scholarly journals Risk of Pregnancy-Related Venous Thromboembolism in Black Women with Sickle Cell Trait

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 2044-2044
Author(s):  
Tijesunimi Oni ◽  
Manuela Plazas Montana ◽  
Mamie Myo Thant ◽  
Sarah Baghdadi ◽  
Jaanvi Mahesh ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Black Women ◽  
Sickle Cell ◽  
Research Funding ◽  
Sickle Cell Trait ◽  
Post Partum ◽  
Search Term ◽  
Vein Thrombosis ◽  
Increased Risk ◽  
Privately Held

Abstract Background: Select inherited thrombophilias have been shown to potentiate the risk of venous thromboembolism (VTE) during pregnancy and the post-partum period. Sickle cell trait (SCT) is associated with an increased risk of VTE in the general Black population; however, prior studies investigating the risk of pregnancy-related VTE among women with SCT have been limited by an overall low number of VTE events. We, therefore, designed a retrospective cohort enriched for pregnancy-related VTE events among Black women at Johns Hopkins Hospital to address this question. Methods: We generated a cohort enriched for pregnancy-related VTE at Johns Hopkins or affiliate hospitals from 2009-2019 by using EPIC and an internal ObGyn database to identify Black women ≥18 years with at least 1 pregnancy encounter in addition to at least 1 VTE-related ICD-10 diagnosis code or comprehensive VTE-related search term. All charts were manually reviewed to confirm hemoglobinopathy status and to verify the presence or absence of a VTE event during pregnancy or 6 weeks post-partum. Individuals with sickle cell disease, history of VTE prior to index pregnancy, catheter-related or superficial vein thrombosis only, or unknown pregnancy VTE outcome were excluded. Results: A total of 418 women were included for analysis. The mean age at pregnancy was 30 years (range 18-48), and the prevalence of SCT was 6.7%, which is similar to the prevalence in the general Black American population. Thirty-seven women (8.9%) were confirmed to have a pregnancy-related VTE event. Among those with VTE, SCT carriers demonstrated a higher proportion of pulmonary embolism (PE), unusual vein thrombosis, and antepartum VTE events compared to women with HbAA (Table 1), though numbers were small. After adjusting for age, the risk of VTE was 2.9-fold (95% CI 1.1-7.9) higher among pregnant Black women with SCT compared to those without. Conclusions: In this enriched cohort, SCT was associated with an increased risk of pregnancy-related VTE among Black women. The pattern of pregnancy-related VTE was different in individuals with SCT compared to those with HbAA, with SCT demonstrating a higher proportion of PE and antepartum events. The higher risk of PE compared to isolated DVT is similar to the pattern observed in prior population-based studies of SCT. Because the prevalence of SCT is high and the overall risk of VTE in pregnancy is low, future studies are needed to determine whether routine thromboprophylaxis is warranted for select high-risk pregnant women with SCT. Figure 1 Figure 1. Disclosures Lanzkron: Novartis: Research Funding; CSL Behring: Research Funding; Shire: Research Funding; Novo Nordisk: Consultancy; Imara: Research Funding; Bluebird Bio: Consultancy; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; GBT: Research Funding. Naik: Rigel: Research Funding.

Sickle cell trait and the risk of venous thromboembolism among blacks

Blood ◽  
2007 ◽  
Vol 110 (3) ◽  
pp. 908-912 ◽  
Author(s):  
Harland Austin ◽  
Nigel S. Key ◽  
Jane M. Benson ◽  
Cathy Lally ◽  
Nicole F. Dowling ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Odds Ratio ◽  
Sickle Cell Trait ◽  
Coagulation System ◽  
Cell Disease ◽  
Hemoglobin C ◽  
Increased Risk ◽  
S Allele

