Gallstones in Sickle Cell Disease: A Single Institution Experience

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 4939-4939
Author(s):  
Thomas Coats ◽  
Kate Gardner ◽  
Swee Lay Thein
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Surgical Complications ◽  
Conflicts Of Interest ◽  
Acute Cholangitis ◽  
Biliary Tree ◽  
Ultrasound Scan ◽  
Cell Disease ◽  
Time Period ◽  
Elective Cholecystectomy

Abstract Background: There is an increased incidence of gallstones in patients with sickle cell disease (SCD), due to haemolysis. Complications of gallstones include cholecystitis, pancreatitis and cholangiopathy and gallstones can trigger an acute sickle cell crisis. It is not known whether patients with asymptomatic gallstones would benefit from elective cholecystectomy to avoid such complications. Method: Electronic patient records of all 767 adult SCD patients attending clinic at King’s College Hospital, London between 1st Jan 2003 and 31st Dec 2013 were retrospectively reviewed to identify cases of gallstones. Medical records and steady state blood values were analysed in all those patients with an ultrasound of the biliary tree during this time period. Results: Amongst the cohort of 767 patients with SCD, 481 (62.7%) were HbSS, 244 (31.8%) HbSC, 35 (4.6%) HbSB+, 6 (0.8%) HbSB0 and 1 (0.1%) HbSHFPH genotype. 43% were male. Mean age at the end of the study period was 36.6 +/- 12.5 years. 344 patients had an ultrasound scan of the biliary tree during the time period of the study. 38 of the 344 patients scanned had had a cholecystectomy prior to 2003. Of the remaining 306 patients with an ultrasound scan, 134 had gallstones identified within the gallbladder. The 134 patients with gallstones comprised 119 (88.8%) HbSS, 12 (9.0%) HbSC, 2 (1.5%) HbSB+ and 1 (0.7%) HbSB0. 39.6% were male. Mean age at the end of the study period was 35.4 +/- 12.2 years. Of the 134 patients with gallstones identified during the study, 35 developed serious complications directly relating to cholelithiasis (5 pancreatitis, 4 acute cholangitis, 8 choledocholithiasis and 18 isolated cholecystitis) and 8 of these patients required sphincterotomies +/- stone removal with endoscopic retrograde cholangio-pancreatogram. 34 of the 134 patients with gallstones went on to have a cholecystectomy during the 11 year study period. Of these 34, 3 had recorded surgical complications following cholecystectomy (2 bile leaks, 1 hepatic injury). All 3 cases had gallstone-related complications prior to the cholecystectomy. Discussion: Our findings of cholelithiasis in 134 of the 306 of sickle cell disease patients scanned, is similar to incidence reported in the literature. Notably, we documented a high incidence of complications associated with cholelithiasis. Furthermore, there were higher than expected rates of surgical complications in cholecystectomy undertaken following the development of a complication relating to gallstones. These findings make routine screening for cholelithiasis followed by elective cholecystectomy for positive cases an attractive approach. Disclosures No relevant conflicts of interest to declare.

Elective Cholecystectomy Decreases the Morbidity of Cholelithiasis and Cholecystectomy in Pediatric Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1544-1544
Author(s):  
Emily F. Goodwin ◽  
Paige M. Ivey ◽  
Jeffrey D. Lebensburger ◽  
Roy P. McDonald ◽  
Thomas H. Howard
Keyword(s):  
Abdominal Pain ◽  
Sickle Cell Disease ◽  
Hospital Admission ◽  
Sickle Cell ◽  
Hospital Admissions ◽  
Conflicts Of Interest ◽  
Cell Disease ◽  
Surgical Preparation ◽  
The Impact ◽  
Elective Cholecystectomy

