Occurrence Of Venous Thromboembolic Events Research Articles

#1828 Venous thromboembolic events in ANCA associated vasculitis patients—data from Croatian referral center

Abstract Background and Aims Our aim was to investigate the prevalence of venous thromboembolic events (VTE) in a cohort of patients with ANCA-associated vasculitis (AAV) and define factors associated with the frequency of VTE considering there is data on high incidence of VTE in AAV patients. In these cohorts VTE occurred mostly early in the course of disease. Method This study included 114 consecutive AAV patients with biopsy proven renal involvement in the period from 2007-2017. Patients were classified according to clinical: granulomatosis with poliangitis (GPA), microscopic polingitis (MPA) and eosinophilic granulomatosis with poliangitis (EGPA) and serological phenotype: MPO-ANCA positive, PR3-ANCA positive, MPO- and PR3-ANCA positive and ANCA-negative. Ordinal variables were analysed using logistical regression test. Statistical analysis was done in MedCalc Statistical Software version 18.11.6 (MedCalc Software Bvba, Ostend, Belgium). Results In the cohort there were 64 (56%) females, mean age was 58 (IQR 16-84) with mean follow up time 46.9 months (IQR 1-127). Clinically there were 84 (73%) patients with MPA, 26 (22%) with GPA and 4 (5%) with EGPA. Serologically there were 20% PR3-ANCA, 54% MPO-ANCA, 8% MPO- and PR-3 ANCA positive patients and 18% ANCA-negative patients. Mean serum creatinine levels (SCr) was 380.9 μmol/l (IQR 65-1402). Mean BVAS (Brimingham vasculitis score) at the time of diagnosis of AAV was 17 (IQR 5-50) and at the time of VTE 0, 9 (0-22). Mean body weight was 71kg (IQR 48-110) and mean CRP was 84 mg/ml (IQR 0, 3-256). During the follow up 7 (6.14%) of the patients had VTE, with 4 having VTE in first month after the diagnosis and other two at month 14 and 19. Logistic regression showed the connection of weight (P = 0.0052) and CRP (0.0138) with VTE with odds ratio of 1,0829 for CRP (1.003-1.027) and 1.0150 for weight (1.0284-1.1736) respectively. There was no statistical significance for clinical or serological phenotype being associated with VTE nor for other clinical or laboratory parameters. Conclusion In our cohort patients with AAV were at risk of VTE, particularly within the first year following onset of disease. In this cohort the frequency of VTE did not depend of clinical or serological AAV phenotype, age or gender. Only CRP and body weight were associated significantly with VTE occurrence. Despite VTE rates in AAV patients, routine anticoagulation is not recommended in AAV patients, given the potential risk of bleeding complications. Prospective studies are needed to assess VTE risk stratification in AAV patients and to evaluate the both benefits and potential risks ratio of prophylactic anticoagulation in AAV patients.

Safety and efficacy of extended thrombophilia screening directed venous thromboembolic events (VTE) prophylaxis in live liver donors: do we really need extended thrombophilia screening routinely?

The study aimed to determine the prevalence of hereditary thrombophilia, and stratify its severity among live liver donors in Pakistan. Also, the authors evaluated the safety and efficacy of thrombophilia profile testing directed venous thromboembolic events (VTE) prophylaxis while balancing bleeding risk and the need for routine thrombophilia testing before live liver donation among living donor candidates. Protein S (PS), protein C (PC), anti-thrombin (AT) III, and anti-phospholipid antibody panel (APLA) levels were measured in 567 potential donor candidates. Donors were divided into normal, borderline and high-risk groups based on Caprini score. The safety endpoints were VTE occurrence, bleeding complications or mortality. Among 567 donors, 21 (3.7%) were deficient in protein C, and 14 (2.5%) were deficient in anti-thrombin-III. IgM and IgG. Anti-phospholipids antibodies were positive in 2/567 (0.4%) and 2/567 (0.4%), respectively. IgM and IgG lupus anticoagulant antibodies were positive in 3/567 (0.5%) and 3/567 (0.5%), respectively. VTE events, bleeding complications and postoperative living donors liver transplantation-related complications were comparable among the three donor groups (P>0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. The mean length of ICU and total hospital stay were comparable. No donor mortality was observed in all donor groups. Due to thrombophilia testing directed VTE prophylaxis, VTE events were comparable in normal, borderline and high-risk thrombophilia donor groups, but more evaluations are required to determine the lower safe levels for various thrombophilia parameters including PC, PS and AT-III before surgery among living donor candidates.

The Application of Existing Risk Assessment Models (RAMS) to Predict the Occurrence of Venous Thromboembolic Events among Patients with Classic Hodgkin Lymphoma.

