scholarly journals Alkaline Phosphatase Is Associated with Red Cell Alloimmunization in the Pulmonary Hypertension and Hypoxic Response (PUSH) Sickle Cell Disease Cohort

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 20-20
Author(s):  
Victoria Brooks ◽  
Oluwalonimi Adebowale ◽  
Victor R. Gordeuk ◽  
Sergei Nekhai ◽  
James G. Taylor
Keyword(s):  
Risk Factors ◽  
Alkaline Phosphatase ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Severe Disease ◽  
Case Control ◽  
Red Cell ◽  
Cell Disease ◽  
History Of

Background: Blood transfusion is a common therapy for sickle cell disease (SCD). Although, highly effective, a major limitation is development of alloantibodies to minor blood group antigens on donor red cells. Alloimmunization has a prevalence of 2-5% for transfusions in the general population, but it is significantly higher in SCD. Risk factors for alloimmunization have been poorly characterized, although number of lifetime transfusions is an important risk factor. Alloimmunization has been clinically observed in children with a prevalence of about 7%. With development of each antibody, blood donor matching becomes increasingly difficult and expensive with an increased risk for transfusion reactions and diminished availability of compatible red cell units for treatment of SCD. The ability to identify risk factors for developing alloantibodies would be beneficial for clinicians. To identify markers for alloimmunization in SCD, we have analyzed children and adults who developed this complication. Methods: We analyzed The Pulmonary Hypertension and Hypoxic Response in Sickle Cell Disease (PUSH) study, which enrolled n=468 pediatric and n=59 adult SCD subjects. In both children and adults, alloimmunization cases were defined as a history of at least 1 alloantibody. Controls in both cohorts were defined as subjects with no history of alloantibodies and receipt of more than 10 lifetime red cell transfusions. All others within the study who did not meet these criteria were assigned to a third comparison group. To identify differences between cases, controls and all others, we performed univariate analyses (using ANOVA or Kruskal Wallace where appropriate) for clinical parameters and laboratories. Case control comparisons were also performed for selected variables and plasma levels for 11 cytokines. Results were further analyzed using regression modeling. Results: The overall prevalence of alloimmunization was 7.3% among children (34/468 subjects; median age 12, range 3-20 years) compared to 28.8% in adults (17/59 subjects; median age 37, range 18-73 years). When only considering those with >10 lifetime transfusions, the prevalence was considerably higher at 29.3% and 54.8% in children and adults, respectively. At the same time, 8 pediatric (23.5%) and 5 adult (29.4%) alloimmunization cases had received fewer than 10 transfusions. In a 3-way pediatric cohort comparison (cases, controls and all others), risk factors associated with alloimmunization included SS genotype, older age and markers of more severe disease (higher ferritin, WBCs, platelets and total bilirubin). Comparison of cases to controls showed alkaline phosphatase (P=0.05) was significantly lower in cases, whereas AST (P=0.02) was significantly higher even with adjustment for age. Levels of plasma cytokines MCP-1 (P=0.01) and IFNgamma (P=0.08) were lower in cases from a subset of the pediatric cohort. In adults, only 4/59 (6.8%) subjects had never received a lifetime transfusion (all non-SS). In the adult 3-way comparisons, only SS genotype and higher ferritin were associated with alloimmunization. The adult case control analysis showed higher absolute monocyte count (P=0.02), absolute eosinophil count (P=0.04) and absolute basophil count (P=0.008) in association with alloimmunization cases. In addition, alkaline phosphatase was again significantly lower among cases (P=0.02) as seen in the pediatric cohort. There were no significant differences in cytokine levels among adults. Conclusions: When considering only transfused SCD patients, the prevalence of alloimmunization is higher than 30%. As seen in prior studies, higher lifetime red cell transfusions are an important risk factor especially among adults where most patients have received transfusions. Children who develop alloantibodies appear to have laboratory markers of more severe disease, but this is not observed in adults. A novel association observed across both pediatric and adult subjects is a significantly lower serum alkaline phosphatase in those with alloantibodies. The results of this study suggest a need for improved tracking of red cell transfusion therapy in the US for SCD patients due to a high prevalence of alloimmunization. Further study is also needed to elucidate the significance of the alkaline phosphatase association. Disclosures Gordeuk: CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Novartis: Consultancy; Ironwood: Research Funding; Imara: Research Funding.

scholarly journals Risk Factors for Adverse Maternal and Fetal Outcomes in Pregnant Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3117-3117
Author(s):  
Sherraine Della-Moretta ◽  
William Marshall ◽  
Rui Li ◽  
Erin Cleary ◽  
Philip Samuels ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Maternal Age ◽  
Acute Chest Syndrome ◽  
Hypertensive Disorders Of Pregnancy ◽  
Cell Disease ◽  
History Of ◽  
Maternal Bmi

