Cancer Patients’ Experiences and Understanding of Venous Thromboembolism

Background: Venous thromboembolism (VTE), comprising deep vein thrombosis (DVT) and pulmonary embolism (PE), presents an extra challenge in the management of patients with cancer, given the increase in morbidity and mortality in having both conditions. Cancer patients are well known to have a high risk of VTE; particularly; those who have had major surgery, chemotherapy and/or hormonal therapy. These groups of patients need to understand the risk factors and the prophylactic measures to prevent developing VTE. This review aims to provide an overview of the literature on cancer patients’ understanding of VTE and their experiences of cancer-associated thrombosis (CAT). Method: A scoping review was carried map the literature and explore the types of evidence available. A structured electronic search was conducted in Embase, Scopus and Medline in June 2020. All titles and abstracts from the search were evaluated independently by two reviewers and disagreements were resolved by a third arbitrator. Eligible papers were qualitative studies and reviews of adult patients' experience of cancer-associated thrombosis. Results: Ten articles met the inclusion criteria, nine primary qualitative studies and one systematic review that explored cancer patients’ experiences of living with CAT. Participants had various cancer types. Most had advanced disease and were receiving palliative care. Four major themes emerged from the data: Lack of meaningful information on CAT, cancer patients unaware of signs and symptoms of VTE, limited awareness of CAT amongst HCPs and acceptability of anticoagulant. Conclusion: All the studies explored patients’ experience of VTE in the cancer context, and all included studies showed that participants had limited information about VTE, VTE risk and VTEs’ signs and symptoms. However, no qualitative studies explored patients' understanding of VTE in prophylactic settings in high-risk cancer patients.

Treatment Algorithm in Cancer-Associated Thrombosis: Updated Canadian Expert Consensus

Patients with cancer-associated thrombosis (CAT) are at high risk of recurrent venous thromboembolism (VTE) and major bleeding complications. Risks vary significantly between individuals based on cancer status, treatment, and other characteristics. To facilitate the evidence-based management of anticoagulant therapy in this patient population, a committee of 11 Canadian clinical experts updated a consensus-based algorithm for the acute and extended treatment of symptomatic and incidental CAT that was developed in 2018. Following a systematic review of the literature, updates to the algorithm were discussed during an online teleconference, and the algorithm was subsequently refined based on feedback from committee members. Clinicians using this treatment algorithm should consider bleeding risk, type of cancer, and drug–drug interactions, as well as patient and clinician preferences, in tailoring anticoagulation for patients with CAT. Anticoagulant therapy should be adapted as the patient’s cancer status and management change over time.

The Feasibility of Edoxaban for Asymptomatic Cancer-associated Thrombosis in Japanese Gastrointestinal Cancer Patients (ExCAVE study)

BackgroundAlthough an initial therapy with a parenteral anticoagulant is required before edoxaban, this strategy is frequently avoided in actual clinical practice because of its complexity. This study assessed the feasibility of edoxaban without initial heparin usage for asymptomatic cancer-associated thrombosis (CAT) in Japanese patients with gastrointestinal cancer (GIC) at a high risk of bleeding.MethodsIn this multicenter prospective feasibility study conducted at 10 Japanese institutions, patients with active GIC who developed accidental asymptomatic CAT during chemotherapy were recruited. Edoxaban was orally administered once daily without initial parenteral anticoagulant therapy within 3 days after detecting asymptomatic CAT. The primary outcome was the incidence of major bleeding (MB) or clinically relevant non-major bleeding (CRNMB) during the first 3 months of edoxaban administration. ResultsOf the 54 patients enrolled from October 2017 to September 2020, one was excluded because of a misdiagnosis of CAT. In the remaining 53 patients, the primary outcome occurred in six patients (11.3%). MB occurred in four patients (7.5%), including gastrointestinal bleeding in three patients and intracranial hemorrhage in one patient. CRNMB occurred in two patients (3.8%), including bleeding from the stoma site and genital bleeding in one patient each. There were no deaths attributable to bleeding, and all patients who had experienced MB and CRNMB recovered.ConclusionsThe risk of bleeding after edoxaban without heparin pretreatment was acceptable, demonstrating new treatment options for asymptomatic CAT in patients with GIC.

The Emerging Role of Neutrophil Extracellular Traps in Arterial, Venous and Cancer-Associated Thrombosis

Neutrophils play a vital role in the formation of arterial, venous and cancer-related thrombosis. Recent studies have shown that in a process known as NETosis, neutrophils release proteins and enzymes complexed to DNA fibers, collectively called neutrophil extracellular traps (NETs). Although NETs were originally described as a way for the host to capture and kill bacteria, current knowledge indicates that NETs also play an important role in thrombosis. According to recent studies, the destruction of vascular microenvironmental homeostasis and excessive NET formation lead to pathological thrombosis. In vitro experiments have found that NETs provide skeletal support for platelets, red blood cells and procoagulant molecules to promote thrombosis. The protein components contained in NETs activate the endogenous coagulation pathway to promote thrombosis. Therefore, NETs play an important role in the formation of arterial thrombosis, venous thrombosis and cancer-related thrombosis. This review will systematically summarize and explain the study of NETs in thrombosis in animal models and in vivo experiments to provide new targets for thrombosis prevention and treatment.

