Abstract
Cancer induces a systemic hypercoagulable state that elevates the baseline thrombotic
risk of affected patients. This hypercoagulable state reflects a complex interplay
between cancer cells and host cells and the coagulation system as part of the host
response to cancer. Although the tissue factor (TF)/factor VIIa pathway is proposed
to be the principal initiator of fibrin formation in cancer patients, clinical studies
have not shown a consistent relationship between circulating TF levels (often measured
as plasma microvesicle-associated TF) and the risk of thrombosis. A renewed interest
in the role of the contact pathway in thrombosis has evolved over the past decade,
raising the question of its role in the pathogenesis of thrombotic complications in
cancer. Recent observations have documented the presence of activation of the contact
system in gastrointestinal, lung, breast and prostate cancers. Although the assays
used to measure contact activation differ, and despite the absence of standardization
of methodologies, it is clear that both the intrinsic and extrinsic pathways may be
activated in cancer. This review will focus on recent findings concerning the role
of activation of the contact system in cancer-associated hypercoagulability and thrombosis.
An improved understanding of the pathophysiology of these mechanisms may lead to personalized
antithrombotic protocols with improved efficacy and safety compared with currently
available therapies.
Keywords
contact activation - cancer - hypercoagulability - intrinsic pathway - thrombosis