Abstract Background Approximately 100,000 Americans are affected by sickle cell disease (SCD), an inherited hematologic disorder. In women with sickle cell disease, pregnancy is associated with increased maternal and fetal adverse outcomes (Elenga et al). However, there is a paucity of data on risk factors for adverse events in this population. This retrospective study seeks to add to the deficient repertoire of information regarding maternal and fetal outcomes in patients with sickle cell disease and their children. Methods We retrospectively evaluated pregnancy outcomes of women with SCD who had previously undergone echocardiography from the year 2000-2021. The associations between clinical variables and adverse hematologic (AHE), cardiac (ACE), obstetric (AOE) and fetal/neonatal (ANE) events were evaluated by the Generalized Linear Model (GLM). The adverse hematologic events were vaso-occlusive crisis (VOC) antepartum and postpartum, acute chest syndrome, venous thromboembolism antepartum and postpartum, and transfusion antepartum. Results We identified 43 women/59 pregnancies with a median maternal age 27 years old (interquartile range [IQR] 20), pre-pregnancy BMI 25 kg/m2 (IQR 16). Maternal sickle cell genotype was SS in 31 (72%) women/37 (63%) pregnancies, SC in 8 (18%) women/18 (31%) pregnancies, and other genotype in 4 (9%) women/4 (7%) pregnancies. Prior venous thromboembolism was present in 12 (27%) women/15 (25%) pregnancies and prior acute chest syndrome (ACS) in 33 (80%) women/41 (75%) pregnancies. In the year before pregnancy, 24 (56%) women were admitted at least once for VOC. There were no maternal deaths during pregnancy or up to 1 year postpartum. AHE (n = 171) occurred in 43 (73%) pregnancies (Figure A), with a median of 2 (range 0-13) AHE per pregnancy. AHE were more common with genotype SS, history of ACS, history of ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, tricuspid regurgitation velocity (TRV) >2.5 m/s on echocardiogram, and increased maternal age, and less common with increased hemoglobin (Figure B). ACE were rare (n = 3) (Figure A) and weakly associated with increased maternal age (Figure C). AOE (n = 37) occurred in 27 (45%) pregnancies (Figure A) and were associated with lower pre-pregnancy maternal BMI (Figure D). ANE (n = 54) occurred in 27 (46%) of pregnancies, and were associated with maternal hypertensive disorders of pregnancy (Figure E). Conclusions We found that AHE during pregnancy in women with SCD were associated with genotype SS, history of ACS, ³ 10 lifetime transfusions, admission for VOC in the year before pregnancy, higher maternal age, and inversely related to hemoglobin. In addition, AHE during pregnancy were associated with TRV >2.5 m/s on echocardiogram, which has not been previously shown in women with SCD. These data may be useful to identify women at increased risk during pregnancy. Data show that patients with sickle cell disease who have more disease-related complications including history of acute chest syndrome, frequent pain crisis, elevated TRV on echocardiogram, and lower hemoglobin are at greater risk for AHE. This suggests that disease severity is directly related to outcomes. The association between increased maternal age and ACE has been demonstrated in the past in women without SCD (DeViti et al). The same can be noted for the association of AOE with lower maternal BMI (Verma et al), and ANE being associated with maternal hypertensive disorders of pregnancy (Lugobe et al). In the future, prevention of these complications will be key. Future directions include determining the effect of disease-modifying therapy on these outcomes, though safety during pregnancy has not yet been demonstrated for more novel agents such as voxelotor and crizanlizumab. With more information on these risk factors, we hope that modification and treatment can result in better outcomes. Figure 1 Figure 1. Disclosures Desai: Pfizer: Other: Publication Fee, Research Funding; Foundation for Sickle Cell Research: Honoraria; Forma: Consultancy; Novartis: Research Funding, Speakers Bureau; Global Blood Therapeutics: Honoraria, Research Funding.

Should Sickle Cell Disease be Among the Risk Factors for Use of Thromboprophylaxis in Adolescents and Young Adults ?

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4855-4855 ◽  
Author(s):  
Erin Morales ◽  
Gabriela Ines Villanueva ◽  
Lewis L. Hsu ◽  
Nili Seleski
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Pediatric Population ◽  
Multivariate Regression Analysis ◽  
Central Line ◽  
Cell Disease ◽  
Vte Prophylaxis ◽  
History Of

