Molecular testing for respiratory pathogens in sickle cell disease adult patients presenting with febrile acute chest syndrome

Abstract Introduction: Amongst patients with sickle cell disease (SCD) the leading cause of death is the acute chest syndrome (ACS). This pneumonia-like complication frequently occurs during or shortly after a vaso-occlusive crisis (VOC). In pediatric patients hospitalized for VOC, incentive spirometry has demonstrated to prevent the development of ACS. This study was designed to determine if a comparable effect of incentive spirometry can be demonstrated in adult patients with SCD. Furthermore, we aimed to validate the ability of the Bartolucci score to identify patients at risk of ACS and assessed the value of procalcitonin as a potential biomarker for ACS . In addition, clinical characteristics and laboratory results were determined to identify potential risk factors. Methods: In this multicenter prospective randomized trial, we included consecutive adult patients (≥18 yr) admitted for VOC presenting with chest or back pain above the diaphragm. Patients were randomly assigned to spirometry or control group. Patients presenting with ACS were excluded. A chest radiograph was performed 5 days after admission, or sooner when clinically indicated, in order to diagnose pulmonary abnormalities. ACS was defined as a new infiltrate/atelectasis combined with pulmonary symptoms. At presentation, procalcitonin plasma levels were assessed and the Bartolucci risk score was calculated to determine to the risk of developing ACS for each patient. In addition, clinical and laboratory parameters were compared between patients with and without ACS during admission. Results: In total 66 episodes of hospitalization for VOC in 48 patients were included. Median age was 26 years and 46 of the hospitalizations concerned patients with a severe genotype (HbSS/HbSβ0 thalassemia) versus 20 hospitalization with a mild genotype (HbSC/HbSβ+thalassemia). The overall incidence of ACS in this study cohort was 19.7%. In the spirometry group, ACS was diagnosed in 5/34 (14.7%) hospitalizations compared to 8/32 (25%) hospitalizations in the control group (OR 0.5 [0.15-1.8]; P=.293). Twelve of the 13 ACS episodes occurred in patients with a severe genotype. The Bartolucci risk score could be calculated for 50 hospitalizations. The scores area under the curve (AUC) was 0.747 (P=.013), with a negative predictive value (NPV) of 94% and a positive predictive value (PPV) of 31%. No difference in procalcitonin plasma levels were found between patients with and patients without ACS (0.52 ± 1.56 μg/ml versus 0.56 ± 1.44 μg/ml, respectively). At baseline, hemoglobin levels were significantly lower while LDH plasma levels, leukocyte and platelet counts were significantly higher in ACS hospitalizations as compared to non-ACS hospitalizations. Patients who developed ACS showed significantly more documented fever during admission (61.5% vs 17.0%) and a longer length of hospital stay (median 10.0 days vs 4.5 days). Conclusion: Incentive spirometry did not significantly reduce the development of ACS in this prospective study in adult patients with SCD admitted with VOC and pain above the diaphragm. Procalcitonin plasma levels and the Bartolucci score could not accurately identify patients that at risk to develop ACS, but a low score appeared to be a reliable tool to identify patients with a low risk of ACS. Disclosures No relevant conflicts of interest to declare.

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Fever In Hospitalized Adult Patients with Sickle Cell Disease

Blood ◽

10.1182/blood.v116.21.2652.2652 ◽

2010 ◽

Vol 116 (21) ◽

pp. 2652-2652

Author(s):

Deepa Jeyakumar ◽

Matthew Zibelman ◽

Ryan Hurth ◽

Lani Krauz ◽

Santosh Saraf ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Conflicts Of Interest ◽

Hospital Setting ◽

Adult Patients ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Indwelling Catheters ◽

