scholarly journals Prevalence and risk factors for venous thromboembolism in children with sickle cell disease: an administrative database study

2018 ◽  
Vol 2 (3) ◽  
pp. 285-291 ◽  
Author(s):  
Riten Kumar ◽  
Joseph Stanek ◽  
Susan Creary ◽  
Amy Dunn ◽  
Sarah H. O’Brien
Keyword(s):  
Risk Factors ◽  
Retrospective Study ◽  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Administrative Database ◽  
Similar Data ◽  
Cell Disease ◽  
Database Study ◽  
Key Points

Key Points Adults with SCD have an increased incidence of VTE, but similar data in children are lacking. In this 7-year, multicenter retrospective study, 1.7% of children with SCD developed VTE.

scholarly journals High Rate of Recurrent Venous Thromboembolism Is Children with Sickle Cell Disease and History of VTE: Analysis of the Trinetx Research Network Database

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 778-778
Author(s):  
Marisol Betensky ◽  
Ernest Amankwah ◽  
Jane S Hankins ◽  
Neil Goldenberg
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Board Of Directors ◽  
Sickle Cell ◽  
Research Network ◽  
Cell Disease ◽  
Advisory Committees ◽  
History Of ◽  
Recurrent Vte

Abstract Background: Sickle Cell Disease (SCD) is associated with a chronic prothrombotic state that increases the risk of venous thromboembolism (VTE). The rate of VTE in hospitalized children with SCD is nearly 2%, substantively higher than the 0.2-0.6% rate seen in the general pediatric population. 1-3 The frequency and risk factors associated with the development of recurrent VTE in this population are vastly unknown. This knowledge gap hinders the development of disease-specific guidelines for the management and secondary prevention of VTE in pediatric SCD. Aim: To investigate the frequency of recurrent VTE in children birth to 21 years of age (inclusive) with SCD and history of prior VTE. Methods: We analyzed patient-level data from the TriNetX Research Network Database, a global federated network of electronic medical record (EMR) data from 42 health care organizations. Children ≤21 years of age with a diagnosis of SCD and history of VTE between January 1 2008 to March 31 2021 were included in the analysis. Index VTE was defined as the first diagnosis of VTE in the patient's EMR. Recurrent VTE was defined as an acute VTE diagnosis that occurred 90 days after the index VTE discharge date in a different anatomic location from the index VTE. Patient demographic and clinical characteristics were summarized using counts and percentages. Missing values were not imputed. Overall, one year and five-year recurrence VTE are reported with the corresponding 95% confidence intervals (CI). Results: A total of 119 children with SCD and VTE were included. Table 1 shows the patients baseline characteristics. Mean age at the time of index VTE diagnosis was 16.7 years (standard deviation 5.5 years). The majority of patients were Black (87%) and female (61%). The most frequent index VTE diagnosis was pulmonary embolism (42%) followed by lower (23%) and upper (22%) extremity VTE. Of the 119 patients,10 (8.4%, 95%CI=4-15%) developed recurrent VTE within 1-year and 25 (21.0%, 95%CI=14-29%) developed recurrent VTE within 5-years from index VTE. Compared to patients without recurrent VTE, patients with recurrent VTE were more frequently female (50% vs. 68%, respectively), and slightly older (mean age 16.6 years vs. 17.2 years, respectively). The most frequent anatomic location for VTE recurrence was the upper extremity (32%) Conclusions: This retrospective database analysis identified, for the first time, high rates of recurrent VTE of 8.4% and 21% at 1- and 5-years post-VTE in children with SCD. These rates stand in contrast with the 3% VTE recurrence at 1-year reported for the general pediatric VTE population. 4 Further analyses of the database are ongoing to identify risk factors for recurrent VTE in this population. These initial findings highlight the need for cooperative multicenter prospective studies to reliably establish rates of- and prognostic factors associated with recurrent VTE in children with SCD, in order to generate evidence for disease-specific treatment guidelines, and to inform future prognostically-stratified interventional trials designed to optimize VTE outcomes in pediatric SCD. 1.Kumar R, Stanek J, Creary S, et al. Prevalence and risk factors for venous thromboembolism in children with sickle cell disease: an administrative database study. Blood Adv 2018;2:285-291. 2. Raffini L, Huang YS, Witmer C, Feudtner C. Dramatic increase in venous thromboembolism in children's hospitals in the United States from 2001to 2007. Pediatrics 2009;124:1001-8. 3. Setty BA, O'Brien SH, Kerlin BA. Pediatric venous thromboembolism in the United States: a tertiary care complication of chronic diseases. Pediatr Blood Cancer 2012;59:258-64. 4. Goldenberg NA, Schulman S, Kittelson JM, et al, Kids-DOTT Trial Investigators and the ATLAS Group. A Six-week versus Three-month Duration of Anticoagulation for Acute Provoked Venous Thromboembolism in Patients < 21 Years Old: Results of the Multinational Kids-DOTT Randomized Controlled Trial. [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 1). Figure 1 Figure 1. Disclosures Hankins: Global Blood Therapeutics: Consultancy; Vindico Medical Education: Consultancy; UpToDate: Consultancy; Bluebird Bio: Consultancy. Goldenberg: Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees; Daiici: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Anthos: Membership on an entity's Board of Directors or advisory committees.