Abstract Introduction: As published by Naik both in single-institution and multi-institution data, adults with sickle cell disease have a baseline hypercoagulable state in addition to traditional risk factors. In pediatrics, venous thromboembolism (VTE) is often overlooked because of the low incidence in children. In addition, there is no unified consensus that supports the use of prophylaxis or screening of the pediatric population at risk. Although the incidence of VTE in the general pediatric population is low, there may be those children, including those with sickle cell disease (SCD), who would benefit from VTE prophylaxis. Objectives: Estimate the contribution of sickle cell disease to rates of VTE in adolescents and young adults, compare rates of prophylaxis in the pediatric units versus the adult units, and determine risk factors associated with VTE occurrence in a hospital serving a large population with sickle cell disease. Methods: This study was a retrospective chart review of patients aged 14-25 admitted to the Pediatric Intensive Care Unit (PICU), to the Pediatric Sickle Cell Service, and to the Medical Intensive Care Unit (MICU) between the dates of April 1, 2014 and April 30, 2015. Anyone older than age 18 admitted to the PICU or Pediatric Sickle Cell Service was considered part of pediatrics. Charts were searched manually for incidence of VTE during hospitalization, risk factors for developing VTE, history of prior VTE, use of therapeutic anticoagulation, and prophylaxis use and type. Data was analyzed using a multivariate regression analysis. Results: In the 13-month period, 251 AYA admissions (108 to the PICU and 143 to the Sickle cell Unit) and 67 MICU admissions were reviewed. 66/67 (99%) MICU patients received either chemical or mechanical prophylaxis against VTE compared to 9/251 (3.5%) children. Event rates of VTE were 3/67 (4.5%) in MICU and 2/251 (0.8%) in the Pediatric units - 1 in the Sickle Cell unit and 1 in the PICU. In the pediatric units, none of the patients receiving prophylaxis had an acute VTE and both patients with VTE were not on prophylaxis. Both adolescents had central lines in place at the time of VTE occurrence. Of the MICU events, one patient had SCD and was taking systemic anticoagulation for previous VTE but had a central line in place. The other MICU patients both had infections, one with Crohns Disease and the other with a central line placed (table 2). The multivariate regression analysis demonstrated that prior history of a VTE and prolonged LOS were positively correlated with increased risk for VTE, both with a confidence interval of 95% and a corrected critical value of 0.003 using the Bonferroni correction (table 1). Conclusion: Of the 5 VTE events in the 318 AYA hospitalizations reviewed, two (40%) were in patients with SCD (ages 17 and 24). As expected, overall VTE incidence in AYA is low in our institution, and appear to be associated with heightened inflammation and central line placement. VTE events in the pediatric unit were in patients not receiving any prophylaxis, which is not surprising when VTE prophylaxis orders were rare on the pediatric units (3.5%). In both our pediatric unit cases, prophylaxis may have prevented the VTE. A consensus protocol to identify high risk children is being implemented and refined with ongoing data collection. The data from our hospital AYA population enriched in SCD reinforces previous data from adult sickle cell populations that the magnitude of VTE risk attributable to SCD can be high. SCD probably should be among the screening criteria when deciding VTE prophylaxis in hospitalized adolescents. Disclosures Hsu: Purdue Pharma: Research Funding; Gerson Lehman Group: Consultancy; Hilton Publishing: Consultancy, Research Funding; Pfizer: Consultancy, Research Funding; Astra Zeneca: Consultancy, Research Funding; Eli Lilly: Research Funding; Sancilio: Research Funding; Centers for Medicare and Medicaid Innovation: Research Funding; EMMI Solutions: Consultancy; Mast Therapeutics: Research Funding.

scholarly journals COVID-19 and Sickle Cell Disease in the Province of Quebec: Morbidity and Mortality Rates Derived from the Provincial Registry

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4064-4064
Author(s):  
Mathias Castonguay ◽  
Nawar Dakhallah ◽  
Marie-Laure Colaiacovo ◽  
Camille Jimenez-Cortes ◽  
Justin Desroches ◽  
...  
Keyword(s):  
Public Health ◽  
Risk Factors ◽  
Sickle Cell Disease ◽  
General Population ◽  
Sickle Cell ◽  
Death Rate ◽  
Research Funding ◽  
Mortality Rates ◽  
Cell Disease ◽  
History Of

