphasize the need for stratification of data analysis by sex in future SCD studies. Disclosures Hankins: Global Blood Therapeutics: Consultancy, Research Funding; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; LINKS Incorporate Foundation: Research Funding; American Society of Pediatric Hematology/Oncology: Honoraria; MJH Life Sciences: Consultancy, Patents & Royalties; UptoDate: Consultancy; Novartis: Research Funding. Treadwell:UpToDate: Honoraria; Global Blood Therapeutics: Consultancy. King:Tioma Therapuetics: Consultancy; WUGEN: Current equity holder in private company; RiverVest: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Bioline: Consultancy; Novimmune: Research Funding; Amphivena Therapeutics: Research Funding. Gordeuk:CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Kanter:bluebird bio, inc: Consultancy, Honoraria; SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; Sanofi: Consultancy; Medscape: Honoraria; Guidepoint Global: Honoraria; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees. Glassberg:Eli Lilly and Company: Research Funding; Pfizer: Research Funding; Global Blood Therapeutics: Consultancy. Shah:Bluebird Bio: Consultancy; Novartis: Consultancy, Research Funding, Speakers Bureau; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau; CSL Behring: Consultancy; Alexion: Speakers Bureau.

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COVID-19 in Hospitalized Patients with Sickle Cell Disease

Blood ◽

10.1182/blood-2021-146973 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 3090-3090

Author(s):

Stephanie Guarino ◽

Sophie M. Lanzkron

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Research Funding ◽

Case Fatality ◽

Hospitalized Patients ◽

Categorical Variables ◽

Fatality Rate ◽

Cell Disease ◽

Increased Risk ◽

Privately Held

Abstract Introduction Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is estimated to affect more than 100,000 Americans. Current Centers for Disease Control statistics indicate that Black Americans die from COVID-19 at a disproportionately high rate, 13.6% of 449, 373 deaths but only account for 12.54% of the United States Population (CDC COVID Data Tracker accessed 5/5/2021). A voluntary clinical reported registry of COVID-19 infections in patients with SCD reported both high hospitalization rates (69%) and case fatality rates (7%) (Panepinto, 2020), but only reported data from March 20-May 21, 2020. A retrospective cohort review from England demonstrated a 4-fold increased risk of hospitalization and 2.6-fold increased risk of death due to COVID-19 for those patients with sickle cell disease compared to the general population (Hippisley-Cox, 2021). The unique constellation of SCD manifestations complicate both the diagnosis and management of COVID-19, particularly related to anticoagulation and transfusion practices. Understanding the impact of early exchange and anticoagulation would guide development of appropriate treatment guidelines and future understanding of pathophysiology. We report on the outcomes for all hospitalized inpatients with SARS-CoV-2 and SCD at institutions using Cerner electronic health record (EHR). Methods Exempted retrospective review approved by ChristianaCare IRB. We obtained deidentified data from the Cerner COVID Data Lab which includes information on all hospitalized inpatients with SARS-CoV-2 and sickle cell disease as documented by ICD 10 D57.XX from 12/10/2019-10/15/2020 at institutions that use the Cerner EHR. Those with sickle cell trait excluded. The data included 209 patients; 1 patient had separate 2 visits, only the first visit in the data. Evaluated anticoagulation use, not dose. Descriptive statistics are given: percentages for categorical variables and mean (standard deviation) for continuous variables. Comparisons between patients who died or went to hospice versus patients who recovered were done using unadjusted chi-squared tests or t-tests. Results: Admission: 124 (74.3%) were afebrile (temp <100) 52 (28.4%) were tachypneic (RR >22) 10 (6.2%) were hypoxic (<92%) 7 (3.3%) were intubated during hospitalization Many patients had comorbidities including diabetes, hypertension, and congestive heart failure, but it was not clear if patients had multiple co-morbidities. Treatment: 16 (7.7%) got transfused RBC between 1.77 and 589.18 hours into admission 5 (2.4%) got Remdesivir, none of these patients died/went to hospice. No exchange transfusions, but maybe wasn't captured in coding data 149 (71.3%) received anticoagulant, dosing unable to be obtained so not known if this was prophylactic or treatment dosing. Outcomes: 158 (80.2%) discharged home 18 (9.1%) discharged facility 8 (4.1%) died 2 (1.0%) discharged hospice 11 (5.6%) left against medical advice 12 (5.7%) missing disposition data Those who died/went to hospice had longer hospital stays, were more likely to be hypoxic and initially tachypneic. None of these patients received remdesivir. Study included small numbers but those who died more likely to have hypertension, diabetes w/ and w/out complications, CHF. Discussion This data only included hospitalized patients, doesn't account for patients who remained outpatient so case fatality rate likely lower. 10/209 patients died- 4.8% fatality rate, 12 patients missing final discharge disposition. 18 went to facility, may have died as outpatient. Only a small number of patients received remdesivir and there were overall low rates of anticoagulation, concerning given SCD is a hypercoagulable state. Study limitations include only hospitalized patients in the dataset and only draws from Cerner EMR institutions, a 26% market share. Based on our own SCD population, only a small percentage of patients with SCD and COVID-19 hospitalized. Additionally, there is likely significant variability between institutions' treatment protocols, particularly in the early months of the data set. Finally, we could not adequately gauge severity of COVID-19 disease given notable variations in institutional resources. TABLES (in process): TABLE 1- Demographics- split by death/hospice vs. other dispositions TABLE 2- Admission Characteristics- Death/hospice vs. others TABLE 3- Treatments- Death/Hospice vs. others Disclosures Lanzkron: Shire: Research Funding; Novartis: Research Funding; Bluebird Bio: Consultancy; CSL Behring: Research Funding; Imara: Research Funding; GBT: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; Novo Nordisk: Consultancy.