Upper Limit ◽

Pain Crisis

Abstract Abstract 2652 Background: Sickle cell disease is complicated by veno-occlusive crises leading to pain crises, chronic end-organ damage and early mortality. With recent advances in the management of sickle cell disease in childhood, sickle cell patients are living longer. However, our understanding of the clinical course of adult sickle cell disease remains limited and is based largely on extrapolation of knowledge from children with sickle cell disease. Unfortunately, adult patients remain at an elevated risk of infections due to encapsulated organisms in the setting of functional asplenia. This risk is exacerbated by possible indwelling catheters and exposure to the health care environment. Fever in these patients can herald a serious infection. Alternatively, brisk hemolysis can be associated with fever. Wierenga, et. al. (2001) described that fevers to 39F in children were associated with acute chest syndrome (21%), painful vaso-occlusive crisis (27%), and bacteremia in 6%. To our knowledge, no such review of fever in hospitalized adult sickle cell patients has been published in the medical literature. Therefore, the clinician is placed in a diagnostic dilemma regarding the management of fever in adult patients with sickle cell disease. Objective: To determine the etiologies of fevers in hospitalized adult patients with sickle cell disease in an urban tertiary hospital setting. Methods: We performed an IRB-approved retrospective analysis of 143 admissions between 1995–2008 with sickle cell pain crisis and had a fever greater than 38.5C during the admission. The aim was to determine the prevalence of fevers due to infectious versus hemolysis-related causes in the population of interest. Elevated white blood cell count (defined as greater than 1.5x upper limit of normal), radiologic and/or culture data were used to classify a fever as due to infection. Elevated LDH and total bilirubin (defined as greater than 2x upper limit of normal) were used to classify a fever as due to hemolysis. The risks of infection in patients on hydroxyurea as well as indwelling catheters (including central lines and foley catheters) were assessed. We also evaluated the risk of hemolysis in patients on hydroxyurea. Finally, the use of antibiotics and duration of the fever in patients with hemolysis and infection were also evaluated. Results: Among patients admitted with sickle cell pain crisis and had a fever during their hospitalization, we found evidence of infection in 65% and hemolysis in 58%. Interestingly, 35% had evidence of both infection and hemolysis. Approximately, 11.8% had no significant evidence of infection or hemolysis. Antibiotics were used in 66% of all patients with pain crisis and fever. Among the patients who received antibiotics, 81% had evidence of infection and 19% had no evidence of infection. Approximately 1/5 patients with fevers received antibiotics despite the absence of evidence of infection. Infections were not increased among hydroxyurea users (61.5% with fever) over non-hydroxyurea users (67.9% with fever), p = 0.4. Fevers due to documented infections were found in 78% of patients with indwelling catheters compared with 62% of patients without catheters, p≤0.05. The risk of fever due to hemolysis was not significantly different between hydroxyurea and non-hydroxyurea users at 58% versus 57% respectively, p=0.9. Of patients with fevers for more than one day, infection was found in 69% of patients compared with 31% of patients who had no evidence of infection p=0.5. Whereas, of patients with fevers for more than one day, hemolysis was found in 57% of patients compared with 42% of patients who did not have evidence of hemolysis with p=0.9. Conclusions: Among adult sickle cell patients hospitalized with pain crisis and fever, hemolysis accounted for 58% of cases while infections accounted for 65% with 35% evidence of both. Infections were not increased among hydroxyurea users. Indwelling catheters did increase the risk of fevers due to infection. The risk of fever due to hemolysis was not significantly increased among patients on hydroxyurea. Finally, in patients with fevers for more than one day, hemolysis accounted for 57% of cases and infection accounted for 45%. These findings provide initial investigation of the etiologies of fevers in adult hospitalized sickle cell patients and further studies are necessary to confirm these findings. Disclosures: No relevant conflicts of interest to declare. Disclosures: No relevant conflicts of interest to declare.