Abstract Introduction Approximately 1500 people live with sickle cell disease (SCD) in the province of Quebec, Canada. Public health has recognized these patients as immunocompromised. SCD patients may be at higher risk of developing severe COVID-19 infection due to their underlying pro-inflammatory and thrombogenic state, splenic dysfunction and secondary organopathies. Descriptions about disease severity and mortality rates in SCD vary widely. From the SECURE-SCD registry, Mucalo et al. recently reported a 0.3% and 4.7% mortality rate in children and adults, respectively. In the French registry, Arlet and colleagues reported a 2.4% death rate among those hospitalized with COVID-19 and SCD, not different from the general population. As a result, the COVID-19 morbidity and mortality rates among the SCD population remain uncertain. Objectives The primary objectives of our study are to describe the epidemiology, baseline characteristics and clinical outcomes of SCD patients with COVID-19 infection in the province of Quebec. In addition, we aim to identify risk factors for hospitalization and severe forms of COVID-19. Methods We built a web-based SCD-COVID-19 registry regrouping 7 adult and 4 paediatric tertiary care hospitals in the province of Quebec in June 2020. All SCD patients with a confirmed SARS-CoV-2 infection by PCR test were included in the study. We compared the prevalence of infection and hospitalization rates of SCD patients to the general population of Quebec using the epidemiological data from the INSPQ (National Institute of Public Health of Quebec) public database. We retrospectively analyzed data included between March 11, 2020 to March 1, 2021. Relative risk was calculated using bilateral association measures (exact fisher, mid-p or chi-squared tests, as appropriate) to compare the incidence of infection and hospitalization of SCD patients to the population of Quebec and to assess risk factors of hospitalization among SCD patients. Results During the first 12 months of the pandemic, 74 patients were included in the registry. The male to female ratio was 1:1.12. Median age was 23 years, ranging from 8 months to 68 years old. SS-Sbeta 0 genotypes were present in 51% of cases, while 49% were SC or Sbeta +. The majority of patients were on disease modifying therapy: 54% were on hydroxyurea and 17.5% on exchange transfusion therapy. The incidence of reported COVID-19 infection was significantly higher in SCD patients compared to the general population (4.9% vs. 3.5% p=0,002) (Table 1). Even more strikingly, SCD had rate of hospitalization 10-times greater than the general population (33.8 vs 3.2%, p<0,001). Nevertheless, the risk of admission to the intensive care unit was similar between SCD patients and the general population (24.0% vs. 24.1%, p=0.99). No death was recorded amongst SCD patients with COVID-19 compared to a death rate in the general population in Quebec of less than 70 years old of 48-78 for 100 000 infections (male-female). A history of acute chest syndrome (ACS) in the last year (OR 2.6 [1.5-4.6], p=0.04) and arterial hypertension (OR 3.3 [2.3-4.8], p=0.01) were associated with a higher risk of hospitalization (Table 2). On the other hand, there was no statistically significant association with age, sex, genotype, ABO blood group, baseline SCD therapy, or other comorbidities (chronic renal disease, obesity, pulmonary hypertension, chronic lung disease and previous admission to ICU) in our cohort. Conclusions Similar to other reports, we found that SCD patients were at much greater risk of hospitalization compared to the general population. We however found no increased risk of mortality or disease complication. This contrasts with results from other registries. A history of ACS and hypertension were associated with a higher risk of hospitalization. Whether social determinants of health could explain some of the outcome variability between different countries merit further investigation. Furthermore, we believe that registries are critical to monitor the impact of preventive measures. As vaccination is ongoing, it will be important to consider its impact on hospitalization and death rate among SCD population. Recruitment to the registry is ongoing and updated data will be presented at the meeting. Figure 1 Figure 1. Disclosures Soulieres: BMS: Membership on an entity's Board of Directors or advisory committees; Novartis: Research Funding. Forté: Novartis: Honoraria; Canadian Hematology Society: Research Funding; Pfizer: Research Funding.

scholarly journals Clinical and Biomarker Predictors for Avascular Necrosis in Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3091-3091
Author(s):  
Michael Rabaza ◽  
Maria Armila Ruiz ◽  
Liana Posch ◽  
Faiz Ahmed Hussain ◽  
Franklin Njoku ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Avascular Necrosis ◽  
Sickle Cell ◽  
Research Funding ◽  
Medical Attention ◽  
Cell Disease ◽  
Advisory Committees ◽  
Early Management

