Arterial Thromboembolism In Patients Research Articles

Shifting focus from venous to arterial thromboembolism in patients with cancer

Shifting focus from venous to arterial thromboembolism in patients with cancer

Arterial Thromboembolism in Patients With Atrial Fibrillation and CHA2DS2-VASc Score 1: A Nationwide Study.

Oral anticoagulation is suggested in patients with atrial fibrillation and a CHA2DS2-VASc score ≥1 (congestive heart failure, hypertension, age ≥75 years, diabetes, stroke, vascular disease, age 65-74 years, and sex score). To assess granular differences within CHA2DS2-VASc 1, the incidence of arterial thromboembolism according to CHA2DS2-VASc 1 subgroups was examined. The Danish National Patient Registry and the Danish Prescription Registry were linked on a nationwide level to identify patients with atrial fibrillation from 2000 to 2021 without oral anticoagulation and categorized according to CHA2DS2-VASc score: CHA2DS2-VASc 0 (male and female subjects); CHA2DS2-VASc 1 (hypertension, heart failure, diabetes, vascular disease, and age 65-74 years); or CHA2DS2-VASc 2 (age ≥75 years without other risk factors). Female sex was not considered a risk factor in any risk group. The outcome was arterial thromboembolism (ischemic stroke, embolism of extremity, or transient cerebral ischemia). Study groups were compared using Cox regression analysis. We included 26 701 patients with a CHA2DS2-VASc 0 score; 22 915 with CHA2DS2-VASc 1 (1483 patients with heart failure, 9066 with hypertension, 843 with diabetes, 770 with vascular disease, and 10 753 who were 65 to 74 years of age); and 14 525 patients with CHA2DS2-VASc 2 (≥75 years of age without other risk factors). With a median of 1 year of observation time, the cumulative incidence of arterial thromboembolism was 0.6% (n=154 [95% CI, 0.6%-0.8%]), 1.4% (n=16 [95% CI, 0.8%-2.2%]), 1.9% (n=141 [95% CI, 1.6%-2.2%]), 1.7% (n=12 [95% CI, 0.9%-2.9%]), 2.0% (n=13 [95% CI, 1.1%-3.4%]), 2.3% (n=187 [95% CI, 2.0%-2.7%]), and 4.4% (n=533 [95% CI, 4.1%-4.8%]) for CHA2DS2-VASc 0, heart failure, hypertension, diabetes, vascular disease, age 65 to 74 years (CHA2DS2-VASc 1), and age ≥75 years (CHA2DS2-VASc 2), respectively. No statistically significant difference was identified among subgroups of CHA2DS2-VASc 1 (P=0.15 for difference). For patients with atrial fibrillation, all subgroups of CHA2DS2-VASc 1 were associated with lower incidence of arterial thromboembolism compared with age ≥75 years without other risk factors (ie, CHA2DS2-VASc 2) and a higher incidence compared with CHA2DS2-VASc 0. No statistically significant difference was identified between the subgroups of CHA2DS2-VASc 1. These findings support current recommendations that patients within this intermediate risk group could be identified with a similar risk of arterial thromboembolism.

Occurrence and Outcomes of Acute Cerebrovascular Events in Patients with Non-Hodgkin Lymphoma

