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Table 1. Selected Factors Relevant to Pancreas Cancer and Thrombosis  

Molecular Associations
      Tissue factor36,42
      Thrombin-antithrombin III complex36
      Plasminogen activator inhibitor-137
      Platelet factor 438
      Tissue factor pathway inhibitor41
Clinical and Treatment Variables
      Hospitalization/sedentary status
      Venous access/catheterization
      Weight extremes14,21
      Blood type group A22
      Medications (erythropoietin-stimulating agents,13,14 chemotherapy,31–33 megestrol86)
      Comorbidities (heart, liver, and kidney disease; diabetes)

Table 2. Incidence of Thrombosis in Pancreas Cancer–Specific Cohorts  

Reference N Study Type %a Notes
Cubilla and Fitzgerald,2 1978 380 Retrospective 14 Histologically confirmed patients at MSKCCb from 1949–1972
Pinzon et al.,5 1986 130 Retrospective 6.9 Consecutive patients at MDACC; mucin production and body/tail location associated with thrombosis
Mandala et al.,3 2007 227 Retrospective 26 Patients with unresectable pancreas cancer in 3 clinical trials
Mitry et al.,6 2007 90 Retrospective 27 No survival differences between patients with and without thrombosis
Oh et al.,4 2008 75 Retrospective 5 Korean authors suggest possible ethnobiologic factors in relatively low incidence
Epstein et al.,75 2011 1915 Retrospective 36 Patients with pancreas cancer at MSKCC receiving chemotherapy
Mikal et al.,70 1950 100 Autopsy series 67 18% in head of pancreas, 49% in body/tail
Thompson et al.,71 1952 157 Autopsy series 31 25 single thromboses, 23 patients with multiple thromboses
Soederstroem and Bjersing,72 1963 50 Autopsy series 52 Included anatomy: inferior vena cava, pelvic and thigh veins
Lowe and Palmer,74 1967 100 Autopsy series 29 8% clinical, 21% autopsy
Mao et al.,73 1995 154 Autopsy series 19.4 Consecutive autopsies at 3 affiliated Ohio teaching hospitals
Blom et al.,1 2006 202 Prospective 108.3b Increased risk with body/tail tumors, chemotherapy, surgery, and metastatic disease

Abbreviations: MDACC, MD Anderson Cancer Center; MSKCC, Memorial Sloan-Kettering Cancer Center.
aPercentage incidence figures are relative to the individual specific study periods.
bIn 1000 patient years

Table 3. Randomized Trials of Primary Thromboprophylaxis in Pancreas Cancer  

Reference N Drug Chemotherapy Median Survival Notes
Maraveyas et al.,77 2009 123 Dalteparin Gemcitabine Lethal thrombosis and sudden death, 0% in dalteparin arm vs. 9% in control (P = .028); but “early death burden,” 7% vs. 11% (P = .62). No overall survival difference Reduction in primary end point of thrombosis (25% to 3.5% over first 100 d; 31% to 12% overall)
Riess et al.,79 2010 312 Enoxaparin Gemcitabine-based (+/– 5FU/cisplatin depending on performance status) 8 mo without enoxaparin, 8.3 mo with enoxaparin (P = .501); median follow-up time of 45 mo Closed early because of significant symptomatic thromboembolism reduction 9.9% vs. 1.3% at 3 mo (primary end point); at 12 mo: 15.1% vs. 5.0%
NCT00031837a 400 Dalteparin Systemic gemcitabine Pending (secondary end point) Pending results, primary end point is quality of life
NCT00662688a 136 Dalteparin Gemcitabine +/–capecitabine Pending (secondary end point) Pending results, primary end point is thromboembolic event rate
NCT00966277a 87 Dalteparin Investigator choice Pending (secondary end point) Pending results, primary end point is thromboembolic event rate identifier.

Table 4. Key Points in Pancreas Cancer Thrombosis and Anticoagulation  

  • Numerous clinical and molecular factors contribute to thrombogenicity in pancreas cancer.
  • The relatively high incidence of thrombosis and its contribution to morbidity and mortality in pancreas cancer calls for vigilance in diagnosis and treatment of these events.
  • Superficial vein thrombosis with proximity to the deep venous system should be treated with at least 4 weeks of anticoagulation (category 2B87) unless the thrombosis is catheter-associated and the catheter is removed.
  • Deep vein thrombosis, including pulmonary embolism, should be anticoagulated.b
  • Primary prophylactic anticoagulation of hospitalized patients with pancreas cancer is recommended.
  • Primary prophylactic anticoagulation of outpatients with pancreas cancer should be performed only in the context of a clinical trial.

aRisk of bleeding must always be considered in the decision to initiate anticoagulation.
bDuration of anticoagulation treatment for deep vein thrombosis is indefinite for as long as pancreas cancer is active, and low-molecular-weight heparin is recommended over warfarin.


