Genetics of equine bleeding disorders

Abstract

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

Blood Transfusion in Equids—A Practical Approach and Review

“…Abnormalities in any aspect of the coagulation cascade can lead to excessive bleeding in response to usually unremarkable levels of trauma [ 29 , 30 ]. Disorders of hemostasis can be genetic or acquired.…”

“…Disorders of hemostasis can be genetic or acquired. Genetic/heritable coagulopathies include Won Willebrand’s disease, Hemophilia A, inherited Prekallikrein deficiency, and Glanzmann’s and atypical Thrombasthenia [ 29 ]. These conditions are characterized by a heritable lack of production of specific proteins in the coagulation cascade.…”