A large-scale, retrospective study has confirmed an increased risk of deep vein thrombosis (DVT) with multiple myeloma or its precursor condition, monoclonal gammopathy of undetermined significance (MGUS).

DVT is a potentially lethal clot formation in the deep veins of the body. If a clot dislodges, it may travel to other areas and block blood flow to vital organs. Researchers estimate that approximately 70 percent of all critical blockages of lung blood vessels originate from DVT in the pelvis or lower extremities.

In this study, which involved over four million male veterans, multiple myeloma patients experienced a nine-fold increase in DVT.

The greatest risk occurred during the first year following diagnosis. Researchers suggested that accelerated cellular activity and tumor burden could have contributed to the greater DVT incidence. At eight years post-diagnosis, DVT had occurred in six percent of multiple myeloma patients.

Likewise, a three-fold increase in DVT accompanied MGUS. This risk steadily increased over time, and at eight years post-diagnosis, 2.5 percent of MGUS patients had experienced DVT. Ten percent of MGUS cases progressed to multiple myeloma during the study period.

Although MGUS is usually asymptomatic and frequently does not advance to malignant disease, it shares similar molecular abnormalities with multiple myeloma. Researchers speculated that characteristics inherent to both disorders, including atypical clonal plasma cell activities in the bone marrow, may cause clotting abnormalities that increase the risk of DVT. Findings of elevated clotting factor levels in multiple myeloma and MGUS patients appear to support this hypothesis.

Researchers emphasized, however, the need for further study to clarify the mechanisms underlying their results.

The study was additionally valuable because it ended in 1996, before the era of treating multiple myeloma with the immunomodulatory drugs thalidomide (Thalomid), Revlimid (lenalidomide), and Actimid (pomalidomide). Scientists have observed a substantially increased risk of DVT with these therapies. This study suggests that a heightened DVT risk in multiple myeloma patients may originate not only from drugs used to treat the disease, but also from molecular abnormalities intrinsic to the disorder.

The full journal article may be found in the November 1, 2008 issue of Blood.