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Designated Donor Program Enrollment Does Not Affect Red Blood Cell Alloimmunization Rates in Children with Sickle Cell Disease on Chronic Transfusion Therapy

Blood ◽

10.1182/blood.v124.21.4291.4291 ◽

2014 ◽

Vol 124 (21) ◽

pp. 4291-4291

Author(s):

Ronald Jackups ◽

Debbie Woods ◽

Robert J. Hayashi ◽

Monica L. Hulbert

Keyword(s):

Sickle Cell Disease ◽

Blood Cell ◽

Sickle Cell ◽

Red Blood Cell ◽

Categorical Variables ◽

Patient Specific ◽

Cell Transplant ◽

Blood Group Antigens ◽

Cell Disease ◽

Transfusion Therapy

Abstract Background: Chronic red blood cell (RBC) transfusion therapy is the predominant treatment modality in children with sickle cell disease (SCD) at high risk of first or recurrent strokes. RBC alloimmunization develops in some patients receiving chronic transfusion therapy, due in part to genetic differences in the prevalence of blood group antigens between the patient population and the blood donor pool. Many children’s hospitals have developed designated donor or “buddy” programs to recruit African-American blood donors and assign them to specific SCD patients with matched phenotypes, particularly in the Rh and Kell antigen groups, to reduce the likelihood of RBC alloimmunization. However, the practical constraints of such programs may make it difficult to ensure that patients’ transfusions always come from designated donors. Moreover, it is unclear whether such programs result in a lower risk of RBC alloimmunization when compared to the use of non-designated-donor but phenotype-matched RBC units. We aimed to determine the proportion of transfusions from designated donors at our institution, hypothesizing that the development of new RBC alloantibodies is associated with a lower proportion of transfused units from designated donors. Methods: This is a single-institution retrospective cohort study of 38 patients with SCD who received chronic transfusion therapy (manual exchange or erythrocytapheresis) for primary or secondary stroke prevention from 1/1/2008 through 12/31/2012. Patients on transfusion therapy for 6 or more months were included. Subjects were censored at last date of follow-up or date of hematopoietic stem cell transplant. The local designated donor program was started in 1999. Designated donors are selected to be ABO/RhD compatible and phenotype-matched to patients for the C, E, and K antigens. When units from designated donors are not available, compatible units phenotype-matched for C, E, and K are issued from general inventory. The number and percentage of units transfused from either designated or non-designated donors, and the identification of new RBC alloantibodies during the study period, were evaluated. The rates of alloimmunization were compared between patients who received a “high” (above the median) or “low” (below the median) proportion of designated donor units. Categorical variables were compared with Fisher’s exact test and medians with the Mann-Whitney U-test in SPSS version 21 (IBM, Armonk, NY). A p-value below 0.05 was statistically significant. Results: During the study period, 38 subjects (42% male) met all inclusion criteria. A median of 120 units (IQR 60-186) was transfused to each subject, and each subject received a median of 63% (IQR 45%-77%) of units from designated donors. Of the 38 subjects, 18 (47%) produced at least one newly identified RBC alloantibody during the study period. Among these 18 antibody producers, a total of 29 new alloantibodies were detected, with a range of 1-3 per subject. Ten of the newly identified alloantibodies were directed against C, D, E, or K. No statistically significant difference between antibody producers and non-producers was identified for total number of RBC units transfused (median 161 vs. 96, p = 0.067), number of units transfused from designated donors (median 107 vs. 49, p = 0.099), number of non-designated-donor, phenotype-matched units transfused from general inventory (median 38 vs. 26, p = 0.059), or proportion of units transfused from designated donors (median 68% vs. 49%, p = 0.28). Although there was a trend toward a higher incidence of alloimmunization in patients who received a high proportion of designated donor units (OR 2.4, CI 0.6-8.7), it was not statistically significant (p= 0.33). Conclusions: Despite receiving phenotypically matched RBC units, almost half of the children with SCD on chronic transfusion therapy in this cohort developed new RBC alloantibodies during a five-year period. The number of units transfused from a designated donor did not significantly affect alloimmunization rate. One-third of the new alloantibodies were directed against antigens specifically matched for in the designated donor program. Patient-specific factors, such as genetic variation in the Rh locus, may be responsible for the risk of alloimmunization. Alternative matching strategies, such as genotypic matching of RBC donors and recipients, should be explored in prospective studies. Disclosures Jackups: Immucor: Consultancy.

