Pathophysiological considerations to thrombophilia in the treatment of multiple myeloma with thalidomide and derivates.
Lenalidomide, a derivate of thalidomide, has recently been approved in Europe for the treatment of patients with multiple myeloma. Although the substance has a better effect/side-effect profile, especially with regard to teratogenicity and neurotoxicity, the rate of therapy-induced thrombosis seems comparable to thalidomide. The observed thromboembolic events were accompanied with a high rate of deleterious pulmonary embolism. Interestingly, the substances alone are not thrombogenic but combination with anthracyclines, dexamethasone or erythropesis-stimulating factors increases the risk considerably. As up to one third of patients treated with such combinations are affected, antithrombotic co-medication is highly recommended. This review elucidates the complex interactions between an activated coagulation-system in myeloma patients and the molecular effects of these drugs. This perception is important to choose the proper prophylactic co-medication without increasing the risk of bleeding, especially in first-line treatment, patients with high paraprotein-levels, or thrombopenia, either therapy-induced or due to bone-marrow infiltration.
Gieseler
Frank
F
Department of Internal Medicine, University Hospital of Kiel, Kiel, Germany. gieseler@oncology.uni-kiel.de
D000970:Antineoplastic Agents / Q000009:adverse effects*; D001777:Blood Coagulation / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000627:therapeutic use; D006801:Humans; D000077269:Lenalidomide; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy*; D015539:Platelet Activation / Q000187:drug effects; D018570:Risk Assessment; D013792:Thalidomide / Q000009:adverse effects / Q000031:analogs & derivatives*; D013917:Thrombin / Q000378:metabolism; D019851:Thrombophilia / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control; D013927:Thrombosis / Q000097:blood / Q000139:chemically induced* / Q000517:prevention & control; D016896:Treatment Outcome; D014841:von Willebrand Factor / Q000378:metabolism
D000970:Antineoplastic Agents; D005343:Fibrinolytic Agents; D014841:von Willebrand Factor; D013792:Thalidomide; D013917:Thrombin; D000077269:Lenalidomide