Abstract Abstract 1544 Poster Board I-567 PURPOSE Cholelithiasis frequently occur in sickle cell disease, are easily diagnosed by ultrasound, and are associated with hospital admissions for abdominal pain. Elective cholecystectomy is controversial in sickle cell disease despite small series which suggest that elective cholecystectomy decreases the morbidity of the procedure. Therefore we examined the impact of cholecystectomy on morbidities associated with cholelithiasis and cholecystectomy in sickle cell disease. METHODS: Records of 191 consecutive pediatric sickle cell patients with cholelithiasis who underwent cholecystectomy between January 1999 and May 2009 were retrospectively reviewed. The cholecystectomies were classified into 3 groups 1) elective: no pre-operative symptoms, cholelithiasis on screening ultrasound, pre-planned surgical preparation; 2) symptomatic: pre-operative symptoms of cholelithiasis on ultrasound, pre-planned surgical preparation; 3) emergent: hospitalization for acute cholecystitis symptoms, cholelithiasis on ultrasound, no pre-planned surgical preparation. We compared the morbidity of cholelithiasis and cholecystectomy by examining pre-operative hospitalizations, cholecystectomy hospitalization, and post-operative hospitalizations. RESULTS: Patients with sickle cell disease underwent a total of 191 cholecystectomies over a ten year period: 51 elective, 110 symptomatic, and 30 emergent. Patients who required an emergent cholecystectomy had a longer post-operative hospitalization time than elective cholecystectomy (7.3 vs 4.3 P< 0.001). Prior to hospitalization for the cholecystectomy, patients needing emergent and elective cholecystectomy had similar number of total of hospital admission days (5.2 vs 5.6 P=0.73). However, the emergent cholecystectomy population required more hospital admission days prior to surgery for abdominal pain than the elective patients (1 vs 0.37, P=0.01). After the cholecystectomy, emergent patients required more total hospital admission days (7.2 vs 2.9, P=0.002) and more admission days for abdominal pain (0.5 vs 0.2, P=0.049) than patients that underwent elective cholecystectomy. In 18 patients with the most severe abdominal pain (>2 inpatient admission days) prior to hospitalization for cholecystectomy, 11 (61%) were not admitted after cholecystectomy for pain. Patients receiving chronic blood transfusions prior to surgery had a reduced need for emergent cholecystectomy as compared to non-transfused patients (8% vs 25%, P= 0.056 by chi-square). Patients receiving hydroxyurea had a similar rate of need for an emergent cholecystectomy as compared to patients not on hydroxyurea (22% vs 13% P= NS). No differences in degree of anemia or reticulocytosis were identified in patients requiring emergent vs. elective cholecystectomy (Hb: 8.7 vs 8.6 g/dL; Reticulocyte percent: 10.9% vs 10.4%). The morbidity of patients in the symptomatic cohort was intermediate between the elective and emergent cohorts without demonstrating statistical significance. CONCLUSIONS: This represents the largest reported series of pediatric cholelithiasis and cholecystectomy in sickle cell disease to date. This data strongly suggests that elective cholecystectomy decreases morbidity associated with cholelithiasis and cholecystectomy in sickle cell disease. 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 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 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.

Sickle Cell Disease Mortality in the United States: Age at Death and Contributing Causes.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 81-81 ◽  
Author(s):  
Carlton Haywood ◽  
Sophie Lanzkron
Keyword(s):  
Sickle Cell Disease ◽  
Cause Of Death ◽  
Sickle Cell ◽  
Causes Of Death ◽  
College Education ◽  
Age At Death ◽  
Cell Disease ◽  
Time Period ◽  
Icd 10 ◽  
The U.S

