Diagnosis and treatment of platelet hyperactivity in relation to thrombosis in dogs and cats

Abstract

Objective To review the mechanisms of platelet activation and options for diagnosing and treating platelet hyperactivity in relation to thrombosis in dogs and cats. Data Sources Prospective, retrospective, and review articles, as well as textbook chapters in both human and veterinary medicine. Articles were primarily, but not exclusively, retrieved via Medline. Human Data Synthesis In people, platelets are known to play a key role in the development of arterial thrombosis in numerous disease states and antiplatelet drugs are the cornerstone in the treatment of acute events and for prevention in patients at risk. For many years, aspirin was used as the sole antiplatelet drug in people, but the introduction of adenosine diphosphate receptor antagonists and integrin αIIbβ3 inhibitors has significantly improved outcome in selective groups of patients. Veterinary Data Synthesis The understanding of platelet activation in disease states has increased dramatically over the past decade. Simultaneously, a host of new methods for evaluating platelet function have been developed, which enable primarily researchers, but also clinicians to monitor the activity of platelets. Many of these methods have been validated for research purposes, but few have found their way to the clinics. Not a single correctly randomized clinical trial has been carried out with any antiplatelet drug for any indication in dogs or cats, and consequently, treatment is empiric and largely based on expert opinion or data from experimental studies. Conclusions The pathogenesis of thromboembolic disease is complex and multifactorial and the role of hyperactive platelets in this etiology remains to be clarified in most of the diseases associated with thrombosis in dogs and cats. Until efficacy data from well‐designed studies are available, antithrombotic therapy should consist of close monitoring, good supportive care, and judicious empirical use of antiplatelet agents.

Biologic variability and correlation of platelet function testing in healthy dogs

“…In the past decade, major advances in the field of hemostasis have been made, and it is now known that the hemostatic system closely interacts with other body systems, especially in states of inflammation or other diseases . Thromboembolism is a leading cause of death in human critical care patients, and is increasingly recognized as a complication that can lead to high morbidity and mortality in veterinary patients . Hypercoagulability due to platelet hyperactivity is likely a major contributor to the development of thromboembolic disease .…”

A Remote Assay for Measuring Canine Platelet Activation and the Inhibitory Effects of Antiplatelet Agents

“…A ltered platelet activity influences morbidity and survival in dogs and cats as well as humans, due to activated platelets contributing to intravascular clot formation. 1,2 Dogs with immune-mediated hemolytic anemia (IMHA), hyperadrenocorticism, those receiving exogenous corticosteroids, protein-losing nephropathies (PLN), various neoplastic and infectious diseases, pancreatitis, and enteropathies are at increased risk of thromboembolic complications from altered platelet activity. [3][4][5][6][7][8][9][10] Antiplatelet medication is often prescribed to reduce the likelihood of clot formation.…”

Thromboelastographic platelet mapping in dogs with complicated Babesia rossi infection

“…However, the study cohort included dogs with the complicated form of the disease, which is associated with an excessive proinflammatory response . Since ADP is released by platelet dense granules during platelet activation to augment the activation response initiated by other agonists, and AA is an important inflammatory mediator, it would seem unlikely that the function of these receptors was unaltered in this population of dogs. It is also possible that the results varied because of biologic variability, as a great deal of heterogeneity regarding the platelet response to various agonists in dogs exists .…”

“…Platelet activation occurs when an agonist binds to a receptor, leading to the activation of downstream signaling pathways to result in degranulation, translocation of negatively charged membrane phospholipids to the outer leaflet, and the activation of the glycoprotein (GP) IIbIIIa receptor responsible for binding fibrinogen. Agonists include thrombin, collagen, adenosine diphosphate (ADP), and thromboxane A 2 (TxA 2 ) generated from arachidonic acid (AA) . Activated platelets provide a procoagulant surface for large‐scale thrombin generation …”

“…Agonists include thrombin, collagen, adenosine diphosphate (ADP), and thromboxane A 2 (TxA 2 ) generated from arachidonic acid (AA) . Activated platelets provide a procoagulant surface for large‐scale thrombin generation …”