Abstract People with sickle cell disease have a chronically activated coagulation system and display hemostatic perturbations, but it is unknown whether they experience an increased risk of venous thromboembolism. We conducted a case–control study of venous thromboembolism that included 515 hospitalized black patients and 555 black controls obtained from medical clinics. All subjects were assayed for hemoglobin S and hemoglobin C genotypes. The prevalence of the S allele was 0.070 and 0.032 for case patients and controls, respectively (P < .001). The odds that a patient had sickle cell trait were approximately twice that of a control, indicating that the risk of venous thromboembolism is increased approximately 2-fold among blacks with sickle cell trait compared with those with the wild-type genotype (odds ratio = 1.8 with 95% confidence interval, 1.2-2.9). The odds ratio for pulmonary embolism and sickle cell trait was higher, 3.9 (2.2-6.9). The prevalence of sickle cell disease was also increased among case patients compared with controls. We conclude that sickle cell trait is a risk factor for venous thromboembolism and that the proportion of venous thromboembolism among blacks attributable to the mutation is approximately 7%.

scholarly journals COVID-19 in Hospitalized Patients with Sickle Cell Disease

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 3090-3090
Author(s):  
Stephanie Guarino ◽  
Sophie M. Lanzkron
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Research Funding ◽  
Case Fatality ◽  
Hospitalized Patients ◽  
Categorical Variables ◽  
Fatality Rate ◽  
Cell Disease ◽  
Increased Risk ◽  
Privately Held

Abstract Introduction Sickle cell disease (SCD) is the most common inherited hemoglobinopathy and is estimated to affect more than 100,000 Americans. Current Centers for Disease Control statistics indicate that Black Americans die from COVID-19 at a disproportionately high rate, 13.6% of 449, 373 deaths but only account for 12.54% of the United States Population (CDC COVID Data Tracker accessed 5/5/2021). A voluntary clinical reported registry of COVID-19 infections in patients with SCD reported both high hospitalization rates (69%) and case fatality rates (7%) (Panepinto, 2020), but only reported data from March 20-May 21, 2020. A retrospective cohort review from England demonstrated a 4-fold increased risk of hospitalization and 2.6-fold increased risk of death due to COVID-19 for those patients with sickle cell disease compared to the general population (Hippisley-Cox, 2021). The unique constellation of SCD manifestations complicate both the diagnosis and management of COVID-19, particularly related to anticoagulation and transfusion practices. Understanding the impact of early exchange and anticoagulation would guide development of appropriate treatment guidelines and future understanding of pathophysiology. We report on the outcomes for all hospitalized inpatients with SARS-CoV-2 and SCD at institutions using Cerner electronic health record (EHR). Methods Exempted retrospective review approved by ChristianaCare IRB. We obtained deidentified data from the Cerner COVID Data Lab which includes information on all hospitalized inpatients with SARS-CoV-2 and sickle cell disease as documented by ICD 10 D57.XX from 12/10/2019-10/15/2020 at institutions that use the Cerner EHR. Those with sickle cell trait excluded. The data included 209 patients; 1 patient had separate 2 visits, only the first visit in the data. Evaluated anticoagulation use, not dose. Descriptive statistics are given: percentages for categorical variables and mean (standard deviation) for continuous variables. Comparisons between patients who died or went to hospice versus patients who recovered were done using unadjusted chi-squared tests or t-tests. Results: Admission: 124 (74.3%) were afebrile (temp &lt;100) 52 (28.4%) were tachypneic (RR &gt;22) 10 (6.2%) were hypoxic (&lt;92%) 7 (3.3%) were intubated during hospitalization Many patients had comorbidities including diabetes, hypertension, and congestive heart failure, but it was not clear if patients had multiple co-morbidities. Treatment: 16 (7.7%) got transfused RBC between 1.77 and 589.18 hours into admission 5 (2.4%) got Remdesivir, none of these patients died/went to hospice. No exchange transfusions, but maybe wasn't captured in coding data 149 (71.3%) received anticoagulant, dosing unable to be obtained so not known if this was prophylactic or treatment dosing. Outcomes: 158 (80.2%) discharged home 18 (9.1%) discharged facility 8 (4.1%) died 2 (1.0%) discharged hospice 11 (5.6%) left against medical advice 12 (5.7%) missing disposition data Those who died/went to hospice had longer hospital stays, were more likely to be hypoxic and initially tachypneic. None of these patients received remdesivir. Study included small numbers but those who died more likely to have hypertension, diabetes w/ and w/out complications, CHF. Discussion This data only included hospitalized patients, doesn't account for patients who remained outpatient so case fatality rate likely lower. 10/209 patients died- 4.8% fatality rate, 12 patients missing final discharge disposition. 18 went to facility, may have died as outpatient. Only a small number of patients received remdesivir and there were overall low rates of anticoagulation, concerning given SCD is a hypercoagulable state. Study limitations include only hospitalized patients in the dataset and only draws from Cerner EMR institutions, a 26% market share. Based on our own SCD population, only a small percentage of patients with SCD and COVID-19 hospitalized. Additionally, there is likely significant variability between institutions' treatment protocols, particularly in the early months of the data set. Finally, we could not adequately gauge severity of COVID-19 disease given notable variations in institutional resources. TABLES (in process): TABLE 1- Demographics- split by death/hospice vs. other dispositions TABLE 2- Admission Characteristics- Death/hospice vs. others TABLE 3- Treatments- Death/Hospice vs. others Disclosures Lanzkron: Shire: Research Funding; Novartis: Research Funding; Bluebird Bio: Consultancy; CSL Behring: Research Funding; Imara: Research Funding; GBT: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; Teva: Current holder of individual stocks in a privately-held company; Novo Nordisk: Consultancy.

