Pancreatic cancer and thromboembolic disease

doi:10.1016/S1470-2045(04)01606-7

The Lancet Oncology

Volume 5, Issue 11, November 2004, Pages 655-663

https://doi.org/10.1016/S1470-2045(04)01606-7 Get rights and content

Summary

Thromboembolic disease is a common complication of pancreatic cancer and is causally associated with the generation of an intrinsic hypercoagulable state. Pancreatic-cancer cells activate platelets and express several procoagulant factors, including tissue factor and thrombin. The activation of coagulation is not simply an epiphenomenon, but might also be related to enhanced tumour growth and angiogenesis. Clinical manifestations of thromboembolic disease in pancreatic cancer include deep venous thrombosis, pulmonary embolism, disseminated intravascular coagulation, portal vein thrombosis, and arterial thromboembolism. Reported incidences of disease range from 17% to 57%. Treatment options include warfarin and low-molecular-weight heparins. Studies over the past decade suggest that long-term use of these heparins in both primary and secondary prevention of venous thromboembolic disease improves outcomes in comparison with warfarin. Further research is needed to understand better the morbidity and mortality associated with this disease in pancreatic cancer and to optimise strategies of prevention and treatment.

Section snippets

A prothrombotic and proangiogenic state in pancreatic cancer

The pathogenesis of the prothrombotic state in cancer is complex, but seems to be associated mainly with the generation of an intrinsic hypercoagulable state that seems to be essential for tumour growth and metastasis. Data in vitro and in vivo shows that the coagulation cascade is activated in human pancreatic carcinoma. Furthermore, proteins that are part of this cascade are important not only for systemic coagulation, but also for other tumour processes such as angiogenesis. Initiation of

Clinical presentation

Pancreatic cancer has long been associated with an increased incidence of thromboembolic disease. Incidence varies among reports and is probably related to other factors including use of chemotherapy, surgical procedures, and presence of an in-dwelling catheter. However, venous thromboembolism can also be the first manifestation of pancreatic cancer. Cancer diagnosed at the same time as, or within 1 year of, an episode of venous thromboembolic disease is associated with an advanced stage, and

Therapy

Thromboembolic disease leads to a poor outlook for patients with cancer.35, 47 At present, the standard treatment for acute venous thromboembolism is initial short-term treatment with a low-molecular-weight heparin or with an unfractionated heparin, followed by long-term therapy with an oral anticoagulant.⁵⁸ Use of filters for the inferior vena cava as initial therapy lowers the incidence of pulmonary embolism, but is associated with an increase in recurrent deep venous thrombosis⁵⁹ and should

Conclusion

Pancreatic cancer is associated with a high risk of developing thromboembolic disease and is related mainly to the generation of an intrinsic hypercoagulable state as a result of tumour induction of platelet aggregation, and of expression of various procoagulant factors including tissue factor and thrombin. Circulating carcinoma mucins can induce platelet-rich microthrombi without thrombin, a process inhibited by heparins but not by warfarin. Activation of the coagulation system seems

Search strategy and selection criteria

Data for this review was identified by searches of MEDLINE, PubMed, and the abstract database of the American Society of Clinical Oncology using the search terms “pancreatic cancer”, “thrombosis”, “embolism”, and “anticoagulation”. Only papers published in English between 1995 and 2003 were included.

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ReviewPancreatic cancer and thromboembolic disease

Summary

Section snippets

A prothrombotic and proangiogenic state in pancreatic cancer

Clinical presentation

Therapy

Conclusion

Search strategy and selection criteria

J Thromb Haemost

J Am Coll Surg

Trends Cardiovasc Med

Biochim Biophys Acta

Eur J Surg Oncol

J Biol Chem

Blood

Lancet Oncol

Cancer Treat Rev

Am J Med Sci

Am J Surg

Int J Radiat Oncol Biol Phys

Cardiovasc Surg

Blood

Chest

Ann Oncol

Lancet

J Vasc Interv Radiol

Blood

Lancet

Lancet

Am J Med

Lectures on clinical medicine

Thrombophlebitis in cancer

Practitioner

Cancer statistics, 2004

CA Cancer J Clin

Improvements in survival and clinical benefit with gemcitabine as first-line therapy for patients with advanced pancreas cancer: a randomized trial

J Clin Oncol

Carcinoma and venous thrombosis: the frequency of association of carcinoma in the body or tail of the pancreas with multiple venous thrombosis

Am J Cancer

Risk factors for deep vein thrombosis and pulmonary embolism: a populationbased case-control study

Arch Intern Med

Biomedicine: clotting factors build blood vessels

Science

Tissue factor controls the balance of angiogenic and antiangiogenic properties of tumour cells in mice

J Clin Invest

Tissue factor expression in breast cancer tissues: its correlation with prognosis and plasma concentration

Br J Cancer

Tissue factor expression and metastatic potential of colorectal cancer

Thromb Haemost

Expression of tissue factor in non-small-cell lung cancers and its relationship to metastasis

Br J Cancer

Tissue factor expression correlates with histological grade in human pancreatic cancer

Br J Surg

Localization of blood coagulation factors in situ in pancreatic carcinoma

Thromb Haemost

A characterization of the coagulant and fibrinolytic profile of human pancreatic carcinoma cells

Haemostasis

Pancreatic cancer complicated by disseminated intravascular coagulation associated with production of tissue factor

J Gastroenterol

Review
Pancreatic cancer and thromboembolic disease