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rates and appear to be as safe as VKAs. These findings, like those seen in the prevention

The standard treatment for acute VTE is anticoagulant therapy. For initial therapy, subcutaneous (SC) LMWH is as effective and safe as intravenous UFH (28, 29). LMWHs are administered once or twice daily by SC injection, have weight-adjusted dosing and do not usually require laboratory monitoring. These advantages over UFH allow LMWHs to be

Duration of therapy: Duration of anticoagulant therapy has not been addressed in cancer patients. Based on the accepted concept that the risk of recurrent thrombosis is increased in the presence of any ongoing risk factor, it is generally recommended that patients with metastases continue with ''indefinite'' therapy because metastatic malignancy is a persistent risk factor. In those without metastases, anticoagulant treatment is recommended for as long

Secondary prophylaxis: Oral anticoagulant therapy with a vitamin K antagonist can be started on the same day as heparin therapy to begin secondary prophylaxis. To effectively reduce recurrent VTE without excessive bleeding, the dose of oral anticoagulants must be adjusted to maintain the INR within a therapeutic range of 2.0 to 3.0. This usually requires twice weekly blood work for the first 1 to 2 weeks until a stable dose is identified. Using this regimen, the annual incidence of recurrent VTE in patients without cancer is approximately

The higher failure rate in cancer patients may reflect the greater difficulty in maintaining therapeutic INR levels because of multiple drug interactions, gastrointestinal upset, vitamin K deficiency, liver dysfunction and poor venous access. Also, temporary discontinuation of anticoagulant therapy is often necessary during periods of thrombocytopenia and to accommodate invasive procedures. Such interruptions can cause lengthy periods of inadequate anticoagulation because vitamin K antagonists have a delayed onset of action and a prolonged period of clearance. Furthermore, warfarin failure, i.e. recurrent VTE despite maintaining therapeutic INR levels, is not uncommonly reported in cancer patients

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**5** 

*Spain* 

**Thrombosis Associated with** 

Jose Ramon Gonzalez-Porras and María-Victoria Mateos

**Immunomodulatory Agents in Multiple Myeloma** 

*Hematology Department, Hospital Universitario de Salamanca and IBSAL, Salamanca* 

Patients with multiple myeloma (MM) are increasingly at risk for thromboembolic events (TEEs), usually venous thromboembolism (VTE) [1]. The introduction of thalidomide and lenalidomide has clearly improved outcomes in MM patients but these immunomodulatory agents (IMiDs) are also associated with higher rates of TEEs [2]. The pathogenesis of thalidomide/lenalidomide-associated thrombosis is multifactorial and poorly understood. Patients with MM who are being treated with schemes including combinations of either thalidomide or lenalidomide plus other agents should receive some form of thrombosis prophylaxis [3]. This chapter discusses the incidence, pathogenic mechanisms, prophylaxis

The risk of developing venous thrombotic complications for patients with cancer is approximately five times that of the general population (0.5 *vs.* 0.1%) [4]. Multiple myeloma (MM), characterized by the malignant proliferation of clonal plasma cells, accounts for approximately 10% of hematologic malignancies and affects older individuals (median age, 70 years) [5]. Thromboembolic events are a key concern in clonal plasma cells disorders, such as monoclonal gammopathy of undetermined significance (MGUS) as well as in MM. The exact incidence of VTE in MGUS is difficult to determine since reported VTE rates probably vary according to the level of diagnostic vigilance. The underlying medical problems that prompted laboratory testing for monoclonal may also increase the risk of VTE. Srkalovic et al [1] noted an increased incidence of VTE among patients with MGUS. They reported that 7.5% (13 of 174 patients) of patients with MGUS developed VTE at a median of 4 months (range, 0–67 months) after diagnosis. The cumulative VTE rate was 16% after 8 years of follow-up. A medical history of VTE, family history of VTE, immobility, low serum albumin level and an increase in leukocyte count were found to be correlated with increased incidence of VTE in patients with MGUS. In another retrospective study (310 patients with MGUS) the incidence of VTE was 6.1% after a median follow-up of 44 months [6]. Univariate analysis showed that age ≥ 65 years, M protein ≥ 16 g/l and disease progression to symptom MM were the significant risk factors for VTE. A retrospective review of U.S. Veterans Affairs hospital records from 1980–1996 reported an incidence of VTE of 0.9, 3.1 and 8.7% in veterans without a plasma cell dyscrasia, diagnosed to have

and treatment of thalidomide/lenalidomide-associated TEEs.

**2. Multiple myeloma and thrombosis** 

**1. Introduction** 

