Although rare, dangerous blood clots can strike some people with VWD
Study finds the risk rises with age, especially alongside other health issues
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Dangerous blood clots that block blood flow are rare in people with von Willebrand disease (VWD), but their risk increases with age and the specific types of clotting problems may vary by biological sex, a new study shows.
These clots, known as thrombo-embolic events, can cause severe damage in the lungs, heart, and other organs.
“Thrombotic events were rare … However, they appeared to occur in a sex-driven subpopulation of VWD patients with additional thrombotic risk factors, suggesting potential implications for therapeutic management,” scientists wrote.
The study, “Venous and Arterial Thrombo-Embolic Events in Patients With von Willebrand Disease From Western France: The TWIGO Study,” was published in Haemophilia.
Why blood clots can occur in VWD
VWD is a bleeding disorder marked by abnormally low levels of functional von Willebrand factor (VWF), a protein that normally helps blood clot. Lacking working VWF, people with the disorder are at risk for symptoms like unusually easy and prolonged bleeding.
Thrombo-embolic events broadly refer to problematic clots that block the flow of blood through blood vessels. This can result in life-threatening complications such as a pulmonary embolism (blockages in the lungs’ vessels) or a myocardial infarction (heart attack).
Since VWD is defined by reduced clotting, it’s long been thought that people with the disease are unlikely to develop thrombo-embolic events. However, an emerging body of research has shown that these events, although rare, can occur in people with VWD. Still, little is known about which patients are at the highest risk.
Brest University Hospital in France is coordinating a clinical trial called Cardiovascular and Venous Thromboembolism Disease in Patients with Von Willebrand Disease in the French West, or TWIGO (NCT05773638), to learn more about thrombo-embolic events in this population. Here, researchers analyzed rates of these events among 1,345 patients in the study.
Thrombo-embolic events were documented in a total of 24 individuals, representing 1.8% of the study group, or slightly less than 1 out of every 50 patients. A few of these individuals experienced multiple events, and 35 events were recorded in total. The researchers noted that, in all cases where patients experienced multiple thrombo-embolic events, the clots affected the same part of the body each time.
Most of these events (30/35) affected arteries, the blood vessels that carry oxygen-rich blood out to the body’s tissues. The most common arterial events were angina (chest pain) and myocardial infarction, both of which are marked by blockages in arteries that carry blood to the heart’s own muscles.
The remaining five events occurred in veins, which carry blood back from tissues to the heart. The most common venous events were pulmonary embolisms. Most of these events were associated with other thrombo-embolic risk factors, such as having undergone a recent surgery or being on prolonged bed rest.
The researchers noted that most of the thrombo-embolic events occurred in men older than 50 or women older than 60, which are sex-specific age cutoffs that are associated with increased risk of cardiovascular problems in the general population. Specific types of events tended to vary by biological sex, with most of the arterial events occurring in men, whereas all of the venous events affected women.
“Given that VWF levels tend to increase with age in VWD, it is plausible that the relative protection against [clotting problems] diminishes over time, particularly as these patients accumulate [other health problems] and cardiovascular risk factors with time,” the researchers wrote.
They also found that 10 of the 35 events required adjustment of VWD treatments, generally involving pausing or decreasing the dose of medications to prevent clotting. Notably, these treatment adjustments generally were not followed by bleeding events. The only exception was in a 90-year-old woman who developed bleeding due to a head injury while on treatment following a heart attack.
These findings “support the principle of not undertreating patients who develop [thrombo-embolic events], since bleeding complications appear minimal with [anti-clotting] therapy, even among patients with severe VWD,” the researchers wrote.
Overall, the researchers said these data underscore the importance of considering dangerous clotting events as a rare but possible health complication in VWD. They encouraged physicians treating people with this disease to remain vigilant, particularly if the patient is older and has additional risk factors for thrombosis.
They also suggested following “the same therapeutic approaches for VWD patients as for the general population, as these appear to be generally well tolerated for both arterial and venous thrombosis.” Additionally, they recommended strengthening “cardiovascular follow-up and [promoting] adherence to basic cardiovascular prevention measures, particularly in men, given their potential cardiac predisposition.”
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