Background: A majority of patients included in risk assessment models (RAMs) developed to predict venous thromboembolic events (VTE) in lymphoma were non-Hodgkin lymphoma. Our study aims to evaluate the incidence and predictors of VTE, utilizing different RAMs, in patients with classic Hodgkin lymphoma (cHL) treated with adriamycin, bleomycin, vinblastine, and dacarbazine (ABVD). Methods: Adult patients with cHL, treated and followed at our center, were included. Correlations between different variables, Khorana score, and thrombosis in lymphoma (ThroLy) RAMs with VTE were examined using Fisher's exact test and logistic regression analysis. Results: A total of 321 patients were included, with a median age of 29 (range: 18-83) years. Of them, 169 (52.6%) had advanced-stage disease. Combined modality treatment was given to 169 (52.6%) patients. A total of 52 (16.2%) patients had relapsed or refractory disease. VTE were reported in 15 (4.7%) patients and were mostly during the administration of first-line (n = 8, 53.3%), or salvage chemotherapy (n = 6, 40.0%). There was no correlation between a Khorana score > 2 (p = 0.689) or ThroLy score > 3 (p = 0.335) and VTE. Older age (p = 0.014) and relapsed or refractory disease (p = 0.003) significantly correlated with VTE. Conclusions: VTE are uncommon in cHL. The commonly used RAMs failed to predict VTE. However, older age and relapsed or refractory disease significantly increased this risk.

Risk Factors for Thrombosis in Pregnant People with Sickle Cell Disease: A Multinational Study.

Background People with sickle cell disease (SCD) have exceptionally high rates of maternal morbidity, including increased risk for venous thromboembolic events (VTE). Data from the National Inpatient Sample shows that VTE risk in hospitalized Black pregnant people with SCD is 14 times that of unaffected Black and non-Black pregnant people. 1 There is little disease-specific data to inform anticoagulation (AC) use during pregnancy. 2 The purpose of this study is to describe VTE events in a SCD pregnancy cohort and to identify risk factors for VTE during pregnancy and compare maternal-fetal outcomes for subjects with or without VTE in pregnancy. Methods The Mount Sinai Hospital (MSH) Research Ethics Board and The Johns Hopkins Hospital (JHH) Institutional Review Board approved this retrospective study of pregnant people with SCD of ≥ 20 weeks gestation cared for at MSH, Toronto (1990-2017) or JHH (2000-2021). At MSH and JHH, all pregnant people with SCD and VTE history are prescribed antenatal prophylactic LMWH and for 6-weeks postpartum. At MSH, but not JHH, all receive AC prophylaxis for 6-weeks postpartum. At both centers, hospitalized pregnant people receive prophylactic AC. We stratified subjects by VTE occurrence during pregnancy. First, we described the cohort with VTE during pregnancy, including subject characteristics, VTE recurrence and pregnancy outcomes. Second, we compared cases with a first pregnancy with VTE to controls without VTE. We excluded repeat pregnancies in both groups. We compared cases and controls by SCD characteristics, medication use before pregnancy, and pregnancy outcomes. Painful events were defined as pain requiring acute care or hospital admission. Chronic transfusion therapy (CTT) was defined as pregnancies treated with scheduled, prophylactic transfusion; opioid use was defined as receiving an outpatient opioid prescription during pregnancy. We used the Chi-squared test for categorical variables and Wilcoxon signed-rank tests for continuous variables. A p-value of <0.05 was considered significant. Results There were 290 singleton pregnancies in 199 subjects. Half of the pregnancies were first pregnancies (142/290), with fewer second (51/290), third (2/290), fourth (3/290) or fifth (1/290) pregnancies. The cohort comprised of 58% subjects with HbSS/HbSβ 0, while 42% had HbSC/HbSβ+ genotype (Table 1). VTE occurred in 7% of pregnancies (20/290) including deep vein thrombosis (DVT, N=9), pulmonary embolism (PE, N=8), DVT+PE (N=3). Median age was 27 years (IQR 23,30). Before pregnancy, most VTE subjects received hydroxyurea (N=10). During pregnancy, six received CTT. Fourteen subjects had VTE in a single pregnancy; three had VTE recurrence in subsequent pregnancies. All three had HbSS/HbSβ 0. Two subjects had VTE history outside of pregnancy. One had DVT in two consecutive pregnancies and was prescribed AC in both pregnancies due to history of VTE. VTE occurred in first (N=4), second (N=8), third (N=4), fourth (N=1) and fifth (N=4) pregnancies. Most VTE occurred at JHH (11 JHH vs 6 MSH, p=0.008). To investigate SCD-specific risk factors for VTE in pregnancy, we compared characteristics in VTE subjects (N=17) to no-VTE subjects (N=182) by first study pregnancy with an event or first study pregnancy while enrolled in the study. VTE was associated with markers of disease severity including history of VTE before pregnancy (6/17 VTE vs 8/182 no-VTE, p<0.001), ACS during pregnancy (7/17 VTE vs 19/182 no-VTE, p<0.001), painful events requiring acute care during pregnancy (16/17 VTE vs 119/182 no-VTE, p=0.015) and hydroxyurea use before pregnancy (10/17 VTE vs 35/184 no-VTE, p<0.001). There was no difference in age or genotype. VTE was associated with earlier delivery and c-section delivery (Table 1). Conclusion In this study, 7% of cohort pregnancies had VTE. This rate exceeds reports from administrative datasets. 1 This may be due to the acuity of patients cared for at our centers and/or reflect undercounting of VTE in administrative datasets. In pregnant people with SCD, VTE is associated with VTE history, intrapartum painful events and ACS. Interventions to reduce acute events in pregnancy may help reduce VTE risk. While AC can be beneficial in preventing thrombotic events, careful assessment is essential to manage bleeding risks. Prospective data is needed to define the subpopulation of pregnant SCD patients who would benefit from AC prophylaxis antenatally.

