scholarly journals Thromboembolic Complications in Patients with Sickle Cell Disease

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4913-4913
Author(s):  
Salam Alkindi ◽  
Anwaar Al-Ghadani ◽  
Samah Al-zeheimi ◽  
Anil Pathare
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Venous Thrombosis ◽  
Sickle Cell ◽  
Significant Risk ◽  
Central Venous Catheters ◽  
Morbidity And Mortality ◽  
Thromboembolic Complications ◽  
Cell Disease ◽  
Central Venous

Abstract Background and Purpose: Venous thromboembolism (VTE) is common in patients with sickle cell disease (SCD). Traditional risk factors such as central venous catheters, frequent hospitalization, orthopedic surgeries for avascular necrosis, and pregnancy often leads to an increased incidence of VTE in the SCD. In addition, SCD itself appears to be a hypercoagulable state with many SCD-specific factors such as genotype, splenectomy and thrombophilia modifying the risk of VTE. This study aims to assess the clinical and pathological characteristics of VTE amongst a cohort of patients with SCD at the Sultan Qaboos University Hospital and determine its relation to morbidity and mortality. Methodology: In this retrospective case control study, medical details of all patients with SCD who developed thromboembolic complications over the past decade were retrieved from the hospital information system. SCD patients matched for age and gender (2:1 ratio) who did not have thromboembolic complications but had a thrombophilia screen performed served as controls. The study was approved by the local Medical Research and Ethics Committee. Results & Discussion: A total of 53 SCD patients were enrolled [34 cases, 19 controls] in this study. Amongst the 34 cases (mean age-30 yrs.), 18 had pulmonary embolism, eight had deep venous thrombosis, whereas, three each had cerebral venous thrombosis and portal venous thrombosis and one each had cerebral arterial thrombosis and VTE. A higher incidence of autosplenectomy(69.7% v/s 52.6%) and central venous catheters(42.4% v/s 5.3%) were significantly associated with thrombosis (p<0.05, Chi Square test). High LDH levels, WBC and Platelet counts were significant risk factors(p<0.05) for VTE. 21 patients [63.6%] amongst the cases developed acute chest syndrome, where 3[9%] had cerebrovascular accident. Mortality was seen in seven cases [21%]. Conclusions: The study shows that thromboembolic complications in SCD has a high impact on the morbidity and mortality. It confirms PE as the leading cause for VTE in SCD with asplenia, central venous catheter, high LDH, WBC and Platelet counts being significant risk factors. Disclosures No relevant conflicts of interest to declare.

Sickle cell disease and pregnancy outcomes: population-based study on 8.8 million births

2014 ◽  
Vol 42 (4) ◽  
Author(s):  
Nada Alayed ◽  
Abbas Kezouh ◽  
Lisa Oddy ◽  
Haim A. Abenhaim
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Pregnant Women ◽  
Sickle Cell ◽  
Perinatal Outcomes ◽  
Population Based ◽  
Morbidity And Mortality ◽  
Cell Disease ◽  
Sickle Cell Crisis ◽  
Hemoglobin Variants

AbstractTo estimate the prevalence of sickle cell disease (SCD) in pregnancy, and to measure risk factors, morbidity, and mortality among women with SCD with and without crisis at the time of birth.We conducted a population-based, retrospective cohort study on all births in the Healthcare Cost and Utilization Project Nationwide Inpatient Sample (HCUP-NIS) from 1999 to 2008. Births to SCD with and without crisis were identified using ICD-9 codes. Adjusted effects of risk factors and outcomes were estimated using logistic regression analyses. Effect of hemoglobin variants among women with SCD was analyzed as a predictor of crisis.There were 4262 births to women with SCD for an overall prevalence of 4.83 per 10,000 deliveries. 28.5% of women with SCD developed crisis at the time of delivery. The maternal mortality rate was 1.6 per 1000 deliveries in women with SCD, compared to 0.1 per 1000 in women without SCD. Pregnant women with SCD had a higher risk of developing preeclampsia, eclampsia, venous thromboembolism, cardiomyopathy, intrauterine fetal demise, and intrauterine growth restriction. Cesarean delivery rates were higher in women with SCD. Among the 1898 SCD women with identified hemoglobin variants, homozygous SS was the greatest risk factor for sickle cell crisis, accounting for 89.8% of all women who developed crisis.Pregnant women with SCD have a high risk of morbidity and mortality. Developing acute sickle cell crisis worsened perinatal outcomes.

scholarly journals Sickle Cell Disease: A Paradigm for Venous Thrombosis Pathophysiology

