Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia

Norris, Jeffrey W.; Pombo, Monica; Shirley, Erin; Blevins, Gina M.; Tablin, Fern

doi:10.1111/jvim.13595

Cited by 7 publications

(4 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelet dysfunction may be hereditary or acquired and may stem from an intrinsic platelet defect or from an extrinsic factor that alters the function of normal platelets. Hereditary Glanzmann's thrombasthenia is a disorder resulting in poor platelet aggregation and clot retraction caused by one or more defects in quantity or quality of platelet surface glycoprotein IIb/IIIa [61]. Glanzmann's thrombasthenia have been showed in a Peruvian Paso mare of 17 years old [62] and an 18month-old Oldenbourg filly [63,64].…”

Section: Platelet Function Defects and Von Willebrand Disease In Horsementioning

confidence: 99%

Interpretation of Platelets in The Horse

2017

View full text Add to dashboard Cite

Currently we can consider that, in addition to its role in hemostasis, platelets also participate in other important processes such as thrombosis, inflammation, tissue remodeling and the innate defense mechanisms. The hemostatic activity of platelets includes different events to stop bleeding. Within these functions we can mention the adhesion to the endothelium of the affected blood vessel, the activation, the aggregation, and the release of substances that initiate hemostatic events, and also the providing a phospholipid surface for activation of numerous coagulation factors. Similarly, platelets release multiple growth factors responsible for regulating the growth and division of endothelial cells and fibroblasts. In this way, among other things, angiogenesis and tissue regeneration are favored. Platelets also participate in inflammatory processes by the release of factors that initiate the inflammatory cascade and favor the chemotaxis of neutrophils, monocytes, macrophages, acute phase proteins and target cell signaling. Finally, platelets participate in the immune response by interacting with the complement system and immunoglobulins.

show abstract

Section: Platelet Function Defects and Von Willebrand Disease In Horsementioning

confidence: 99%

Interpretation of Platelets in The Horse

2017

View full text Add to dashboard Cite

show abstract

“…The biochemical differences, however, have been thoroughly investigated. A number of proteins in the thrombin signalling pathway are decreased in quantity or activity in affected horses 53 . The biochemical hallmark of AET is that thrombin stimulated platelets from affected horses do not activate normally and bind fibrinogen less efficiently 55 .…”

Section: Inherited Equine Disorders Affecting Platelet Functionmentioning

confidence: 99%

“…AET is caused by abnormal platelet signalling leading to epistaxis and abnormal clotting after injury. 53,54 While pedigree analysis indicates that AET is heritable, the genetic cause has not yet been elucidated.…”

Section: Atypical Equine Thrombasthenia (Aet)mentioning

confidence: 99%

Genetics of equine bleeding disorders

Dahlgren

Tablin

Finno

2020

Equine Veterinary Journal

View full text Add to dashboard Cite

Clotting is an essential biologic process. Several genetic bleeding disorders have been identified in horses, affecting the coagulation cascade and platelet function. These disorders are typically heritable and therefore passed down from parent to offspring. Genetic mechanisms have been identified for some equine bleeding disorders while others remain unknown. This review is focused on the genetics of equine diseases affecting the coagulation cascade and platelet function (Figures 1 and 2, Table 1). 2 | HAEMOS TA S IS TE S TING Haemostasis tests are the cornerstone of diagnosing bleeding disorders across species. To appreciate how bleeding disorders in horses are diagnosed, it is necessary to understand how several of these tests work. Platelet count is important as it can indicate an ongoing disease or infection if the count is higher or lower than the normal range (94-232 × 10 3 /µL at Cornell Clinical Pathology Laboratory). In addition to assessing overall platelet number on a complete blood count, a basic large animal coagulation panel, which includes activated partial thromboplastin time (aPTT), prothrombin time (PT) and fibrinogen should be evaluated. The first two quantify the time for blood to clot following the addition of standard amounts of agonists to plasma. Blood is drawn into a tube that contains citrate, which acts as an anticoagulant by binding all the extracellular calcium. Plasma is separated by centrifugation and removed. An excess of calcium is added to the plasma to allow it to clot. To determine aPTT, an activating substance for Factor XII (eg silica, celite, kaolin, ellagic acid) is added to simulate the intrinsic (also known as the contact) pathway. 1 To determine PT, tissue factor is added to activate the extrinsic pathway. 1 To measure fibrinogen activity, thrombin is added to plasma and the time it takes for a clot to form is optically measured and compared to a reference interval. 1 The amount of fibrinogen is also compared to a species-specific standard curve to quantify how much fibrinogen is present in a volume of blood. 1 It is important to also keep in mind that increased fibrinogen can also be indicative of inflammation, not just a bleeding disorder. 2 Some laboratories also include the test for fibrin degradation products (FDPs) or D-dimers that are the result of the breakdown of a clot. FDPs and D-dimers differ in that D-dimers include the smallest crosslinked dimers of

show abstract

“…A platelet function defect distinct from GT has been reported in Thoroughbreds [64,65]. Affected horses demonstrated prolonged thombotest (TBT), abnormal platelet aggregation to certain agonists, and impaired fibrinogen binding by flow cytometric assay.…”

Section: Glanzmann Thrombastheniamentioning

confidence: 99%

Genetic Disorders Affecting Equine Blood Cells and Coagulation Factors: A-State-of-The-Art Review

Satué

Muñoz

2019

J. Hematol. Res.

View full text Add to dashboard Cite

Genetic diseases that affect blood cells and clotting factors in the horse are uncommon. Unfortunately, the prognosis is reserved, because the treatment in many cases is only symptomatic and when it fails, euthanasia of the patient is the only viable option. The detection of carriers is of pivotal importance in order to prevent the spread of these disorders in the equine population. This manuscript reviews the current state of knowledge of genetic diseases that affect red blood cells, leukocytes, platelets and clotting factors in the horse. The genetic diseases that affect equine red blood cells are defects in the activity of enzymes and cofactors involved in erythrocytes metabolism, such as glucose 6 phosphate dehydrogenase, flavin adenine dinucleotide, glutathione reductase and glutathione. Therefore, their deficiency triggers methemoglobinemia and hemolytic anemia. Genetic disorders affecting granulocytes are rare in horses, but a Pelget-Hüet anomaly has been reported. Primary immunodeficiencies described in horses and arising from defects in the immune system are severe combined immunodeficiency, X-linked agammaglobulinemia and Fell pony immunodeficiency syndrome. Because of the immunodeficiency, foals usually develop fatal infections during the first weeks or months of life, caused for opportunistic organisms. Prognosis of these animals is poor. The most common genetic defect of platelet is Glanzmann thrombasthenia, which results in prolonged bleeding time and hematoma formation. Spontaneous bleeding or impaired hemostasis after trauma or surgery are clinical findings in types 1 and 2 von Willebrand disease. Hemophilia A, resulting from a decreased activity of coagulation factor VIII has also been described in male horses of different breeds, being the most common genetic disorder affecting coagulation factor in the horse. Prekallikrein deficit, although described in some horses, is a rare genetic coagulation factor deficiency.

show abstract

Association of Factor V Secretion with Protein Kinase B Signaling in Platelets from Horses with Atypical Equine Thrombasthenia

Cited by 7 publications

References 38 publications

Interpretation of Platelets in The Horse

Interpretation of Platelets in The Horse

Genetics of equine bleeding disorders

Genetic Disorders Affecting Equine Blood Cells and Coagulation Factors: A-State-of-The-Art Review

Contact Info

Product

Resources

About