Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer

The risk of venous and arterial thromboembolism (VTE/ATE) associated with immune checkpoint inhibitors is currently unclear, and clinical trials evaluating these agents in patients with cancer did not provide information. Our aim was to quantify risk of VTE/ATE in a cohort of patients treated with immune checkpoint inhibitors, explore clinical impact, and investigate potential clinical risk factors. Patients treated with an immune checkpoint inhibitor at the Medical University of Vienna from 2015-2018 were identified using the in-house pharmacy records (n=672; most frequent entities: 30.4% melanoma, 24.1% non-small-cell lung cancer; 86% stage-IV-disease). A retrospective chart-review was performed to screen for VTE and/or ATE. Cumulative incidences and between-group differences were analysed within a competing-risk framework. Multi-state modelling was applied to study the impact of VTE/ATE on mortality. Over a median follow-up of 8.5 months, 47 VTE and 9 ATE were observed. Cumulative incidences of VTE and ATE were 12.9% [95% confidence interval (CI): 8.2-18.5)] and 1.8% [95%CI: 0.7-3.6]. Occurrence of VTE was associated with increased mortality (transition hazard-ratio (THR): 3.09 [95%CI: 2.07-4.60]. History of VTE predicted VTE occurrence (subdistribution hazard ratio (SHR): 3.69 [2.00-6.81]) and distant metastasis was non-significantly associated with VTE risk (SHR: 1.71 [95%CI: 0.62-4.73]). No association of VTE with ECOG performance-status, Charlson-Comorbidity-Index or the Khorana-score was observed, and rates of VTE were comparable among subgroups of tumour types and checkpoint-inhibitory agents. In conclusion, patients with cancer under immune checkpoint inhibitor therapy are at high risk of thromboembolism, especially VTE. Furthermore, VTE occurrence was associated with increased risk of mortality.

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Premature Arterial Disease Associated with Familial Antithrombin III Deficiency

Thrombosis and Haemostasis ◽

10.1055/s-0038-1645677 ◽

1990 ◽

Vol 63 (01) ◽

pp. 013-015 ◽

Cited By ~ 15

Author(s):

E J Johnson ◽

C R M Prentice ◽

L A Parapia

Keyword(s):

Risk Factors ◽

Venous Thromboembolism ◽

Potential Risk ◽

Antithrombin Iii ◽

Arterial Disease ◽

Coagulation System ◽

Early Age ◽

Arterial Thromboembolism ◽

Potential Risk Factors ◽

Antithrombin Iii Deficiency

SummaryAntithrombin III (ATIII) deficiency is one of the few known abnormalities of the coagulation system known to predispose to venous thromboembolism but its relation to arterial disease is not established. We describe two related patients with this disorder, both of whom suffered arterial thrombotic events, at an early age. Both patients had other potential risk factors, though these would normally be considered unlikely to lead to such catastrophic events at such an age. Thrombosis due to ATIII deficiency is potentially preventable, and this diagnosis should be sought more frequently in patients with arterial thromboembolism, particularly if occurring at a young age. In addition, in patients with known ATIII deficiency, other risk factors for arterial disease should be eliminated, if possible. In particular, these patients should be counselled against smoking.

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Faculty Opinions recommendation of Upper limb arterial thromboembolism: a systematic review on incidence, risk factors, and prognosis, including a meta-analysis of risk-modifying drugs.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717985805.793474100 ◽

2013 ◽

Author(s):

David Kuter ◽

Rachel Rosovsky

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Upper Limb ◽

Meta Analysis ◽

Arterial Thromboembolism ◽

Incidence Risk

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Faculty of 1000 evaluation for Upper limb arterial thromboembolism: A systematic review on incidence, risk factors, and prognosis including a meta-analysis of risk-modifying drugs.

F1000 - Post-publication peer review of the biomedical literature ◽

10.3410/f.717985805.793473210 ◽

2013 ◽

Author(s):

Paolo Della Bella ◽

Pasquale Vergara

Keyword(s):

Risk Factors ◽

Systematic Review ◽

Upper Limb ◽

Meta Analysis ◽

Arterial Thromboembolism ◽

Incidence Risk

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COVID-19 and cancer registries: learning from the first peak of the SARS-CoV-2 pandemic

British Journal of Cancer ◽

10.1038/s41416-021-01324-x ◽

2021 ◽

Author(s):

Alvin J. X. Lee ◽

Karin Purshouse

Keyword(s):

Risk Factors ◽

Performance Status ◽

Poor Performance ◽

Cancer Registries ◽

Adverse Outcomes ◽

Smoking History ◽

Poor Performance Status ◽

International Studies ◽

Patients With Cancer ◽

Increased Risk

AbstractThe SARS-Cov-2 pandemic in 2020 has caused oncology teams around the world to adapt their practice in the aim of protecting patients. Early evidence from China indicated that patients with cancer, and particularly those who had recently received chemotherapy or surgery, were at increased risk of adverse outcomes following SARS-Cov-2 infection. Many registries of cancer patients infected with SARS-Cov-2 emerged during the first wave. We collate the evidence from these national and international studies and focus on the risk factors for patients with solid cancers and the contribution of systemic anti-cancer treatments (SACT—chemotherapy, immunotherapy, targeted and hormone therapy) to outcomes following SARS-Cov-2 infection. Patients with cancer infected with SARS-Cov-2 have a higher probability of death compared with patients without cancer. Common risk factors for mortality following COVID-19 include age, male sex, smoking history, number of comorbidities and poor performance status. Oncological features that may predict for worse outcomes include tumour stage, disease trajectory and lung cancer. Most studies did not identify an association between SACT and adverse outcomes. Recent data suggest that the timing of receipt of SACT may be associated with risk of mortality. Ongoing recruitment to these registries will enable us to provide evidence-based care.

