[Thromboembolic risk associated with use of angiogenesis inhibitors used for the treatment of cancers].
Among antiangiogenic agents, thalidomide is not the most potent nor the most specific even so when venous thromboembolic events have been reported with the prescription of thalidomide in multiple myeloma. This side effect has been related to the antiangiogenic effect of this immunomodulator. In keeping with this observation venous thromboembolic events have been reported in other indications of thalidomide and with thalidomide analogues (Lenalidomide and Actimid). The thrombotic side effects are mostly venous but arterial thrombotic events are also observed with the use of these molecules. With the other and more specific antiagiogenic agents an increase in thrombotic events are also observed. This increase was not immediately evident since the situation in which they are prescribed (metastatic cancers) are already characterized by a high rate of thrombotic events. The prothrombotic effect of antiangiogenic agents are probably linked to an effect on endothelium (decrease of antithrombotic activities and stimulation of a prothrombotuic state). The other sides effects of antiangiogenic agents (hemorrhages, hypertension, proteinuria, microangiotpahia, delay in scaring) are also probably related to endothelial effects. The prothrombotic effect of antoangiogenic agents appears as potentiating the prothrombotic conditions of the disease (myeloma, cancer) and the prothombotic effects of the associated treatments (chemotherapy, high dose corticosteroids, erythropoietin). The increased thrombotic risk linked to prescription of antiangiogenic agents and specially of thalidomide and analogues for multiple myeloma is such that it is recommended to associate a preventive antithrombotic treatment. Some efficacy has been reported with the use of aspirin, oral anticoagulant or low molecular weight heparin. No head to head comparative trial do not allow to prefer one strategy. From published data full dose oral anticoagulants appear to confer the highest hemorrhagic risk and perhaps low molecular weight heparin the best benefit-risk ratio.
Drouet
L
L
Service angiohematologie, clinique des antithrombotiques d'Ile-de-France, hôpital Lariboisière, 2, rue Ambroise-Paré, 75475 Paris cedex 10, France. ludovic.drouet@lrb.aphp.fr <ludovic.drouet@lrb.aphp.fr>
D020533:Angiogenesis Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy*; D012307:Risk Factors; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D013923:Thromboembolism / Q000139:chemically induced* / Q000209:etiology / Q000503:physiopathology; D054556:Venous Thromboembolism / Q000139:chemically induced / Q000503:physiopathology
D020533:Angiogenesis Inhibitors; D013792:Thalidomide