PB0957 The Application of Existing Risk Assessment Models (RAMs) to Predict the Occurrence of Venous Thromboembolic Events among Patients with Classic Hodgkin's Lymphoma

PB0957 The Application of Existing Risk Assessment Models (RAMs) to Predict the Occurrence of Venous Thromboembolic Events among Patients with Classic Hodgkin's Lymphoma

Risk Factors of Venous Thromboembolic Disease in Cancer Patients Treated with Immune Checkpoint Inhibitor.

Immune checkpoint inhibitors (ICIs) have revolutionized the management of cancers. The risk factors and pathophysiological mechanisms of venous thromboembolic events (VTEs) of this new therapeutic class are still to be specified. The included patients had to have cancer and should be treated with ICI. Data analyzed included demographic data, biological data, and immune-related adverse events (IRAEs). We studied the prevalence of VTEs and the factors associated with VTEs. Of 374 patients on ICI, over a median follow-up period of 15.2 months, the number of VTE was 50 (13.4%). The majority of patients were treated for metastatic melanoma or nonsmall cell lung cancer. There was no difference in prevalence or survival between cancer types. Patients with combined therapy composed of nivolumab and ipilimumab had higher 1-year cumulative VTE occurrence (29.3% [95% confidence interval [CI]: 9.7; 44.6]) than patients with pembrolizumab (14.9%, [95%CI: 2.5; 25.8], p = 0.03) or nivolumab (9.1%, [95% CI: 5.0; 12.9], p < 0.01). The presence of IRAE was associated with a higher risk of VTE occurrence compared with patients without any IRAE (1-year VTE cumulative incidence: 17.42% [95% CI: 9.5; 24.65] vs. 9.46% [95% CI: 5.18; 13.55], p = 0.04). There was a higher risk of VTE in patients treated with the combination of nivolumab and ipilimumab (adjusted subdistribution hazard ratio [SHR]: 3.71 [95% CI: 1.74; 7.90], p < 0.001) and in patients with IRAE (adjusted SHR: 2.14 [95% CI: 1.22; 3.75], p < 0.01). The prevalence of VTE was 14.2% under ICIs. IRAE and combine treatment of nivolumab and ipilimumab were associated with VTE. The pathophysiological mechanisms are multiple and complex with a possible link to aberrant activation of the immune system.

Risk of venous thromboembolic events after COVID-19 infection: a systematic review and meta-analysis.

Data regarding the occurrence of venous thromboembolic events (VTE), including acute pulmonary embolism (PE) and deep vein thrombosis (DVT) in recovered COVID-19 patients are scant. We performed a systematic review and meta-analysis to assess the risk of acute PE and DVT in COVID-19 recovered subject. Following the PRIMSA guidelines, we searched Medline and Scopus to locate all articles published up to September 1st, 2022, reporting the risk of acute PE and/or DVT in patients recovered from COVID-19 infection compared to non-infected patients who developed VTE over the same follow-up period. PE and DVT risk were evaluated using the Mantel-Haenszel random effects models with Hazard ratio (HR) as the effect measure with 95% confidence interval (CI) while heterogeneity was assessed using Higgins I2 statistic. Overall, 29.078.950 patients (mean age 50.2 years, 63.9% males), of which 2.060.496 had COVID-19 infection, were included. Over a mean follow-up of 8.5 months, the cumulative incidence of PE and DVT in COVID-19 recovered patients were 1.2% (95% CI:0.9-1.4, I2: 99.8%) and 2.3% (95% CI:1.7-3.0, I2: 99.7%), respectively. Recovered COVID-19 patients presented a higher risk of incident PE (HR: 3.16, 95% CI: 2.63-3.79, I2 = 90.1%) and DVT (HR: 2.55, 95% CI: 2.09-3.11, I2: 92.6%) compared to non-infected patients from the general population over the same follow-up period. Meta-regression showed a higher risk of PE and DVT with age and with female gender, and lower risk with longer follow-up. Recovered COVID-19 patients have a higher risk of VTE events, which increase with aging and among females.

Evaluation of the occurrence of venous thromboembolic events in COVID-19 outpatients

Evaluation of the occurrence of venous thromboembolic events in COVID-19 outpatients

S1277 The Selection of Donors in Living Donors of Liver Transplantation Based on Results of Thrombophilia Screening Tests and Prophylactic Strategy for Venous Thromboembolic Events (VTE)