2020 ◽  
Vol 21 (15) ◽  
pp. 5279
Author(s):  
Maria A. Lizarralde-Iragorri ◽  
Arun S. Shet
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Venous Thrombosis ◽  
Mouse Models ◽  
Sickle Cell ◽  
Venous Stasis ◽  
Cell Disease ◽  
Cellular Mechanisms ◽  
Blood Clots ◽  
Venous Vasculature

Venous thromboembolism (VTE) is an important cause of vascular morbidity and mortality. Many risk factors have been identified for venous thrombosis that lead to alterations in blood flow, activate the vascular endothelium, and increase the propensity for blood coagulation. However, the precise molecular and cellular mechanisms that cause blood clots in the venous vasculature have not been fully elucidated. Patients with sickle cell disease (SCD) demonstrate all the risk factors for venous stasis, activated endothelium, and blood hypercoagulability, making them particularly vulnerable to VTE. In this review, we will discuss how mouse models have elucidated the complex vascular pathobiology of SCD. We review the dysregulated pathways of inflammation and coagulation in SCD and how the resultant hypercoagulable state can potentiate thrombosis through down-regulation of vascular anticoagulants. Studies of VTE pathogenesis using SCD mouse models may provide insight into the intersection between the cellular and molecular processes involving inflammation and coagulation and help to identify novel mechanistic pathways.

scholarly journals Venous Access Problems in Sickle Cell Disease Patients: Results of Upper Extremity Thrombolysis in the setting of Catheter Related Thrombosis

2020 ◽  
Author(s):  
Jonathan G. Martin
Keyword(s):  
Sickle Cell Disease ◽  
Upper Extremity ◽  
Sickle Cell ◽  
Thrombus Formation ◽  
Central Venous Catheters ◽  
Cell Disease ◽  
Central Venous ◽  
Initial Procedure ◽  
Catheter Related Thrombosis

AbstractPurposeSickle cell disease is the most common monogenic disorder. All the elements of Virchow’s triad – hypercoagulability, endothelial dysfunction and impaired blood flow – are present in sickle cell disease patients, and can lead to thrombosis and vaso-occlusive crises. Central venous catheters are commonly used in sickle cell disease patients for rapid transfusion to avoid a vaso-occlusive crisis or for treatment after crises onset. However, central venous catheters themselves are an additional source for thrombus formation. We investigate a single day thrombolysis protocol for the treatment of catheter related thrombosis.Materials and MethodsWe present an Institutional Review Board approved retrospective analysis spanning from June 2016 to April 2018 evaluating upper extremity thrombolysis in the setting of catheter related thrombosis. All patients underwent a similar protocol involving peripheral upper extremity access, pharmomechanical thrombolysis, and angioplasty, which is described in detail. In 33% of the procedures, a recalcitrant stenosis was then stented. Maximal balloon size and stent sizes are included for reference.ResultsIn follow up, one patient had a severe complication possibly related to the large thrombus burden, and expired. One patient who did not initially have recalcitrant stenosis and therefor did not have a stent placed during the initial procedure, had recurrent stenosis and thrombosis 6 months after the initial procedure, and had repeat pharmomechanical thrombolysis performed, with stent placement at that time. The other procedures were without complication, and the upper extremity and central venous systems remained patent at most recent follow-up, up to 30 months post procedure.ConclusionsIn the circumstance of severe catheter related thrombosis, we present a protocol which can be considered for therapeutic use without further intervention required in 78% of cases at 2 years.

scholarly journals A Nationwide Analysis of Trends in in-Hospital Mortality in Patients with Sickle Cell Disease from 2000 to 2014

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4808-4808
Author(s):  
Imran Ahmad ◽  
Muhammad Sarfraz Nawaz ◽  
Girindra Ghanshyam Raval ◽  
Achuta Kumar Guddati
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Hospital Mortality ◽  
Sickle Cell ◽  
Significant Risk ◽  
Cell Disease ◽  
Hospital Size ◽  
Medical Comorbidities ◽  
The Past ◽  
Significant Difference

