Cancer-Associated Atherothrombosis: The Challenge

Abstract

The association between venous thrombosis and malignancy, having typical features of a paraneoplastic syndrome, has been established for a century. Currently, it is recognized that arterial thromboembolism (ATE) may also behave as a paraneoplastic syndrome. Recent matched cohort studies, systematic reviews, and observational studies concur in showing an increased incidence of acute coronary events, ischemic stroke, accelerated peripheral arterial disease, and in-stent thrombosis during the 6-month period before cancer diagnosis, peaking for 30 days immediately before cancer diagnosis. Cancer patients with ATE are at higher risk of in-hospital and long-term mortality as compared with noncancer patients. In the present review, we focus on the epidemiology, clinical variants and presentation, morbidity, mortality, primary and secondary prevention, and treatment of cancer-associated ATE. The awareness that cancer can be a risk factor for ATE and that cancer therapy can initiate cardiovascular complications make it mandatory to identify high-risk patients, modify preexistent cardiovascular risk factors, and adopt effective antithrombotic prophylaxis. For ATE prophylaxis, modifiable patient-related risk factors and oncology treatment–related factors are levers for intervention. Statins and platelet antiaggregants have been studied, but their efficacy for prevention of cancer-associated ATE remains to be demonstrated. Results of revascularization procedures for cancer-associated ATE are worse than for ATE in noncancer patients. It is important that a multidisciplinary approach is adopted for making informed decisions, by involving the vascular surgeon, interventional radiologist, oncologist, and palliative medicine, as well as the patients and their family.

Development of an algorithm for identifying paraneoplastic ischemic stroke in association with lung, pancreatic, and colorectal cancer

“…It is well established that the risk of both venous 5 and arterial thromboembolism 1 is increased in newly diagnosed malignancies. Arterial thromboembolism in cancer frequently presents as ischemic stroke.…”

“…Arterial thromboembolism in cancer frequently presents as ischemic stroke. 1 , 7 Typically, paraneoplastic ischemic stroke affects multiple if not all vascular territories of the brain. 37 Due to often relentlessly recurring ischemic events, it is associated with a bleak prognosis.…”

“…Cancer-associated paraneoplastic hypercoagulability frequently results in arterial thromboembolism into the brain, 1 which thus can be referred to as paraneoplastic ischemic stroke. Upon autopsy, cerebral post-ischemic lesions can be detected in up to 15% of cancer patients.…”

“… 3 Paraneoplastic ischemic stroke may even be the first symptom of occult cancer. 4 In known cancer, the frequency of paraneoplastic venous as well as arterial thromboembolism 1 , 5 such as ischemic stroke 6 – 8 peaks early after diagnosis of cancer and decreases thereafter, indicating that cancer treatment prevents additional events. Compared to cerebral ischemia with conventional risk factors, paraneoplastic ischemic stroke often involves multiple territories and is associated with a high stroke-associated morbidity and mortality.…”

Inhibition of Factor XI: A New Era in the Treatment of Venous Thromboembolism in Cancer Patients?

“…An increasing number of studies have examined the link between VTE events and atherothrombosis, including in patients with cancer [67,68]. As with VTE, arterial thrombosis also involves exposure to TF during the rupture of an atherosclerotic plaque or its expression on activated monocytes or TF-bearing microvesicles, triggering the generation of small amounts of thrombin [68,69]. Thrombus expansion depends on the amplification of coagulation via thrombin-mediated activation facilitated by FXI, as well as thrombin itself, a potent platelet agonist [70].…”