The association between cancer and venous thrombosis was first recognized more than 140 years ago by Armand Trousseau [Citation1]. He wrote that ‘spontaneous coagulation is common in cancerous patients’ because of a ‘special crasis of the blood.’ Later studies have confirmed that cancer significantly increases the risk of venous thromboembolism, which is particularly high during the first few months following diagnosis and in the presence of distant metastasis [Citation2]. Thrombotic complications are frequently observed in patients with solid tumors, such as cancer of the pancreas, lung, stomach, breast, ovaries, and the brain [Citation3,Citation4] In a study by Prandoni et al. an almost 10-fold increased risk of overt cancer was observed in patients with recurring idiopathic deep vein thrombosis [Citation5]. Furthermore, in a study by Sörensen et al. a diagnosis of cancer at the same time as or within 1 year after an episode of venous thromboembolism was associated with an advanced stage of cancer [Citation6]. In addition, patients with an unprovoked venous thromboembolism are more likely to have an underlying occult malignancy when compared to those with a known risk factor for venous thromboembolism [Citation5].
The mechanisms for venous thromboembolism in cancer are multifactorial, and include hypercoagulability, vessel wall injury, and stasis [Citation7]. The coagulation system is activated in patients with malignancy. The prothrombotic mechanisms often relate to the host response to the tumor, including inflammation, necrosis, and hemodynamic factors, that can also be exacerbated by chemotherapy. In addition, tumor-specific clot-promoting mechanisms, such as the expression of procoagulant and fibrinolytic activities by the tumor cells, and interaction with endothelial cells and blood cells, play a role in the pathogenesis of thrombosis in patients with cancer. Venous vessel wall injury can be caused by surgery and by cell-to-cell interactions. Finally, venous stasis predisposes to thromboembolism by diluting and reducing the clearance of activated coagulation factors, and may cause endothelial cell damage.
The most important consequence of venous thromboembolism in cancer patients is its effect on mortality. The occurrence of deep vein thrombosis or pulmonary embolism in the general population is associated with a decreased survival [Citation8]. Patients with cancer and a venous thromboembolism have much higher mortality compared to cancer patients without thrombosis [Citation9]. In a study by Sörensen et al., when analyzing prognosis, the group with cancer at the time of venous thromboembolism had a 1-year survival rate of 12%, as compared with 36% in the control group (p < 0.001) [Citation9]. Furthermore, patients in whom cancer was diagnosed within 1 year after an episode of venous thromboembolism had a significantly inferior survival at 1 year. In a prospective observational study on 4466 patients with cancer receiving chemotherapy, causes of death were analyzed, and among non-cancer causes of death, 9% of the patients died due to thrombosis, making it the leading contributor to death [Citation10].
In the study by Anderson et al. in the current issue of Leukemia and Lymphoma, the authors evaluated how and to what extent concomitant or antecedent diagnosis of deep vein thrombosis affected overall survival among more than 400 000 males with cancer [Citation11]. They make two important observations. First, patients with a concomitant deep vein thrombosis and cancer had a significant 38% higher risk of dying, compared to patients with cancer but without deep vein thrombosis. Those patients with lung, gastric, prostate, bladder, and renal cancer had the highest excess mortality. This may be caused by differences in tumor stage, as well as underlying comorbidity and lifestyle factors. Second, risk of death was significantly increased among patients with cancer diagnosed with deep vein thrombosis 1, 1–5, and even more than 5 years prior to their cancer diagnosis. As the authors discuss, this indicates that deep vein thrombosis is not only a serious consequence of a cancer diagnosis but that similar genetic or environmental risk factors may be associated with deep vein thrombosis and poorer cancer survival.
We have come a long way since Trousseau. However, the association of prognosis in cancer and venous thromboembolism is complex and not completely understood. Thorough analyses on causes of death among patients with cancer with a concomitant and antecedent thrombosis could elucidate the underlying mechanism behind the findings of Anderson et al. [Citation11]. The importance of anticoagulation therapy in patients with cancer cannot be emphasized enough. In addition, future studies will hopefully increase our understanding of the mechanisms and biology of the hypercoagulable state and cancer and its prognosis, and help us to better define those patients with idiopathic venous thrombosis who should be subject to in-depth clinical examination for cancer.
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