scholarly journals Sickle Cell Disease and Vestibular Dysfunction

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 4183-4183
Author(s):  
Nicholas S Andresen ◽  
Tiffany McIntyre ◽  
Bryan K Ward ◽  
Melanie Dawn Nelson ◽  
Amir Kheradmand ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sickle Cell Disease ◽  
General Population ◽  
Sickle Cell ◽  
Research Funding ◽  
Cell Structure ◽  
Vestibular Dysfunction ◽  
Cell Disease ◽  
Increased Risk ◽  
Privately Held

Abstract Introduction: Sickle cell disease (SCD), a common genetic disease involving red blood cell structure and function, is associated with cerebral vasculopathy and increased risk of ischemic events that may also affect the inner ear. Individuals with SCD are at increased risk for hearing loss; however, little is known regarding the effects of SCD on the vestibular system or the relationship between hearing loss and vestibular symptoms in these patients. Vestibular dysfunction affects 15-20% of the general population can lead to significant morbidity through falls, fall-related injuries, missed work, and overall reduction in quality of life. Methods: To assess the burden of vestibular dysfunction amongst individuals with SCD, we surveyed individuals with SCD who answered questions about symptoms of dizziness, imbalance, and hearing loss. The survey also captured demographic information, current symptoms of dizziness/imbalance, symptoms of hearing loss, and history of falls. Fisher's exact test was performed to test for associations between clinical characteristics including SCD genotype, hearing loss, dizziness or imbalance, and headache history. Results: Twenty-six participants, ages 20 to 73 years (median 37.5 years) completed the survey. All participants were Black or African-American. Five participants (19.2%) were male, 15 (58%) had hemoglobin SS, 8 (32%) hemoglobin SC, and 3 (12%) S-β + thalassemia. Three (11.5%) participants reported hearing loss. Twelve (46.2%) participants reported dizziness or imbalance, of which 8 (66%) reported recent falls. Of the 12 participants experiencing dizziness, 9 (75%) reported having dizziness for 1 to 3 days a month, 2 reported having dizziness for 4 to 9 days a month, and 1 reported having dizziness for more than 15 days a month. Three participants reported their dizziness symptoms resolved within seconds, 7 within minutes, and 2 within hours. Eleven (42.3%) participants reported headaches. Self-reported dizziness or imbalance was not associated with hearing loss (X 2=0.57; p=0.45), SCD genotype (X 2=0.75; p=0.68), or sex (X 2=0.09; p=0.76). Headache history was associated with dizziness or imbalance (X 2=9.76; p=0.002). Conclusions: In this small pilot study, 46% of individuals with SCD reported dizziness or imbalance, which is twice the rate reported amongst the general population. Headache history is associated with dizziness and imbalance amongst individuals with SCD. Further investigation is warranted to determine the specific effects of SCD on the vestibular end-organs. Disclosures Lanzkron: Imara: Research Funding; Pfizer: Current holder of individual stocks in a privately-held company; GBT: Research Funding; Shire: Research Funding; Teva: Current holder of individual stocks in a privately-held company; Novartis: Research Funding; Novo Nordisk: Consultancy; Bluebird Bio: Consultancy; CSL Behring: Research Funding. Lance: Novartis: Other: participated in research advisory board in 2020.