Abstract Introduction Sickle cell disease (SCD) affects 1 in 365 African Americans and approximately 25 million people world-wide. A common skeletal system complication is avascular necrosis (AVN), which can cause substantial pain and a reduced quality of life. While early management of AVN is focused on increasing range of motion with physical therapy and pain relief, there are no clear predictors for who is more likely to develop AVN and earlier institution of these preventive measure could help decrease disease progression. Vascular endothelial growth factor (VEGF) is a biomarker of endothelial injury and may indicate reduced vascular supply to the femoral or humeral head. Here we describe potential risk factors and biologic pathways for AVN in SCD, as understanding these may lead to improvements in future monitoring, early detection, and early intervention practices. Methods We investigated clinical and laboratory risk factors associated with AVN in a cohort of 435 SCD patients from our center. Blood samples, clinical, and laboratory data were collected at the time of enrollment during a clinic visit. Genotyping for alpha thalassemia was performed by PCR and the serum concentration of VEGF was measured by ELISA. AVN status was confirmed by review of the medical record and available imaging. We conducted a cross-sectional analysis comparing categorical and linear variables by AVN status using the chi-square and Kruskal-Wallis test, respectively. The independent association of the clinical and laboratory variables with AVN status was determined by logistic regression analysis. The initial model included variables with a P-value < 0.1 on univariate analysis and the final model was ascertained by stepwise forward and backward selection. Median values and interquartile range (IQR) are provided. Results The median age of the cohort was 32 (IQR, 24 - 43) years, 57% (250/435) were female, and 46% (198/435) were on hydroxyurea. AVN was observed in 34% (149/435) of SCD patients. SCD patients with AVN were older, had more frequent vaso-occlusive crises requiring medical attention, and had a higher body mass index (Table I) (P ≤ 0.002). We measured VEGF in 241 of the SCD patients with serum samples available at the time of enrolment. Serum VEGF concentrations trended higher in SCD patients with versus without AVN (420 vs. 359 pg/mL, respectively; P = 0.078). In the multivariate analysis model, AVN was independently associated with increased number of vaso-occlusive crises (OR 1.1, 95% CI: 1.0 - 1.14; P = 0.02), AST concentration (natural log OR 0.5, 95% CI: 0.2 - 0.9; P = 0.03), VEGF concentration (natural log OR 1.4, 95% CI: 1.0 - 1.9; P = 0.047), and tobacco use (OR 1.9, 95% CI: 0.9 - 3.7; P = 0.078). Discussion In conclusion, we demonstrate a high prevalence of AVN in an adult cohort of SCD patients. The presence of AVN was independently associated with a greater frequency of vaso-occlusive pain episodes, which may demonstrate a shared pathophysiology between AVN and vaso-occlusion that merits further investigation. We demonstrate that serum VEGF concentrations are higher in SCD patients with AVN and may be a clinical tool to identify those at high-risk and for earlier intervention for this complication. Figure 1 Figure 1. Disclosures Gordeuk: Modus Therapeutics: Consultancy; Novartis: Research Funding; Incyte: Research Funding; Emmaus: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; CSL Behring: Consultancy. Saraf: Pfizer: Research Funding; Global Blood Therapeutics: Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding.

Sickle Cell Disease

Hematology ◽  
2004 ◽  
Vol 2004 (1) ◽  
pp. 35-47 ◽  
Author(s):  
George R. Buchanan ◽  
Michael R. DeBaun ◽  
Charles T. Quinn ◽  
Martin H. Steinberg
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Short Chain Fatty Acids ◽  
Clinical Severity ◽  
Careful Study ◽  
Red Cell ◽  
Cell Disease ◽  
The Past ◽  
Hydroxyurea Treatment

Abstract Much progress has been made during the past several decades in gaining understanding about the natural history of sickle cell disease and management approaches aimed at treating or even preventing certain disease complications. The characterization of the human genome now offers the opportunity to understand relationships regarding how gene polymorphisms as well as how environmental factors affect the sickle cell disease phenotype, i.e., the individual patient’s overall clinical severity as well as their specific organ function. This chapter explores some of these recent advances in knowledge. In Section I, Dr. Michael DeBaun characterizes the problem of silent stroke in sickle cell disease, comparing and contrasting its clinical and neuroimaging features with overt stroke. Combined, these events affect virtually 40% of children with sickle cell anemia. New understanding of risk factors, associated clinical findings, and imaging technologies are impacting substantially on treatment options. The appreciable cognitive dysfunction and other sequelae of silent infarct demand more effective treatments and ultimate prevention. In Section II, Dr. Charles Quinn addresses the conundrum of why some patients with sickle cell disease do well whereas others fare poorly. Some risk factors have been known for years, based upon careful study of hundreds of patients by the Cooperative Study for Sickle Cell Disease and investigators studying the Jamaican newborn cohort. Other prognostic measures have only recently been defined. Dr. Quinn devotes special attention to stroke and chest syndrome as organ-related complications but also describes attempts to measure overall disease severity and to predict survival. Recently, investigators have attempted to predict factors responsible for early mortality in children and following onset of pulmonary hypertension in adults. In Section III, Dr. Martin Steinberg reviews pharmacologic approaches to sickle cell disease and the rationale for their use. In addition to the inhibition of hemoglobin S polymerization, newer targets have been defined during the past one to two decades. These include the erythrocyte membrane, changes in the red cell intracellular content (especially loss of water), endothelial injury, and free radical production. Hydroxyurea treatment attracted the greatest interest, but many uncertainties remain about its long-term benefits and toxicities. Newer “anti-sickling” agents such as decitabine and short-chain fatty acids also receive attention. Prevention of red cell dehydration, “anti-endothelial” therapy, and marshaling the potentially beneficial effects of nitric oxide are other new and exciting approaches.