Background Stroke or Cerebrovascular Accident (CVA) is one of the leading causes of mortality in the world whether it be ischemic or hemorrhagic 1,2. There has been an association of increased incidence of stroke in patients with cancer due to multiple factors 3. Regarding hematologic malignancies, there have been studies to assess the risk of developing stroke in patients with Hodgkin lymphoma (HL), however the information on non-Hodgkin lymphoma (NHL) is limited and not well understood4. We conducted a retrospective case-control study to assess the incidence, risks, and complications and length of stay of patients with current or prior history of NHL who developed an ischemic stroke. Methods This case-control study identified 29,632 patients older than 18 years, with or without CVA and with or without active or history of Non-Hodgkin Lymphoma (NHL) who were admitted to diverse private hospitals between 2018-2022. The patients were divided into two groups, one with current or prior NHL (n=10,699) and a control group of patients (n=18,933) with similar characteristics. Patients with active hemorrhagic stroke, pregnancy, malignancies other than NHL, prior hemorrhagic or ischemic stroke, infective endocarditis, atrial fibrillation, and acute coronary syndrome on admission were excluded. We compared patient's characteristics and the risk of developing a stroke based on the presence or absence of NHL as well as the factors that increased hospital mortality. Length of stay was evaluated as a secondary outcome. Bivariate statistical analysis was used to calculate the odds ratios using RStudio 4.2.2 and JMP Pro 16.0 for all data analysis. Results Of the group with NHL 46.39 % (n=4958) were female, and 53.61% (n=5729) were male, 42% were current or former smokers (n=4497), 27.49% (n=2941) had diabetes, 44.68% (n=4780) had hypertension; 3.34% (357) of them passed away. Of the control group 57.51 % (n=10876) were female, and 42.49% (n=8036) were male, 35% were current or former smokers (n=6763), 16.43% (n=3111) had diabetes, 28.89% (n=5469) had hypertension; 0.47% (n=88) of them passed away. The mean length of stay of patients with stroke was 7.99 days in the NHL group, and 5.99 days in the control group. Regarding the admissions due to stroke, there were 214 patients in the group with NHL, and in the control group where there were 113. Patients with NHL are more likely to have a CVA compared to the control group (OR 2.39 p<0.0001 CI 1.47~3.85) Patients who have NHL are more likely to die (OR=6.08 p<0.001) CI 4.77~7.74) compared to patients without NHL from all causes. Conclusion Patients with Non-Hodgkin lymphoma have an increased risk of developing a stroke compared to patients with similar characteristics but without NHL (or other malignancies). It was also noted that patients had an increased length of stay. Other variables and characteristics of patients that were identified to be more likely to have a CVA and statistically significant for this sample are already well-known risk factors for CVA including diabetes, hypertension, and cardiovascular disease. However, this study aimed to isolate those variables to identify the risk for stroke in this unique population. Our study limitation is the broad spectrum of NHL and possible confounders between the different variants of NHL. More studies are needed to investigate this. References Navi B, Reiner A, Kamel H, et al. Risk of Arterial Thromboembolism in Patients with Cancer. J Am Coll Cardiol. 2017 Aug, 70 (8) 926-938.Turner, M., Murchie, P., Derby, S. et al. Is stroke incidence increased in survivors of adult cancers? A systematic review and meta-analysis. J Cancer Surviv 16, 1414-1448 (2022). https://doi.org/10.1007/s11764-021-01122-7Dardiotis E, Aloizou AM, Markoula S, et al. Cancer-associated stroke: Pathophysiology, detection, and management (Review). Int J Oncol. 2019;54(3):779-796. doi:10.3892/ijo.2019.4669Wei Y, Yang Q, Qin Q, et al. Profiling of the Risk Factors and Designing of a Model to Identify Ischemic Stroke in Patients with Non-Hodgkin Lymphoma: A Multicenter Retrospective Study. Eur Neurol. 2020;83(1):41-48. doi:10.1159/000506046

Arterial thromboembolism in patients with atrial fibrillation and CHA2DS2-VASc score 1: a nationwide study

Abstract Background Knowledge is sparse on whether rate of stroke differs in patients with atrial fibrillation (AF) and a CHA2DS2-VASc of 1 according to how this point is obtained. Objectives To examine the associated rate of thromboembolism according to subgroups with a CHA2DS2-VASc of 1. Methods From nationwide registries, patients with incident AF from 2000–2021 and without oral anticoagulants were categorized according to the CHA2DS2-VASc score (CHA2DS2-VASc 0, CHA2DS2-VASc 1: heart failure [HF], hypertension [HT], diabetes mellitus [DM], vascular disease, age 65-74, or CHA2DS2-VASc 2, due to age ≥75 years). Female sex was not considered a risk factor. Outcome was one-year rate of thromboembolism (ischemic stroke, embolism of extremity, or transient cerebral ischemia). Main safety outcome was hospitalization with bleeding. The cumulative incidence of thromboembolism and bleeding were computed for CHA2DS2-VASc 0, the five subgroups of CHA2DS2-VASc 1, and CHA2DS2-VASc 2 (due to age ≥75 years) accounting for death as competing risk. For comparison between study groups crude Cox proportional hazard analysis was used. Results We included 29,369 patients with CHA2DS2-VASc 0; 27,845 patients with CHA2DS2-VASc 1: 1,890 (6.8%) patients with HF, 9,649 (34.7%) with HT, 968 (3.5%) with DM, 906 (3.3%) with vascular disease, 14,432 (51.8%) with age 65-74 years; 19,387 patients with CHA2DS2-VASc 2 (age ≥75 years). At one year of follow-up, the cumulative incidence of thromboembolism was 1.1% for CHA2DS2-VASc 1, 2.7% for CHA2DS2-VASc 1 (overall), and 4.9% for CHA2DS2-VASc 2 (age ≥75 years). Within subgroups of CHA2DS2-VASc 1, the cumulative incidence of thromboembolism was 1.7% for HF, 2.6% for HT, 2.2% for DM, 2.7% for vascular disease, and 2.9% for age 65-74 years (Figure 1). Within subgroups of CHA2DS2-VASc 1, age (65-74 years) was associated with the highest rate of thromboembolism, while HF was associated with the lowest rate (Figure 2). The one-year cumulative incidence of hospital admission with bleeding was 0.4%, 1.2%, 1.1%, 1.4%, 1.8%, 1.2%, and 2.2% for CHA2DS2 -VASc 0, CHA2DS2-VASc 1: HF, HT, DM, vascular disease, age 65-74, and CHA2DS2 -VASc 2 (age ≥75), respectively. Conclusion Within the spectrum of CHA2DS2-VASc 1, age seemed to be the risk factor with most impact on the rate of thromboembolism, while HF seemed to have the least impact. All subgroups of CHA2DS2-VASc 1 were associated with lower rate of arterial thromboembolism as compared with CHA2DS2-VASc 2 and a higher rate as compared with CHA2DS2-VASc 0. These findings lay the ground for a better understanding of when to initiate oral anticoagulation in patients with CHA2DS2-VASc 1.

