Venous thromboembolism (VTE) is a recognized complication of malignant disease and
multiple risk factors contribute to the hypercoagulability that commonly accompanies
malignancy. Thromboprophylaxis with antithrombotic drugs such as the low-molecular-weight
heparins (LMWHs) can be used to control the hypercoagulable state and to reduce the
incidence of VTE in patients with cancer. Clinical and biochemical data suggest that
LMWHs may also inhibit tumor growth, leading to a survival benefit in these patients.
Many cancer patients reportedly have a hypercoaguable state, with recurrent thrombosis
due to the impact of cancer cells and chemotherapy or radiotherapy on the coagulation
cascade. Studies have demonstrated that unfractionated heparin (UFH) or its low-molecular-weight
fractions interfere with various processes involved in tumor growth and metastasis.
Clinical trials in cancer patients with thromboembolic disorders have suggested a
clinically relevant effect of LMWHs (as compared with UFH) on the survival of cancer
patients with deep vein thrombosis. Similarly, the impact of warfarin on the survival
of cancer patients with thromboembolic disorders was demonstrated in certain tumor
types. Studies from our laboratory demonstrated a significant role for LMWH, warfarin,
anti-VIIa, and LMWH releasable tissue factor pathway inhibitor on the regulation of
angiogenesis, tumor growth, and tumor metastasis. However, a direct anticancer effect
for heparin in cancer patients without thrombosis still remains to be clinically documented.
KEYWORDS
Heparin - LMWH - TF/VIIa - TFPI - FGF2 - VEGF - cancer - coagulation - platelet -
angiogenesis - venous thrombosis - tumor dissemination
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Shaker A MousaPh.D.
Albany College of Pharmacy, 106 New Scotland Avenue
Albany, NY 12208-3492
eMail: mousas@acp.edu
