A potential dose-dependent relationship may exist between occurrences of venous thromboembolism (VTE) and plasma von Willebrand factor (VWF) levels, according to results of a population-based study published in the journal Blood Advances.

“VWF is an unspecific biomarker, and elevated levels indicate platelet activation and, in particular, endothelial cell activation,” explained the researchers in their report.

In this prospectively designed, case-control study, 414 cases of VTE were compared with 843 age- and sex-matched controls from the Tromsø study cohort in Norway, for whom baseline data had been obtained from 1994 to 1995. Baseline data included results from physical examinations, blood analyses, and surveys. Included patients were followed up for outcomes until September 1, 2007.

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VTE events occurred at a mean age of 67.5 years, and 62.6% of these events were deep vein thrombosis (DVT) events, while 37.4% were pulmonary embolisms. More than half of VTEs were considered to be provoked (58.2%), while 41.8% were considered unprovoked VTEs.

VWF levels were stratified into quartiles, and VTE risk showed a linear relationship with VWF levels across quartiles in an age- and sex-adjusted model (P =.023). For the highest quartile of plasma VWF, the odds ratio (OR) for VTE was 1.45 (95% CI, 1.03-2.03), when compared with the lowest quartile of plasma VWF. The association between VWF levels and VTE risk remained robust over several years of follow-up time.

In age- and sex-adjusted analyses, unprovoked VTE showed the most potent relationship with VWF levels (OR, 2.74; 95% CI, 1.66-4.54; P <.001), with unprovoked DVT showing an especially strong link to VWF levels (OR, 6.73; 95% CI, 3.07-14.76; P <.001). However, provoked DVT, overall PE, unprovoked PE, and provoked PE did not demonstrate significant relationships with plasma VWF levels.

The researchers also evaluated the effects of several features on VTE risk estimates. Body mass index, C-reactive protein, hypertension, use of estrogen, and smoking status were examined to determine influence on VTE risk, but these factors reportedly contributed only minor attenuations to risk estimates.

The researchers concluded that a higher plasma VWF level may be associated with future incident VTE risk, especially for unprovoked DVT, and that this association can persist for an extended time. “Our findings suggest that VWF may serve as a reliable biomarker for future risk of VTE,” concluded the researchers in their report.


Edvardsen MS, Hindberg K, Hansen E, et al. Plasma levels of von Willebrand factor and future risk of incident venous thromboembolism. Blood Adv. 2021;5(1):224-232. doi:10.1182/bloodadvances.2020003135