scholarly journals Risk of Venous Thromboembolism in Hospitalized Patients with Sickle Cell Disease

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4755-4755
Author(s):  
Joshua Taylor ◽  
Alexandra Anghel ◽  
Daniel J Corsi ◽  
Marc Carrier ◽  
Alan Tinmouth ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Tertiary Care ◽  
Previous History ◽  
Cell Disease ◽  
Poisson Models ◽  
Increased Risk ◽  
History Of

Abstract Background: Patients with sickle cell disease (SCD) are at an increased risk of developing venous thromboembolism (VTE). However, the underlying risk of VTE complication during hospitalization is unclear in this patient population. We sought to report the incidence of VTE and its associated risk factors in hospitalized SCD patients. Patients/Methods: A retrospective cohort study of SCD patients requiring hospitalization was undertaken at a tertiary care center. Incidence ratios of VTE per hospitalization for different risk factors (Thromboprophylaxis use, central venous catheter (CVC), past history of VTE, surgery during hospitalization) were assessed. Univariate, age adjusted and multivariate Poisson models were estimated accounting for the repeated hospitalizations per patients. Results: A total of 101 patients with at least one hospitalization were included in the study. The mean of number of admissions per patients was 8.9. Overall, 17 out of 896 (1.9%) admissions were complicated by VTE. The incidence of VTE varied by risk factors, from 0.8% in patient without CVC to 6.7% among patients admitted with previous history of VTE. Age adjusted and multivariate Poisson models for incidence rate ratios of VTE per hospitalization among patients with SCD for different risk factors are depicted in Table 1. Conclusion: The risk of VTE seems low in hospitalized SCD. A prior history of VTE and a hospitalization for surgery might be associated with higher risk of VTE complication. Future studies assessing these risk factors to tailor thromboprophylaxis regimens are needed. 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 The effect of anticoagulant choice on venous thromboembolism recurrence and bleeding in sickle cell disease

2020 ◽  
Author(s):  
Vishal K. Gupta ◽  
Rachel Strykowski ◽  
Brittany Scarpato ◽  
Romy Lawrence ◽  
Sarah L. Khan ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Cell Disease ◽  
Venous Thromboembolism Recurrence

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.

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 Red blood cell alloimmunization in sickle cell disease: pathophysiology, risk factors, and transfusion management

Blood ◽  
2012 ◽  
Vol 120 (3) ◽  
pp. 528-537 ◽  
Author(s):  
Karina Yazdanbakhsh ◽  
Russell E. Ware ◽  
France Noizat-Pirenne
Keyword(s):  
Risk Factors ◽  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Cell Disease ◽  
Factors Associated ◽  
Life Threatening ◽  
Red Blood Cell Transfusions ◽  
Transfusion Reactions

Abstract Red blood cell transfusions have reduced morbidity and mortality for patients with sickle cell disease. Transfusions can lead to erythrocyte alloimmunization, however, with serious complications for the patient including life-threatening delayed hemolytic transfusion reactions and difficulty in finding compatible units, which can cause transfusion delays. In this review, we discuss the risk factors associated with alloimmunization with emphasis on possible mechanisms that can trigger delayed hemolytic transfusion reactions in sickle cell disease, and we describe the challenges in transfusion management of these patients, including opportunities and emerging approaches for minimizing this life-threatening complication.

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