scholarly journals Sickle Cell Trait and Renal Function in Hispanics in the United States: the Northern Manhattan Study

2017 ◽  
Vol 27 (1) ◽  
pp. 11 ◽  
Author(s):  
Nicole D. Dueker ◽  
David Della-Morte ◽  
Tatjana Rundek ◽  
Ralph L. Sacco ◽  
Susan H. Blanton
Keyword(s):  
United States ◽  
Chronic Kidney Disease ◽  
African Americans ◽  
Kidney Disease ◽  
Sickle Cell ◽  
Sickle Cell Trait ◽  
The United States ◽  
Genetic Mutation ◽  
Single Mutation ◽  
Increased Risk

<p class="Pa7">Sickle cell anemia (SCA) is a common hematological disorder among individu­als of African descent in the United States; the disorder results in the production of abnormal hemoglobin. It is caused by homozygosity for a genetic mutation in HBB; rs334. While the presence of a single mutation (sickle cell trait, SCT) has long been considered a benign trait, recent research suggests that SCT is associated with renal dysfunction, including a decrease in estimated glomerular filtration rate (eGFR) and increased risk of chronic kidney disease (CKD) in African Americans. It is currently unknown whether similar associations are observed in Hispanics. Therefore, our study aimed to determine if SCT is associated with mean eGFR and CKD in a sample of 340 Dominican Hispanics from the Northern Manhattan Study. Using regression analyses, we tested rs334 for association with eGFR and CKD, adjusting for age and sex. eGFR was estimated using the Chronic Kidney Disease Epidemiology Collaboration equa­tion and CKD was defined as eGFR &lt; 60 mL/min/1.73 m2. Within our sample, there were 16 individuals with SCT (SCT carriers). We found that SCT carriers had a mean eGFR that was 12.12 mL/min/1.73m2 lower than non-carriers (P=.002). Additionally, SCT carriers had 2.72 times higher odds of CKD compared with non-carriers (P=.09). Taken together, these novel results show that Hispanics with SCT, as found among African Americans with SCT, may also be at increased risk for kidney disease.</p><p class="Pa7"><em>Ethn Dis. </em>2017; 27(1)<strong>:</strong>11-14; doi:10.18865/ed.27.1.11.</p><p class="Pa7"> </p>

Atrial fibrillation associated with increased risk of venous thromboembolism

2015 ◽  
Vol 113 (01) ◽  
pp. 185-192 ◽  
Author(s):  
Chun-Cheng Wang ◽  
Cheng-Li Lin ◽  
Guei-Jane Wang ◽  
Chiz-Tzung Chang ◽  
Fung-Chang Sung ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Incidence Rates ◽  
Vein Thrombosis ◽  
Kaplan Meier ◽  
Increased Risk ◽  
Long Term Follow Up ◽  
Deep Vein

