Risk stratification and prevention of venous thromboembolic disease in cancerology

Abstract

Patients with cancer are at high risk of venous thromboembolism (VTE), which leads to significantly increased morbidity and mortality. The rates of VTE vary between 0.5% and 20% per year and depend mainly on cancer-specific and treatment-related risk factors. Also individual risk factors related to patientś characteristics contribute to occurrence of cancer-associated VTE. Risk factors and biomarkers may help identify patients at high risk of developing VTE. In several clinical studies, risk factors for the occurrence of VTE events in patients with cancer have been investigated. The type and stage of cancer have been found to be amongst the most important risk factor for VTE occurrence. Also the histological grade of a tumor has been reported to be associated with the occurrence of VTE. In other investigations, venous diseases including a history of previous VTE, a history of superficial thrombophlebitis and the presence of varicose veins, have been associated with the risk of VTE. Some studies have recently focused on the identification of biomarkers or laboratory parameters predictive of future VTE occurrence. Parameters of blood count analysis (such as elevated leukocyte and platelet count and decreased hemoglobin) have turned out to be useful in risk stratification for VTE. In a prospective and observational cohort study, the Vienna Cancer and Thrombosis Study (CATS), associations between elevated levels and risk of future VTE have been found for D-dimer, prothrombin fragment 1 + 2, and soluble P-selectin and also for clotting factor VIII and the thrombin generation potential. The role of circulating microparticles for predicting risk of VTE in patients with cancer is unclear and has to be further investigated. Risk assessment models for prediction of VTE were developed including clinical and laboratory markers. First, Khorana and colleagues published a risk assessment score that incorporates readily available parameters: primary site of cancer, pre-chemotherapy platelet count of 350 × 109/L or more, haemoglobin level less than 10 g/dL and/or use of erythropoiesis stimulating agents, pre-chemotherapy leukocyte count of more than 11 × 109/L, and a body mass index of 35 kg/m2 or more. This score was validated in other studies. In CATS the score was expanded by adding two biomarkers (D-dimer and soluble P-selectin), and the prediction of VTE was considerably improved. In the high risk categories, patients with a VTE rate up to a 20% or higher within 6 months can be identified. In recent randomized controlled trials including cancer patients with different malignancies – without applying specific VTE risk assessment – it was shown that thromboprophylaxis is safe and effective. However, the overall VTE rates were low in these studies. To date, no data is available from interventional studies applying thromboprophylaxis in cancer patients categorized into high-risk groups on the basis of risk assessment scores. In conclusion, risk stratification for VTE is feasible in cancer patients. Further improvement in risk stratification would help better identify patients for VTE prevention using anticoagulant agents. However, interventional studies are needed to investigate the safety and efficacy of thromboprophylaxis in a high-risk cancer population.