Porcine and Canine von Willebrand Factor and von Willebrand Disease: Hemostasis, Thrombosis, and Atherosclerosis Studies

Abstract

Use of animal models of inherited and induced von Willebrand factor (VWF) deficiency continues to advance the knowledge of VWF-related diseases: von Willebrand disease (VWD), thrombotic thrombocytopenic purpura (TTP), and coronary artery thrombosis. First, in humans, pigs, and dogs, VWF is essential for normal hemostasis; without VWF bleeding events are severe and can be fatal. Second, the ADAMTS13 cleavage site is preserved in all three species suggesting all use this mechanism for normal VWF multimer processing and that all are susceptible to TTP when ADAMTS13 function is reduced. Third, while the role of VWF in atherogenesis is debated, arterial thrombosis complicating atherosclerosis appears to be VWF-dependent. The differences in the VWF gene and protein between humans, pigs, and dogs are relatively few but important to consider in the design of VWF-focused experiments. These homologies and differences are reviewed in detail and their implications for research projects are discussed. The current status of porcine and canine VWD are also reviewed as well as their potential role in future studies of VWF-related disorders of hemostasis and thrombosis.

Recurrent hemorrhage caused by type 3 von Willebrand disease in a domestic long‐haired cat

“…Additionally, due to increased sensitivity of VWF assays utilizing ELISA methodology, this report definitively identifies a feline case of type 3 VWD. The clinical signs of spontaneous epistaxis and prolonged hemorrhage from minor wounds that prompted diagnosis in this case are typical of type 3 VWD described in other species . Von Willebrand factor is a plasma protein that plays a vital role in platelet adhesion.…”

Staphylococcus aureus Host Tropism and Its Implications for Murine Infection Models

“…Depending on the relatedness of two host species between which S. aureus moves, the host environmental factors can change drastically. Surface receptors for attachment of S. aureus [ 50 , 51 , 52 ], nutrient availability [ 31 ], properties of the immune system [ 53 ], coagulation factors involved in immune evasion [ 54 , 55 ], and many more factors can differ in a way that requires genetic modification of all three parts of the S. aureus genome [ 27 , 56 ]. Hence, adaptation to a new host occurs through adaptive evolution and is marked by genomic decay, genomic rearrangements, and gene acquisition as typical genomic signatures [ 44 ].…”

A review of current methods for assessing hemostasis in vivo and introduction to a potential alternative approach

“…Several variations of the primary bleeding time have been used to detect disorders of primary hemostasis such as von Willebrand disease (VWD) [25,26] and monitor the response to therapy. We have used the 1°SBT described by Mertz [27] in canine and porcine models of type 3 VWD [9,28]. This test is done with the tip of the ear immersed in 37 °C 0.9% saline for 2 minutes, then the tip is transfixed with a scalpel blade over ~0.5 cm, the cut ear tip is resub-merged in the warm saline, and the time to cessation of bleeding is recorded.…”

“…Table 1 shows results of performing the 1° SBT [27,34], in 11 dogs with VWD and the 2° CBT in 20 dogs with hemophilia A [9,28]. Recall a normal value is defined as <5 min, and abnormal value is defined as >15 min.…”