SummaryWhether atrial fibrillation (AF) is associated with an increased risk of venous thromboembolism (VTE) remains controversial. From Longitudinal Health Insurance Database 2000 (LHID2000), we identified 11,458 patients newly diagnosed with AF. The comparison group comprised 45,637 patients without AF. Both cohorts were followed up to measure the incidence of deep-vein thrombosis (DVT) and pulmonary embolism (PE). Univariable and multivariable competing-risks regression model and Kaplan-Meier analyses with the use of Aelon-Johansen estimator were used to measure the differences of cumulative incidences of DVT and PE, respectively. The overall incidence rates (per 1,000 person-years) of DVT and PE between the AF group and non-AF groups were 2.69 vs 1.12 (crude hazard ratio [HR] = 1.92; 95 % confidence interval [CI] = 1.54-2.39), 1.55 vs 0.46 (crude HR = 2.68; 95 % CI = 1.97-3.64), respectively. The baseline demographics indicated that the members of the AF group demonstrated a significantly older age and higher proportions of comorbidities than non-AF group. After adjusting for age, sex, and comorbidities, the risks of DVT and PE remained significantly elevated in the AF group compared with the non-AF group (adjusted HR = 1.74; 95 %CI = 1.36-2.24, adjusted HR = 2.18; 95 %CI = 1.51-3.15, respectively). The Kaplan-Meier curve with the use of Aelon-Johansen estimator indicated that the cumulative incidences of DVT and PE were both more significantly elevated in the AF group than in the non-AF group after a long-term follow-up period (p<0.01). In conclusion, the presence of AF is associated with increased risk of VTE after a long-term follow-up period.

scholarly journals VTE Rates and Safety Analysis of Newly Diagnosed Multiple Myeloma Patients Receiving Carfilzomib-Lenalidomide-Dexamethasone (KRD) with or without Rivaroxaban Prophylaxis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1835-1835 ◽  
Author(s):  
Katrina M Piedra ◽  
Hani Hassoun ◽  
Larry W. Buie ◽  
Sean M. Devlin ◽  
Jessica Flynn ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Venous Thromboembolism ◽  
Board Of Directors ◽  
Research Funding ◽  
High Dose ◽  
Newly Diagnosed ◽  
Advisory Committees ◽  
Cancer Trial ◽  
Oncology Research ◽  
Increased Risk