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Antibiotic Use and Respiratory Pathogens in Adults With Sickle Cell Disease and Acute Chest Syndrome

Annals of Pharmacotherapy ◽

10.1177/1060028019846118 ◽

2019 ◽

Vol 53 (10) ◽

pp. 991-996

Author(s):

Alyssa M. Claudio ◽

Lindsey Foltanski ◽

Tracie Delay ◽

Ashley Britell ◽

Ashley Duckett ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Cohort Analysis ◽

Empirical Therapy ◽

Antibiotic Use ◽

Chlamydophila Pneumoniae ◽

Acute Chest Syndrome ◽

Respiratory Pathogens ◽

Cell Disease ◽

Syncytial Virus

Background: Acute chest syndrome (ACS) is an acute complication of sickle cell disease (SCD). Historically, the most common pathogens were Chlamydophila pneumoniae, Mycoplasma pneumoniae, and respiratory syncytial virus. Pediatric patients receiving guideline-adherent therapy experienced fewer ACS-related and all-cause 30-day readmissions compared with those receiving nonadherent therapy. This has not been evaluated in adults. Objectives: The primary objectives were to characterize antibiotic use and pathogens. The secondary objective was to assess the occurrence of readmissions associated with guideline-adherent and clinically appropriate treatment compared with regimens that did not meet those criteria. Methods: A retrospective cohort analysis was conducted for adults with SCD hospitalized between August 1, 2014, and July 31, 2017, with pneumonia (PNA) or ACS. The study was approved by the institutional review board. Results: A total of 139 patients with 255 hospitalizations were reviewed. Among 41 respiratory cultures, 3 organisms were isolated: Cryptococcus neoformans, Pseudomonas aeruginosa, and budding yeast. Respiratory panels were collected on 121 admissions, with 17 positive for 1 virus; all were negative for Chlamydophila pneumoniae and M pneumoniae. There were significantly more ACS-/PNA-related 7-day readmissions from patients on guideline-adherent regimens compared with nonadherent regimens (3.7% vs 0%; P = 0.04). Conclusion and Relevance: These findings challenge existing knowledge regarding the most common pathogens in adults with SCD with ACS or PNA. Routine inclusion of a macrolide may not be necessary. Future studies focused on pathogen characterization with standardized assessment are necessary to determine appropriate empirical therapy in this population.

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Veno-Venous Extracorporeal Membrane Oxygenation in Adult Patients with Sickle Cell Disease and Acute Chest Syndrome: a Single-Center Experience

Hemoglobin ◽

10.1080/03630269.2020.1745827 ◽

2020 ◽

Vol 44 (2) ◽

pp. 71-77

Author(s):

Ferras Alashkar ◽

Frank Herbstreit ◽

Alexander Carpinteiro ◽

Julia Baum ◽

Asterios Tzalavras ◽

...

Keyword(s):

Sickle Cell Disease ◽

Extracorporeal Membrane Oxygenation ◽

Sickle Cell ◽

Adult Patients ◽

Acute Chest Syndrome ◽

Single Center ◽

Cell Disease ◽

Membrane Oxygenation ◽

Single Center Experience

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Sickle Cell Disease and COVID-19 Infection: A Single-Center Experience

Blood ◽

10.1182/blood-2021-154240 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 985-985

Author(s):

Sindhu Devarashetty ◽

Kimberly Le Blanc ◽

Udhayvir Singh Grewal ◽

Jacqueline Walton ◽

Tabitha Jones ◽

...

Keyword(s):

