Should Patients with MGUS Be on Anticoagulation?
No, patients with MGUS should not be placed on routine chronic anticoagulation in the absence of other risk factors. 1
Evidence-Based Recommendation
The European Myeloma Network explicitly states that although the risk of venous thromboembolism in MGUS is increased, the absolute risk remains low, and therefore there is no indication for standard thrombosis prophylaxis in these patients. 1
Understanding the Thrombotic Risk in MGUS
While MGUS does carry an increased thrombotic risk compared to the general population, this needs to be contextualized:
Venous thrombosis risk is modestly elevated: Recent population-based screening data from Iceland (75,422 screened individuals) showed MGUS patients had a hazard ratio of 1.43 (95% CI: 1.19-1.73) for venous thrombosis after adjusting for confounders. 2
Arterial thrombosis risk is NOT increased: The same large screening study found no association between MGUS and arterial thrombosis (HR = 0.96; 95% CI: 0.87-1.13). 2
M-protein concentration does not predict thrombotic risk: Neither venous nor arterial thrombosis correlated with the level of monoclonal protein. 2
Absolute event rates remain low: Even with the increased relative risk, venous thrombotic events occurred at only 10.3 per 1000 person-years in MGUS patients versus 6.0 per 1000 person-years in non-MGUS patients. 2
When Anticoagulation WOULD Be Indicated
Anticoagulation should be considered only in these specific circumstances:
Standard VTE indications apply: If a patient with MGUS develops an actual venous thromboembolism, treat according to standard VTE guidelines (not because of the MGUS itself). 1
Rare monoclonal protein-mediated thrombosis: In exceptional cases where the monoclonal protein itself has thrombogenic properties (cryoglobulinemia, cryofibrinogenemia, cryo-crystaloglobulinemia, or MGUS-related antiphospholipid syndrome), treatment targeting the underlying clone may be warranted rather than anticoagulation alone. 3
Progression to multiple myeloma on treatment: If MGUS progresses to myeloma requiring immunomodulatory therapy (lenalidomide, thalidomide, pomalidomide), thromboprophylaxis becomes indicated due to the high thrombotic risk of these agents—but this is no longer MGUS. 3
Clinical Pitfalls to Avoid
Do not extrapolate myeloma thrombosis risk to MGUS: The hypercoagulable state in active myeloma (especially on treatment) is distinct from the modest risk in MGUS. 3
Bleeding risk may outweigh benefit: Chronic anticoagulation carries its own morbidity and mortality risks that likely exceed the modest absolute thrombotic risk in MGUS patients. 1
Focus on modifiable risk factors instead: Address standard VTE risk factors (obesity, immobility, smoking) rather than prescribing anticoagulation for MGUS alone. 1