SAT513 Venous Thromboembolism and Thyroid Cancer. Analysis of National Inpatient Sample

Abstract Disclosure: M. Botros: None. N. Mazzaferro: None. P. Greenberg: None. D.A. Cohen: None. Introduction: Current literature describes the strong association between thrombosis risk and cancer. Multiple studies have shown a relationship between cancer and venous thromboembolism (VTE), a condition that occurs when a blood clot forms in a vein and includes deep vein thrombosis (DVT) and pulmonary embolism (PE) (1). Few European studies have shown an association between VTE and thyroid cancer (2). However, research studying the association of thyroid cancer with VTE in the United States or on a large scale is lacking. The discovery of thyroid cancer as a risk factor in the development of VTE may improve the detection of thyroid cancer and prevent future morbidity and mortality from thyroid cancer and VTE. Objectives: Using the National (Nationwide) Inpatient Sample (NIS) database, this study reports VTE incidence in various cancer types to determine if the association between VTE prevalence is higher in thyroid cancer than in other cancer types. The study also compared the coexistence of VTE and thyroid cancer in hospitalized patients to the prevalence in the general population. Methods: NIS uses ICD 9 and 10 diagnosis codes for extracting data. For this study, we obtained data for the years 2015-2017. In this analysis, we reviewed the number of patients over 18 admitted with ICD 10 codes with any of sixteen different cancer types and the diagnosis of VTE. We reviewed the literature comprehensively and selected sixteen types of cancer most commonly associated with VTE. Patients with coagulation disorders and pregnant patients with ICD-10-related codes were excluded. Other variables included smoking status, obesity, and gender. Results: Data from 3,471,240 hospitalized patients were collected. 1,662,710 (48%) were females. The cancers most commonly associated with VTE were lymphoid leukemia (22.3%), non-Hodgkin’s lymphoma (14.6 %), Hodgkin’s lymphoma (13%), pancreatic cancer (11.3%), and lung cancer (10%). The cancers with the lowest cancers VTE co-diagnosis were gall bladder (9.8%), urinary bladder (9%), stomach (9%), ovarian (8.7%), melanoma (7.7%), breast (7.2%), prostate (6.8%), uterine (6%), kidney (5.7%), colon (5.4%), and thyroid (3.3%). Conclusion: In this analysis, 3.3% of all patients with thyroid cancer carried a diagnosis of VTE. Although this suggests a relatively low risk, it is still higher than VTE incidence in the general population (0.001%) (3). The increased frequency of thyroid cancer in patients with VTE may warrant further screening for underlying thyroid cancer in patients with unprovoked PE. 1.Gervaso L, et al. Venous and Arterial Thromboembolism in Patients with Cancer. J Am Coll CardiolCardioOnc. 2021. 2.Walker AJ, et al. Incidence of venous thromboembolism in patients with cancer - A cohort study using linked United Kingdom databases. European Journal of Cancer. 3.Kearon C. Epidemiology of venous thromboembolism. Semin Vasc Med. 2001. Presentation Date: Saturday, June 17, 2023

Increased risk of venous and arterial thromboembolism in patients with colorectal cancer receiving cetuximab-based combination chemotherapy: A population-based study in Korea

