scholarly journals Ordering of Home Hydroxyurea By Residents for Hospitalized Patients with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 3521-3521
Author(s):  
Rebekah Shaw ◽  
Sarah Kappa ◽  
Robert Sheppard Nickel
Keyword(s):  
Sickle Cell Disease ◽  
Policy Change ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Hospitalized Patients ◽  
Fisher Exact Test ◽  
Not Given ◽  
Cell Disease ◽  
Hospital System

Abstract Background: Hydroxyurea is daily oral medication proven to decrease complications of sickle cell disease (SCD). While concerns have been raised about the safety of hydroxyurea, it is now generally viewed as a well-tolerated medication for SCD. The primary toxicity of hydroxyurea that requires holding of treatment is reversible cytopenia. Due to its classification as a chemotherapeutic agent and safety concerns regarding inappropriate chemotherapy ordering, hydroxyurea can only be ordered by "chemotherapy-certified" providers at some hospitals. At our hospital system, pediatric resident physicians were restricted from ordering hydroxyurea. Instead of being a part of a resident's hospital admission orders, hydroxyurea for inpatients had to be ordered separately by a hematology fellow or attending physician. In June 2016 our hospital changed its policy to allow residents to order hydroxyurea for patients with SCD admitted to the hospital who were already on hydroxyurea at home. We hypothesized that this change in policy to allow residents to order hydroxyurea would increase the proportion of patients with SCD appropriately receiving their home hydroxyurea by hospital day 1. We also hypothesized that this policy change would not result in an increase in the proportion of patients inappropriately receiving hydroxyurea when it should have been held based on the admission complete blood count (CBC). Methods: We conducted a retrospective review of the medical records of a random sample of patients admitted to the hematology service the year before (2015) and the year after (2017) the policy change in 2016. Patients were eligible for study if they were admitted to the hematology service and were taking hydroxyurea as documented by a clinic note within the last three months. Patients were excluded if they were admitted to the intensive care unit or for surgery. Patients were also excluded if discharged on hospital day 0 or 1. Institutional guidelines advise holding hydroxyurea if any of the following: absolute neutrophil count <1250/µL; platelet count <80K/µL; reticulocyte count <100K/µL, unless hemoglobin >8.0 gm/dL. Hydroxyurea was classified as "inappropriately given" if a patient received hydroxyurea despite having an admission CBC value below a hold parameter. Hydroxyurea was classified as "appropriately not given" if a patient did not receive hydroxyurea when having a CBC value below a hold parameter. Patients who were on hydroxyurea who never received hydroxyurea inpatient with CBC values above the hold parameters were classified as "inappropriately not given." Patients admitted in 2015 (before resident ordering) were compared with patients admitted in 2017 (after resident ordering) using a chi-square test or Fisher exact test. Results: In total, 217 hospitalizations of eligible patients were reviewed: 91 before the policy change and 126 after the policy change. Based on the admission CBC, hydroxyurea should have been held for 8 patients. Excluding these patients who should not have received hydroxyurea, patients after the policy change were significantly more likely to have received their home hydroxyurea by hospital day 1: before 62/90 (69%) vs. after 105/119 (88%), p=0.0005. The proportion of patients who inappropriately received hydroxyurea was very low in both groups: before 1/91 (1%) vs. after 3/126 (2%), p=0.64. No serious adverse clinical events occurred from this "inappropriate" administration of hydroxyurea. The figure graphically displays the proportion of patients in the two groups who: appropriately received on hospital day 0/1/2+, inappropriately did not receive, appropriately did not receive, and inappropriately received hydroxyurea. Conclusion: Resident ordering of home hydroxyurea for hospitalized patients with SCD appears to be safe. Policies that permit residents to order hydroxyurea as part of a patient's admission orders can help increase the proportion of patients who receive this important medication while inpatient. Figure. Figure. Disclosures No relevant conflicts of interest to declare.

scholarly journals Utility of Procalcitonin in Differentiating Acute Chest Syndrome from Vaso-Occlusive Crisis in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 10-11
Author(s):  
Satish Maharaj ◽  
Simone Chang ◽  
Karan Seegobin ◽  
Marwan Shaikh ◽  
Kamila I. Cisak
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Complete Blood Count ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Acute Chest Syndrome ◽  
Adult Males ◽  
Cell Disease ◽  
Unequal Variances ◽  
Recorded Data