Introduction: Vascular events after living donor liver transplantation (LDLT) are one of the most feared complications that usually lead to graft and donor loss. The main aim of this study was to determine the frequency of hereditary thrombophilia in the Pakistani population and share our centers’ safety and venous thromboembolic events (VTE) prophylaxis protocols in the borderline and high-risk groups in live liver donors. Methods: This prospective, observational study included thrombophilia testing, which was done on 567 living donor candidates between July 2018 and April 2021. Donors were divided into the normal, border-line, and high-risk groups according to the Caprini scoring system. Usual prophylaxis with enoxaparin along with elastic stockings and intermittent pneumatic compression (IPC) was given postoperatively to donors in the borderline and high-risk groups. The safety endpoints were VTE occurrence, bleeding complications, or mortality. Results: Among 567 donors, 21 (3.7%) donors were deficient in protein C, 14(2.5%) were deficient in anti-thrombin-III and 45(7.9%) were having Leiden factor-V mutation. 31/416 (7.45%) were deficient in factor-II. IgM & IgG Anti-phospholipids antibodies were positive in 2/567(0.4%) and 2/567(0.4%) respectively. Donor operation was performed on 44 candidates in the borderline group and 7 in the high-risk group. Complications after surgery were comparable between the 2 groups (p >0.05). One donor in the normal donor group developed pulmonary embolism, but none of the donors in either borderline or high-risk group developed VTE. (Table) Conclusion: Early hepatic artery thrombosis (eHAT), deep venous thrombosis, and pulmonary embolism are one of the most common vascular events after liver transplantation.The majority of LDLT centers exclude donors from high-risk groups (according to the Caprini scoring system) and are used to give low molecular weight heparin in borderline donor groups. But we are the only LDLT center where not only did we perform right lobe hepatectomy on high-risk donor group on thrombophilia screening tests, but we also gave usual prophylaxis with enoxaparin (rather than low molecular weight heparin) along with elastic stockings, and intermittent pneumatic compression (IPC) postoperatively to donors in the borderline and high-risk groups (Fifty-one donors ) to decrease the risk of VTE. Table 1. - Comparison of demographics, surgical features, and postoperative complications of LLDs in donor groups Variables Normal Group (n=516) Borderline Group (n=44) High-Risk Group (n=7) P-value Mean age (Years) 23.43 ± 5.53 23.91± 5.25 26.86 ± 6.54 0.17 Mean BMI (Kg/m2) 21.40 ± 7.99 20.5 ± 2.71 21.53 ± 3.29 0.69 GenderMaleFemale 290(56.2%)226(43.7%) 24(54.5%)20(45.4%) 4(57.1%)3(42.8%) 0.97 Marital statusUnmarriedMarried 351(68.1%)165 (31.9%) 25(56.9%)19 (43.1%) 5(71.4%)2(28.5%) 0.06 Donor's relation to recipientsSonBrotherNephewDaughterSisterFatherSwapOthersType of Graft Modified right lobe graftModified extended right lobe graftLeft lobe graftLeft lateral segment graftGRWRMean warm ischemia time (minutes)Mean operation time (hours)Mean blood loss (ml)Blood transfusions (no of patients/ %) 63 (12.2%)99 (19.1%)25 (4.8%)35 (6.7%)32 (6.2%)88 (17.1%)10 (1.9%)157(30.4%)437 (84.6%)62 (12.0%)4 (0.7%)11 (2.1%)6(1.1%)1.26 ± 0.6310.99 ± 6.09407.94 ± 64.86516 6 (13.6%)5 (11.3%)5(11.3%)5 (11.3%)5 (11.3%)3 (6.8%)011 (25.0%)36 (81.8%)8 (18.1%)7 (15.9%)001.4 ± 0.6810.68 ± 4.08412.27 ± 89.1144 1(14.2%)2(28.5%)1(14.2%)00003(42.8%)6(85.7%)1(14.2%)001.2 ± 0.6313.86 ± 7.26422.86 ± 62.377 0.008NSNSNS0.76 Personal History of Thrombosis 0 0 0 _ Total number of complications 62 (12.0%) 15 (34.1%) 2(28.5%) 0.43 Grade 1 & 2 Wound infections Wound hematoma UTI Fever Paralytic ileus 20 (3.8%)2 (0.3%)4 (0.7%)3 (0.5%)2 (0.3%) 3 (6.8%)1 (2.2%)2 (4.5%)2 (4.5%)1 (2.2%) 2(28.5%)0000 0.12 Grade 3A Bile leakage Bile duct stricture Post-op bleeding Pleural effusion/Aspiration ERCP & Stenting 6 (1.1%)3(0.5%)3 (0.5%)9 (1.7%)3 (0.5%) 1 (2.2%)01 (2.2%)1 (2.2%)1 (2.2%) 00000 0.15 Grade 3B Re-open 6(1.1%) 1 (2.2%) 0 0.45 Grade 4A Need ICU care/ ventilatorGrade 4B Multi-organ failure 1 (0.1%)0 1 (2.2%)0 00 0.95-- Grade 5 0 0 0 -- Mean ICU stay (Days) 3 ± 1 2.53 ± 1 3 ± 1 0.15 Mean hospital stay (Days) 6 ± 2 5 ± 2 6 ± 2 0.17 Mortality 0 0 0 -- Abbreviations: BMI: body mass index; GRWR= graft to recipient weight ratio; ICU: Intensive care unit; UTI: Urinary tract infection.

Blood pressure and risk of venous thromboembolism: a cohort analysis of 5.5 million UK adults and Mendelian randomization studies.