Introduction Immunomodulatory agents (IMiD's) are associated with an increased risk of venous thromboembolism (VTE), particularly when combined with high dose steroids. Studies evaluating the use of lenalidomide-bortezomib-dexamethasone (RVD) and carfilzomib-lenalidomide-dexamethasone (KRD) in the frontline setting for multiple myeloma (MM) have reported a 6% and 24% incidence of thrombosis, respectively, despite primary thrombotic prophylaxis with aspirin (ASA) (Richardson, et al. Blood. 2010; Korde, et al. JAMA Oncol 2015). Recent data, including the Hokusai VTE Cancer Trial, have suggested that safety and efficacy of direct oral anticoagulants (DOACs) are preserved in the setting of treatment of solid malignancy-associated thrombosis (Raskob, et al. N Engl J Med. 2018; Mantha, et al. J Thromb Thrombolysis. 2017). Despite this data, there is limited experience and use of DOACs in prevention of thromboses in the setting of hematologic malignancies, specifically MM. After careful review of literature, since early 2018, we changed our clinical practice and routinely placed newly diagnosed MM (NDMM) patients receiving KRD at Memorial Sloan Kettering Cancer Center (MSKCC) on concomitant rivaroxaban 10 mg once daily, regardless of VTE risk stratification. In the following abstract, we present VTE rates and safety data for newly diagnosed MM patients receiving RVD with ASA vs. KRD with ASA vs. KRD with rivaroxaban prophylaxis. Methods This was an IRB-approved, single-center, retrospective chart review study. All untreated patients with newly diagnosed MM, receiving at least one cycle of RVD or KRD between January 2015 and October 2018 were included. The period of observation included the time between the first day of therapy until 90 days after completion of induction therapy. Patients were identified by querying the pharmacy database for carfilzomib or bortezomib administration and outpatient medication review of thromboprophylaxis with rivaroxaban or ASA. VTE diagnoses were confirmed by ICD-10 codes and appropriate imaging studies (computed tomography and ultrasound). Descriptive statistics were performed. Results During the observation period, 241 patients were identified to have received RVD or KRD in the frontline (99 RVD with ASA; 97 KRD with ASA; 45 KRD with rivaroxaban). Baseline characteristics were well distributed among the three arms, with a median age of 60 (30-94) in the RVD ASA arm, 62 (33-77) in the KRD ASA arm, and 60 (24-79) in the KRD rivaroxaban arm. Patients had International Staging System (ISS) stage 3 disease in 13% (N=13), 9.3% (N=9), and 11% (N=5) of the RVD ASA, KRD ASA, and KRD rivaroxaban arms, respectively. Median weekly doses of dexamethasone were higher in both KRD arms, 40 mg (20-40) vs. 20 mg (10-40) in the RVD ASA arm. The average initial doses of lenalidomide were 22 mg in the RVD ASA arm compared to 25 mg in both the KRD ASA and KRD rivaroxaban arms. After querying the pharmacy database, no patients were identified to have a history or concomitant use of erythropoietin stimulating agent (ESA) use. Treatment-related VTE's occurred in 4 patients (4.0%) in the RVD ASA arm, 16 patients (16.5%) in the KRD ASA arm, and in 1 patient (2.2%) in the KRD rivaroxaban arm. Average time to VTE was 6.15 months (Range 5.42, 9.73) after treatment initiation in the RVD ASA group, while it was 2.61 months (Range 0.43, 5.06) in the KRD ASA group and 1.35 months in the KRD rivaroxaban group. Minor, grade 1 bleeding events per the Common Terminology Criteria for Adverse Events (CTCAE) were identified in 1 (1.1%) patient in the RVD ASA arm, 5 (5.2%) patients in the KRD ASA arm, and 1 (2.2%) patient in the KRD rivaroxaban arm. Conclusion More efficacious MM combination therapies have been found to increase the risk of VTE when using ASA prophylaxis, indicating better thromboprophylaxis is needed. We found patients receiving ASA prophylaxis with KRD were more likely to experience a VTE and these events occurred earlier compared to patients receiving ASA prophylaxis with RVD. Importantly, the rate of VTE was reduced to the same level as ASA prophylaxis with RVD when low-dose rivaroxaban 10 mg daily was used with KRD, and without necessarily increasing bleeding risk. Our retrospective data support the development of prospective clinical trials further investigating DOAC use in thromboprophylaxis for NDMM patients receiving carfilzomib-based treatments. Figure Disclosures Hassoun: Novartis: Consultancy; Janssen: Research Funding; Celgene: Research Funding. Lesokhin:BMS: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Janssen: Research Funding; GenMab: Consultancy, Honoraria; Serametrix Inc.: Patents & Royalties; Genentech: Research Funding; Juno: Consultancy, Honoraria. Mailankody:Juno: Research Funding; Celgene: Research Funding; Janssen: Research Funding; Takeda Oncology: Research Funding; CME activity by Physician Education Resource: Honoraria. Smith:Celgene: Consultancy, Patents & Royalties, Research Funding; Fate Therapeutics and Precision Biosciences: Consultancy. Landgren:Theradex: Other: IDMC; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Merck: Other: IDMC; Sanofi: Membership on an entity's Board of Directors or advisory committees; Adaptive: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. OffLabel Disclosure: Off-label use of rivaroxaban for outpatient prophylaxis of venous thromboembolism (VTE) will be explicitly disclosed to the audience.

scholarly journals Predictors of Maternal Morbidity Among Participants Enrolled in the Sickle Cell Disease Implementation Consortium Registry

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 3-3
Author(s):  
Rita V Masese ◽  
Dominique Bulgin ◽  
Liliana Preiss ◽  
Mitchell Knisely ◽  
Eleanor Stevenson ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Sickle Cell ◽  
Research Funding ◽  
Transfusion Requirement ◽  
The United States ◽  
Acute Chest Syndrome ◽  
Maternal Outcomes ◽  
Maternal Complications ◽  
Advisory Committees ◽  
Increased Risk