Pulmonary Embolism ◽

Sickle Cell Disease ◽

Mortality Rate ◽

Sickle Cell ◽

Adult Patients ◽

Living Alone ◽

Morbidity And Mortality ◽

Acute Chest Syndrome ◽

Single Center ◽

Cell Disease

Abstract Background and Objectives: The COVID-19 (CO19) pandemic caused by SARS-CoV-2 remains a significant issue for global health, economics, and society. Several reports have shown that African Americans (AA) have been disproportionately affected by the CO19 pandemic. Limited data have suggested that sickle cell disease (SCD) could be one of the several reasons for higher morbidity and mortality related to CO19 among AA. Recent reports have suggested higher-than-average morbidity and mortality related to CO19 among patients with SCD. We conducted a retrospective, single-institution study in adult patients with SCD who were diagnosed with CO19 infection and their outcomes. Methods: After IRB approval, we conducted a chart review of adult patients (greater than 18 years) with SCD who were diagnosed with CO19 infection between March 1st, 2020, and March 31st, 2021. We recorded demographic data including age, gender, social factors (the type of insurance, availability of primary care provider (PCP), living alone/not), clinical parameters (type of SCD, co-morbidities), outpatient management of SCD, and how CO19 infection was managed like inpatient admission and complications. In patients who were admitted or seen in the emergency department (ED), we collected additional data including vitals, labs, the severity of illness, complications, length of stay, and outcomes. Computations were performed using statistical software SAS 9.4 for Windows. Results: We found a total of 51 patients with SCD diagnosed with CO19 infection in the above period. The median age of patients was 30 years. 61% were females and 39 % were males. All of them were AA. 11.76% were living alone, 49.02% were living with family, 1.96% (1 patient) was institutionalized, and the living situation was unknown in 37.25%. Most of the patients had Medicaid Insurance (52.94%), Medicare in 33.3%, private insurance in 13.73 % and 2% were uninsured. Only 64.71% of patients had a PCP. 60% had HbSS disease, 32% had HbSC disease, 4% had HbS-beta thalassemia, one patient each had HbSS with hereditary persistence of HbF and HbS/HbD. Comorbidities and previous history included acute chest syndrome in 65.96%, avascular necrosis in 36.96%, leg ulcers in 8.7%, hypertension in 8.7%, sickle cell retinopathy in 14.57%, cerebrovascular disease in 26.19%, chronic kidney disease in 7.69%, venous thromboembolism (VTE) in 20.41%, 10.41% were on anticoagulation, history of HIV and hepatitis C infection in 6.38%. 28.21% of patients were maintained on partial exchange transfusions as an outpatient for various indications. 72.73% were on hydroxyurea, 7.5% were on crizanlizumab, 5.26% were on voxelotor and 26.83% were on iron chelation. Vitals and pertinent lab values on initial assessment were recorded and many patients had missing data. On presentation, 25.53% were febrile, 29.17% of patients were tachycardic, 31.25% were hypoxic (SpO2 < 95%), 38.46% were tachypneic, 59.18% had a body mass index (BMI) of > 24.9. Median hemoglobin and hematocrit were 8.9/27.4 g/dL. The median white blood cell count was 9490/uL and platelets were 315,000/uL. Median ferritin was 1573 ug/L. Median bilirubin and creatinine were 2.05 mg/dL and 0.86 mg/dL. The patients were further stratified based on the clinical location where CO19 infection was managed (Table 1). 39.3% were diagnosed in the outpatient setting/ED and 60.3% in the inpatient setting. Among 51 patients, 5.71% (n=2) required ICU admission and was mechanically ventilated. 17.5% received dexamethasone, 7.69% received remdesivir, 2.76% received convalescent plasma, 17.07% had infections and 47% received antibiotics. Only one patient received an exchange transfusion during admission. One patient developed a new VTE after CO19 infection. On statistical analysis, the only factor which impacted the clinical location of management was tachycardia (P=0.007). Of the 51 patients, only 3.9% (2 patients) died of complications of CO19 infection, one with hypoxic respiratory failure, disseminated intravascular coagulation, shock, and the other one with pulmonary embolism. 13% were readmitted within a month, one of them was admitted with a new pulmonary embolism and the others were admitted for acute painful episodes. Conclusion: We found a mortality rate of 3.9% in our single-center study of patients with SCD and CO19 infection. This mortality rate is lower than other published experiences in patients with SCD and CO19 infection. Figure 1 Figure 1. Disclosures Master: Blue Bird Bio: Current holder of individual stocks in a privately-held company.