Evidence for the effect of elevated blood pressure (BP) on the risk of venous thromboembolism (VTE) has been conflicting. We sought to assess the association between systolic BP and the risk of VTE. Three complementary studies comprising an observational cohort analysis, a one-sample and two-sample Mendelian randomization were conducted using data from 5 588 280 patients registered in the Clinical Practice Research Datalink (CPRD) dataset and 432 173 UK Biobank participants with valid genetic data. Summary statistics of International Network on Venous Thrombosis genome-wide association meta-analysis was used for two-sample Mendelian randomization. The primary outcome was the first occurrence of VTE event, identified from hospital discharge reports, death registers, and/or primary care records. In the CPRD cohort, 104 017(1.9%) patients had a first diagnosis of VTE during the 9.6-year follow-up. Each 20 mmHg increase in systolic BP was associated with a 7% lower risk of VTE [hazard ratio: 0.93, 95% confidence interval (CI): (0.92-0.94)]. Statistically significant interactions were found for sex and body mass index, but not for age and subtype of VTE (pulmonary embolism and deep venous thrombosis). Mendelian randomization studies provided strong evidence for the association between systolic BP and VTE, both in the one-sample [odds ratio (OR): 0.69, (95% CI: 0.57-0.83)] and two-sample analyses [OR: 0.80, 95% CI: (0.70-0.92)]. We found an increased risk of VTE with lower BP, and this association was independently confirmed in two Mendelian randomization analyses. The benefits of BP reduction are likely to outweigh the harms in most patient groups, but in people with predisposing factors for VTE, further BP reduction should be made cautiously.

Venous thromboembolic events in glioblastoma patients: An epidemiological study.

Background and purposeVenous thromboembolic events (VTEs) are a major complication in cancer patients, and therefore, also in brain cancer patients, anticoagulants are considered appropriate in the treatment of VTEs.MethodsFrequency, risk factors, and treatment of VTEs, as well as associated complications, were assessed in a population‐based cohort of glioblastoma patients in the Canton of Zurich, Switzerland. Correlations between clinical data and survival were retrospectively analyzed using the log‐rank test and Cox regression models.ResultsFour hundred fourteen glioblastoma patients with isocitrate dehydrogenase wild‐type status were identified. VTEs were documented in 65 patients (15.7%). Median time from tumor diagnosis to the occurrence of a VTE was 1.8 months, and 27 patients were diagnosed with VTEs postoperatively (within 35 days; 42.2%). History of a prior VTE was more common in patients who developed VTEs than in those who did not (p = 0.004). Bevacizumab treatment at any time during the disease course was not associated with occurrence of VTEs (p = 0.593). Most patients with VTEs (n = 61, 93.8%) were treated with therapeutic anticoagulation. Complications occurred in 14 patients (23.0%), mainly intracranial hemorrhages (n = 7, 11.5%). Overall survival did not differ between patients diagnosed with VTEs and those who had no VTE (p = 0.139). Tumor progression was the major cause of death (n = 283, 90.7%), and only three patients (1.0%) died in association with acute VTEs.ConclusionsVenous thromboembolic events occurred early in the disease course, suggesting that the implementation of primary venous thromboembolism prophylaxis during first‐line chemoradiotherapy could be explored in a randomized setting.

Recurrence rate of venous thromboembolic events in granulomatosis with polyangiitis.

ObjectiveThe incidence of first-time venous thromboembolic events (VTEs) is high in granulomatosis with polyangiitis (GPA). The incidence of recurrent VTEs is unknown. We aimed to describe the recurrence rate of second VTEs in patients with GPA.MethodsRetrospective chart review was performed in patients with GPA and at least one VTE at a single centre from 2002 to 2016. Inclusion criteria were 1990 ACR criteria or 2012 Revised International Chapel Hill nomenclature for GPA, at least two follow-up visits, at least one VTE during the study period, and VTE occurrence after or within 3 months before GPA diagnosis. Second VTE event-free survival rates were estimated.ResultsOut of 147 patients initially screened for GPA and with at least one VTE, 84 met inclusion criteria. Median age at first VTE was 57 years. Incidence rate for second VTE was 8.4 events per 100 patient-years (95% CI: 5.7, 12.3). Eighty-three point three per cent of first VTEs and 57.7% of second VTEs occurred when disease was active (P < 0.001). Renal involvement and constitutional symptoms at the time of first VTE were associated with VTE recurrence.ConclusionGPA has a high rate of VTE recurrence compared with the reported data in the general population with unprovoked VTE. Our results suggest that VTE in GPA is a recurrent co-morbidity, not always during active vasculitis, and more so in those with renal involvement and constitutional symptoms at the time of first VTE.

Clinical characteristics, physiological features, and outcomes associated with hypercapnia in patients with acute hypoxemic respiratory failure due to COVID-19---insights from the PRoVENT-COVID study.