IntroductionLimited data exist on the risk of venous and arterial thromboembolisms (VTE and ATE) in patients receiving cetuximab plus chemotherapy. We aimed to determine the thromboembolic risk of patients with recurrent/metastatic colorectal cancer (CRC) treated with cetuximab plus chemotherapy compared to chemotherapy alone. MethodsThis population-based study used nationwide claims data from the Health Insurance Review and Assessment Service of South Korea from 2013 to 2020. Patients with recurrent/metastatic CRC treated with first-line oxaliplatin- or irinotecan-based doublets with or without cetuximab and no secondary prevention for VTE and ATE were included. Primary outcomes were the occurrence of any thromboembolic events, VTE, and ATE, which were determined using the cumulative incidence method incorporating death as a competing event. ResultsWe identified 19,723 patients (cetuximab plus chemotherapy, N = 7630; chemotherapy alone, N = 12,093). The cumulative incidence of any thromboembolic events in patients with cetuximab plus chemotherapy was significantly higher than in those receiving chemotherapy alone (6-month, 5.62 % vs. 3.58 %, P < 0.0001). The rates of VTE (6-month, 5.11 % vs. 3.28 %, P < 0.0001) and ATE (6-month, 0.53 % vs. 0.32 %, P = 0.0218) were also higher in patients receiving cetuximab plus chemotherapy. In multivariable analysis, cetuximab plus chemotherapy was independently associated with developing any thromboembolic events (hazard ratio [HR], 1.63; 95 % confidence interval [CI], 1.42–1.87), VTE (HR, 1.62; 95 % CI, 1.40–1.87), and ATE (HR, 1.77; 95 % CI, 1.16–2.71). ConclusionsCetuximab with irinotecan- or oxaliplatin-based doublet chemotherapy was associated with an increased risk of any thromboembolic events, VTE, and ATE; further studies are warranted to examine the underlying mechanisms.

Arterial Thromboembolism in Patients With AF and CHA2DS2-VASc Score 0-2 With and Without Cancer

It is unclear whether newly diagnosed cancer adds to the risk of arterial thromboembolism (ATE) in patients with atrial fibrillation/flutter (AF). This is especially relevant for AF patients with low to intermediate CHA2DS2-VASc scores in whom the risk-benefit ratios between ATE and bleeding are delicately balanced. The objectives were to evaluate the ATE risk in AF patients with a CHA2DS2-VASc score of 0 to 2 with and without cancer. A population-based retrospective cohort study was performed. Patients with a CHA2DS2-VASc score of 0 to 2 not receiving anticoagulation at cancer diagnosis (or the matched index date) were included. Patients with embolic ATE or cancer before study index were excluded. AF patients were categorized into AF and cancer and AF and no cancer cohorts. Cohorts were matched for multinomial distribution of age, sex, index year, AF duration, CHA2DS2-VASc score, and low/high/undefined ATE risk cancer. Patients were followed from study index until the primary outcome or death. The primary outcome was acute ATE (ischemic stroke, transient ischemic attack, or systemic ATE) at 12months using International Classification of Diseases-Ninth Revision codes from hospitalization. The Fine-Gray competing risk model was used to estimate the HR for ATE with death as a competing risk. The 12-month cumulative incidence of ATE was 2.13% (95% CI: 1.47-2.99) in 1,411 AF patients with cancer and 0.8% (95% CI: 0.56-1.10) in 4,233 AF patients without cancer (HR: 2.70; 95% CI: 1.65-4.41). The risk was highest in men with CHA2DS2-VASc=1 and women with CHA2DS2-VASc=2 (HR: 6.07; 95% CI: 2.45-15.01). In AF patients with CHA2DS2-VASc scores of 0 to 2, newly diagnosed cancer is associated with an increased incidence of stroke, transient ischemic attack, or systemic ATE compared with matched controls without cancer.

Venous and Arterial Thromboembolism in Patients with Metastatic Lung Cancer.

Lung cancer is the leading cause of cancer-related mortality worldwide with an increasing incidence in many countries. There were few studies on arterial and venous thromboembolism (ATE/VTE) in patients with metastatic lung cancer. Our study focused on the clinical characteristics of stage IV lung cancer patients with ATE or VTE to further explore the risk factors and prognosis. Patients diagnosed with metastatic lung cancer were enrolled from January 2011 to June 2019 at a tertiary hospital in Jiangyin, China. Log-rank test was used to reveal the survival for patients with ATE or VTE. Univariable analysis and multivariable logistic regression were used to study the risk factors for ATE. A total of 587 patients were enrolled in our study, including 52 patients with VTE and 48 with ATE. ATE occurred earlier than VTE. Patients with ATE had a worse prognosis. Multivariable logistic regression revealed that older age and a history of hypertension were independent risk factors for ATE. Patients with metastatic lung cancer were at high risk of VTE and ATE. ATE occurred earlier and was associated with a worse prognosis. Attention should be paid to metastatic lung cancer patients who may develop thromboembolism, especially ATE.