Introduction Pregnancy in sickle cell disease (SCD) is associated with an exacerbation of SCD-related complications and an increased risk of maternal complications. The increased risk is partly due to physiologic adaptations in pregnancy, which include increased metabolic demands and a hypercoagulable state. The maternal death rate for SCD is 629 per 100,000 deliveries, compared to 12 per 100,000 deliveries in black women and 6 per 100,000 deliveries in the general population (Raider et al., 2016). Studies on maternal and perinatal outcomes of patients with SCD present inconsistent and conflicting results. Some studies have reported an increase in maternal complications such as pre-eclampsia, acute chest syndrome and thromboembolic events, while other studies have reported no significant risk in adverse maternal outcomes. The inconsistent findings reported in prior studies may be attributed to small sample sizes and single-centered sites. Our study aims to determine the prevalence and predictors of maternal morbidity among participants enrolled in the SCD Implementation Consortium (SCDIC) registry, which is the largest, most geographically diverse SCD participant sample in the United States. Methods This cross-sectional study included women enrolled in the SCDIC registry who had at least one pregnancy event. The SCDIC is composed of eight academic SCD centers across the United States and one data-coordinating center. Participants were enrolled in the SCDIC registry if they were 18 to 45 years of age and had a confirmed diagnosis of SCD. Enrolled participants completed a series of surveys that collected sociodemographic information, SCD and pregnancy history and data abstractions of participants' medical records was completed. Medical complications queried during pregnancy included: vaso-occlusive episodes, acute chest syndrome, blood transfusion requirement, preeclampsia, maternal diabetes and deep venous thrombosis. Descriptive analysis of sociodemographic, clinical and maternal characteristics was conducted. Bivariate analysis was performed using Chi-Square test, Mann-Whitney U test, t-test, and logistic regressions, as appropriate. A p-value of ≤ 0.05 was considered statistically significant for all analysis. Results The study sample included 743 women who had at least one pregnancy event, and a total of 1066 live births. Almost all women (96.3%) were African American, with a median age of 21 years (inter-quartile range of 19 to 23 years) at first birth. The majority had Hb SS SCD genotype (69.5%; 513 of the 738 with SCD genotype data). Of all reported pregnancies, participants did not use hydroxyurea during conception (78%), and pregnancy (84.5%). Only 2.7 % of the women reported using fertility drugs or assisted reproductive procedures. Seventy five percent of the pregnancies that ended in live births had maternal complications. The leading complications were vaso-occlusive episodes (61.2%), pregnancy requiring blood transfusion(s) (33.2%), preeclampsia (15.4%), deep venous thrombosis (5.6%) and acute chest syndrome (7.7%). When the pregnancies were stratified by SCD genotype, women with Hb SS had a higher occurrence of acute chest syndrome (63.4% vs. 26.7%), transfusion requirement (70.8% vs. 21%) and preeclampsia (66.7% vs 22.4%). In the univariate logistic regressions, multiparous women, with a history of adverse maternal outcomes in a previous pregnancy, had higher odds of vaso-occlusive episodes (OR: 3.42; 95% CI: 2.42-4.94) acute chest syndrome (OR:4.99; 95% CI:2.56- 9.48), transfusion requirement (OR:3.86; 95% CI:2.64- 5.69), and pre-eclampsia (OR:3.36; 95% CI:2.05-5.45). Conclusion In this large multicenter registry, we found pregnant women with SCD have significant maternal complications. Early antenatal care by healthcare providers knowledgeable about risk factors for adverse maternal outcomes in SCD is essential improve maternal and fetal outcomes and reduce the maternal death rate for SCD. Disclosures Hankins: Novartis: Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; MJH Life Sciences: Consultancy, Patents & Royalties; UptoDate: Consultancy; National Heart, Lung, and Blood Institute: Honoraria, Research Funding; LINKS Incorporate Foundation: Research Funding; American Society of Pediatric Hematology/Oncology: Honoraria. Treadwell:Global Blood Therapeutics: Consultancy; UpToDate: Honoraria. King:Amphivena Therapeutics: Research Funding; Bioline: Consultancy; Celgene: Consultancy; Cell Works: Consultancy; Incyte: Consultancy; Magenta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Novimmune: Research Funding; RiverVest: Consultancy; Tioma Therapuetics: Consultancy; WUGEN: Current equity holder in private company. Gordeuk:CSL Behring: Consultancy, Research Funding; Global Blood Therapeutics: Consultancy, Research Funding; Imara: Research Funding; Ironwood: Research Funding; Novartis: Consultancy. Kanter:SCDAA Medical and Research Advisory Board: Membership on an entity's Board of Directors or advisory committees; AGIOS: Membership on an entity's Board of Directors or advisory committees; BEAM: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy; GLG: Honoraria; Jeffries: Honoraria; Cowen: Honoraria; Wells Fargo: Honoraria; NHLBI Sickle Cell Advisory Board: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Guidepoint Global: Honoraria; bluebird bio, inc: Consultancy, Honoraria; Sanofi: Consultancy. Glassberg:Pfizer: Research Funding; Global Blood Therapeutics: Consultancy; Eli Lilly and Company: Research Funding. Shah:Novartis: Consultancy, Research Funding, Speakers Bureau; Alexion: Speakers Bureau; CSL Behring: Consultancy; Bluebird Bio: Consultancy; Global Blood Therapeutics: Consultancy, Research Funding, Speakers Bureau.

