Venous Thromboembolism in Multiple Myeloma

Abstract

As for other malignancies, multiple myeloma is associated with an increased risk of venous thromboembolism (VTE). The incidence of VTE is estimated as 8 to 22 per 1,000 person-years; risk factors can be patient related (advanced age, other risk factors shared with the general population), disease related, and treatment related. Disease-related risk factors can derive from the monoclonal component (rarely hyperviscosity or inhibition of natural anticoagulants) or hypercoagulability sustained by inflammatory cytokines (increased von Willebrand factor, factor VIII, fibrinogen levels, decreased protein S levels, acquired activated protein C resistance). The 1 to 2% baseline of incident VTE associated with conventional therapies as melphalan and prednisone is at least doubled by the use of doxorubicin or other chemotherapeutic agents. The VTE rate associated with thalidomide or lenalidomide as monotherapy is similar, whereas combination with high-dose dexamethasone or multiple chemotherapeutic agents induces a multiplicative effect on the VTE rate up to 25%. Low-molecular-weight heparin (LMWH), fixed low-dose warfarin, and aspirin are acceptable strategies for antithrombotic prophylaxis, reducing VTE to 5 to 8% in thalidomide-treated patients and 1 to 3% in lenalidomide-treated patients. LMWH shows an advantage in efficacy not statistically significant. Prophylaxis should be tailored considering individual risk factors for VTE, the stage of disease, the possible occurrence of thrombocytopenia, or renal insufficiency.

Network-based analysis of the molecular mechanisms of multiple myeloma and monoclonal gammopathy of undetermined significance

“…Crowely et al ( 33 ) suggested that patients with MGUS have an intermediate coagulation profile, between that of patients with myeloma and that of healthy controls. There is evidence that MM is associated with an increased risk of venous thromboembolism ( 34 ). These findings indicate that these downregulated complement and coagulation genes may be involved in the development of MM and MGUS through the regulation of the complement and coagulation cascade pathways.…”

Erythropoietin treatment in murine multiple myeloma: immune gain and bone loss

“…The vast majority of MM patients currently receive either imunomodulatory agents (IMIDs) or proteasome inhibitors as first line therapy 62 . Higher incidence of venous thromboembolism (VTE) was reported in MM in general, but it was aggravated by the use of IMIDs 63 64 65 . Moreover, the combined use of IMIDS with EPO might increase the risk of VTE 66 .…”

Efficacy and Safety of Danshen Compound Tablets in Preventing Thalidomide-Associated Thromboembolism in Patients with Multiple Myeloma: A Multicenter Retrospective Study

“…Thalidomide-based regimens have undeniably improved the outcomes of multiple myeloma (MM), but increased the risk of thromboembolic events [ 6 – 8 ]. As shown in this retrospective study, we observed a VTE incidence of 2.24% in all of the patients investigated, and a 7.87% VTE incidence rate in the absence of thromboprophylaxis, consistent with previous reports from Asians [ 18 ], but lower than the reports from Western countries [ 19 ], where VTE incidence was highly variable among the different trials and could be as high as 58% when thalidomide was given in combination with doxorubicin and dexamethasone in the absence of thromboprophylaxis [ 20 ].…”

“…VTEs increased up to 3.1 times, when thalidomide is administered in combination with high-dose dexamethasone [ 6 ]. Incidences of VTE were more frequent during the first 3–6 months of thalidomide treatment [ 7 , 8 ]. Thus, the use of thalidomide-containing regimens should be carefully monitored to prevent thrombosis events [ 9 ].…”