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

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.

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

Blood ◽

10.1182/blood-2020-143036 ◽

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.

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

Blood ◽

10.1182/blood.v128.22.4855.4855 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4855-4855 ◽

Cited By ~ 1

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.

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Abnormal Pulmonary Function in Adults and Children with Sickle Cell Disease.

Blood ◽

10.1182/blood.v106.11.2319.2319 ◽

2005 ◽

Vol 106 (11) ◽

pp. 2319-2319 ◽

Cited By ~ 1

Author(s):

Claudia R. Morris ◽

Jennifer Gardner ◽

Andrew Wen ◽

Shanda Robertson ◽

Ward Hagar ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Lung Function ◽

Pulmonary Function ◽

Sickle Cell ◽

Acute Chest Syndrome ◽

Asthma Treatment ◽

Cell Disease ◽

History Of ◽

Adults And Children

Abstract Introduction: Chronic lung disease is a fatal complication in sickle cell disease (SCD) often undiagnosed until late stages. Early detection and treatment of risk factors may improve survival. Since asthma, pulmonary hypertension (PHT), and acute chest syndrome (ACS) are potential risk factors, in 1998, we began screening patients with history of ACS or wheezing with pulmonary function tests (PFT) and echocardiogram (echo). Methods: A chart review was completed on the 362 adults and children evaluating history of asthma, lung function (PFT) and PHT (echo, tricuspid regurgitant jet velocity ≥ 2.5). Results: PFT Findings All Ages Adults Children PHT (All Ages) Study performed 34% (124/362) 41% (95/232) 22% (29/130) Echo: 90% (111/124) Abnormal 85% (106/124) 87% (83/95) 79% (23/29) 51% (54/106) Obstructive (OBS) only 31% (33/106) 31% (26/83) 30% (7/23) 42% (14/33) Restrictive (REST) only 30% (32/106) 28% (23/83) 39%(9/23) 38% (12/32) Both OBS + REST pattern 27% (29/106) 29% (24/83) 22% (5/23) 69% (20/29) “Abnormal,” not specified 11% (12/106) 12% (10/83) 9% (2/23) 67% (8/12) DLCO < 65% predicted 48% (45/94) 53% (42/80) 21% (3/14) 54% (26/48) Diagnosis & Treatment Clinical asthma diagnosis 13% (47/362) 14% (33/232) 11% (14/130) 43% (20/47) Receiving asthma treatment 51% (24/47) 45% (15/33) 64% (9/14) 50% (12/24) Bronchodilator only 23% (11/47) 24% (8/33) 21% (3/14) 45% (5/11) Inhaled steroid 23% (11/47) 18% (6/33) 36% (5/14) 55% (6/11) Singulair 4% (2/47) 3% (1/33) 7% (1/14) 50% (1/2) PFT suggests asthma 50% (62/124) 53% (50/95) 41% (12/29) 53% (33/62) +PFT, + asthma treatment 16% (10/62) 14% (7/50) 25% (3/12) 80% (8/10) One hundred twenty-four patients underwent PFTs, of which 111 (85%) were abnormal. Obstructive and/or restrictive disease with abnormal diffusion capacity were widespread. Of patients with an obstructive pattern, only 16% were receiving any asthma treatment. Forty-seven patients (33 adults and 14 children) were diagnosed with asthma. However, only half were receiving any treatment: 23% bronchodilators, and 23% inhaled steroids. Echo was performed on 90% of patients with PFT data. Half of all patients with abnormal PFTs, and 69% of those with obstructive/restrictive patterns, had PHT. Conclusion: While a more severe population may have been tested, this data suggests abnormal lung function is prevalent in SCD and is associated with PHT. Recent data suggests abnormal NO metabolism may link asthma and PHT in SCD. In conclusion, our data suggests patient morbidity will be decreased by regular screening with PFT and echo followed by early treatment for asthma and PHT.

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

Blood ◽

10.1182/blood-2021-151361 ◽

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.

