Prospective evaluation of coagulopathy in multiple myeloma patients before, during and after various chemotherapeutic regimens

Marion, Ariënne M W van; Auwerda, J. J. A.; Lisman, Ton; Sonneveld, Pieter; Maat, M.P.M. de; Lokhorst, Henk M.; Leebeek, Frank W.G.

doi:10.1016/j.leukres.2007.12.002

Cited by 63 publications

(53 citation statements)

References 30 publications

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“…In multiple myeloma patients a strong increase of FVIII levels during chemotherapy was reported. 24 To avoid a treatment related bias of FVIII measurement, we excluded patients with chemotherapy within the last 3 months before inclusion. Recent investigations show that low-density lipoprotein receptor-related protein-1 (LRP-1) and polymorphisms of its gene are important for the regulation of FVIII plasma levels.…”

Section: Discussionmentioning

confidence: 99%

High Factor VIII Levels Independently Predict Venous Thromboembolism in Cancer Patients

Vormittag

Simanek

et al. 2009

ATVB

144

107

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Objective-Patients with cancer are at an increased risk for venous thromboembolism (VTE). Clotting factor VIII activity (FVIII) has been established as risk factor of primary and recurrent VTE. We investigated FVIII as predictive parameter of VTE in cancer patients. Methods and Results-The prospective observational Cancer and Thrombosis Study (CATS) includes patients with newly diagnosed cancer or disease progression, study end point is symptomatic VTE. FVIII was measured on a Sysmex CA 7000 analyzer. Data on 840 patients (median age: 62 years, 25th to 75th percentile 53 to 68, 378 women) were available for analyses, of these 111 patients had hematologic malignancies and 729 solid cancer. During a median observation time of 495 days 62 events occurred. Cumulative probability of VTE after 6 months was 14% in patients with elevated FVIII-levels and 4% in those with normal levels (Pϭ0.001). The association was strongest in younger patients: whereas in 40-year-old patients a 2-fold VTE risk per factor VIII increase of 20% was observed (HRϭ2.

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Section: Discussionmentioning

confidence: 99%

High Factor VIII Levels Independently Predict Venous Thromboembolism in Cancer Patients

Vormittag

Simanek

et al. 2009

ATVB

144

107

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“…Increases in von Willebrand factor and factor VIII have been found, and were associated with a more advanced stage of disease, even before the start of treatment. 20 The association between the increased level of these factors and VTE is unclear and requires larger prospective studies. The increase in the procoagulant factors can also reflect an inflammatory reaction.…”

Section: Proposed Mechanisms In MMmentioning

confidence: 99%

“…12,16 Thalidomide has been shown to increase the levels of von Willebrand factor and factor VIII. 20 In addition, thalidomide regulates the level of the prothrombotic factor COX-2. 24 Furthermore, there is some evidence to support an effect on the endothelial cells in patients treated with thalidomide and lenalidomide, possibly via tumor necrosis factor.…”

Section: Proposed Mechanisms In MMmentioning

confidence: 99%

Thrombosis in Multiple Myeloma

Kristinsson

2010

Hematology

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Patients with multiple myeloma (MM) are at an increased risk of venous and arterial thrombosis. The pathogenesis remains unclear, but probably involves several factors such as activation of procoagulant factors, acquired activated protein C resistance, and inflammation. In addition to general risk factors for venous thromboembolism, such as older age, immobility, surgery, and inherited thrombophilia, there are some MM-specific and treatment-related factors that contribute to the increased risk. The risk for venous thromboembolism is high when patients are treated with thalidomide or lenalidomide in combination with dexamethasone or multi-agent chemotherapy. Thromboprophylaxis should be given in these settings. Which agent is the most appropriate is a matter of debate, but aspirin, low-molecular-weight heparin, and warfarin all seem to be effective. This review discusses risk factors for thromboembolism in MM and general, disease-specific and treatment-related mechanisms for thrombosis. Recommendations for thromboprophylaxis are described and treatment choices for venous thrombosis in MM patients are reviewed.

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“…Recent studies suggest that treatment of multiple myeloma with dexamethasone and Adriamycin combined with either vincristin (VAD), thalidomide or bortezomib (PAD) result in an augmented prothrombotic coagulation state with significantly higher levels of factor VIII, vWF and fibrinogen. In patients with multiple myeloma, levels of these pro-coagulant factors are elevated at presentation and increase with induction therapy [6]. Higher levels of clotting factors are known to be associated with increased risk of thrombotic events in the general population [7].…”

Section: Discussionmentioning

confidence: 99%