Background: Acute chest syndrome (ACS) frequently complicates sickle cell disease (SCD) and is a leading cause of hospitalization and mortality. Many factors have been implicated in ACS, including infections, thrombosis, fat and pulmonary emboli. However, a clear etiology is not defined in 50% of the cases and ACS is considered a clinical endpoint for different pathogenic processes (Vichinsky et al 2000). The non-specific nature of ACS makes diagnostic tests challenging, and there are no serum tests clinical used to aid diagnosis. Procalcitonin (PCT) is a prohormone of calcitonin and serum PCT rises within hours of an inflammatory stimulus. PCT has clinical utility as a marker of severe systemic inflammation, infection, and sepsis (Becker et al. 2008). Few studies have evaluated PCT as a biomarker for ACS in patients presenting with vaso-occlusive crises (VOC). Two studies have reported no difference in PCT (Biemond et al. 2018 and Stankovic et al 2011), while one study reported higher PCT between ACS and VOC (Patel et al 2014). Methods: We retrospectively reviewed 106 patients with SCD who presented to the emergency department with fever and painful crises during 2015-2019. The patients were divided into two categories based on discharge diagnoses - patients with VOC only (n=88) and patients with ACS (n=18). Inclusion criteria for both groups were patients with SCD, 17 years and older and PCT measurement on presentation. Exclusion criteria were defined as patients who had received empiric antibiotics prior to PCT testing. Data collected on presentation included genotype, age, gender, complete blood count, PCT, creatinine, total bilirubin and hydroxyurea use. Length of stay was recorded. Data was analyzed between the two groups using descriptive statistics and accounting for unequal variances, withp-value set at 0.05 for significance. Results: Demographics and clinical characteristics are summarized in Table 1 (Figure). The sample included primarily adult males (77%), with about two-thirds on hydroxyurea. Genotype HbSS (73.6%) was most prevalent followed by HbSC (22.6%) and HbSβ (3.8%). The ACS group had a higher percentage of HbSS, lower use of hydroxyurea and higher mean bilirubin. Mean PCT for the ACS group was 0.52 ng/mL (range, 0.05-2.04), compared to 0.31 ng/mL (range, 0.02-6.82) in the VOC group; withp=0.084. ROC analysis showed a PCT&gt;0.5ng/mL had 39% sensitivity and 85% specificity for ACS in this sample. Conclusion: In this sample, PCT on presentation was higher in those with ACS compared to VOC, but this difference did not achieve statistical significance. Further study in a larger population would be useful to evaluate this finding. Disclosures No relevant conflicts of interest to declare.

scholarly journals Propensity Score Matched Analysis of Risk for Malignancies in Sickle Cell Anemia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5885-5885
Author(s):  
Amber Afzal ◽  
Nauman Siddiqui ◽  
Amandeep Godara ◽  
Zarmina Khan ◽  
Hande H. Tuncer
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Sickle Cell Anemia ◽  
Hematological Malignancies ◽  
Conflicts Of Interest ◽  
Hospitalized Patients ◽  
P Value ◽  
Cell Disease ◽  
Protective Mechanisms ◽  
Chi Square

Abstract BACKGROUND: The survival of sickle cell patients is limited as compared to the general population. The major morbidity and mortality comes from sickle cell complications including cardiovascular disease, renal failure, infections and thrombosis (Manci Br J Haematol 2013). However, literature is conflicting about risk for malignancies in this population and remains to be investigated by larger studies. Our retrospective study is aimed at studying the prevalence of different malignancies in a large cohort of hospitalized sickle cell patients in the year 2014 using the National Inpatient Sample (NIS). METHODS: Study Population: We identified hospitalized sickle cell patients in NIS using ICD-9 codes (282.5,282.6X -282.6X) for year 2014. We also identified the various malignancies through ICD-9 codes and studied the prevalence of individual malignancies in hospitalized sickle cell patients (SCD/cases) compared to a matched cohort of hospitalized patients with no sickle cell disease (No SCD/controls). Statistical Analysis: The 1:N Case-Control Matching Macro (Parsons LS et al SUGI 29) was used to match cases with controls with respect to potential confounders including age, race, gender in the ratio of 1:4. Chi Square was used to determine the difference in the proportions of individual malignancies between the two groups. P value <0.05 was considered statistically significant. All analyses were performed using SAS 9.4. RESULTS: We identified 117,405 hospitalized sickle cell patients in the NIS database who were matched to 469,620 controls (Table 1). A total of 1890 malignancies were found in sickle cell cohort. The prevalence of malignancies in hospitalized sickle cell patients was 1.6% as compared to 4.6% in controls (OR 0.34; range:0.30-0.38). The prevalence of all studied malignancies including hematological malignancies was lower in hospitalized sickle cell patients as compared to a matched population of hospitalized patients with no sickle cell disease (Table 2). CONCLUSION: Our study showed a lower prevalence of both solid tumors and hematological malignancies in patients with sickle cell disease as compared to matched cohorts. Future prospective cohort studies are needed to evaluate the risk of malignancies in sickle cell anemia and identify if any protective mechanisms exist against the development of malignancy in this patient population. Disclosures No relevant conflicts of interest to declare.