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To Give or Not to Give: RhD Immunoglobulin for an RHD*39 Pregnant Woman with Sickle Cell Disease

Transfusion Medicine and Hemotherapy ◽

10.1159/000512644 ◽

2021 ◽

pp. 1-5

Author(s):

Justin E. Juskewitch ◽

Craig D. Tauscher ◽

Sheila K. Moldenhauer ◽

Jennifer E. Schieber ◽

Eapen K. Jacob ◽

...

Keyword(s):

Pregnant Woman ◽

Sickle Cell Disease ◽

Sickle Cell ◽

Pregnancy Termination ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Childbearing Age ◽

Procedural Complications ◽

History Of ◽

Chronic Hemolysis

Introduction: Patients with sickle cell disease (SCD) have repeated episodes of red blood cell (RBC) sickling and microvascular occlusion that manifest as pain crises, acute chest syndrome, and chronic hemolysis. These clinical sequelae usually increase during pregnancy. Given the racial distribution of SCD, patients with SCD are also more likely to have rarer RBC antigen genotypes than RBC donor populations. We present the management and clinical outcome of a 21-year-old pregnant woman with SCD and an RHD*39 (RhD[S103P], G-negative) variant. Case Presentation: Ms. S is B positive with a reported history of anti-D, anti-C, and anti-E alloantibodies (anti-G testing unknown). Genetic testing revealed both an RHD*39 and homozygous partial RHCE*ceVS.02 genotype. Absorption/elution testing confirmed the presence of anti-G, anti-C, and anti-E alloantibodies but could not definitively determine the presence/absence of an anti-D alloantibody. Ms. S desired to undergo elective pregnancy termination and the need for postprocedural RhD immunoglobulin (RhIG) was posed. Given that only the G antigen site is changed in an RHD*39 genotype and the potential risk of RhIG triggering a hyperhemolytic episode in an SCD patient, RhIG was not administered. There were no procedural complications. Follow-up testing at 10 weeks showed no increase in RBC alloantibody strength. Discussion/Conclusion: Ms. S represents a rare RHD*39 and partial RHCE*ceVS.02 genotype which did not further alloimmunize in the absence of RhIG administration. Her case also highlights the importance of routine anti-G alloantibody testing in women of childbearing age with apparent anti-D and anti-C alloantibodies.

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Clinical and Biomarker Predictors for Avascular Necrosis in Sickle Cell Disease

Blood ◽

10.1182/blood-2021-147829 ◽

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.

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Low‐risk factors for severe bacterial infection and acute chest syndrome in children with sickle cell disease

Pediatric Blood & Cancer ◽

10.1002/pbc.27667 ◽

2019 ◽

Vol 66 (6) ◽

pp. e27667 ◽

Cited By ~ 1

Author(s):

Elena María Rincón‐López ◽

María Luisa Navarro Gómez ◽

Teresa Hernández‐Sampelayo Matos ◽

Jesús Saavedra‐Lozano ◽

Yurena Aguilar de la Red ◽

...

Keyword(s):

Risk Factors ◽

Sickle Cell Disease ◽

Bacterial Infection ◽

Sickle Cell ◽

Low Risk ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Severe Bacterial Infection

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Prevalence of Pulmonary Hypertension (PHTN) in Sickle Cell Disease (SCD) Adolescents with Pulmonary Complications.

Blood ◽

10.1182/blood.v104.11.3759.3759 ◽

2004 ◽

Vol 104 (11) ◽

pp. 3759-3759

Author(s):

Onyinye C. Onyekwere ◽

Andrew Campbell ◽

James Williams ◽

Peter Gaskin ◽

Sohail Rana ◽

...

Keyword(s):

