Vwf-KO Mouse

Von Willebrand factor (VWF), encoded by the Vwf gene, is a large adhesive multimeric glycoprotein crucial for hemostasis. It plays an essential role in regulating the balance between blood clotting and bleeding, acting as a bridge between platelets and the subendothelial matrix after vessel damage [3,4,6]. Aberrant VWF regulation can lead to a spectrum of diseases from bleeding disorders like von Willebrand disease (VWD) to thrombotic thrombocytopenic purpura (TTP) [4].

Regarding low VWF levels, international guidelines suggest diagnosing low VWF when plasma VWF antigen (VWF:Ag) levels are in the range of 30-50 IU/dL. However, its pathogenesis remains poorly understood, causing challenges in genetic counseling, diagnosis, and management. Some studies indicate that the number of rare nonsynonymous VWF variants significantly predicts VWF:Ag levels, and enhanced VWF clearance may contribute to the pathobiology of low VWF, but the VWF propeptide (VWFpp)-to-VWF antigen (VWF:Ag) ratio may have limitations in reflecting this [1,2,5]. Also, in children undergoing tonsillectomy, low VWF levels do not seem to correlate with bleeding [7]. In COVID-19, increased VWF levels and an altered VWF/ADAMTS-13 axis may promote (micro)thrombosis [3]. Additionally, higher plasma VWF:Ag levels in acute myocardial infarction patients are associated with long-term major adverse cardiopulmonary and cerebrovascular events (MACEs) [6].

In conclusion, Vwf is vital for maintaining hemostasis. Research on Vwf, including through studies related to low VWF levels, its variants, and its role in diseases like COVID-19 and acute myocardial infarction, helps in understanding the molecular mechanisms underlying bleeding and thrombotic disorders. This knowledge can potentially guide better diagnosis, genetic counseling, and treatment strategies for related diseases [1-7].

References:

1. O'Donnell, James S. . Low VWF: insights into pathogenesis, diagnosis, and clinical management. In Blood advances, 4, 3191-3199. doi:10.1182/bloodadvances.2020002038. https://pubmed.ncbi.nlm.nih.gov/32663299/

2. Sadler, Brooke, Christopherson, Pamela A, Haller, Gabe, Montgomery, Robert R, Di Paola, Jorge. . von Willebrand factor antigen levels are associated with burden of rare nonsynonymous variants in the VWF gene. In Blood, 137, 3277-3283. doi:10.1182/blood.2020009999. https://pubmed.ncbi.nlm.nih.gov/33556167/

3. Favaloro, Emmanuel J, Henry, Brandon Michael, Lippi, Giuseppe. 2021. Increased VWF and Decreased ADAMTS-13 in COVID-19: Creating a Milieu for (Micro)Thrombosis. In Seminars in thrombosis and hemostasis, 47, 400-418. doi:10.1055/s-0041-1727282. https://pubmed.ncbi.nlm.nih.gov/33893632/

4. Xiang, Yaozu, Hwa, John. . Regulation of VWF expression, and secretion in health and disease. In Current opinion in hematology, 23, 288-93. doi:10.1097/MOH.0000000000000230. https://pubmed.ncbi.nlm.nih.gov/26771163/

5. Doherty, Dearbhla, Byrne, Mary, Nolan, Margaret, James, Paula D, O'Donnell, James S. . Enhanced VWF clearance in low VWF pathogenesis: limitations of the VWFpp/VWF:Ag ratio and clinical significance. In Blood advances, 7, 302-308. doi:10.1182/bloodadvances.2022007340. https://pubmed.ncbi.nlm.nih.gov/35523118/

6. Xier, Zulipiyemu, Zhu, Yu-Xia, Tang, Shou-Wei, Huojia, Guzailinuer, Peng, Hui. 2023. Plasma VWF: Ag levels predict long-term clinical outcomes in patients with acute myocardial infarction. In Frontiers in cardiovascular medicine, 9, 1013815. doi:10.3389/fcvm.2022.1013815. https://pubmed.ncbi.nlm.nih.gov/36684571/

7. Gill, Joan Cox, Conley, Stephen F, Johnson, Victoria P, Montgomery, Robert R, Flood, Veronica H. . Low VWF levels in children and lack of association with bleeding in children undergoing tonsillectomy. In Blood advances, 4, 100-105. doi:10.1182/bloodadvances.2019000992. https://pubmed.ncbi.nlm.nih.gov/31905240/