Abstract Background: Patients with Sickle cell disease (SCD) have high rates of hospitalizations in the US annually and carry a higher rate of in-hospital mortality compared to the general population. There have been very few therapeutic innovations for the treatment of SCD in the past few decades. Changes in mortality in these patients reflect the availability of healthcare delivery and improvements in management of long term complications of SCD. A nationwide analysis was conducted to study the mortality of patients in SCD over a period of 15 years (2000 to 2014). The national inpatient sample is a database supported by the Agency of Healthcare Research and Quality. Methods: In this study, all patients who were hospitalized between the years 2000 to 2015 were analyzed and mortality was studied in SCD patients. Mortality during hospital stay was studied with respect to hospital size, rural vs. urban location and the most common medical comorbidities. Data pertaining to demographic factors of gender, geographic location and hospital size (measure of expertise and facilities available) were extracted. Access to healthcare was assessed using insurance coverage as a surrogate and its effect on mortality was evaluated. The effect of common medical comorbid conditions such as atrial fibrillation (Afib), hypertension (HTN), hyperlipidemia (HLP), diabetes mellitus (DM), chronic kidney disease (CKD) and tobacco smoking was assessed. Chi-square test analysis was used to validate the statistical significance of difference seen between the groups with a significance identified with a p value< 0.05. Multivariate analysis was used to determine independent predictors of mortality. Results: Out of a total of 1280693 hospitalizations over 15 years there were 9230 deaths of which 4230 were males and 5000 were females. There was no difference in the rate of mortality between hospitals of different sizes (small vs. medium vs. large) teaching and non-teaching hospitals. The mortality/hospitalization ratio was statistically different between Northeast, Midwest, South and West regions (0.63%, 0.65%, 0.76% and 0.89 respectively; p = 0.008). A statistically significant difference was noted between the insurance status (Medicaid vs. Medicare vs. private vs. self) amongst sickle cell patients who died during hospitalization. The odds of dying during hospitalization has gradually decreased from 2000 to 2014 (p = 0.007). The average age of death was 43.8 years and the age group of 35-49 years accounted for the highest amount of mortality (33%). Univariate analysis showed a significant difference in the common medical comorbidities of HTN, HLP, DM, CKD and smoking status in SCD patients who died during hospitalization. Multiple regression analysis revealed females are less likely to suffer from in-hospital mortality than males (OR 0.80; P < 0.04), medical comorbidities of Afib, DM, HTN and CKD are significant risk factors (ORS: 4.3, 1.4, 1.8 and 1.3). Conclusions: In-hospital mortality in SCD patients has improved significantly over the past 2 decades which may reflect some improvements in health care delivery and possibly the usage of hydroxyurea. However, common medical comorbidities such as Afib, HTN, DM and CKD continue to remain significant risk factors for mortality in these patients. Aggressive management of these medical comorbidities may further decrease morbidity and mortality in SCD patients in the future. Disclosures No relevant conflicts of interest to declare.

scholarly journals Neuropathic Pain in Children with Sickle Cell Disease: The Hidden Side of the Vaso-Occlusive Crisis

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 84
Author(s):  
Jeanne Sigalla ◽  
Nathalie Duparc Alegria ◽  
Enora Le Roux ◽  
Artemis Toumazi ◽  
Anne-Françoise Thiollier ◽  
...  
Keyword(s):  
Risk Factors ◽  
Neuropathic Pain ◽  
Sickle Cell Disease ◽  
Sex Ratio ◽  
Prospective Study ◽  
Sickle Cell ◽  
Clinical Presentation ◽  
Early Stage ◽  
Cell Disease ◽  
A Prospective Study

The majority of hospitalizations of patients with sickle cell disease (SCD) are related to painful vaso-occlusive crises (VOCs). Although the pain of VOC is classically nociceptive, neuropathic pain (NP) has also been demonstrated in SCD patients. The aim of our study is to specify the prevalence of NP during VOCs in SCD children using a dedicated scale and to measure its characteristics. We performed a prospective study that included SCD children hospitalized for an acute VOC. The presence of NP was sought with the DN4 scale on the second and fourth days of hospitalization. A total of 54 SCD children were included in the study. Overall, 41% of the patients (n = 22) experienced neuropathic pain during the VOC, mostly at an early stage (Day 2). The median age, the sex ratio, the location of the pain, and the morphine consumption were similar for patients with and without NP. Our study shows that neuropathic pain is very common during VOCs in SCD children. The absence of identified risk factors should prompt us to be vigilant regardless of the patient’s age, sex, and clinical presentation.

scholarly journals Morbidity and mortality of sickle cell disease patients starting intermittent haemodialysis: a comparative cohort study with non- Sickle dialysis patients

2016 ◽  
Vol 174 (1) ◽  
pp. 148-152 ◽  
Author(s):  
Louise Nielsen ◽  
Florence Canouï-Poitrine ◽  
Jean-Philippe Jais ◽  
Djamal Dahmane ◽  
Pablo Bartolucci ◽  
...  
Keyword(s):  
Cohort Study ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Morbidity And Mortality ◽  
Cell Disease ◽  
Dialysis Patients ◽  
Intermittent Haemodialysis ◽  
Comparative Cohort Study

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 &lt; 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.

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 &gt;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.

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