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The Immature Reticulocyte Fraction As an Aid in the Diagnosis and Prognosis of Parvovirus B19 Infection in Sickle Cell Disease

Blood ◽

10.1182/blood-2018-99-117152 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 3678-3678

Author(s):

Robert Mitrani ◽

Kandace Gollomp ◽

Michele P. Lambert ◽

Amrom Obstfeld

Keyword(s):

Sickle Cell Disease ◽

Board Of Directors ◽

Sickle Cell ◽

Reticulocyte Count ◽

Parvovirus B19 ◽

Acute Chest Syndrome ◽

Molecular Testing ◽

Cell Disease ◽

Advisory Committees ◽

Chronic Hemolysis

Abstract Background Sickle cell disease (SCD) is characterized by hemoglobin polymerization leading to vaso-occlusion, chronic hemolysis and vasculopathy. Parvovirus B19 (B19) infection causes an acute arrest of erythropoiesis leading to reticulocytopenia and potentially life-threatening anemia in patients with chronic hemolysis such as SCD. Diagnosis of B19 infection relies on clinical history in combination with expensive and often belated serological and molecular testing. The immature reticulocyte fraction (IRF) is a relatively new reticulocyte parameter available on automated hematology analyzers that assesses the maturity of circulating reticulocytes by quantifying the fraction that stain strongest for RNA. Aims We hypothesized that the IRF could provide diagnostic information in the evaluation and management of patients with SCD who are being evaluated for B19 infection. Specifically, given that the IRF quantifies the fraction of circulating reticulocytes that have just exited the bone marrow and are least mature, we speculated that changes in IRF would precede changes seen in the reticulocyte counts in aplastic crisis and recovery. Methods We performed a retrospective analysis of records at the Children's Hospital of Philadelphia of complete blood count (CBC) and reticulocyte indices in patients with sickle cell disease in whom B19 infection by PCR testing was assessed between January 1, 2015 and October 31, 2017. CBC testing was performed on the Sysmex XN 3000 analyzer. Medical records were reviewed to verify that the B19 testing was sent during an acute aplastic episode. Diagnostic performance of reticulocyte percent (RET%) and count (RET) compared to the IRF and the absolute IRF count (AIR) was assessed by receiver-operator characters (ROC) curves on GraphPad Prism. For recovery studies, an increasing IRF was defined as an increase of 10 per 24 hour period and a recovering reticulocyte count was defined as an increase of 50,000 cells/uL per 24 hour period. Results At baseline, patients with SCD have an average IRF of 27.2% (16.7 - 37.7%), far higher than the reference interval (9.3 - 17.4%). This parallels the elevations in reticulocyte counts in this population and relates to their chronically high RBC turnover. A total of 119 patients had B19 testing performed in the study period of which 26 were found to have acute infection. The most common diagnoses amongst the B19 negative patients were unspecified fever/viral syndrome, vaso-occlusion/pain crisis, and acute chest syndrome. ROC curve analysis demonstrates that RET%, RET, IRF, and AIR lab values are predictive of B19 infection on the day that B19 PCR testing was sent with an AUC of 0.73, 0.76, 0.76, and 0.83 (p < 0.001 for all) respectively. The AUC for each parameter increased when the respective minimum value was analyzed; RET%, RET, IRF, and AIR showed an AUC of 0.83, 0.87, 0.87, and 0.91 (p < 0.0001 for all, figure 1 and table 1). In particular, an IRF value below 2.45% demonstrated a sensitivity of 50% and a specificity of 99% for B19 infection in the study population. Finally, amongst B19 positive patients we found that an increasing IRF was strongly associated with a reticulocyte recovery within the following 48 hour period (chi-square p-value = 0.015). A rising IRF was associated with a higher mean reticulocyte increase in the following assessment (2,500/24 hour period vs. 33,000/24 hour period, p < 0.05, figure 2). Moreover, an increasing IRF had a sensitivity of 31% and a specificity of 92% for a recovery in reticulocyte count. These results were consistent amongst all aplastic patients who were tested for B19 as well (data not shown). These data suggest that a high IRF is closely associated with a rising reticulocyte count within the following 24-48 hours. Conclusions Our data confirms that amongst a cohort of complicated patients with SCD and other causes for reticulocytopenia, the IRF is highly specific for detecting the severe aplasia caused by B19 infection in this group. This additional data may be useful in better triaging patients with SCD and reticulocytopenia and potentially in improving utilization of the more expensive B19 diagnostic testing. Furthermore our study suggests that an increasing IRF predicts reticulocyte recovery in reticulocytopenic patients with SCD and could have utility in clinical decision making such as whether to transfuse packed red blood cells or whether they can be safely discharged from the hospital. Disclosures Lambert: Amgen: Membership on an entity's Board of Directors or advisory committees; Sysmex: Consultancy; Bayer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Educational Concepts in Medicine: Consultancy; Summus: Consultancy; Rigel: Consultancy; Shionogi: Consultancy; CSL: Consultancy.