Abstract BACKGROUND: In the early 1990’s, the Cooperative Study of Sickle Cell Disease (CSSCD) estimated a median life expectancy of 42 years for males, and 48 years for females with sickle cell anemia. We used death certificate data from the late 1990’s and early 2000’s to examine age at death and contributing causes of death for persons with sickle cell disease (SCD). METHODS: We used the National Center for Health Statistics Multiple Cause of Death (MCOD) files to examine age at death and contributing causes of death for persons in the U.S. with SCD during the years 1999 to 2004. The MCOD files contain data from all death certificates filed in the U.S. Each observation in the data has listed an underlying (primary) cause of death, as well as up to 20 conditions thought to contribute to the death. We used ICD-10 codes D570-D578 to identify all deaths attributed to SCD during the time period under study. Records with the ICD-10 code for sickle cell trait (D573) were excluded from further analyses. We used the Clinical Classification Software provided by the Healthcare Cost and Utilization Project to collapse all listed ICD-10 codes into smaller categories. Analyses of age at death were conducted using t-tests, median tests, ANOVA, and multiple linear regression as appropriate. RESULTS: From 1999 to 2004, there were 4553 deaths in the U.S. attributed to SCD (mean = 759/yr, sd = 42.6). SCD was listed as the primary cause in 65% of the deaths. 95% of the deaths were attributed to HbSS disease, and approximately 1% of the deaths were attributed to double heterozygous sickle cell disorders (SC/SD/SE/Thal). 50.4% of the deaths were among males. 64% of the decedents had a high school education or less. 54% of the decedents lived in the South. 68% of the decedents died as inpatients in a hospital. The mean age at death for the time period was 38.2 years (sd = 15.6). There was no change in the mean age at death during the time period. Females were older than males at death (39.4 vs. 36.9, p < 0.0001). Those with HbSS were younger than those with a double heterozygous disorder (38 vs. 47, p < 0.02). Having SCD listed as the primary cause of death was associated with younger age at death (36.8 vs. 40.7, p < 0.0001). Decedents with at least some college education were older at death than those with high school educations or less (40.9 vs. 37.0 p < 0.0001). There were no regional differences in mean age at death. In a multivariate model of age at death with the predictors gender, region, education, and whether or not SCD was listed as the primary cause of death, being female and having some college education remained associated with older age at death, while having SCD listed as the primary cause of death remained associated with younger age at death. Septicemia, pulmonary heart disease, liver disease and renal failure were among the top contributing causes of death for adults, while septicemia, acute cerebrovascular disease and pneumonia were among the top contributing causes of death for kids. CONCLUSIONS: Persons dying from SCD during 1999 to 2004 experienced ages at death that are not improved over those reported by the CSSCD, suggesting the continued need for societal efforts aimed at improving the quality of care for SCD, especially among adults with the condition. Educational attainment is associated with age at death among the SCD population, though it is not possible from the cross-sectional nature of this data to determine the causal directionality of this association.

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.

Measurement of Urine Pyridinoline and Deoxypyridinoline as Markers of Increased Bone Degradation in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2572-2572
Author(s):  
Erfan Nur ◽  
Willem Mairuhu ◽  
Dees P. Brandjes ◽  
Ton van Zanten ◽  
Bart J. Biemond ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Bone Resorption ◽  
Sickle Cell ◽  
Conflicts Of Interest ◽  
Healthy Controls ◽  
Cell Disease ◽  
Skeletal Involvement ◽  
Asymptomatic Patients ◽  
Bone Degradation ◽  
Painful Crisis

Abstract Abstract 2572 Poster Board II-549 Introduction: Sickle cell disease (SCD) is commonly manifested through skeletal involvement. Besides the characteristic acute musculoskeletal pain, SCD is also associated with chronic skeletal complications such as osteopenia and osteoporosis. During bone resorption, the collagen cross-links pyridinoline (PYD) and deoxypyridinoline (DPD) are released into circulation with subsequent urinary excretion. Measurements of urinary PYD and DPD could serve as valuable tools in detecting osteoporosis in the follow-up of SCD patients but perhaps also in determining the severity of bone infarction during painful crises. Therefore we compared urinary concentrations of PYD and DPD of SCD patients during asymptomatic state and painful crisis with those of race- and age-matched healthy controls. Methods: Urinary concentrations of PYD and DPD, adjusted for urine creatinine, were measured in SCD patients both during asymptomatic state (n=38) and painful crisis (n=27) and healthy controls with normal HbA hemoglobin (n=25) using high performance liquid chromatography (HPLC). Results: PYD and DPD concentrations were higher in asymptomatic SCD patients compared to controls ((54.8 (41.5–68.6) vs. 44.1 (37.7–49.9),P=0.005 and 11.6 (9.3–15.2) vs. 8.5 (6.8–10.4),P=0.004 respectively), with further increments during painful crisis (63.3 (51.8–76.0),P=0.041 and 15.3(13.0–21.5),P=0.003 respectively). In the asymptomatic patients levels of PYD and DPD were significantly correlated to the degree of hemolysis. Conclusion: In sickle cell patients bone resorption is increased and significantly correlated to the degree of hemolysis, compatible with their susceptibility to osteopenia and osteoporosis. Measurement of pyridinoline and deoxypyridinoline could have additional value as biomarkers of osteoporosis in SCD. During painful crises a further increment in bone degradation was observed. Disclosures: No relevant conflicts of interest to declare.