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Complications of Implantable Venous Access Devices In Patients with Sickle Cell Disease

Blood ◽

10.1182/blood.v116.21.1649.1649 ◽

2010 ◽

Vol 116 (21) ◽

pp. 1649-1649

Author(s):

Nirmish Shah ◽

Daniel Landi ◽

Radhika Shah ◽

Jennifer Rothman ◽

Courtney Thornburg

Keyword(s):

Sickle Cell Disease ◽

Bloodstream Infection ◽

Sickle Cell ◽

Pediatric Patients ◽

Conflicts Of Interest ◽

Bloodstream Infections ◽

Venous Access ◽

Categorical Variables ◽

Cell Disease ◽

Venous Access Devices

Abstract Abstract 1649 INTRODUCTION: Implantable venous access devices (VADs) are used in sickle cell disease (SCD) for patients with poor venous access to facilitate chronic blood transfusions and management of acute complications. Children and adults with chronic illnesses have high rates of VAD-related complications including bloodstream infection and thrombosis. Patients with SCD may be at higher risk given the presence of functional asplenia and evidence of a hypercoaguable state. The objective of this study was to define the frequency of VAD related bloodstream infections and thrombosis in adults and children with SCD. PATIENTS AND METHODS: We performed a single institution retrospective review of VAD placement in patients with SCD. Subjects were identified through the sickle cell clinic database and the Hospital Information System. Subjects were included if they had SCD, VAD placement between December 1, 1998 to December 1, 2009 and had completed at least 12 months of follow-up. VAD-related bloodstream infection was defined by positive blood culture and VAD-related thrombosis (deep vein thrombosis, superior vena cava syndrome, and pulmonary embolism without lower extremity thrombosis) was defined by imaging. Comparisons were made between pediatric and adult sickle cell patients using Student's t-test for continuous variables and Fisher's exact test was used to compare categorical variables; p<0.05 was considered significant. RESULTS: Of the greater than 800 sickle cell patients followed at our Comprehensive Sickle Cell Center, 32 subjects were eligible for inclusion (median age 20 years, range 1–59). There were 81 VAD placed (median 2.6 VAD per patient, range 1–7) with a total of 49268 catheter days (median 608, range 323–3999). The mean catheter lifespan in adults (1798 days ± 266) was significantly higher than pediatric patients (971 ± 328, p=0.039). There were a total of 66 VAD-related bloodstream infections (1.34 infections per 1000 catheter days) occurring in 17 of 32 (53%) subjects. Although not statistically significant, children had fewer VAD-related bloodstream infections (3 of 10; 30%) compared to adults (14 of 22; 64%, p=0.08). There were 24 catheter-related thromboses (0.49 thromboses per 1000 catheter days) occurring in 10 of 32 (41%) of subjects. Children also had fewer VAD-related thrombosis (1 of 10; 10%) compared to adults (9 of 22; 40%, p=0.08). The overall rates of infection and thrombosis per 1000 catheter days were not significantly different between adult and pediatric patients. CONCLUSION: In summary, we report a long lifespan and low rate of infection in the subjects who had VADs during the study period. Most concerning was a high proportion of adults with catheter-related thrombosis, which adds the burden of anticoagulation to patient management and put patients at risk for post-thrombotic syndrome. Potential lifespan of VADs, risk of bloodstream infection and thrombosis as well as its long-term consequences should be discussed with patients and families considering VAD placement. Disclosures: No relevant conflicts of interest to declare.