scholarly journals Modifiable Cardiovascular Risk Factors in Adults with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1088-1088
Author(s):  
Foluso Joy Ogunsile ◽  
Kerry Stewart ◽  
Hang Wang ◽  
Sophie Lanzkron
Keyword(s):  
Risk Factors ◽  
Body Composition ◽  
Sickle Cell Disease ◽  
Body Fat ◽  
Sickle Cell ◽  
Exercise Testing ◽  
Research Funding ◽  
Knee Extension ◽  
Normative Values ◽  
Cell Disease

Abstract Introduction: Body composition, cardiorespiratory fitness (CRF) and muscular strength(MusS) are important predictors of cardiovascular (CV) mortality and morbidity. Poor CRF, body composition and MusS are each associated with higher rates of musculoskeletal injury, inflammation, heart disease, and all-cause mortality. Fortunately, these parameters in the general population, are partly influenced by lifestyle habits and can improve with modifying unhealthy behaviors such as increasing activity levels. Few studies have examined fitness parameters, in particularly MusS, in adults with sickle cell disease (SCD). As cardiopulmonary disease is a leading cause of death in SCD, we sought to better characterize fitness and body composition in adults with SCD. The objective of this study is to describe modifiable CV risk factors of fitness along with other risk factors of smoking, hypertension, and cholesterol in a population of adults with SCD. Methods: Forty-six participants (ages 21-66 yrs.; 74% female; sickle cell anemia n =29, sickle variant genotype n=17) were recruited from a comprehensive adult sickle center. Non-pregnant adults in steady-state SCD disease without an absolute contraindications to exercise were eligible to participate. CRF was measured using symptom-limited exercise testing performed on a cycle ergometer following an incremental ramp protocol. Maximal oxygen uptake (VO2 max), a key measure of CRF, was calculated during exercise testing. MusS was assessed using an isokinetic dynamometer, the Biodex system 3, the gold standard to measure MusS in rehabilitative medicine. Peak isokinetic torques of knee extension and flexion were determined at 60 degrees per second, and adjusted for body weight on the Biodex system 3. A medical history, fitness assessments, anthropometric testing, and laboratory testing were completed on all SCD participants. Sixteen SCD participants had dual energy x-ray absorptiometry imaging to assess fat, lean, and bone mass. The remaining 30 SCD patients underwent isokinetic CRF and MusS testing. Lean muscle mass and body fat of participants were compared to US national guidelines, VO2max was compared to predicted norms. As there are no well-established normative values for MusS, we compared values to a cohort of 60 adults without SCD (age 21-40 yrs.; 63% female) who underwent MusS testing as a part of a separate study. For muscle strength, multivariate regression was performed to control for the effects of age, BMI, gender, and SCD status on peak torques. Results: All SCD and control participants were able to complete testing safely without any adverse events. 34.7% of SCD participants (n=16) had a smoking history with a mean pack year history of 9 years (Table 1). 18% of participants (n=10) received medical treatment for hypertension (Table 1). 64% (n=32) of participants had reduced HDL levels and 8% (n=3) had elevated triglycerides. Median (IQR) waist-hip circumference (F=0.89(0.14), M=0.93 (0.11)) and total percent body fat (F=37.7(11.5), M=22.3(11.5)) for SCD participants were higher than national normative values and 66% were classified as obese (Table 1). SCD participants had reduced mean (SD) VO2max, 16.77 (3.29) and 19.56 (7.27) ml/min/kg for females and males respectively compared with norms. In 90% of SCD participants (n=28), percent-predicted VO2max was less than normal (i.e. < 84 percent-predicted) with 4 adults having markedly reduced VO2max with a percent-predicted value less than 50%. Hemoglobin, hydroxyurea use and SCD genotype were not predictive of VO2max. Compared to controls, mean (SD) peak torque values for knee extension (82.7 Nm (19) vs 44.33 Nm (18.85), p<0.0001) and flexion ( 38.6 Nm (9.03)vs 19.19 Nm (13.2), p<0.0001) at 60 degrees were lower in SCD participants even after adjusting for age, sex, and body mass index (BMI) (Table1). Limitations: Study limitations include a small sample size, and the lack of controls matched for race, age, BMI, and hemoglobin. Conclusion: In this pilot study we show that both CRF and MusS are decreased in adults with SCD. Additionally, this cohort had a number of CV risk factors including smoking, hypertension and reduced HDL levels. As we know these are important predictors of poor CV outcomes additional research is needed to determine whether a carefully designed exercise and diet program can improve these modifiable CV risk factors and ultimately health status in adults living with SCD. Disclosures Wang: PCORI: Research Funding. Lanzkron:Pfizer: Consultancy, Research Funding; NHLBI: Research Funding; Ironwood: Research Funding; PCORI: Research Funding; GBT: Consultancy, Research Funding; Selexys: Research Funding; Prolong: Research Funding.

scholarly journals TRANSFUSION PRACTICE, POST-TRANSFUSION COMPLICATIONS AND RISK FACTORS IN SICKLE CELL DISEASE IN SENEGAL, WEST AFRICA.

