Trousseau's syndrome: multiple definitions and multiple mechanisms

Abstract

In 1865, Armand Trousseau noted that unexpected or migratory thrombophlebitis could be a forewarning of an occult visceral malignancy. An analysis by Sack and colleagues in 1977 extended the term Trousseau's syndrome to include chronic disseminated intravascular coagulopathy associated with microangiopathy, verrucous endocarditis, and arterial emboli in patients with cancer, often occurring with mucin-positive carcinomas. In recent times the term has been ascribed to various clinical situations, ranging all the way from these classic descriptions to any kind of coagulopathy occurring in the setting of any kind of malignancy. These multiple definitions of Trousseau's syndrome are partly the consequence of multiple pathophysiologic mechanisms that apparently contribute to the hypercoagulability associated with cancer. Even the classic syndrome probably represents a spectrum of disorders, ranging from exaggerated fluid-phased thrombosis dependent on prothrombotic agents such as tissue factor to a platelet-and endotheliumum-based selectin-dependent microangiopathy associated with mucinproducing carcinomas, along with thrombin and fibrin production. Also considered here are recent hypotheses about genetic pathways within tumor cells that might trigger these thrombotic phenomena, and the reasons why therapy with heparins of various kinds remain the preferred treatment, probably because of their salutary actions on several of the proposed pathologic mechanisms.(Blood.

The role of platelet activation in tumor metastasis

“…A first step is to find a cancer type, where cancer progression is shown to be dependent on platelet activation. Platelet microthrombi formation associated with Trousseau's syndrome is often found in mucinproducing carcinomas, yet the underlying mechanism remains unclear [2]. The current evidence that carcinoma mucins can induce platelet aggregation similar to Trousseau' syndrome [68] indicates that platelet activation plays an important role in mucin-carrying carcinomas.…”

“…Originally, Trousseau's syndrome describes the formation of venous and arterial platelet-rich microthrombi with secondary microangiopathic hemolytic anemia, and a frequent association with mucinous carcinomas [2]. Nowadays, Trousseau's syndrome applies to thrombotic events preceding the detection of an occult cancer.…”

“…In some cases, patients with occult malignancy develop deep vein thrombosis or pulmonary embolism [1]. In other cases, clinical findings may relate to disseminated intravascular coagulation (DIC) or to thrombohemorrhagic syndromes, which are commonly referred to as cancer coagulopathy [2,27]. The pathophysiology of thrombosis in cancer is complex but likely includes all aspects of Virchow's triad: stasis of blood, vascular trauma and hypercoagulability of blood itself [1,4].…”

“…Based on this broader definition of Trousseau's syndrome, several molecular mechanisms regulating tumor cell induced platelet aggregation were described [65-67]. Since thrombosis occurs in the setting of occult carcinomas, it is reasonable to expect that a factor produced by tumor cells is being released into the bloodstream, which is responsible for thrombotic propensity [2]. There were two main studies investigating Trousseau's syndrome in animal models [6,68].…”

“…Although the initial clinical observations of migratory thromboses and platelet-rich microthrombi are mostly associated with gastrointestinal malignancies, the majority of advanced cancer patients develop thrombotic abnormalities and hypercoagulable state [1][2][3][4].…”