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The prevalence of human immunodeficiency and of hepatitis B viral infections is not increased in patients with sickle cell disease in Tanzania

BMC Infectious Diseases ◽

10.1186/s12879-021-06726-z ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Grace Shayo ◽

Irene Makundi ◽

Lucio Luzzatto

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Hepatitis B ◽

Sickle Cell ◽

Viral Infections ◽

Cross Sectional Study ◽

Dar Es Salaam ◽

Categorical Variables ◽

Cell Disease ◽

Cross Sectional

Abstract Background Tanzania ranks as the fourth country in the world with respect to the number of sickle cell disease (SCD) births; it is also endemic to the human immunodeficiency virus (HIV) and the hepatitis B virus (HBV). This study was done to determine the prevalence of HIV and HBV infections among SCD patients in Dar es Salaam, Tanzania. Methods A multicenter hospital-based descriptive cross sectional study was carried out among participants aged ≥ 16 years with a proven diagnosis of SCD. Socio-demographic and clinical data were recorded. Blood samples were drawn for HIV and HBV diagnosis. All categorical variables were summarized into frequencies. Results There were 185/325 (56.9 %) females. The mean age (SD) was 23.0 ± 7.5 years. The prevalence of HIV was 1.8 %; the prevalence of HBV was 1.2 %. Conclusions The prevalence of both HIV and HBV in SCD patients is no greater than in the general population of Dar es Salaam or Tanzania. For associations, a large study would be needed. From a detailed blood transfusion history of SCD patients we found no evidence that HIV or HBV infection was transmitted through blood transfusion.

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The Effect Of Microalbuminuria On Duration Of Hospitalization In Adult Sickle Cell Disease Patients With Pain Crisis

Blood ◽

10.1182/blood.v122.21.4694.4694 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4694-4694

Author(s):

Mohammed Shaik ◽

Borys Hrinczenko

Keyword(s):

Sickle Cell Disease ◽

Length Of Stay ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Categorical Variables ◽

Cell Disease ◽

Exact Test ◽

Blood Disorder ◽

Significant Difference ◽

Pain Crisis

Introduction Sickle cell disease (SCD) is a genetic blood disorder of hemoglobin resulting in severe morbidity and early mortality. The prevalence of microalbuminuria and/or proteinuria in children with SCD varies from 18 to 28% and increases with age. However, the exact prevalence in adults in not known. In the general population, the presence of albuminuria has been shown to be associated with all cause mortality. The urine microalbumin to creatinine ratio (MA) is considered to be an early sign of impending sickle cell nephropathy. We sought to investigate the association of MA with various SCD genotypes (HbSS, HbSC, HbS/β-thalassemia) in our clinic and also the length of stay (LOS) in hospitalized SCD patients with acute pain crisis. Methods Twenty-eight consecutive SCD patients diagnosed in our clinic by hemoglobin electrophoresis were included in our study. The patients (pts) age, gender, hemoglobin electrophoresis, and baseline MA were obtained. Based on their MA level they were divided into two groups, abnormal MA (MA ≥ 30 mg/g creatinine) or normal MA (< 30 mg/g creatinine). Eleven of these 28 patients were eventually hospitalized for a sickle cell related pain crisis. Their MA level was obtained within 24-hours of hospital admission and their hospitalization length of stay (LOS) was also recorded. We analyzed the association between the two groups of patients, those with normal or abnormal MA, with the different genetic variants of SCD in both our clinic and hospitalized pts. Furthermore, for hospitalized pts we also assessed an association of MA with their mean LOS. The Chi-square test/Fisher’s exact test was used for categorical variables and the T-test/Mann-Whitney test was used for numerical variables. Results All twenty-eight patients were African American without significant renal impairment, with 11, 10, and 7 pts with SS, SC and S β-thalassemia (Sβ), respectively. Fifteen of these pts had abnormal MA, 12 pts were female. The median age was 35.5 yrs (range, 19 - 59), median LOS was 3.5 days (range, 2-8). The SS pts had higher abnormal MA levels followed by SC and then Sβ (p=0.03) (Table 1). There was no significant difference in gender between the two groups (p=0.2). SCD pts admitted to the hospital for pain crisis with an abnormal MA within 24-hours of admission had a significantly higher mean LOS when compared to pts with normal MA (p=0.0089) (Table 1). Conclusion Microalbuminuria is more prevalent in the severe genotypes of SCD disease such as SS and SC vs. Sβ pts. Thereby, MA might be a useful biomarker of generalized SCD vasculopathy, in addition to a known marker of progressive nephropathy. Furthermore, MA has a significant impact on length of hospitalization. An abnormal MA obtained within the first 24-hrs of hospitalization of a SCD pt in pain crisis was predictive of prolonged hospital duration. Early and more aggressive supportive care symptom management for those patients might be a reasonable option but requires more study. Further large prospective clinical trials are needed to validate our findings. Disclosures: No relevant conflicts of interest to declare.

