From the Guidelines
MGUS does increase the risk for a hypercoagulable state, with patients having approximately a 2-3-fold increased risk of developing deep venous thrombosis or pulmonary embolism, as reported in a study published in Haematologica in 2014 1. The increased risk of thrombosis in MGUS patients is attributed to several mechanisms, including prothrombotic changes such as increases in FVIII and von Willebrand factor, which may be causally related to the increased thrombosis risk 1. Some key points to consider include:
- The risk of arterial thrombosis, including coronary artery disease and cerebrovascular disease, is also increased in MGUS patients 1
- The increased risk of venous and arterial thrombosis was only observed in IgG and IgA MGUS, but not in IgM MGUS 1
- The risk of thrombosis did not vary by M-protein level in one study, whereas in other studies, the risk of venous thrombosis was increased in patients with higher M-protein levels 1 While routine anticoagulation prophylaxis is not recommended for all MGUS patients, those with additional risk factors for thrombosis should be monitored more closely, and healthcare providers should maintain a lower threshold for investigating symptoms suggestive of thrombosis in MGUS patients and consider thromboprophylaxis during high-risk periods.
From the Research
MGUS and Hypercoagulable State
- MGUS has been associated with an increased risk of thrombosis, including both arterial and venous thrombosis 2, 3, 4, 5.
- The underlying mechanisms for the hypercoagulable state in MGUS are not completely understood, but may involve biomarker studies that suggest shared biologic features between multiple myeloma and MGUS, including hypercoagulability and platelet activation 2.
- A retrospective multicentre cohort study found that the incidence of arterial or venous thrombosis in patients with MGUS did not increase relative to that reported in the general population for similarly aged members, but the risk of venous thrombosis did increase when the M-protein concentration exceeded >16 g/l 4.
- A prospective population-based screening study found that MGUS was associated with an increased risk of venous thrombosis, but not arterial thrombosis, and that M protein concentration was not associated with venous or arterial thrombosis 5.
Risk Factors for Thrombosis in MGUS
- Cardiovascular risk factors, such as hypertension and hyperlipidemia, may increase the risk of arterial thrombosis in patients with MGUS 4.
- A high M-protein concentration (>16 g/l) may increase the risk of venous thrombosis in patients with MGUS 4.
- The use of immunomodulatory drugs, such as thalidomide and lenalidomide, in combination with dexamethasone and/or chemotherapy, may increase the risk of venous thromboembolism in patients with multiple myeloma, and possibly also in patients with MGUS 3.
Hypercoagulable States
- Hypercoagulable states are characterized by laboratory abnormalities or clinical conditions that are associated with an increased risk of thrombosis, or by recurrent thrombosis without recognizable predisposing factors 6.
- Primary hypercoagulable states are generally inherited abnormalities of coagulation, such as antithrombin III deficiency, protein C and protein S deficiency, and dysfibrinogenemias 6.
- Secondary hypercoagulable states are generally acquired disorders in patients with underlying systemic diseases or clinical conditions known to be associated with an increased risk of thrombosis, such as malignancy, pregnancy, and myeloproliferative disorders 6.