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Prevalence of Disease Related Complications from in Adult Patients with Sickle Cell Disease

Blood ◽

10.1182/blood.v128.22.4862.4862 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4862-4862

Author(s):

Samip Master ◽

Shajadi Patan ◽

Shashank Cingam ◽

Richard Preston Mansour

Keyword(s):

Sickle Cell Disease ◽

Iron Overload ◽

Renal Dysfunction ◽

Retrospective Analysis ◽

Sickle Cell ◽

Health Science ◽

Adult Patients ◽

Acute Chest Syndrome ◽

Leg Ulcers ◽

Cell Disease

Abstract Introduction: Sickle cell disease can lead to variety of complications like strokes, acute chest syndrome (ACS), sickle cell hepatopathy, priapism, renal dysfunction, avascular necrosis (AVN) ofjoints , pulmonary hypertension and leg ulcers. Average life expectancy of patient with SCD has improved with better treatments available. Most of literature on SCD in form pediatric literature and data on adults is considerably lacking. We did a retrospective analysis to investigate the prevalence of complications in adult patients with SCD. Methods: We take care of around 300 adult active patients with SCD at our hematology clinic. We did a retrospective analysis from 458 adult patients seen at our clinic between 2001 and 2016. We collected data on gender, race, type of SCD, complications like stroke, acute chest syndrome, iron overload, leg ulcers, AVN, hepatopathy and renal dysfunction. Results: A total of 458 adult patients with SCD were analyzed. 231 were female and 227 were males. The total number of patients with SC disease was 114, SS was 263, sickle beta thal was 75 and 4 had SS with hereditary persistence of Hemoglobin F (SS HPF). The number patient with complication has been listed in table below. Conclusion: Adult Centers for the treatment of Sickle Cell Disease need to optimize care directed at these high frequency, life changing and life shortening complications. Multidisciplinary care teams have to focus on these chronic complications that include transfusion program, iron overload treatment and prevention, orthopedic care and Hepatitis C and B directed carealong with acute complication care. This retrospective study serves as the basis for our adult Sickle Cell Disease program at Louisiana State University Health Science Center in Shreveport, Louisiana. Table Table. Disclosures No relevant conflicts of interest to declare.

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Blood Transfusion in Adult Patients with Sickle Cell Disease: Incidence of Alloimmunization

Blood ◽

10.1182/blood.v128.22.4859.4859 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4859-4859 ◽

Cited By ~ 1

Author(s):

Samip Master ◽

Menchu Ong ◽

Richard Preston Mansour

Keyword(s):