PurposeWe determined the incidence of hypercapnia and associations with outcome in invasively ventilated COVID–19 patients.MethodsPosthoc analysis of a national, multicenter, observational study in 22 ICUs. Patients were classified as ‘hypercapnic’ or ‘normocapnic’ in the first three days of invasive ventilation. Primary endpoint was prevalence of hypercapnia. Secondary endpoints were ventilator parameters, length of stay (LOS) in ICU and hospital, and mortality in ICU, hospital, at day 28 and 90.ResultsOf 824 patients, 485 (58.9%) were hypercapnic. Hypercapnic patients had a higher BMI and had COPD, severe ARDS and venous thromboembolic events more often. Hypercapnic patients were ventilated with lower tidal volumes, higher respiratory rates, higher driving pressures, and with more mechanical power of ventilation. Hypercapnic patients had comparable minute volumes but higher ventilatory ratios than normocapnic patients. In hypercapnic patients, ventilation and LOS in ICU and hospital was longer, but mortality was comparable to normocapnic patients.ConclusionHypercapnia occurs often in invasively ventilated COVID–19 patients. Main differences between hypercapnic and normocapnic patients are severity of ARDS, occurrence of venous thromboembolic events, and a higher ventilation ratio. Hypercapnia has an association with duration of ventilation and LOS in ICU and hospital, but not with mortality.

Incidence of Venous Thromboembolic Events in Patients With Endogenous Cushing Syndrome

Background: Hypercortisolemia is a hypercoagulable state associated with increased risk of venous thromboembolic events (VTE). The reported incidence of VTE in patients with ACTH-dependent or independent Cushing Syndrome (CS) is variable, ranging from 3 to 14%. Our aim was to assess the incidence of clinically significant VTE among patients with endogenous CS and to identify risk factors for the development of VTE. Methods: We conducted a single center retrospective longitudinal study of adult patients diagnosed with endogenous CS between 2010 and 2020. Patients with a known prothrombotic disease (e.g. Factor V Leiden), insufficient data, or non-neoplastic hypercortisolism were excluded. Data collected included patient demographics, presenting symptoms, biochemical and radiological workup, treatment details, and incidence of clinically significant VTE. Results: A total of 114 patients (mean age of 45.55 ± 14.78 years, 79.8% women) followed for mean of 3.26 ± 2.9 years were included. Of the 114 patients, 58 (50.9%) had Cushing disease (CD), 40 (35.1%) had CS due to adrenal adenoma/hyperplasia, 6 (3.5%) had adrenocortical carcinoma (ACC), and 10 (8.8%) had ectopic Cushing syndrome (eCS). The overall incidence of VTE at any time point was 14/114 (12.3%); 11 (79%) VTEs were associated with presence of an additional VTE risk factor (8 surgery and 3 malignancy). Prior to any intervention for CS, 3 of 114 (2.6%) patients had a VTE. Surgery for CS (adrenalectomy, transsphenoidal surgery, tumor resection) was performed in 97 patients (85.1%) whereas 17 were treated medically (n=10), died before treatment (n=1) or observed (n=6). VTE occurred in 2 patients receiving medical therapy for CS. The post-operative incidence of VTE was 9 (9.3%; 4 in CD, 1 in adrenal CS, 3 in ACC, and 1 in eCS). VTE occurred ≤ 3-month post-operative in 4 patients (44.4%). Among the 5 patients in whom VTE occurred >3 months post-operative, 3 had recurrent metastatic ACC with hypercortisolemia and 2 were in remission (1 with CS and 1 with eCS). The median time from surgery to VTE occurrence was 315 days (8-1006). Compared to those who did not develop VTE, those who developed VTE had higher mean 24-hour urine free cortisol (4663.6 vs 558.21 mcg/dL; n = 100, P < 0.0001) and mean 1 mg overnight dexamethasone suppression test (36.3 vs 11.8 mcg/dL; n = 69, P = 0.0003), but similar mean late-night salivary cortisol (0.591 vs 0.790 ng/dL, n = 84, P = 0.71) at diagnosis of CS. Discussion: Among those with CS, the overall incidence of VTE was 12.3% and the majority of VTE were provoked (surgery, malignancy). Moreover, VTE was more likely in those with higher UFC and 1 mg overnight dexamethasone suppression test in our cohort. This suggests that in patients with CS who have an active malignancy, severe CS or those undergoing a surgical procedure may be at increased risk of VTE. Future studies should investigate the optimal type and duration of the VTE prophylaxis.

213P Incidence of venous thromboembolic events in lung cancer patients receiving immunotherapy: A single-institution experience

Background: Lung cancer and lung cancer therapies such as chemotherapy and antiangiogenic agents have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in lung cancer patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in lung cancer patients receiving immunotherapy and ascertain its prognostic utility. Methods: We conducted a single-institution retrospective study, including all lung cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). Results: We selected 110 patients. The majority (n = 79, 71.8%) were males with a median age of 66 years (range 43–86 years). Most patients (m = 106, 96.4%) had stage IV at the beginning of immunotherapy treatment. 9 of 110 patients (8.2%) were under use of blood thinners. Pembrolizumab monotherapy was the agent most commonly used (n = 59, 53.6%) and nivolumab plus ipilimumab was the most common multidrug regimen (n = 7, 6.4%). VTE occurred in 10 of 110 patients (9.1%). Female sex was independently associated with an increased risk of VTE (OR 6.11 [95%CI: 1.31–28.40], p = 0.02). 7 of 10 VTE (70%) were symptomatic. Progressive disease to immunotherapy (HR 17.06 [95%CI: 6.03–48.26], p = 0.00) was independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS (HR 1.43 [95%CI: 0.45–4.49], p = 0.53). Conclusions: In our cohort, the incidence of VTE in lung cancer patients receiving immunotherapy was low. Female sex was a risk factor for thrombosis. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions. Legal entity responsible for the study: The authors. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

Association of venous thromboembolic events with skin, pulmonary and kidney involvement in ANCA-associated vasculitis: a multinational study.