Arterial Thromboembolism in Cancer Patients Treated with Apixaban

Introduction: Arterial thromboembolism is a rising concern in patients with cancer. Data considering incidence and risk factors are scarce. Here we describe arterial thrombosis in a cohort of cancer patients receiving apixaban as treatment for venous thromboembolism. Methods: A total of 298 cancer patients with any type of venous thromboembolism were treated up to 6 months with apixaban 5 mg twice daily. After six months, the 196 patients left in the study further received secondary prophylaxis with apixaban 2.5 mg twice daily for up to 30 months. Primary efficacy outcome was recurrent venous thromboembolism and safety outcome was bleeding. Arterial thromboembolism was registered as a serious adverse event during the whole study period. This is a post-hoc analysis of the arterial events. Results: Arterial events were registered in 16/298 (5.4 %, CI: 3.1-8.6) patients. Leucocyte count at baseline were higher (p=0.006) in patients with arterial thromboembolism compared to patients without arterial thromboembolism. Factors that increased the risk of arterial thromboembolism in our patient cohort was pancreatic cancer (OR: 11.41 (95 % CI: 3.81-34.17)), ovarian cancer (OR: 20 (95 % CI: 2.62-152.61)), BMI <22.3 (OR: 3.14 (95 % CI: 1.12-8.79)) and previous venous thromboembolism (OR: 4.673 (1.503-14.524)). Patients with pancreatic cancer had a much higher frequency of arterial thromboembolism than other cancers (figure 1). During the first 6 months, 7/25 (28 %, CI: 12-49)) patients with pancreatic cancer had a stroke. Among pancreatic cancer patients, d-dimer at baseline was higher in those who experienced arterial thromboembolism compared to those who did not (p=0.037). Conclusion: In our cohort of cancer patients treated for venous thromboembolism with apixaban, there seems to be an increased risk of arterial thromboembolism in patients with pancreatic cancer, low BMI and previous venous thromboembolism. High leukocyte count may be a biomarker for increased risk of arterial thrombosis. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Risk of arterial thromboembolism in patients with concomitant atrial fibrillation and cancer: a systematic review and meta-analysis

Abstract Background/Introduction Atrial fibrillation (AF) and cancer often co-exist and have been independently associated with increased risk of arterial thromboembolism (TE), all cause death and bleeding; however, no cumulative data exist regarding the clinical course of AF patients with comorbid cancer. Purpose The aim of this systematic review and meta-analysis is to synthesize the available data regarding the incidence of major adverse cardiovascular events in AF patients in association with concurrent cancer. Methods The composite outcome of any TE (ischemic stroke, transient ischemic attack, or arterial thrombosis) was defined as the primary study outcome, while all-cause mortality and major or clinically relevant non-major bleeding occurrence as the secondary ones. Literature search was conducted in PubMed (MEDLINE), WebOfScience, Scopus, CENTRAL, OpenGrey, and EThOS databases. A random-effects model meta-analysis was performed. Subgroup analyses were conducted assessing the effect of active cancer history and various cancer subtypes on the outcomes of interest. Meta-regression analyses were also performed to examine the relative impact of CHA2DS2VASC and HASBLED prognostic scores on the risk of TE and bleeding, respectively. Results Overall 17 studies were included in our analysis, encompassing a total of 3,151,861 AF patients. Comorbid cancer was non-significantly associated with lower odds of TE than AF alone (pooled odds ratio (pOR) = 0.85, 95% confidence interval (CI): 0.69–1.03, I2=87%). The likelihood for all-cause death and bleeding occurrence was significantly higher in AF patients with cancer (pOR = 2.27, 95% CI: 1.69–3.06, I2=99%); pOR = 1.58, 95% CI: 1.26–1.97, I2=97% respectively) compared to those without cancer. Subgroup analysis on active cancer status did not yield any substantial difference, marginally improving the heterogeneity of our analysis. The highest all-cause mortality likelihood was observed in Liver-Pancreas-Gallbladder category (pOR = 10.58, 95% CI: 4.69–23.88, I2=98%) while the highest bleeding likelihood was encountered in Genitourinary cancer (pOR = 1.90, 95% CI: 1.42–2.55, I2=71.9%). The performed meta-regression analyses did not yield any significant results. Conclusions Our meta-analysis of 17 eligible studies demonstrated that cancer does not seem to be associated with increased risk of TE, while with increased all-cause death and bleeding occurrence in AF patients. This correlation might be explained by higher cancer-driven mortality rates (competing risk), many cases of TE being left undiagnosed within the scope of palliative cancer care, misdiagnosed episodes of TE due to the presence of brain metastases, optimal cardio-oncology monitoring, and more frequent usage of prophylactic anticoagulation treatment for cancer-associated venous thromboembolism. Nonetheless, further competing-risk survival analyses are warranted before reaching definite conclusions. Funding Acknowledgement Type of funding sources: None.