7 DOACs: a new skyline in cancer-associated thrombosis resistant to heparin. A clinical case of seminoma in BEP chemotherapy protocol solved with edoxaban

Aims TEV is a common cancer complication with 20% incidence. LMWH is the standard therapy for efficacy, safety and ease of use. However, some scenarios are deeply challenging for intercurrent prothrombotic anticancer drugs. Methods A 35-year-old man reported dysphagia, EGDS: oesophagus ulcers, thyroid echography: thoracic mass compressing proximal borders. Vascular ultrasound: thrombosis of left internal giugular, subclavian, axillary and brachial veins; he began enoxaparin 6000 IU ×2/die (65 kg). CT-scan: solid anterior–superior mediastinum vascularized mass (16 × 13 cm) incorporating great thoracic vessels with 20 cm cranio-caudal longitudinal extension with trachea dislocation. PET-CT: massive superior-anterior mediastinum pathological 18F-FDG accumulation suggestive for malignancy. Lung perfusion scan: absence of left lung perfusion. Angio-CT: showed compression of pulmonary artery trunk and of branches. He presented marked asthenia, sweating and presyncope. D-dimer: 6026 µg/L, NT-proBNP: 1417 pg/mL. Mediastinum biopsy exhibited seminoma (ki67+: 65%), he started BEP Protocol (etoposide, cisplatin, bleomycin). TTE: periaortic cuff from mediastinum mass which ab extrinseco compressed pulmonary artery trunk and branches with occlusion of left one, right chambers dilatation, sovra-epatic veins and inferior vena cava (21 mm) ectasia, decreased inspiratory collapse, pulmonary hypertension (SPAP: 52 mmHg), EF: 55%. After 2 months of enoxaparin, vein ultrasound: persistent DVT and positive CUS. So, we replaced enoxaparin with edoxaban 60 mg/die. After 2 months of edoxaban, overall regression of vein thrombosis with minimal residual thrombosis of left internal giugular vein; D-dimer: 1554 µg/L. Results After 2 months of BEP Protocol, CT-scan: decrease mediastinum mass (6 × 12 cm) dimensions. Conclusions Cancer associated thrombosis is a frequent complication, worsening mortality, morbidity and decision-making. Cancer stage and drugs favour development of severe thrombosis, not solvable with LMWH, the cornerstone of anticoagulant therapy in cancer-related thrombosis. DOACs appear as a new and successful therapeutical option, especially in the most challenging cases of highly thrombotic profile after ‘heparin failure’.

Cancer Patients’ Experiences of the Diagnosis and Treatment of Incidental Pulmonary Embolism

Background: The diagnosis of symptomatic cancer-associated thrombosis often causes distress and alarm for patients, especially for those unaware of the risk, or the signs and symptoms to look out for. There are few data about cancer patients’ experiences of incidentally diagnosed pulmonary embolism (IPE), where lack of warning (recognised signs, symptoms) may cause delayed diagnosis and aggravate distress.Objectives: To explore cancer patients’ experience of the diagnosis of and living with incidental pulmonary embolism treated with anticoagulation. Methods: A qualitative study using modified grounded theory approach. Semi-structured interviews were conducted as part of a mixed- methods prospective observational survey study of consenting patients with IPE. Data were subjected to thematic analysis. The qualitative findings are presented. Findings: Eleven participants were interviewed (mean age 68.3 years, range 38-82 years; various forms of cancer and stages). Three major themes and one cross-cutting theme were generated. Theme (1): IPE is experienced in the context of cancer and concomitant comorbidities. Issues are understood in the shadow of – and often overshadowed by - current serious illness. Theme (2): Being diagnosed with IPE. Misattribution to cancer or other comorbidities caused delay in help-seeking and diagnosis. Theme (3): Coping with anticoagulation. Participants’ incorporated anticoagulation treatment and its effects into their daily routine with acceptance and stoicism. Finally, the cross-cutting theme relates to a lack of information and uncertainty, contributing to distress throughout the experienceConclusion: The diagnosis of IPE was upsetting and unexpected. Expert and timely information was valued by those with IPE. Education called for about the increased risk of cancer-associated thrombosis and the signs and symptoms to be aware of.

The regulatory mechanism of neutrophil extracellular traps in cancer biological behavior

As the predominant host defense against pathogens, neutrophil extracellular traps (NETs) have attracted increasing attention due to their vital roles in infectious inflammation in the past few years. Interestingly, NETs also play important roles in noninfectious conditions, such as rheumatism and cancer. The process of NETs formation can be regulated and the form of cell death accompanied by the formation of NETs is regarded as “NETosis”. A large amount of evidence has confirmed that many stimuli can facilitate the release of NETs from neutrophils. Furthermore, it has been illustrated that NETs promote tumor growth and progression via many molecular pathways. Meanwhile, NETs also can promote metastasis in many kinds of cancers based on multiple studies. In addition, some researchs have found that NETs can promote coagulation and cancer-associated thrombosis. In the present review, it will highlight how NETosis, which is stimulated by various stimuli and signaling pathways, affects cancer biological behaviors via NETs. Given their crucial roles in cancer, NETs will become possible therapeutic targets for inhibiting proliferation, metastasis and thrombosis in cancer patients.