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Comparison of the Efficacy of Simple, Partial Manual and Automated Exchange Transfusions in the Management of Sickle Cell Disease in Pediatric Patients

Blood ◽

10.1182/blood-2021-154368 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 4283-4283

Author(s):

Joy Muthoni Mburu ◽

Natalie Pitch ◽

Hana Al-Julaih ◽

Suzan Williams

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Central Venous Line ◽

Categorical Variables ◽

Cell Disease ◽

Central Venous ◽

Transfusion Therapy ◽

Hemoglobin S ◽

Sick Children ◽

Over Time

Abstract Background: Chronic transfusion therapy in sickle cell disease is used to prevent complications of sickle cell disease by reducing hemoglobin S levels, most commonly used for primary or secondary stroke prophylaxis, amongst other indications. Transfusions can be completed as simple, partial manual exchange or automated exchange.Comparative evidence on the long term efficacy of simple, partial manual or automated exchange in the management of children with sickle cell disease is lacking. Methods: A retrospective study of patients aged less than 18 years with a diagnosis of sickle cell disease on a chronic transfusion program (simple top-up transfusion, partial manual exchange or automated exchange transfusion), followed at the Hospital for Sick Children, Toronto, Ontario from January 2003- July 2020.We excluded patients who received transfusions for acute complications. Data collected included: demographics, indication for transfusion, type of transfusion (simple, partial manual exchange or automated exchange), access for transfusion (peripheral intravenous (PIV), central venous line (CVL)), pre-transfusion hemoglobin and hemoglobin S values. Analysis: Exploratory data analysis was conducted where descriptive statistics were used to summarize data for both continuous and categorical variables. Continuous variables were summarized using measures of central tendency and dispersion where mean and standard deviations for normally distributed data and medians and interquartile ranges were used where the data was skewed. Chi-squared tests were employed when demonstrating relationships between two categorical variables. All statistical analyses were two-sided tests with 0.05 as the critical level of significance. Ethics: This study was approved by The Hospital of Sick Children Research Ethics Board(REB). Results: Sixty-one participants were observed between January 2003 and July 2020. Majority 38 out of (62.3%) of the participants were male. The most common indication for transfusion was primary stroke prevention (following abnormal transcranial doppler (TCD) 36 %) followed by vasculopathy 11 (%, stroke 9 % , abnormal TCD & silent infarct 8 %, and splenic sequestration 2 %) There were 744 total transfusions. 491/744 (66%) transfusions were simple transfusions, 168/744 (22.6%) were PMEs while 85/744 (11.4%) were apheresis transfusions. Average pre-transfusion hemoglobin S (HbS) was similar between the two types of access (p=0.416) and also across the three types of transfusion (p=0.158). The type of access did not appear to have an effect on the changes in HbS per transfusion(p=0.561.) The trends of pre-transfusion HbS %were similar over time between participants whose access was PIV and those whose access was CVL/ PORT.(Figure 1 below). Achievement of target HbS was similar between peripheral intravenous and central venous line access (p=0.337) and across the three types of transfusion (p=0.086).See Table 1 below. The type of transfusion had an effect on the reduction in HBS with simple transfusion having the highest percentage change of HbSS(-3.69%) followed by Apheresis (-1.32%) and PME (-0.75%), p=0.018., that is per every transfusion. The reason for this is that is the values being compared are quite different. The automated exchange values are on established patients (pre transfusion hemoglobin S had already been lowered), while the simple transfusion values are on new to transfusion patients (pre transfusion S high), the patients on partial manual exchange started off with lower HbS levels, so consequently their change was less. Conclusion: All three types of transfusion had equal efficiency in reducing HbS over time. Apheresis showed a quicker reduction in the hemoglobin S level in the initial transfusions. Simple transfusions and PME are as efficient as apheresis in achieving target HbS levels to prevent complications associated with SCD. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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