Venous and arterial thromboembolism in patients with cancer treated with targeted anti-cancer therapies

Patients with cancer have an increased risk of venous- and arterial thromboembolism (VTE/ATE). Anti-cancer treatments including surgery, radiotherapy, and certain chemotherapies contribute to the increased risk of VTE and/or ATE. Over the past years, the therapeutic landscape in medical oncology has changed dramatically with the introduction of targeted anti-cancer therapies and cancer immunotherapy. These novel treatment approaches have revolutionized patient care with significant improvements in response rates and survival times of patients. These agents specifically target refined pathophysiological pathways engaged in tumour development and progression involving, among others, angiogenesis, growth factor receptor signalling and anti-tumoral immune regulation. Therefore, distinct off-target effects lead to characteristic adverse event profiles for certain treatments. For several targeted and immunotherapeutic anticancer agents, increased rates of VTE and/or ATE have been reported. For example, a prothrombotic effect has been reported for antiangiogenic agents, EGFR-targeted treatments, CDK4/6-inhibitors, and 2nd generation BCR-ABL-inhibitors. Further, very recently, data emerged on substantial rates of thrombotic complications in patients treated with immune checkpoint inhibitors. In this review, we comprehensively summarize currently available evidence on risk profiles and potential mechanisms of thrombosis in patients with cancer treated with targeted anti-cancer therapies, and discuss current limitations in available data and potential future perspectives.

PO-36: The impact of oral anticoagulant drugs for arterial thromboembolism in patients with cancer

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Arterial and Venous Thromboembolism in Critically Ill, COVID-19 Positive Patients Admitted to Intensive Care Unit

Arterial and Venous Thromboembolism in Critically Ill, COVID-19 Positive Patients Admitted to Intensive Care Unit

Risk of venous and arterial thromboembolism in patients with giant cell arteritis and/or polymyalgia rheumatica: A Veterans Health Administration population-based study in the United States.

Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are systemic inflammatory diseases that primarily affect elderly women. To compare the risk of thromboembolic events and retinal vascular occlusions in GCA and/or PMR with that in osteoarthritis (OA), evaluating a veteran-based population. A total of 1535 patients with GCA, 10,265 with PMR, and 1203 with overlapping disease, as well as 39,009 age- and sex-matched patients with OA were identified in this retrospective study. The incidence rate ratios (IRRs) of pulmonary embolism (PE), deep venous thrombosis (DVT), arterial thromboembolism, central retinal artery occlusion, and central retinal vein occlusion were calculated and examined over time. The cumulative incidence was plotted and hazard ratios (HRs) of thromboembolic events were calculated, adjusting for independent risk factors of thromboembolism. Patients with GCA and overlapping disease exhibited higher IRRs for all thromboembolic events compared to patients with OA. Patients with GCA had a higher risk of developing DVT and retinal vascular occlusions than those with overlapping disease (HR: 2.01, 95% confidence interval [CI]: 1.35-2.99, p < 0.001; HR: 2.37, 95% CI: 1.23-4.53, p = 0.009, respectively) or PMR alone (HR: 1.89, 95% CI: 1.50-2.41, p < 0.001; HR: 4.68, 95% CI: 3.10-7.07, p < 0.001, respectively). Patients with GCA had a higher risk of developing PE than those with PMR (HR: 1.55, 95% CI: 1.1-2.18, p = 0.01). The risk of thromboembolic events differs between GCA, PMR, and overlapping diseases. Our findings may help predict the risk of thromboembolic events based on disease phenotype.

Venous and arterial thromboembolism in patients with inflammatory bowel diseases.

The risk of thromboembolism (TE) is increased in patients with inflammatory bowel disease (IBD), mainly due to an increased risk of venous TE (VTE). The risk of arterial TE (ATE) is less pronounced, but an increased risk of cardiovascular diseases needs to be addressed in IBD patients. IBD predisposes to arterial and venous thrombosis through similar prothrombotic mechanisms, including triggering activation of coagulation, in part mediated by impairment of the intestinal barrier and released bacterial components. VTE in IBD has clinical specificities, i.e., an earlier first episode in life, high rates during both active and remission stages, higher recurrence rates, and poor prognosis. The increased likelihood of VTE in IBD patients may be related to surgery, the use of medications such as corticosteroids or tofacitinib, whereas infliximab is antithrombotic. Long-term complications of VTE can include post-thrombotic syndrome and high recurrence rate during post-hospital discharge. A global clot lysis assay may be useful in identifying patients with IBD who are at risk for TE. Many VTEs occur in IBD outpatients; therefore, outpatient prophylaxis in high-risk patients is recommended. It is crucial to continue focusing on prevention and adequate treatment of VTE in patients with IBD.

Accelerated fibrin clot degradation is associated with arterial thromboembolism in patients following venous thrombosis: a cohort study

Several lines of evidence have suggested that patients following venous thromboembolism (VTE) are at higher risk of arterial thromboembolism (ATE). Prothrombotic fibrin clot characteristics were reported in individuals with cardiovascular risk factors. We investigated whether specific fibrin clot properties measured after 3–4 months of anticoagulation characterize VTE patients with subsequent ATE. We enrolled 320 patients following VTE aged below 70 years (median age, 46). Ten patients were lost to follow-up. ATE occurred in 21 individuals after a median 54 (31–68) months during a follow-up of 87.5 months (incidence 0.94%; 95% confidence interval [CI], 0.59–1.4 per patient-year). Patients with ATE had faster fibrin clot degradation, reflected by maximum rate of D-dimer increase during plasma clot lysis induced by tissue-type plasminogen activator (D-Drate) at baseline. Clot permeability, turbidimetric variables, clot lysis time, and thrombin generation were unrelated to ATE. Univariable Cox proportional hazards analysis showed that age, diabetes, and D–Drate were risk factors for subsequent ATE. Increased D–Drate (by 0.001 mg/L/min; hazard ratio, 1.08; 95% CI 1.02–1.14) was an independent predictor of ATE after adjustment for potential confounders. Faster fibrin clot degradation at 3 months since VTE may increase the risk of ATE among VTE patients during follow-up.