A Novel Connection Between Stress Erythropoiesis and Coagulation Activation in Sickle Cell Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 905-905
Author(s):  
Julia E. Brittain ◽  
David Manly ◽  
Leslie V. Parise ◽  
Nigel Mackman ◽  
Kenneth I. Ataga
Keyword(s):  
Flow Cytometry ◽  
Sickle Cell Disease ◽  
Tissue Factor ◽  
Sickle Cell ◽  
Whole Blood ◽  
Conflicts Of Interest ◽  
Cell Disease ◽  
Coagulation Activation ◽  
Monocytic Cells ◽  
Stress Erythropoiesis

Abstract Abstract 905 Introduction: Sickle cell disease (SCD) is associated with a hypercoagulable state. Multiple studies show that plasma from these patients exhibit: 1) increased thrombin generation; 2) decreased levels of natural anticoagulant proteins; and 3) a defect in the activation of fibrinolysis. The mechanism of coagulation activation in SCD is presumed to be multi-factorial, with contributions from abnormal erythrocyte phospholipid asymmetry and induction of tissue factor (TF) following hemolysis. In addition, hemolysis in SCD leads to elevated levels of erythropoietin (EPO) in patients, increased reticulocyte counts and the presence of stress (or shift) reticulocytes in circulating blood. These stress reticulocytes retain expression of the α4b1 integrin and are demonstrably adhesive to vascular factors in SCD. We have previously reported that these stress reticulocytes bind to blood monocytes in SCD patients via the α4b1 integrin, but the effect of this interaction on either cell remained unknown in SCD. Objective: With the increasing evidence that hemolysis and subsequent stress erythropoiesis associates with coagulation activation, we sought to evaluate the role of erythropoietin and the effect of stress reticulocyte adhesion to monocytes on coagulation activation in SCD patients. Methods: Coagulation activation in plasma samples was examined by evaluating TF activity on microparticles derived from patients with SCD. Stress reticulocytes were visualized and enumerated from these same patients using Wright Giemsa stained blood smears counter stained with new methylene blue to detect reticulocytes. Reticulocytes were scored as a stress reticulocytes based on the amount of punctuate reticular material, cell size, and presence of nuclear material. Stress reticulocyte induction of monocyte tissue factor expression was measured by flow cytometry after incubation of THP-1 monocytic cells with purified SS RBCs or control RBCs. To determine if induced THP-1 TF expression was due stress reticulocyte binding, THP-1 TF expression was examined in the presence or absence of known inhibitors of the monocyte/stress reticulocyte interaction. TF expression on CD14+ monocytes was examined in whole blood from SCD patients using flow cytometry. Plasma erythropoietin levels were quantified by ELISA. Results: We found that direct binding of the stress reticulocyte increased THP-1 TF expression 2.5 fold. This increase in TF expression was completely ablated by function blocking antibodies against the α4 integrin, but not by an isotype-matched control IgG. In whole blood samples, we also found increased TF expression on CD14+ monocytes with stress reticulocytes directly bound, compared to those monocytes in the same patient without stress reticulocytes bound (p = 0.002, n =3).We noted a strong correlation between stress reticulocyte count and TF activity on plasma microparticles in SCD (rspearman = 0.8656, CI = 0.5382 – 0.9660, p = 0.0006, n=11). Furthermore, we found that EPO induced α4b1 activation on the stress reticulocyte. This activation may promote both adhesion to the monocyte and an increase in TF expression. Consequently, we noted a strong trend towards an association of EPO with microparticle TF activity in SCD (rspearman = 0.5740, CI=-0.06 – 0.8780, p=0.068, n= 11) suggesting that EPO, by promoting the interaction between the stress reticulocyte and the monocyte, may contribute to TF activity in SCD. Conclusion: Taken together, we find that stress reticulocyte adhesion to monocytes and monocytic cells induces TF expression and may promote TF activity in patients. These data suggest a novel connection between stress erythropoiesis and coagulation activation in SCD. Disclosures: No relevant conflicts of interest to declare.

