Most DVT patients are currently treated with low molecular weight heparin and warfarin, with few receiving additional treatment to remove the thrombus by thrombolysis or thrombectomy. Anticoagulation allows slow natural resolution of the thrombus, but does not reduce the incidence of post-thrombotic syndrome or accelerate resolution, and may result in excessive bleeding [32–34]. Thrombolytic agents are contraindicated in some cases, and this treatment also increases the risk of bleeding [35]. Recent advances in catheter-directed thrombolysis with or without pharmacomechanical adjuncts may increase the efficacy of lysis, reduce the amount of lytic agent used, and with it, the risk of bleeding. Catheter-directed or pharmacomechanical thrombolysis has been used in selected patients with symptomatic iliofemoral DVT [36]. There is, however, a paucity of data regarding their effectiveness in patients without cancer, and currently no study examining their effect in this group of patients.

Although therapies under development for the treatment of DVT often aim to target specific molecular pathways, it may be that complex pathologies (such as Trousseau’s syndrome) would be better combatted using treatments with multiple actions [15]. Heparin, for example, is the preferred treatment for patients with Trousseau’s syndrome, while vitamin K antagonists, or thrombin inhibitors, appear insufficient in many cases [15]. The primary actions of heparin are to irreversibly inactivate coagulant factor Xa and thrombin, which impairs platelet activation and thrombus formation. Heparin may also reduce cancer-induced thrombus formation by: (i) activating heparin cofactor II and protein C [37, 38]; (ii) inhibiting the adhesion molecules L- and P-selectin [39, 40]; and (iii) stimulating the release of TF pathway inhibitor [41]. Low molecular weight heparin, which can be administered in a single dose, is another treatment option for Trousseau’s syndrome patients; the CLOT trial, for instance, showed that low molecular weight heparin (versus warfarin) reduced the risk of recurrent thromboembolism in cancer patients, without increasing the risk of bleeding [42]. Novel oral anti-coagulants are under active investigation in clinical trials [43]. Such agents may ultimately prove effective in the prevention and treatment of venous thrombosis in cancer patients, but the effects of such agents should first be thoroughly investigated in large-scale randomised clinical trials, and compared with established treatments [44]. Combination therapies may also eventually come to fruition, although these may carry an increased incidence of side effects [15]. Future studies could investigate therapeutic targeting of the multiple pathways that regulate cancer-induced thrombus formation.

Venous thrombi resolve naturally with time, but this is a slow process that takes more than 6 months in man [45]. Veins that recanalise rapidly have preserved valve integrity and a lower incidence of venous reflux [46, 47]. Rapid recanalisation times are consequently associated with favourable clinical outcome [48]. Thrombus resolution is a complex process of intravascular remodelling, similar to the formation of granulation tissue that is crucial for wound healing [49]. Natural resolution involves recruitment of white cells (initially neutrophils then monocytes), endothelial cells and their progenitors, and myofibroblasts [49]. Vein recanalisation is achieved through a combination of new blood vessel formation in the thrombus and thrombus contraction from the vein wall [49]. The endothelial-lined channels that form within and around the thrombus coalesce and form larger vascular channels, which together with thrombus contraction help to restore blood flow [49]. Vein recanalisation and thrombus resolution are accelerated when the angiogenic response to thrombus formation is stimulated in the thrombus and surrounding vein [50–52].

Mechanisms that regulate cancer-associated thrombus formation are complex and multi-faceted. Cancer chemotherapies can increase the incidence of venous thrombosis, but the mechanisms responsible for this effect are not fully characterised. Although priority should be given to prevention of disease progression and increased survival in cancer patients, potentially pro-thrombotic effects of cancer treatments should be carefully considered in the clinic. A better understanding of the mechanisms that regulate cancer-induced thrombus formation and resolution may lead to the development of novel treatments for patients such as those with Trousseau’s syndrome.