Sickle Cells and Anesthesia

PEDIATRICS ◽  
1974 ◽  
Vol 53 (3) ◽  
pp. 446-446
Author(s):  
Herbert T. Abelson
Keyword(s):  
Sickle Cell ◽  
Sickle Cell Trait ◽  
Sickle Cells ◽  
Risk Of Death ◽  
Increased Risk

The implication by McGarry and Duncan that sickle cell trait carries an increased risk of death following anesthesia should be carefully weighed against their proffered evidence. In two of their five cases, a hematologic diagnosis was not established, but rather implied by postmortem findings. These two cases could therefore represent an additional, mixed, sickle hemoglobinopathy. In addition, postmortem sickling can hardly serve as an indicator of premortem pathophysiology. Since previous firm documentation of anesthetic deaths associated with sickle cell trait are not available, the following questions would seem to be pertinent: (1) what is the overall incidence of anesthetic deaths in the authors' institution and (2) over what period of time were these cases collected?

Abstract 15395: Immune Checkpoint Inhibitors for Cancer Are Associated With Increased Venous Thromboembolism Events

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Jingyi Gong ◽  
Zsofia Drobni ◽  
Raza Alvi ◽  
Sean Murphy ◽  
Sarah Hartmann ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Immune Activation ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Massachusetts General Hospital ◽  
Control Period ◽  
Fold Increase ◽  
Vein Thrombosis ◽  
Increased Risk

Introduction: Immune checkpoint inhibitors (ICI) lead to immune activation, increased inflammation and cancer cell death. Both immune activation and inflammation are critical pathobiological drivers for venous thromboembolism (VTE). There are no robust data testing the effect of ICIs on the risk of developing VTE. Methods: This is a retrospective study of 2854 patients who received ICIs at Massachusetts General Hospital, Boston, MA. VTE events, defined as a composite of deep vein thrombosis (DVT) or pulmonary embolism (PE), were identified by individual chart review and were blindly adjudicated using standard criteria. A case-crossover design was applied with an “at-risk period” defined as the two-year period after and the “control period” as the two years prior to treatment. Incidence rate ratio (IRR) was calculated using Poisson’s regression. Results: Immune checkpoint inhibitor use increased VTE risk by 1.84-fold from 4.85 per 100-person years to 8.91 per 100 person-years (IRR 1.84, 95% confidence interval: 1.54 - 2.19, p <0.001). Of the individual components, there was a 2.44-fold increase in DVT risk (2.30 to 5.58 per 100 person-years) and 1.68-fold increase in PE risk (2.96 to 5.00 per 100 person-years). Comparing patients with and without a VTE event, those with a VTE event after ICI initiation had a higher rate of prior VTE, lung cancer, urothelial cancer, and a higher platelet count and white blood cell count at baseline. At 6 months post ICI initiation, 165 (8.6%) patients had a VTE event and of these patients 136 (7.1%) had no prior VTE. Conclusions: Patients with cancer treated with ICIs are at increased risk of developing VTE. Whether prophylaxis for VTE among patients starting an ICI reduces this risk is unclear.

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