To investigate the occurrence of venous thromboembolic events (VTE) in a large cohort of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) across the European Union, Turkey, Russia, UK and North America. Patients with a definite diagnosis of AAV who were followed for at least 3 months and had sufficient documentation were included. Data on VTE, including either deep vein thrombosis or pulmonary embolism, were collected retrospectively from tertiary vasculitis centres. Univariate and multivariate regression models were used to estimate odds ratios (ORs) and 95% CIs. Over a median follow-up of 63 (interquartile range: 29, 101) months, VTE occurred in 278 (9.7%) of 2869 AAV patients with a similar frequency across different countries (from 6.3% to 13.7%), and AAV subtype [granulomatosis with polyangiitis: 9.8% (95% CI: 8.3, 11.6%); microscopic polyangiitis: 9.6% (95% CI: 7.9, 11.4%); and eosinophilic granulomatosis with polyangiitis: 9.8% (95% CI: 7.0, 13.3%)]. Most VTE (65.6%) were reported in the first-year post-diagnosis. Multiple factor logistic regression analysis adjusted for sex and age showed that skin (OR 1.71, 95% CI: 1.01, 2.92), pulmonary (OR 1.78, 95% CI: 1.04, 3.14) and kidney [eGFR 15-60 ml/min/1.73 m2, OR 2.86 (95% CI: 1.27, 6.47); eGFR <15 ml/min/1.73 m2, OR 6.71 (95% CI: 2.94, 15.33)] involvement were independent variables associated with a higher occurrence of VTE. Two-thirds of VTE occurred during the initial phase of active disease. We confirmed previous findings from smaller studies that a decrease in kidney function, skin involvement and pulmonary disease are independently associated with VTE.

Incidence of venous thromboembolic events in cancer patients receiving immunotherapy: a single-institution experience

Cancer and cancer therapies have been associated with an increased incidence of venous thromboembolic events (VTE). However, the incidence of VTE in patients on immunotherapy has not been well characterized. The aim of this study was to assess the incidence of VTE in cancer patients receiving immunotherapy and ascertain its prognostic utility. We conducted a single-institution retrospective study, including all cancer patients treated with anti-Programmed cell Death 1 (PD-1), anti-Programmed cell Death Ligand-1 (PD-L1), anti-Cytotoxic T-Lymphocyte-Associated Protein 4 (CTLA4), a combination of anti-PD-1/anti-PD-L1 and anti-CTLA4 or a combination including any of these drugs with chemotherapy, antiangiogenic agents or both between June 2013 and April 2019 at La Paz University Hospital, Madrid (Spain). We selected 229 patients. VTE occurred in 16 of 229 patients (7%). VTE occurred more frequently in patients with lung cancer followed by melanoma. Female sex and melanoma were independently associated with an increased risk of VTE. 12 of 16 VTE (75%) were symptomatic. Progressive disease to immunotherapy [HR 31.60 (95% CI 11.44-87.22), p = 0.00], lung cancer [HR 2.55 (95% CI 1.34-4.86), p = 0.00] and melanoma [HR 2.42 (1.20-4.86), p = 0.01] were independently associated with shorter OS. VTE occurrence was not independently associated with shorter OS [HR 1.33 (95% CI 0.63-2.80), p = 0.44]. The incidence of VTE in cancer patients receiving immunotherapy in our study appeared to be similar to the incidence previously reported in other series of cancer patients treated with systemic therapies. VTE occurrence did not correlate with the prognosis. Further and prospective studies are needed to derive definitive conclusions.

Risk of Venous Thromboembolism Associated With Tofacitinib and Baricitinib: A Systematic Review and Indirect Meta-Analysis.

To conduct a systematic review and meta-analysis investigating the effect of tofacitinib and baricitinib on venous thromboembolism (VTE) risk. Search of PubMed, EMBASE, Web of Science, Scopus, ClinicalTrials.gov, LILACS, and Google Scholar databases to identify controlled observational and clinical trials reporting on adverse effects in patients treated with oral tofacitinib or baricitinib up to July 2020. The outcome measure was occurrence of VTE events. We analyzed 59 studies involving 14,335 patients treated with tofacitinib or baricitinib and 11,612 patients who received another active drug or placebo. The meta-analysis showed an odds ratio (OR) for VTE events of 0.29 (95% confidence interval [CI] = 0.10-0.84) overall for tofacitinib based on data from 10 clinical trials with 15 treatment arms; similar ORs were observed for the 10mg/d dose (OR=0.18; 95% CI = 0.02-1.60) and the 20mg/d dose (OR=0.19; 95% CI = 0.04-0.91). The ORs for VTE events for baricitinib were 3.39 (95% CI = 0.82-14.04) overall, 3.05 (95% CI = 0.12-75.43) for 2mg, 3.64 (95% CI = 0.59-22.46) for 4mg, and 3.0 (95% CI = 0.12-76.49) for 7mg. The indirect meta-analysis comparing tofacitinib with baricitinib (10 clinical trials with 15 treatment arms) showed an OR for VTE events of 0.086 (95% CI = 0.02-0.51) for tofacitinib and a superior safety profile for VTE events. In the meta-regression analysis (19 clinical trials with 21 treatment arms), the effect was 0.02 (95% CI = -0.04 to 0.08) for tofacitinib and -0.01 (95% CI = -1.29 to 1.26 for baricitinib. Plotting of the data for tofacitinib showed that VTE risk increased with high doses. The effect, however, was less than 1 for the 10-mg and 20-mg doses, indicating a protective effect. This effect was not observed for baricitinib. Tofacitinib is not associated with an increased risk of VTE and has a superior safety profile to baricitinib in this respect. Tofacitinib may exert a protective effect against VTE.