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

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

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

scholarly journals Interferon Induction By HbS, SERINC5 Upregulation and Reduction of HIV-1 Nef and AP2 Contribute to HIV-1 Restriction in Sickle Cell Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 5-6
Author(s):  
Namita Kumari ◽  
Marina Jerebtsova ◽  
Songping Wang ◽  
Sharmin Diaz ◽  
Sergei Nekhai
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Mononuclear Cells ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Interferon Response ◽  
Cell Disease ◽  
Restriction Factors ◽  
Peripheral Blood Mononuclear ◽  
Hiv 1

Concerted action of numerous positively acting cellular factors is essential for Human immunodeficiency virus type 1 (HIV-1) replication but in turn is challenged by anti-viral restriction factors. Previously we showed that ex vivo one round HIV-1 replication and replication of fully competent T-tropic HIV-1(IIIB) is significantly reduced in peripheral blood mononuclear cells (PBMCs) obtained from patients with Sickle Cell Disease (SCD). Further, we identified and confirmed CDKN1A (p21) and CH25H as host restriction factors expressed in SCD PBMCs that may contribute to the HIV-1 inhibition, in addition to the previously reported SAMHD1 and IKBα. Since CH25H is an interferon stimulated gene (ISG), we analyzed IRFs and interferon expression in SCD PBMCs. Higher levels of IRF7 and IFNβ mRNA were observed in SCD PBMCs compared to controls. We probed further to ascertain if hemin or sickle Hb was responsible for interferon response. We found upregulation of IFNβ in THP-1 - derived macrophages treated with lysates of HbSS RBCs or purified HbS as compared to untreated or HbA treated controls. HbSS RBCs lysates and purified HbS inhibited HIV-1 gag mRNA expression in monocyte-derived macrophages infected with HIV-1(Ba-L). Recent clinical study showed increased levels of CD4 in HIV-1 infected SCD patients in Africa. Thus we analyzed CD4 levels in HIV-1 IIIB infected SCD PBMCs, and found them to be higher compared to controls. Levels of HIV-1 nef mRNA, that controls CD4 expression was lower in HIV-1 IIIB infected SCD PBMCs. As Nef counteracts SERINC3/5 restriction factor, we analyzed its expression as well as the expression of AP2 clathrin adaptor that is required for Nef mediated internalization of CD4. AP2 expression was lower and SERINC5 expression was higher in SCD PBMCs. CONCLUSIONS: SCD PBMCs could resist HIV-1 infection because of the increased IFNβ production by macrophages exposed to HbSS or sickle cell RBCs. SCD PBMC have increased levels of SERNIC5 and lower levels of HIV-1 Nef and host AP2 expression that, culumlatively, can increased CD4 levels and lead to the overall improved immunological health of SCD patients. ACKNOWLEDGMENTS: This work was supported by NIH Research Grants (1P50HL118006, 1R01HL125005, 1SC1HL150685, 5U54MD007597, 1UM1AI26617 and P30AI087714). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Disclosures No relevant conflicts of interest to declare.

scholarly journals American Society of Hematology 2020 guidelines for sickle cell disease: transfusion support

2020 ◽  
Vol 4 (2) ◽  
pp. 327-355 ◽  
Author(s):  
Stella T. Chou ◽  
Mouaz Alsawas ◽  
Ross M. Fasano ◽  
Joshua J. Field ◽  
Jeanne E. Hendrickson ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Guideline Development ◽  
Practice Research ◽  
Evidence Based ◽  
Red Cell ◽  
Cell Disease ◽  
American Society