Klotho Polymorphisms and Priapism In Sickle Cell Disease.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1653-1653 ◽  
Author(s):  
Claudia R Lustosa Souza ◽  
Marily M Azevedo Shimmoto ◽  
Perla Vicari ◽  
Martha Mariana A S Arruda ◽  
Marina Roizenblatt ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Vascular Function ◽  
Conflicts Of Interest ◽  
Significant Proportion ◽  
Cell Disease ◽  
Specific Pcr ◽  
Allele Specific ◽  
Male Patients ◽  
Allele Specific Pcr

Abstract Abstract 1653 Background: Sickle cell disease (SCD) is a monogenic disorder with phenotypic heterogeneity, possibly determined by polymorphisms (SNPs) in genes whose products modify the pathophysiology of the disease. Priapism is one of the most common vaso-occlusive complications of SCD, and it occurred in more than 30% of males. The Klotho (KL) gene appears to be associated with vascular function and nitric oxide biology and the presence of SNPs could affect its function. Association between KL and priapism in SCD patients was suggested by Nolan et al. in 2004. However, other authors could not confirm this finding (Elliot et al., 2007). Objective: We decided to evaluate the relevance of SNPs rs2249358, rs211234 and rs9536314 to the occurrence of priapism in patients with SCD followed at Outpatient clinic at Escola Paulista de Medicina/UNIFESP. Methods: Forty male patients with SCD were enrolled, 39 (97.5%) with sickle cell anemia (SS) and one (2.5%) SC hemoglobinopathy. The manifestation of priapism was identified through analyses of medical records. The SNP rs2249358 was identified by PCR followed by restriction with XbaI. The other SNPs, rs211234 and rs9536314, were analyzed by allele specific PCR. Statistical analysis: t test, Chi2 or Fisher. This study was approved by Ethical Committee, and all patients agreed in participate. Results: The median age of the patient was 28.5 years-old (20-68 y.o.). Fourteen out of 40 patients had priapism (35%), each one with SS disease. The group of patients with priapism were older (32.5 y.o., 25–68 y.o.) than the group without this manifestation (27.5 y.o., 20–56 y.o.) (p=0.03). There was no statistical difference in the distribution of the SNPs rs211234 and rs9536314 between the two groups of patients (p=0.51 and p= 0.09, respectively). Regarding the distribution of SNP rs2249358, the group with priapism presented 8 individuals (57.1%) with GG genotype, 5 (35.7%) with AA and 1 (7.17%) with AG, whereas in the group without priapism, the distribution was different: 5 (19.2%) with GG, 7 (26.9%) with AA and 14 (53.8%) with AG genotype (p=0.0212). When we compare the presence of at least one A allele (AA or A-) with the G allele in homozygosis (GG), we observed that the A allele has a protector effect (OR: 0.1786; CI: 0.04232–0.7535) (p=0.031). Conclusions: In a relatively small group of patients with SCD, it was observed a significant proportion of individuals with priapism, which reinforces the importance of this manifestation. We also observed correlation between SNP rs2249358 of KL gene and priapism, as suggested previously. Disclosures: No relevant conflicts of interest to declare.

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