Sickle Cell Disease ◽

Blood Transfusion ◽

Blood Cell ◽

Sickle Cell ◽

Red Blood Cell ◽

Disease Incidence ◽

Adult Patients ◽

Red Blood Cell Transfusion ◽

Acute Chest Syndrome ◽

Cell Disease

Abstract Background: Chronic red blood cell transfusion has been proven to be effective in prevention of strokes, silent cerebral infarcts, acute chest syndrome, recurrent priapism and in pregnancy. The use of regular transfusions to mitigate other morbidities of sickle cell disease (SCD) is evolving. In the silent infarct transfusion (SIT) trial in children, chronic transfusion lead to a significant improvement in quality of life. Some of the common reasons patient with SCD do not get chronic transfusion is fear of alloimmunization, iron over load and risk of viral infections. We did a retrospective analysis of adult patients with SCD who need chronic blood transfusion to determine the incidence of alloimmunization. At our institute all pediatric sickle cell patients needing chronic transfusion are placed on protocol, receive C, E, and K matched blood, and remain on the protocol until they become adults. Methods: We electronically collected data from 180 adult SCD patients who need chronic transfusions and analyzed the data for the number of transfusions received, incidence of allo- immunization and most common antibodies identified. Results: A total of 3967 red blood cell transfusions were administered on 180 adult sickle cell disease patients. Twenty five patients developed antibodies (13.8 %). Fifteen out of the 25 had multiple antibodies (60%). The alloantibodies identified were : anti- K(11), anti- E(12), anti- Fya(5), anti-C (4), anti-V (4), anti- S (3), anti-D (2), anti- Jkb (1), anti-Jsa(1) , and anti- Lutherana (3). Two patients had cold and 5 patients had warm autoantibodies. Conclusion: The policy to place patients with SCD needing chronic transfusion on protocol to receive C, E, and K matched red blood cells has decreased the alloimmunization rate to 13.8 %. We conclude that, fear of alloimmunization should not preclude physicians from using chronic red cell transfusions to prevent complications in sickle cell disease. Disclosures No relevant conflicts of interest to declare.

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Predictors of Renal Insufficiency in Sickle Cell Disease.

Blood ◽

10.1182/blood.v104.11.3747.3747 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3747-3747

Author(s):

Margaret A. Keller ◽

Meggin K. Borowski ◽

Marcella Devoto ◽

Hui-Hua Li ◽

Morgan Brown ◽

...

Keyword(s):

Sickle Cell Disease ◽

Renal Insufficiency ◽

Renal Disease ◽

Sickle Cell ◽

Fetal Hemoglobin ◽

Adult Patients ◽

Acute Chest Syndrome ◽

Enos Gene ◽

Genetic Modifiers ◽

Cell Disease

Abstract Renal insufficiency is the source of significant morbidity and mortality in adults with sickle cell disease (SCD). A population of adult patients with SCD and end-stage renal disease (ESRD) requiring hemodialysis was examined for factors that predict ESRD. ESRD patients (mean age 36.8 +/− 7.74) were compared with patients without ESRD over 50 years old (mean age 59.3 +/− 8.31). We found that the ESRD population was characterized by more males (14 males, 8 females ESRD vs. 4 males, 15 females non-ESRD), a higher occurrence of the CAR beta-like globin cluster haplotype (44 % ESRD vs. 11 % non-ESRD) and relatively lower fetal hemoglobin levels (3.6 +/− 2.16 ESRD vs. 8.6 +/− 6.35 non-ESRD). In order to further examine potential predictors of renal disease, including genetic modifiers unlinked to the beta-globin cluster, we examined a broader population of patients with elevated creatinine, defined as levels greater than 1.0 mg/dl, who did or did not require hemodialysis. We hypothesize that gender, beta-like globin cluster haplotype, fetal hemoglobin levels and polymorphisms in critical regulators of vasomotor tone are predictors of renal insufficiency in SCD. Genotyping of a single nucleotide polymorphism (SNP) in endothelial nitric oxide synthase (eNOS or NOS3) and an insertion/deletion polymorphism (I/D) in the angiotensin-converting enzyme (ACE) gene will allow us to determine if these polymorphisms are over-represented in this cohort. The eNOS T-786C SNP alters the level of transcription of the eNOS gene and the amount of eNOS activity. We recently showed that this polymorphism was associated with a history of acute chest syndrome in females with SCD (Br. J. Haematol., 2004, 124:240). The ACE I/D polymorphism has been associated with altered plasma ACE levels. Twenty-one adult patients with sickle cell disease with renal insufficiency and 25 age- and gender-matched control patients seen at Thomas Jefferson University are being examined. Genotype results and statistical analysis will be presented. It is hoped that identification of predictors of renal insufficiency in patients with SCD might lead to early identification of at-risk patients, allowing for therapeutic intervention.

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