Background: Red cell transfusions remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. Guidance for specific indications and administration of transfusion, as well as screening, prevention, and management of alloimmunization, delayed hemolytic transfusion reactions (DHTRs), and iron overload may improve outcomes. Objective: Our objective was to develop evidence-based guidelines to support patients, clinicians, and other healthcare professionals in their decisions about transfusion support for SCD and the management of transfusion-related complications. Methods: The American Society of Hematology formed a multidisciplinary panel that was balanced to minimize bias from conflicts of interest and that included a patient representative. The panel prioritized clinical questions and outcomes. The Mayo Clinic Evidence-Based Practice Research Program supported the guideline development process. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to form recommendations, which were subject to public comment. Results: The panel developed 10 recommendations focused on red cell antigen typing and matching, indications, and mode of administration (simple vs red cell exchange), as well as screening, prevention, and management of alloimmunization, DHTRs, and iron overload. Conclusions: The majority of panel recommendations were conditional due to the paucity of direct, high-certainty evidence for outcomes of interest. Research priorities were identified, including prospective studies to understand the role of serologic vs genotypic red cell matching, the mechanism of HTRs resulting from specific alloantigens to inform therapy, the role and timing of regular transfusions during pregnancy for women, and the optimal treatment of transfusional iron overload in SCD.

scholarly journals Characterization of HIV risks in a Brazilian sickle cell disease population

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.

Polymorphisms in TNFα Are Associated with Cerebrovascular Events in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1540-1540 ◽  
Author(s):  
Latorya A Barber ◽  
Allison E Ashley-Koch ◽  
Melanie E. Garrett ◽  
Karen L Soldano ◽  
Marilyn J. Telen
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Umbilical Vein ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Data Set ◽  
Clinical Complications ◽  
Cerebrovascular Events ◽  
Increased Risk

Abstract Abstract 1540 Poster Board I-563 Tumor necrosis factor alpha (TNFα) is a pro-inflammatory cytokine that stimulates phagocytosis, neutrophil recruitment, and expression of adhesion molecule VCAM-1. Plasma levels of TNFα have been found to be increased in sickle cell disease (SCD), and in vitro studies show that TNFα causes increased adherence of sickle red blood cells to human umbilical vein endothelial cells. A polymorphism in the promoter region of the TNFα gene has previously been associated with stroke in children with SCD (Hoppe et al., 2007). The current study was designed to identify associations of additional TNFα single nucleotide polymorphisms (SNPs) with SCD clinical complications. We analyzed five SNPs in the TNFα gene in 509 DNA samples of SCD patients from Duke University, University of North Carolina at Chapel Hill, and Emory University. In our data set, cerebrovascular events (CVEs), including overt stroke, seizures, and transient ischemic attacks, occurred in 133 out of 509 SCD patients (26.1%). SNP genotyping was performed using Taqman genotyping assays from Applied Biosystems. Due to low minor allele frequencies (<0.05) for all the SNPs examined, genetic associations with SCD clinical complications were examined by using allele tests. After controlling for age, gender, and use of hydroxyurea, two of the five TNFα SNPs, rs2228088 and rs3093665, were significantly associated with CVEs (p=0.013 and 0.029, respectively). The odds that SCD patients with a G allele at rs2228088 suffered from CVEs were 0.485 times that for patients with the T allele, suggesting that the G allele had a protective effect. The odds of having the A allele at rs3093665 and suffering from CVEs was also reduced, at 0.45 compared to the C allele. Neither SNP was found to be in linkage disequilibrium (LD) with any of the other SNPs analyzed (r2≤0.002). There was also strong association of SNP rs2228088 with acute chest syndrome (ACS; p=0.003), occurring in 382 out of 509 SCD patients (75%). However, in this analysis, the G allele was associated with increased risk for ACS (OR=2.313). In addition to the association with CVEs, the SNP rs3093665 was also significantly associated with priapism (p=0.03), reported by 86 of 223 male SCD patients (38.6%). In this analysis, the A allele was protective, as had been observed for CVE (OR=0.188). Additionally, we found no difference in steady state plasma TNFα levels between genotypes for the two SNPs. The functional significance of these SNPs is presently unknown. SNP rs2228088 is a synonymous SNP located in the coding region, and rs3093665 is located in the 3' untranslated region of the TNFα gene. While the G to T change at SNP rs2228088 does not translate to a change in amino acid sequence, the A to C change at SNP rs3093665 may affect mRNA stability due to its location. It is also possible that one or both of these SNPs is in LD with another functionally relevant SNP. Our findings thus support previous data implicating TNFα polymorphisms in risk for central nervous system events. Interestingly, ACS has been previously associated with seizures, stroke and altered mental status in adults and children with SCD (Vinchinsky et al., 2000) and with silent cerebral infarcts and reversible posterior leukoencephalopathy syndrome in children with SCD (Henderson et al., 2003). However, in our dataset, ACS and the occurrence of CVEs were not associated (p=0.24). Further studies are required to elucidate these and other factors that potentially correlate with SCD clinical complications. Disclosures No relevant conflicts of interest to declare.

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