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Mechanisms of Disease: the impact of antithrombotic therapy in cancer patients

Nature Clinical Practice Oncology volume 2, pages 356–363 (2005)Cite this article

Abstract

Venous thromboembolism is a common complication in patients with malignant disease. It is associated with a systemic hypercoagulable state that is secondary to tumor elaboration of tissue factor (the physiological initiator of blood coagulation), activation of other procoagulant mechanisms and downregulation of anticoagulant mechanisms. The consequent generation of activated coagulation serine protease in the peritumoral environment influences tumor growth, invasion, metastasis and angiogenesis. The use of antithrombotic agents, such as the low-molecular-weight heparins, might influence survival in cancer patients through several mechanisms. These mechanisms include a reduction in the frequency of overt and silent fatal thromboembolic events, interference with the activation of blood coagulation and generation of coagulation serine proteases that affect the tumor phenotype, and direct cellular effects of heparin on both epithelial and endothelial tumor elements.

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Figure 1: Tissue factor (TF) is a cellular transmembrane receptor with an internal cytplasmic tail.
Figure 2: Survival rates in the Fragmin® Advanced Malignancy Outcome Study (FAMOUS).
Figure 3: Survival rates in a subgroup of patients in the Fragmin® Advanced Malignancy Outcome Study (FAMOUS).
Figure 4: Low molecular weight heparins (LMWH) may prolong survival in cancer patients.

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Author information

Authors and Affiliations

  1. Clinical Trials Centre for Surgical Sciences,

    Gloria A Petralia, Nick R Lemoine & Ajay K Kakkar

  2. Institute of Cancer and the Cancer Research UK Clinical Centre,

    Gloria A Petralia, Nick R Lemoine & Ajay K Kakkar

  3. Centre for Surgical Sciences,

    Gloria A Petralia, Nick R Lemoine & Ajay K Kakkar

  4. Barts and The London School of Medicine, UK

    Gloria A Petralia, Nick R Lemoine & Ajay K Kakkar

Authors
  1. Gloria A Petralia
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  2. Nick R Lemoine
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  3. Ajay K Kakkar
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Corresponding author

Correspondence to Ajay K Kakkar.

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The authors declare no competing financial interests.

Glossary

SUPERFICIAL THROMBOPHLEBITIS

A condition in which a blood clot forms in a vein near the surface of the body as a result of inflammation

MONOCYTES

Phagocytic white blood cells that can develop into macrophages following migration into tissue

MEGAKARYOCYTE

A giant bone-marrow cell that generates platelets

THROMBOCYTHEMIA

A myeloproliferative disorder that is characterized by overproduction of platelets in the bone marrow

SHORT HAIRPIN RNA

A short sequence of RNA that forms a hairpin structure and can be used to silence gene expression at the transcriptional level

RNA INTERFERENCE

Use of double-stranded RNA to interfere with normal RNA processing, causing rapid degradation of endogenous RNA and precluding translation; a simple method of studying the effect of absence of a gene product

NUDE MICE

Hairless mice homozygous for a recessive mutation of the nu gene; they have no thymus and cannot generate mature T lymphocytes

G PROTEIN

GTP-binding regulatory proteins in the cell membrane, which act as intermediaries between cell-surface receptors and intracellular enzymes, enabling regulation of enzyme activity in response to extracellular signals

CHORIOALLANTOIC MEMBRANE

A chick extraembryonic membrane that is often used as an in vivo model to study the formation of new blood vessels

INTERNATIONAL NORMALIZED RATIO

A method used to compare the activity of different batches of thromboplastin

HAZARD RATIO (HR)

The relative likelihood of experiencing a particular event; an HR of 0.5 indicates that one group has half the risk of the other group

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Petralia, G., Lemoine, N. & Kakkar, A. Mechanisms of Disease: the impact of antithrombotic therapy in cancer patients. Nat Rev Clin Oncol 2, 356–363 (2005). https://doi.org/10.1038/ncponc0225

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  • DOI: https://doi.org/10.1038/ncponc0225

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