2022 ◽  
Vol 14 (1) ◽  
pp. e2022004
Author(s):  
Moussa Seck ◽  
Alioune Badara Senghor ◽  
Mossane Loum ◽  
Sokhna Aissatou Touré ◽  
Blaise Félix Faye ◽  
...  
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Iron Overload ◽  
Sickle Cell ◽  
Median Number ◽  
Transfusion Practice ◽  
Red Cell ◽  
Cell Disease ◽  
Hiv Antibodies ◽  
Transfusion Complications

Context and Objectives: Blood transfusions (BT) remain a mainstay of therapy for patients with sickle cell disease (SCD), but pose significant clinical challenges. We aim to assess infectious markers, red cell alloimmunization and iron overload secondary to BT in SCD patients. Materials and Methods: This is a case-control study included 253 SCD (153 SCD-transfused and 100 SCD non-transfused). We evaluated the transfusion practice (modalities, indications), post-transfusion complications (infections, alloimmunization, iron overload) and risk factors of these complications (socio-demographic, clinical, biological). Results: Median age was 28.5 years (5 - 59). Sex ratio was 0.86. Homozygous SCD was more common (95.3%). Simple BT was performed in 92.8% and transfusion exchange in 18.9%. Transfusion indications were dominated by acute anemia (57.06%) and vaso-occlusive crisis (VOCs) (14%). Red blood cell concentrates (RBC) were administered to 93.46%. Median number of RBC received per patient was 10 (2 - 48). The prevalence of VHC in SCD-transfused was 1.33% and 2% for VHB. Anti-HIV antibodies were not found. Red cell alloimmunization frequency was 16%. The most common alloantibodies were anti-rhesus (34.19%) and anti-Kell (23.67%). Iron overload was detected in 7.84%. The number of RBC transfused was the only risk factor for alloimmunization (p = 0.03) and iron overload (p = 0.023). BT frequency was not related to infectious transmission. Conclusion: Despite advances in blood safety, BT therapy is still a risk for SCD polytransfused patients. Although infectious transmission has rare, the risk of alloimmunization and iron overload is high in these patients.

scholarly journals Use of Thromboprophylaxis for Central Venous Access Devices in Patients with Sickle Cell Disease: A Survey of Canadian Providers

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4173-4173
Author(s):  
Kristine Matusiak ◽  
Stephanie Forte ◽  
Jameel Abdulrehman ◽  
Madeleine Verhovsek ◽  
Kevin H.M. Kuo
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Central Venous Access ◽  
Venous Access ◽  
Cell Disease ◽  
Central Venous ◽  
Advisory Committees ◽  
History Of

Abstract Background: Sickle cell disease (SCD) induces a chronic prothrombotic state, with a cumulative incidence of venous thromboembolism (VTE) reported to be 11% by age 40. Central venous access devices (CVAD) are commonly used for chronic transfusions and iron chelation in this patient population.The presence of a CVAD is an additional risk factor for venous thromboembolism (VTE), with a catheter related thrombosis rate of 24%. Despite this high risk of VTE, the role of thromboprophylaxis in this setting is uncertain due to a lack of high quality data. Methods: A survey was administered in March 2021 to physicians caring for adult sickle cell disease patients via the Canadian Haemoglobinopathy Association (CanHaem), covering nine SCD comprehensive care centers in Canada. One reminder email was distributed after 3 weeks to encourage participation. Questions were directed at characterizing the practice size, number of patients with CVADs, and the role of thromboprophylaxis for CVADs. Physicians were also surveyed about their willingness to enroll their SCD patients with CVADs in a randomized trial of thromboprophylaxis versus placebo. Items were generated and selected based on face and content validity. Results are reported in medians and percentages, where applicable. Results: Responses were collected from 14 physicians who care for a median of 100 (IQR 185) adult sickle cell disease patients in practices across Canada. Physicians reported approximately 5% of their patients currently require a CVAD, and physicians estimated no CVAD patients are lost to follow up. Respondents use a variety of CVADs, including port-a-caths (75%), followed by PICC lines (58%), tunneled (25%) and non-tunneled CVCs (25%) (Figure 1). Duration of venous access was reported to be &lt;1 month (17%), 1-3 months (8%), 3-6 months (0%), 6-12 months (8%), and &gt;12 months (67%). Fifty percent of respondents indicated they do not use thromboprophylaxis for CVADs. Responses varied with respect to choice and dose of antiplatelet or anticoagulant in cases where thromboprophylaxis is used (Figure 2). Forty-two percent of physicians indicated they were not very confident or not at all confident in choice of prophylaxis. Past history of VTE was the most cited factor influencing the choice to use thromboprophylaxis. Physicians were generally in favour of enrolling patients in an RCT using thromboprophylaxis for CVADs. The exception was that 69% answered "No" when asked about enrolling patients with a prior history of VTE who are not currently on anticoagulation. One-hundred percent of physicians agreed that an RCT would improve their confidence in decision-making around thromboprophylaxis in their patients with CVADs. Conclusions: While there is evidence for an increased risk of VTE for SCD patients with CVADs, our results suggest there remains clinical equipoise with respect to the use of thromboprophylaxis. Thromboprophylaxis options were variable when physicians chose to use them, as there is no evidence to support specific antithrombotic regimens. All physicians surveyed are supportive of an RCT to clarify this management approach, and many would enroll their patients. As a result of this survey, a Canadian multicenter pilot RCT addressing this question is currently underway. Figure 1 Figure 1. Disclosures Forte: Pfizer: Research Funding; Canadian Hematology Society: Research Funding; Novartis: Honoraria. Verhovsek: Vertex: Consultancy. Kuo: Alexion: Consultancy, Honoraria; Celgene: Consultancy; Bluebird Bio: Consultancy; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Research Funding; Agios: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Honoraria; Apellis: Consultancy. OffLabel Disclosure: This survey explored the use of LMWH, direct oral anticoagulants, warfarin and ASA for prophylaxis among patients with sickle cell disease using a central venous access device.