Exocrine Pancreas Cancer and Thromboembolic Events: A Systematic Literature Review

  • Authors: Andrew S. Epstein, MD; Eileen M. O'Reilly, MD
  • CME Released: 7/7/2012
  • Valid for credit through: 7/7/2013, 11:59 PM EST
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Target Audience and Goal Statement

This activity is intended for primary care physicians, oncologists, gastrointestinal specialists, surgeons, and other physicians who care for patients with pancreatic cancer.

The goal of this activity is to evaluate the risks for thromboembolism among patients with pancreatic cancer as well as appropriate management of thromboembolism among these patients.

Upon completion of this activity, participants will be able to:

  1. Distinguish risk factors for thromboembolism among patients with pancreatic cancer
  2. Analyze recommendations for primary prophylaxis against thromboembolism among patients with pancreatic cancer
  3. Assess the best treatment for thromboembolism among patients with pancreatic cancer
  4. Evaluate outcomes improved with treatment of thromboembolism among patients with pancreatic cancer


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  • Andrew S. Epstein, MD

    Memorial Sloan-Kettering Cancer Center, New York, New York


    Disclosure: Andrew S. Epstein, MD, has disclosed no relevant financial relationships.

  • Eileen M. O'Reilly, MD

    Memorial Sloan-Kettering Cancer Center, New York, New York


    Disclosure: Eileen M. O'Reilly, MD, has disclosed no relevant financial relationships.


  • Kerrin M. Green, MA

    Assistant Managing Editor, Journal of the National Comprehensive Cancer Network


    Disclosure: Kerrin M. Green, MA, has disclosed no relevant financial relationships.

CME Author

  • Charles P. Vega, MD

    Health Sciences Clinical Professor; Residency Director, Department of Family Medicine, University of California, Irvine


    Disclosure: Charles P. Vega, MD, has disclosed no relevant financial relationships.

CME Reviewer

  • Nafeez Zawahir, MD

    CME Clinical Director, Medscape, LLC


    Disclosure: Nafeez Zawahir, MD, has disclosed no relevant financial relationships.

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Exocrine Pancreas Cancer and Thromboembolic Events: A Systematic Literature Review

Authors: Andrew S. Epstein, MD; Eileen M. O'Reilly, MDFaculty and Disclosures

CME Released: 7/7/2012

Valid for credit through: 7/7/2013, 11:59 PM EST


Abstract and Introduction


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. (JNCCN 2012;10:835–846)


Malignancy is a well-established risk factor for the development of venous thromboembolic events, both in hospitalized and ambulatory patients. Venous thromboembolic events are a major contributor to cancer- and treatment-related morbidity and mortality. Exocrine pancreas cancer is one of the most common malignancies associated with thrombosis, with most modern studies reporting incidence ranging from 5% to 27%.[1–6] Various patient-, treatment-, and increasingly recognized pancreas tumor–related factors contribute to thrombosis ( Table 1 ). Additionally, venous thromboembolic events have been found to portend a poorer prognosis in patients with pancreas cancer,[3] and have been implicated in early deaths after diagnosis.[7] Patients with various cancers diagnosed within 1 year of a thrombosis often have more extensive malignancy and worse outcome.[8] This association between thrombosis and shorter survival has been validated in a prospective case-control study by Mandala et al.[9] Anticoagulants may have treatment effects on the malignancy.[10,11]

Pancreas cancer is notoriously difficult to treat, and current chemotherapy regimens offer only modest disease control. Therefore, new therapies are clearly needed in hopes of impacting survival and treatment- and disease-related morbidity, including that from thrombosis. Although both superficial thrombophlebitis and arterial thromboses, such as myocardial infarction and stroke, have been well described in pancreas cancer, this article focuses on deep venous thromboses (hereafter referred to as thrombosis), because these predominate. The clinical and molecular underpinnings of thrombosis in patients with cancer are first discussed, highlighting key studies performed not only in pancreas cancer but also in other tumor types.