Lead thrombus under standard-dose edoxaban in a patient with normal to high creatinine clearance and protein S deficiency

BackgroundNon-vitamin K antagonist oral anticoagulants (NOACs) are as effective and safe as warfarin for thromboembolic prevention and treatment. The efficacy of NOACs lacks evidence from large and randomized studies in patients with inherited severe thrombophilia, including protein S deficiency. Further, some concerns still exist regarding the relative efficacy of edoxaban in preventing arterial thromboembolism in patients with normal to high creatinine clearance (CrCl). We present a case of a rare complication of lead thrombus under standard-dose edoxaban in a patient with protein S deficiency and supernormal renal function.Case presentationA 65-year-old man experienced persistent chest tightness and a high level of D-dimer. Chest computed tomography (CT) showed a lead thrombus at the superior vena cava. He had a medical history including, paroxysmal atrial fibrillation (PAf), sick sinus syndrome after permanent pacemaker implantation, and transient ischemic attack. He received standard-dose edoxaban (60 mg daily) after PAf was diagnosed. His estimated CrCl was 98.6–102.1 mL/min. However, protein S deficiency (22.8%; normal range: 55–130%) was diagnosed. After switching to dabigatran (150 mg twice daily) for 3 months, the chest CT showed lead thrombus resolution and no symptoms were seen during the follow-up period.ConclusionsThis case was a rare complication of lead thrombus in a protein S deficient patient with normal renal function receiving standard-dose edoxaban. Edoxaban efficacy is uncertain in patients with protein S deficiency, and intracardiac devices also increase the risk of thromboembolic events.

Incidence and Risk of Various Types of Arterial Thromboembolism in Patients With Cancer

ObjectiveTo describe the temporal association and identify risk factors between cancer diagnosis and various types of arterial thromboembolism (ATE). Patients and MethodsWe inquired an aggregated electronic health record database (Explorys, IBM Corp., Armonk, New York) and identified patients with cancer from January 1999 to October 2019, with various types of ATE, including myocardial infarction, acute ischemic stroke, acute limb ischemia, acute mesenteric ischemia, acute renal infarction, and retinal artery occlusion. We investigated the temporal relationship between cancer diagnosis and ATE events by examining the incidence ratio (IR) of ATE before and after diagnosis of cancer. ResultsWe identified 305,384 patients with cancer and ATE. The 30-day interval IR of total ATE was elevated shortly before and after cancer diagnosis, which was consistent among different ATE and cancer types. The incidence was highest within a 330-day window (90 days before and 240 days after cancer diagnosis), and IR peaked at 13.9 (95% confidence interval [CI], 13.6 to 14.2) in the first 30 days following diagnosis of cancer. Compared with patients with cancer who never developed ATE, patients with ATE had more cardiovascular risk factors at baseline. Patients with brain cancer, lung cancer, colorectal cancer, and pancreatic cancer had the highest risk of developing ATE, whereas ATE type was anatomically associated with cancer type. ConclusionIn this observational study of an aggregated US patient population, those with newly diagnosed cancer had increased risk of ATE events. This risk was most elevated in a 330-day window around cancer diagnosis and was consistent across different types of ATE and cancer.

Risk of Venous and Arterial Thromboembolism in Patients With Giant Cell Arteritis and/or Polymyalgia Rheumatica: A Veterans Health Administration Population-Based Study in the United States