Pulmonary Hypertension Is Not Associated with An Increased Risk of Death in Children with Sickle-Cell Disease Followed for a Mean of 3 Years.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1443-1443
Author(s):  
Margaret T. Lee ◽  
Tania Small ◽  
Muhammad Amar Khan ◽  
Erika Berman Rosenzweig ◽  
Robyn J. Barst ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Pulmonary Hypertension ◽  
Platelet Count ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Risk Of Death ◽  
Increased Risk ◽  
History Of

Abstract To determine if pulmonary hypertension (PH) is associated with increased mortality in children with sickle-cell disease (SCD), we prospectively followed 88 pediatric patients for a mean of 3 years after echocardiographic screening for PH. Subjects (45 males, 43 females) were 5–20 years old (median 13) at initial screening and included 59 SS, 23 SC, 4 S/β0Thalassemia, 1 S/β+Thalassemia and 1 S/HPFH. PH was defined as tricuscipid regurgitant jet velocity (TRV) of ³2.5 m/s. Of the 88 subjects, 18 (20%) had TRV ³2.5 m/s (median 2.6, range 2.5–3.1). Subjects with PH ranged from 7 to 19 years old (median 15), were predominantly male (12 of 18) and included 14 (78%) SS, 2 SC, 2 S/β0Thalassemia. After a mean follow-up of 36.3 ± 9.4 (SD) months, all 18 patients with PH were alive. None had received specific treatment for PH; one had undergone a successful bone marrow transplant from a matched sibling donor. After a mean follow-up of 33.5 ± 13.3 months, 67 subjects with normal TRV were alive; 3 had been lost to follow-up. To compare risk factors for PH in our children with those reported for adults, we reviewed the clinical data for our subjects. Children with PH had significantly increased serum lactate dehydrogenase (LDH; P=0.04), higher platelet count (P=0.02), and, in males, a history of priapism (P=0.009). No significant differences were observed with respect to age, gender, sickle-cell type, white blood cell count, hemoglobin, reticulocyte count, bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, creatinine, ferritin, history of painful crisis, acute chest syndrome, asthma, splenectomy, or hydroxyurea therapy. To further examine the association of PH and hemolysis, a subanalysis was done excluding 18 chronically transfused patients because transfusion can alter laboratory indicators of hemolysis. Independent variables with P≤0.1 on univariate analysis (LDH, female gender, and platelet count) were entered into a logistic regression model. Only LDH was independently associated with PH (Odds Ratio=1.6, 95% CI=1.2–2.1, P=0.004). Our results show that PH diagnosed by Doppler echocardiography was not associated with an increased risk of death in children with SCD followed for a mean of 3 years. A greatly increased risk of death (rate ratio, 10.1) has been reported in adults followed for a mean of 1.5 years (N Eng J Med2004;350:886–95). In our children, as in the adults, increased LDH, a marker of hemolysis, and, in males, a history of priapism were associated with PH. By contrast, our children with PH did not have increases in serum creatinine, direct bilirubin, alkaline phosphatase and ferritin that have been linked epidemiologically to PH in adults with SCD (Pediatr Hematol Onc2007;24:159–70). These findings suggest that PH of itself may not be a direct cause of death in SCD. Rather, PH may be a manifestation of progressive, cumulative organ damage resulting from chronic hemolysis and systemic vasculopathy that ultimately leads to increased mortality in adulthood. Early recognition and preventive therapy for increased hemolysis may be needed to avert premature death in adults with SCD.

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