The effect of physician educational intervention on venous thromboembolism pharmacological prophylaxis in medical inpatients from the respiratory department: a retrospective cohort study.

Venous thromboembolism (VTE) is a serious health problem for which pharmacological prophylaxis has been proven to be effective. However, there are significant gaps between the guidelines and clinical practice. This study is to evaluate the effect of physician educational intervention (PEI) on VTE pharmacological prophylaxis in medical inpatients from the respiratory department. Medical inpatients from the respiratory department between February 2014 and December 2016 were recruited in this retrospective cohort study. They were assigned to the PEI group or the control group according to whether their physicians undertook a quality improvement (QI) project carried out in hospital to raise physician awareness of pharmacological thromboprophylaxis by educational intervention. Any and appropriate pharmacological VTE prophylaxis rates, the use of appropriate anticoagulants, and the occurrence of VTE events in the two groups were calculated and compared using a chi-square test and continuity correction. Poisson regression analysis was used to evaluate the relative risk (RR) of PEI on the occurrence of VTE events. The any pharmacological VTE prophylaxis rate (11.3% vs. 5.9%, P=0.048) and appropriate pharmacological VTE prophylaxis rate (9.3% vs. 5.5%, P=0.036) in high-risk patients without high major bleeding risk were both significantly higher than the control group. Compared with the control group, appropriate anticoagulants in the PEI group took up a larger proportion of all used anticoagulants (90.3% vs. 78.7%, P=0.007). In anticoagulants used for high-risk patients without high major bleeding, appropriate anticoagulants show no statistical difference between the two groups (93.8% vs. 77.8%, P=0.153). There was no difference in the occurrence of VTE events between the two study groups in overall patients (0.5% vs. 0.6%, P=0.913), and among those with high VTE risk (1.7% vs. 1.0%, P=0.554). PEI had no association with the probability of VTE event occurrence (RR, 1.246; 95% CI, 0.478-2.188, P=0.954). Educational intervention effectively increased physician awareness of VTE prophylaxis in the respiratory department. Further interventions are still necessary since the guidelines were implemented to a relatively low degree.

Venous thromboembolic events in glioblastoma patients: Common complication but not a major reason for death.

e14530 Background: Venous thromboembolic events (VTE) are a major complication in cancer patients. Anticoagulant use is the appropriate treatment for acute VTE in cancer patients, although associated with increased risk for bleeding, especially in brain tumor patients. In glioblastoma patients it remains unclear whether occurrence of VTE is associated with survival and to what extent thromboprophylaxis is necessary and efficient. Methods: Frequency, risk factors, and treatment of VTE as well as its complications were assessed in an epidemiological glioblastoma cohort in the Canton of Zurich, Switzerland, in the years 2005 to 2014. Association of clinical data with survival were retrospectively analyzed using the log rank test. Results: Four-hundred-nineteen patients diagnosed with isocitrate dehydrogenase wildtype glioblastoma were identified in the 10-year time-frame. Median overall survival (OS) was 12.4 months (95% CI 11.4-13.4) with a median follow up of 64.5 months (95% CI 46.6-82.4).VTE were seen in 65 patients (15.7%; 5 patients with missing information on VTE).Median time from diagnosis of glioblastoma to occurrence of VTE was 2.0 months (95% CI 0.8-3.1). A history of VTE was found in 6 patients (9.2%). Thirty-nine patients were on steroids (62.5%; 1 patient with missing data) at time of diagnosis of VTE, and 35 patients (56%; 3 patients with missing data) had a Karnofsky Performance Score of less than 70%. At the time patients were diagnosed with VTE the majority of patients (93.8%) were treated with therapeutic anticoagulation. Complications resulting in stop of anticoagulation occurred in 11 patients (18.0%; 4 patients had no anticoagulation) mainly because of intracranial bleedings (9 patients). OS was not different (p = 0.355) between patients who were diagnosed with VTE and those who were not. Tumor progression (283 patients, 77.3%) was the major reason for death (366 patients with confirmed death) in this patient cohort, only 3 patients (0.8%) died because of confirmed VTE and another 5 patients (1.4%) had an unexpected sudden death. Conclusions: Although VTE was identified in 65 patients (16%) diagnosed with glioblastoma, VTE was no major reason for death. On a population-based level these data do not support the implementation of primary thromboprophylaxis in this cohort of patients.