Patients with myeloma are at an increased risk for deep venous thrombosis and pulmonary embolism, particularly when known risk factors are present. These risk factors are:
— History of prior venous thromboembolism (VTE), immobilization, and/or dehydration
Genetic predispositions include high levels of homocysteine; deficiencies of antithrombin, protein C, and protein S; and factor V Leiden or prothrombin gene mutations.
The incidence of VTE is highest during the first 3 to 4 months following diagnosis and occurs in approximately 3% to 4% of patients receiving either dexamethasone alone or melphalan and prednisone (MP) but is much higher when newer agents are combined with dexamethasone and melphalan.
— A number of procoagulant abnormalities have been described in myeloma, including endothelial damage, paraprotein interference with fibrin structure, elevated von Willebrand multimers, elevated factor VIII, decreased protein S, and acquired activated protein C resistance.
The incidence of VTE with single-agent thalidomide is approximately 2% to 4% in newly diagnosed and in relapsed patients, comparable to that observed with dexamethasone alone or MP, implying that thalidomide alone does not increase the risk of VTE.
— However, the risk of VTE increases significantly when thalidomide is combined with either dexamethasone, melphalan, doxorubicin, or cyclophosphamide, or with other multiagent chemotherapy.
— Most VTEs occur within the first 60 days of therapy.
Single-agent lenalidomide does not appear to increase VTE, at least not in the setting of myeloma relapse, but it is associated with a marked increased in VTE risk when lenalidomide is combined with dexamethasone.
Bortezomib did not seem to increase the risk of VTE.
Prevention of VTE is based on the assessment for known risk factors for VTE:
— Myeloma-related (hyperviscosity, newly diagnosed status)
— Therapy-related (high-dose dexamethasone [≥ 480 mg/month], doxorubicin, multiagent chemotherapy)
— Individual factors (age, history of VTE, inherited thrombophilia, obesity, immobilization, central venous line, infections, surgery, administration of erythropoietin)
— Factors related to comorbidities (acute infection, diabetes mellitus, cardiac or renal dysfunction)
Therapy-related risks factor most in the risk-equation of VTE.
The following thromboprophylaxis is recommended:
— Acetylsalicylic acid (aspirin) in either a standard oral dose of 325 mg/day or in a low-dose of 81 mg/day for patients with one or no risk factor
— Low-molecular-weight heparin, or LMWH, once a day, or full-dose warfarin for patients if two or more risk factors or therapy-related risks are present
The recommended duration of prophylaxis in general is 6 to 12 months.
Long-term prophylaxis may be indicated in some patients.