People with multiple sclerosis may be twice as likely to develop deep-vein blood clots, a condition known as venous thromboembolism, than healthy people do, a study reports.

But data linking the two is limited, and its researchers say further work is needed to understand if MS is directly related to venous thromboembolism, or if this condition is a secondary effect of limited mobility.

The review article, “ Multiple sclerosis and the risk of systemic venous thrombosis: A systematic review, ” was published in the journal Multiple Sclerosis and Related Disorders.

A loss of flexibility and range of movement in the body or joints — called hypomobility — is a known risk factor for venous thromboembolism. In this condition, blood clots form commonly in the deep veins of the leg, groin, or arm, and travel in circulating blood to lodge in the lungs.

Certain neurological diseases are associated with partial paralysis and venous thromboembolism, including spinal injury and stroke.

Research into the incidence of venous thromboembolism in MS patients has only skimmed the surface. MS has a range of clinical features, such as disease type, duration, and severity, that could be associated with a higher risk of venous thromboembolism.

Researchers at Oxford University Hospitals and the Royal Berkshire NHS Foundation Trust examined how often venous thromboembolism occurred in MS patients. To do so, they compiled clinical data going back to the 1950s, and compared MS patients with healthy individuals.

Their literature review found 10 MS studies looking at the risk of venous thromboembolism. Of these, six studies involved large cohorts — more than 1,000 patients in each — and were included in the analysis.

Results showed that, on average, MS patients had a 1.91 times increased risk of a venous thromboembolism compared those without this disease. But this was not an entirely consistent result, with one study reporting that MS had a protective effect and lowered risk.

Disease severity, as defined by number and length of MS-related hospitalizations and need for walking aids, seemed to be the only factor predictive of venous thromboembolism.

But most of the studies did not characterize MS groups well enough for the researchers to make further conclusions. They could not examine if the MS type, disease duration, and treatment were associated with a higher venous thromboembolism risk.

Importantly, researchers were unable to determine if MS itself increases the risk of venous thromboembolism , or if secondary complications, such as hypomobility, are responsible.

“Immobility associated with severe disease is an obvious risk factor but MS has also been linked to elevated markers of endothelial damage and activation of the coagulation pathway,” the researchers wrote. “The increased risk of venous thromboembolism in MS patients could, therefore, be due not only to immobility but systemic autoimmune mechanisms increasing thrombotic risk.”

Curiously, researchers found that steroids and anti-depressants were linked to an increased venous thromboembolism risk. Steroids and antidepressants have been linked to venous thromboembolism in the general population and in specific diseases; however, these may be markers of disease severity and this link could simply be a byproduct of some other effect.

Overall, the team concluded that MS patients are at increased risk of developing venous thromboembolism, and suggest that “there may be a role for VTE [venous thromboembolism] prophylaxis in high risk patients.”

“More detailed data sources are needed to recognize specific MS-related risk factors and just how much risk they present,” the researchers added. “This important data would have direct clinical relevance in risk stratification for potential venous thromboembolism prophylaxis.”