Sickle Cell Disease ◽

Pulmonary Artery ◽

Sickle Cell ◽

Pulmonary Complications ◽

Acute Chest Syndrome ◽

University Of Michigan ◽

Cell Disease ◽

Hemoglobin F ◽

Howard University ◽

History Of

Abstract Despite the high prevalence of PHTN in adults with SCD, the prevalence in the pediatric population with SCD is not known. We hypothesized that elevated pulmonary artery pressures may be found in SCD adolescents with history of pulmonary complications, such as acute chest syndrome (ACS), obstructive sleep apnea (OSA), asthma, and reactive airway disease. Thirty such sickle cell disease adolescents were screened at Howard University or University of Michigan for PHTN with Doppler echocardiography. We defined PHTN as a tricuspid regurgitant jet velocity (TRV) of at least 2.5 m/sec (corresponding to a pulmonary artery systolic pressure greater than 35 mm Hg). PHTN was found in 16 SCD patients (53.3%) and 5 (16.7%) had TRV > 3.0 m/sec. Clinical findings according to the presences or absence of PHTN are shown in the table. Potential factors contributing to PHTN in patients with SCD include chronic hemolysis and chronic hypoxia. Our results suggest that PHTN is common among SCD adolescents with a history of pulmonary complications. Consideration should be given to screening such patients for PHTN and exploring treatment options. Further studies are urgently needed to clarify the prevalence and mechanisms of PHTN in adolescents with SCD. Clinical and demographic data of 30 SCD adolescents with pulmonary findings who underwent echocardiography at Howard University Hospital or University of Michigan PHTN (N = 16) No PHTN (N = 14) P Age in years (mean +/− SD) 15.9 +/− 3.2 17.4 +/− 2.3 0.17 Females (no. and %) 5 (31.3) 7 (50) 0.5 Hemoglobin SS Phenotype (no and %) 14 (87.5 11 (78.6) 0.5 Hemoglobin concentration (mean +/− SD) 8.0 +/− 2.1 9.3 +/−1.9 0.11 White blood cells (mean +/− SD) 10.9 +/− 2.9 9.7 +/− 3.7 0.4 Platelet (mean +/− SD) 475 +/− 172 364 +/− 240 0.17 Hemoglobin F percent (mean +/− SD) 5.1 +/− 3.5 6.4 +/− 5.5 0.6 Lactate dehydrogenase (mean +/− SD) 505 +/− 162 264 +/− 50 0.002 Total bilirubin (mean +/− SD) 4.1 +/− 2.6 3.4 +/− 2.6 0.5 Creatinine concentration (mean +/− SD) 0.6 +/− 0.2 0.7 +/− 0.2 0.18 Aspartate transaminase (mean +/− SD) 48 +/− 27 36 +/− 16 0.18 Alanine transaminase (mean +/− SD) 51 +/− 37 39 +/− 20 0.3

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Corrected QT Interval Is Related to Markers of Hemolysis and Tricuspid Regurgitant Jet Velocity in a Young Cohort with Sickle Cell Disease.

Blood ◽

10.1182/blood.v110.11.2258.2258 ◽

2007 ◽

Vol 110 (11) ◽

pp. 2258-2258

Author(s):

Robert I. Liem ◽

Luciana T. Young ◽

Alexis A. Thompson

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Qt Interval ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Qtc Prolongation ◽