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EGFR-mutant NSCLC presenting with stroke and massive systemic embolization as the first manifestation: case report

BMC Neurology ◽

10.1186/s12883-021-02236-2 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Zheng Wang ◽

Jiangyong Miao ◽

Lina Wang ◽

Ying Liu ◽

Hui Ji ◽

...

Keyword(s):

Risk Factors ◽

Ischemic Stroke ◽

Cancer Therapy ◽

Acute Ischemic Stroke ◽

Oral Anticoagulants ◽

Initial Manifestation ◽

Arterial Thromboembolism ◽

Systemic Embolization ◽

Effective Cancer Therapy

Abstract Background Presentation with massive systemic embolization as the initial manifestation of occult malignancy is infrequent. The standard management of cancer-related arterial thromboembolism has not yet been established. Case presentation We described a case of Trousseau’s syndrome resulting in acute ischemic stroke concomitant with multiple embolizations in the spleen and kidney during oral administration of dabigatran for pulmonary embolism preceding the diagnosis of a malignant tumor. A cancer-related hypercoagulable state was suspected because the patient was admitted to the neurology department due to acute ischemic stroke with three territory infarcts on diffusion-weighted imaging (DWI) in the absence of identifiable conventional risk factors and brain vessel narrowing. The patient was subsequently diagnosed with epidermal growth factor receptor (EGFR) mutation–positive non-small-cell lung cancer (NSCLC) (stage IV) with pleural metastasis. Administration of low-molecular-weight heparin followed by long-term dabigatran under effective cancer therapy comprising gefitinib and subsequent chemotherapy did not cause stroke relapse during the 1-year follow-up. Conclusions This case suggests that cancer-related hypercoagulability should be considered an important etiology for stroke patients who develop unexplained disseminated acute cerebral infarction without conventional stroke risk factors, especially concomitant with multiple organ embolization. Novel oral anticoagulants may be an alternative therapy for the long-term management of cancer-related arterial thromboembolism under effective cancer therapy.

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798. Metronidazole Exposure Prior to Clostridiodes difficile Infection (CDI) is a Risk Factor for Severe C. difficile Disease in Cancer Patients

Open Forum Infectious Diseases ◽

10.1093/ofid/ofaa439.988 ◽

2020 ◽

Vol 7 (Supplement_1) ◽

pp. S442-S443

Author(s):

Denise Marie A Francisco ◽

Liangliang Zhang ◽

Ying Jiang ◽

Adilene Olvera ◽

Eduardo Yepez Guevara ◽

...

Keyword(s):

Risk Factors ◽

Risk Factor ◽

Cancer Patients ◽

Research Study ◽

Research Support ◽

Factors Associated ◽

Patients With Cancer ◽

Study Investigator ◽

Severity Levels ◽

Permutation Analysis

Abstract Background Antibiotic use is a risk factor for CDI. Few studies have correlated use of prior antibiotics with CDI severity in cancer patients. This study identified clinical and microbiology risk factors associated with severe CDI in patients with cancer. We hypothesized that previous antibiotic exposure and microbiome composition at time of CDI presentation, are risk factors for severe disease in cancer patients. Methods This non-interventional, prospective, single-center cohort study examined patients with cancer who had their first episode or first recurrence of CDI between Oct 27, 2016 and Jul 1, 2019. C. difficile was identified using nucleic acid amplification testing. Multivariate analysis was used to determine significant clinical risk factors for severe CDI as defined in the 2018 IDSA/SHEA guidelines. Alpha, and beta diversities were calculated to measure the average species diversity and the overall microbial composition. Differential abundance analysis and progressive permutation analysis were used to single out the significant microbial features that differed across CDI severity levels. Results Patient (n=200) demographics show mean age of 60 yrs., 53% female, majority White (76%) and non-Hispanic (85%). Prior 90 day metronidazole use (Odds Ratio OR 4.68 [1.47-14.91] p0.009) was a significant risk factor for severe CDI. Other factors included Horn’s Index > 2 (OR 7.75 [1.05-57.35] p0.045), Leukocytosis (OR 1.29 [1.16-1.43] p< 0.001), Neutropenia (OR 6.01 [1.34-26.89] p0.019) and Serum Creatinine >0.95 mg/dL (OR 25.30 [8.08-79.17] p< 0.001). Overall, there were no significant differences in alpha and beta diversity between severity levels. However, when identifying individual microbial features, the high presence of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were associated with protection from severe CDI (p< 0.05). Table 1 - Results of multivariate logistic regression analysis of factors associated with severe CDI Figure 1. Microbiome features identified by progressive permutation analysis as seen in a volcano plot. Conclusion A number of risk factors for severe CDI were identified among this population, including prior 90 day metronidazole use. Also, increased relative abundance of Bacteroides uniformis, Ruminococceae, Citrobacter koseri and Salmonella were linked to protection from severe CDI. Reducing metronidazole use in patients with cancer may help prevent subsequent severe CDI. Disclosures Adilene Olvera, MPH MLS (ASCP), MERK (Grant/Research Support, Scientific Research Study Investigator) Kevin W. Garey, PharmD, MS, FASHP, Merck & Co. (Grant/Research Support, Scientific Research Study Investigator) Ryan J. Dillon, MSc, Merck & Co., Inc., (Employee) Engels N. Obi, PhD, Merck & Co. (Employee)

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