Role of von Willebrand factor in venous thromboembolic disease

Abstract

Objective Evolving evidence of the shared risk factors and pathogenic mechanisms in arterial and venous thrombosis questions of the strict vascular dichotomy of arterial vs venous. The connection between arterial and venous thrombosis has been highlighted by common underlying inflammatory processes, a concept known as thromboinflammatory disease. Using this relationship, we can apply knowledge from arterial disease to better understand and potentially mitigate venous disease. A protein that has been extensively studied in atherothrombotic disease and inflammation is von Willebrand factor (VWF). Because many predisposing and provoking factors of venous thromboembolism (VTE) have been shown to directly modulate VWF levels, it is, perhaps, not surprising that VWF has been highlighted by several recent association studies of patients with VTE. Methods In the present narrative review, we investigated more deeply the effects of VWF in venous disease by synthesizing the data from clinical studies of deep vein thrombosis of the limbs, pulmonary embolism, portal and cerebral vein thrombosis, and the complications of thrombosis, including post-thrombotic syndrome, venous insufficiency, and chronic thromboembolic pulmonary hypertension. We have also discussed the findings from preclinical studies to highlight novel VWF biochemistry in thrombosis and therapeutics. Results Across the spectrum of venous thromboembolic disease, we consistently observed that elevated VWF levels conferred an increased risk of VTE and long-term venous complications. We have highlighted important findings from VWF molecular research and have proposed mechanisms by which VWF participates in venous disease. Emerging evidence from preclinical studies might reveal novel targets for thromboinflammatory disease, including specific VWF pathophysiology. Furthermore, we have highlighted the utility of measuring VWF to prognosticate and risk stratify for VTE and its complications. Conclusions As the prevalence of inflammatory processes, such as aging, obesity, and diabetes increases in our population, it is critical to understand the evolving role of VWF in venous disease to guide clinical decisions and therapeutics.

Comparison of coagulation parameters associated with fibrinogen concentrate and cryoprecipitate for treatment of bleeding in patients undergoing cytoreductive surgery for pseudomyxoma peritonei: Subanalysis from a randomized, controlled phase 2 study

“…A number of other studies have suggested that VWF is associated with TEEs. [24][25][26] For example, the prospective LITE study, 26 which included 19,237 patients aged 45-64 years, who experienced a total of 159 venous thromboembolisms (VTEs), found a dosedependent relationship between plasma VWF levels and risk of VTE.…”

“…However, they did subsequently appear to show a higher increase in VWF:RCo activity and VWF antigen levels compared with patients who did not develop PE. A number of other studies have suggested that VWF is associated with TEEs 24–26 . For example, the prospective LITE study, 26 which included 19,237 patients aged 45–64 years, who experienced a total of 159 venous thromboembolisms (VTEs), found a dose‐dependent relationship between plasma VWF levels and risk of VTE.…”

The Association between Platelet Glycocalicin and High Microsatellite Instability in Colorectal Cancer

“…The shedding of glycocalicin occurs when GPIb α binds to VWF, followed by the increased glycocalicin content in plasma [ 7 ]. Increased VWF is a risk factor for venous thromboembolism and long-term venous complications [ 27 ]. Microsatellite has been reported as a part of the VWF promoter region and promotes glucocorticoid-induced VWF levels [ 28 ].…”

Biomarkers and the post-thrombotic syndrome: A systematic review of biomarkers associated with the occurrence of the post-thrombotic syndrome after lower extremity deep venous thrombosis

“…vWF is a clotting factor that is a marker of endothelial dysfunction and is associated with a risk of developing DVT. [70][71][72][73] However, the available data in the studies by Schulman et al 58 and Iding et al 51 suggest there is not an association between vWF-antigen and PTS.…”