Corrected Qt Interval ◽

Conduction Abnormalities ◽

History Of ◽

Tricuspid Regurgitant Jet Velocity

Abstract Recent evidence suggests that prolongation in QT interval may be a frequent finding in patients with sickle cell disease (SCD). Few studies, however, have examined the relationship between conduction abnormalities and other cardiac complications, such as left ventricular hypertrophy (LVH) and tricuspid regurgitant jet velocity (TRJV) elevation, in this population. Moreover, long QT may be a marker of increased mortality in conditions, other than SCD, associated with LVH. We therefore sought to evaluate QT interval and its relationship to echocardiographic findings, laboratory parameters and disease severity in a cohort of children and young adults with SCD. Methods We prospectively evaluated the corrected QT interval (QTc) on standard 12-lead ECG in a cross-sectional, convenience sample of 73 subjects (41 males, mean age 14.2±3 years, range 10 to 24) with Hb SS, SC and S-β0 thalassemia undergoing screening for TRJV elevation. Subjects on chronic transfusions were excluded and all studies were performed at baseline on the same day. A review of available medical records was also performed. Results In our cohort, QTc (mean 436±24 ms, range 387 to 531) was prolonged > 440 ms in 30/73 (41%) of subjects at steady state. We also found TRJV elevation ≥ 2.5 m/s in 24/73 (33%) and LVH by ECG or echocardiographic criteria in 32/73 (44%) subjects. Using Pearson’s correlation coefficient, we observed significant correlations between QTc and TRJV (r=0.38, p=0.002), WBC (r=0.37, p=0.001) and several markers of hemolysis, including LDH (r=0.46, p=0001), Hb (r=-0.32, p=0.005), retic (r=0.29, p=0.013), plasma Hb (r=0.27, p=0.03) and AST (r=0.38, p=0.001). Using Student’s t-test for independent samples, only TRJV (2.55±0.33 vs. 2.34±0.26 m/s, p=0.006), LDH (450±166 vs. 329±143 U/L, p=0.001), WBC (10.6±4.7 vs. 8.6±3.3×109/L, p=0.048), retic (14.4±9.2 vs. 10.6±6.1%, p=0.039) and AST (50±22 vs. 38±15 U/L, p=0.009) were significantly higher and Hb (9.1±1.3 vs. 9.9±1.7 g/dL, p=0.04) lower in subjects with QTc > 440 ms compared to those with QTc ≤ 440 ms. We found no significant relationship between QTc and age, LV mass, platelet count or fetal Hb. By χ2 analysis, a larger proportion of subjects with QTc > 440 ms also had a history of acute chest syndrome (p=0.007), gallstones (p=0.047), exchange transfusion (p=0.04) and to a less significant degree, TRJV elevation (p=0.112). Prolonged QTc was not affected by sex, hydroxyurea use or a history of LVH, frequent pain, asthma, splenectomy, priapism and tonsilloadenoidectomy. Given sample size limitations and data reduction methods, we found by logistic regression analysis that the combination of TRJV and history of acute chest syndrome best predicted QTc prolongation, correctly identifying 80% of cases and resulting in positive and negative predictive values of 76% and 81%, respectively. Conclusions We conclude that QTc prolongation is common in a prospectively screened cohort of young sickle cell patients at baseline and is associated with evidence of hemolysis and to a lesser degree, TRJV elevation. Our results contrast with findings in other conditions that link QTc prolongation primarily to LVH. Future studies will be critical to further define QTc variability, pathophysiologic determinants as well as the clinical consequences of conduction abnormalities, which may or may not relate to TRJV elevation, in the sickle cell population.

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Five years of experience with hydroxyurea in children and young adults with sickle cell disease

Blood ◽

10.1182/blood.v97.11.3628 ◽

2001 ◽

Vol 97 (11) ◽

pp. 3628-3632 ◽

Cited By ~ 132

Author(s):

Alina Ferster ◽

Parvine Tahriri ◽

Christiane Vermylen ◽

Geneviève Sturbois ◽

Francis Corazza ◽

...

Keyword(s):

Sickle Cell Disease ◽

Sickle Cell ◽

Laboratory Data ◽

Acute Chest Syndrome ◽

Cell Disease ◽

Significant Difference ◽

History Of ◽

Ischemic Attack

The short-term beneficial effect of hydroxyurea (HU) in sickle cell disease (SCD) has been proven by randomized studies in children and adults. The Belgian registry of HU-treated SCD patients was created to evaluate its long-term efficacy and toxicity. The median follow-up of the 93 patients registered is 3.5 years; clinical and laboratory data have been obtained for 82 patients at 1 year, 61 at 2 years, 44 at 3 years, 33 at 4 years, and 22 after 5 years. On HU, the number of hospitalizations and days hospitalized dropped significantly. Analysis of the 22 patients with a minimum of 5 years of follow-up confirm a significant difference in the number of hospitalizations (P = .0002) and days in the hospital (P < .01), throughout the treatment when compared to prior to HU therapy. The probabilities of not experiencing any event or any vaso-occlusive crisis requiring hospitalization during the 5 years of treatment were, respectively, 47% and 55%. On HU, the rate per 100 patient-years of severe events was estimated to be 3.5% for acute chest syndrome, 1.2% for aplastic crisis, 0.4% for splenic sequestration; it was 0% for the 9 patients with a history of stroke or transient ischemic attack followed for an average of 4 years. No important adverse effect occurred. Long-term chronic treatment with HU for patients with SCD appears feasible, effective, and devoid of any major toxicity; in patients with a history of stroke, HU may be a valid alternative to chronic transfusion support.

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