Article

Exocrine pancreas cancer and thromboembolic events: A systematic literature review

Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Journal of the National Comprehensive Cancer Network: JNCCN (Impact Factor: 4.24). 07/2012; 10(7):835-46.
Source: PubMed

ABSTRACT Exocrine pancreas cancer continues to represent a significant therapeutic challenge, with high rates of mortality and morbidity, including from thromboembolic events, which have long been described as a frequent complication of the disease. This article provides a systematic and comprehensive review of the literature to address the clinical and pathologic features recognized in pancreas cancer pertaining to thrombosis, and to discuss ongoing investigations of prophylactic anticoagulation in the hopes of improving disease-related outcomes.

0 Followers
 · 
137 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Tissue factor (TF), the physiologic initiator of coagulation, is over-expressed in pancreatic cancer, and is associated with a pro-coagulant and pro-angiogenic state. We hypothesized that in patients with pancreaticobiliary cancers (PBC), elevated circulating microparticle-associated TF (MP-TF) activity would be associated with thrombosis and worsened survival. Clinical data and plasma were obtained for consecutive patients with PBC seen at Roswell Park Cancer Institute from 2005-08. MP-TF activity levels were measured using a TF-dependent FXa generation assay. The study population comprised 117 patients, including pancreatic (n=80), biliary (n=34) or unknown primary histologically consistent with PBC (n=3). Of these, 52 patients (44.5%) experienced thromboembolism, including pulmonary embolism (n=15), deep venous thrombosis (n=21) and other arterial or venous events (n=32). Mean TF was 2.15 (range 0.17- 31.01) pg/mL. Median survival was 98.5days for MP-TF activity ≥2.5pg/mL versus 231days for MP-TF activity<2.5pg/mL (p<0.0001). In multivariate analysis, elevated MP-TF activity was associated with both VTE (OR 1.4, 95% CI 1.1-1.6) and mortality (HR 2.5, 95% CI 1.4-4.5). Elevated circulating MP-TF activity is associated with thrombosis and worsened survival in patients with PBC. MP-TF activity as a prognostic biomarker warrants further prospective evaluation.
    Thrombosis Research 07/2013; 132(2). DOI:10.1016/j.thromres.2013.06.026 · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Rates of venous thromboembolism (VTE) vary substantially between cancer patients. Multiple clinical risk factors including primary site of cancer and systemic therapy, and biomarkers including leukocyte and platelet counts and tissue factor are associated with increased risk of VTE. However, risk cannot be reliably predicted based on single risk factors or biomarkers. New American Society of Clinical Guidelines recommend that patients with cancer be assessed for VTE risk at the time of chemotherapy initiation and periodically thereafter. This narrative review provides an update on risk stratification approaches including a validated Risk Score. Potential applications of risk assessment including targeted thromboprophylaxis are outlined. © 2014 Elsevier Ltd. All rights reserved.
    Thrombosis Research 05/2014; 133 Suppl 2:S35-8. DOI:10.1016/S0049-3848(14)50006-0 · 2.43 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Microvascular thrombosis indicates a pathological occlusion of microvessels by fibrin- and/or platelet-rich thrombi. It is observed during systemic infections, cancer, myocardial infarction, stroke, neurodegenerative diseases and in thrombotic microangiopathies. Microvessel thrombosis can cause greatly differing symptoms that range from limited changes in plasma coagulation markers to severe multi-organ failure. Because microvessel thrombi are difficult to detect and often occur only transiently, their importance for disease development and host biology is likely markedly under-appreciated. Recently, clear indications for a biological basis of microvascular thrombosis have been obtained. During systemic infections microvessel thrombosis can mediate an intravascular innate immune response (immunothrombosis). This biological form of thrombosis is based on the generation of fibrin inside blood vessels and is critically triggered by neutrophils and their interactions with platelets which result in the release of neutrophil extracellular traps (extracellular nucleosomes). Immunothrombosis is critically supported by neutrophil elastase and the activator molecules of blood coagulation tissue factor and factor XII. Identification of the biological driving forces of microvascular thrombosis should help to elucidate the mechanisms promoting pathological vessel occlusions in both microvessels and large vessels.
    Thrombosis Research 05/2014; 133 Suppl 1(Suppl 1):S35-7. DOI:10.1016/j.thromres.2014.03.016 · 2.43 Impact Factor
Show more