Background: Giant cell arteritis (GCA) and polymyalgia rheumatica (PMR) are two chronic systemic inflammatory diseases that primarily affect elderly women. Both GCA and PMR can be complicated by thromboinflammation. We evaluated the risk of thromboembolic events as well as retinal vascular occlusive events in patients with giant cell arteritis (GCA), polymyalgia rheumatica (PMR), and overlap of GCA with PMR compared to patients with a non-inflammatory condition such as osteoarthritis (OA) in a Veteran based population. Methods: 1,535 patients with GCA, 10, 265 with PMR, and 1,203 with overlap of GCA with PMR as well as 39,009 age- and sex-matched patients with OA were identified in this retrospective study. Incidence rate ratios (IRR) of pulmonary embolism (PE), deep venous thrombosis (DVT), arterial thromboembolism (ATE), central retinal artery occlusion (CRAO) and central retinal vein occlusion (CRVO) were calculated among all three-study groups and trended over time after diagnosis. We also plotted cumulative incidence and calculated hazard ratios (HRs) of thromboembolic events in the study groups, adjusting for independent risk factors of thromboembolism. Findings: Patients with GCA, PMR and overlap of GCA with PMR had higher IRR of all thromboembolic events compared to patients with OA. IRRs of all thromboembolic events were highest within the first year of diagnosis for GCA and gradually decreased over time, whereas for the overlap and PMR groups the time trend of IRRs varied for each of the thromboembolic events. Patients with GCA had a higher risk of developing DVT and retinal vascular occlusive events compared to patients with overlap disease (2.01, 95%CI: 1.35-2.99, p<0.001, and 2.37, 95%CI: 1.23-4.53, p=0.009 respectively) and PMR (1.89, 95%CI: 1.50-2.41, p<0.001, and 95%CI: 4.68, 95%CI: 3.10-7.07, p<0.001 respectively). Patients with GCA had a higher risk of developing PE compared to patients with PMR (1.55, 95%CI: 1.1-2.18, p=0.01). Patients with overlap disease were at higher risk of developing retinal vascular occlusions compared to patients with PMR (1.97, 95%CI: 1.05-3.69, p=0.03). Interpretation: The risk of thromboembolic events differs in patients with GCA, PMR and overlap disease. Our findings may help physicians predict risk of thromboembolic events determined by disease phenotype and duration, and assist with the development of venous thromboembolism risk stratification tools in patients with GCA and/or PMR that would allow identification of high risk patients. Funding Information: D.M. is supported by the T32 NIH grant from Nutrition, Obesity and Atherosclerosis (#5T32HL007028-44) and Pfizer US Pharmaceuticals Group grant, award number 53857367 Declaration of Interests: DM received Advisory Board fee from Chemocentryx. All other authors report no competing interests. Ethics Approval Statement: MIRB#01854.

Frequency of Arterial Thromboemobolic Events in Patients with Cancer Associated Venous Thromboembolism

Background:Patients with cancer are at high risk of both venous thromboembolism (VTE) and arterial events, however, little is known about the association between venous and arterial thromboembolic events in patients with cancer. In this study, we evaluated the incidence and relative risk of subsequent arterial thromboembolism in patients with a confirmed diagnosis of acute cancer-associated VTE. Methods:We conducted a retrospective cohort study at the Cleveland Clinic Taussig Cancer Institute of cancer patients with confirmed VTE who were referred to a centralized thrombosis clinic between January 2017-October 2019 with at least 6 months of follow-up. Arterial thrombotic events (ATE), including myocardial infarction, peripheral arterial thrombosis, and ischemic stroke, were identified by manual review of electronic medical records. The cumulative incidence rate of each ATE event was calculated. Results:The study population comprised 294 patients with a median age of (63.5) years (range 27-90), and 49.7 % were male. The cumulative incidence rate of overall ATE during the 6-month, 1-year, and 2-year follow-up period was 3.07%, 3.42%, and 3.42%, respectively. A total of 10 patients who experienced arterial events of whom 7 had ischemic stroke, 2 had myocardial infarction, 2 had peripheral arterial thrombosis where one patient had two arterial events of myocardial infarction and peripheral arterial thrombosis(Table 1 shows the incidence rates of arterial events). Amongst patients with ATE, 30 % were active smokers (n=3), 90% had hypertension (n=9), 20% had diabetes mellitus (n=2), 50% had a family history of coronary artery disease (n=5), 40% were on statin and daily aspirin use (n=4), 40% were obese with BMI &amp;gt;30 (n=4). 40% of ATE patients(n=4) were on a therapeutic anticoagulant therapy at the time of arterial thrombotic event (3 on enoxaparin, 1 on apixaban) Conclusion:Cancer patients with acute VTE have a substantial increased risk of subsequent arterial thromboembolism particularly in the first six months after VTE. Ischemic stroke was the most frequent arterial event and ATE events occured despite therapeutic anticoagulation in a large subset of our cohort. Further prospective studies are needed to better understand the risk of ATE in cancer patients, and further studies should be designed to mitigate the risk of arterial events in this patient population. Disclosures McCrae: Momenta Pharmaceuticals:Consultancy;Novartis:Honoraria;Rigel:Consultancy;Dova:Consultancy.Khorana:Pharmacyclics:Honoraria;Pharmacyte:Honoraria;Seattle Genetics:Honoraria;Leo Pharma:Honoraria;Medscape:Honoraria;Sanofi:Honoraria;Pfizer:Honoraria;Bayer:Honoraria;Janssen:Honoraria;Array:Other: Research funding (to institution);Merck:Research Funding;BMS:Honoraria, Research Funding;Leap:Research Funding.