Disorders of platelet function

image of Disorders of platelet function
Online Access: £ 25.00 + VAT
BSAVA Library Pass Buy a pass


The platelet disorders encountered most commonly in veterinary practice are quantitative abnormalities, particularly thrombocytopenia. Abnormalities in platelet function have been documented in domestic animals and result in abnormal bleeding in affected individuals. This chapter looks at platelet structure; platelet function; diagnosis of thrombopathias; defects in platelet function; management.

Preview this chapter:
Loading full text...

Full text loading...



Image of 24.1
24.1 Schematic illustration of platelet ultrastructure.
Image of 24.3
24.3 Schematic illustration of assembly of the tenase and prothrombinase complexes on the platelet surface. During platelet activation, phosphatidylserine is enriched in the outer leaflet of the platelet membrane. The tenase complex consists of the platelet membrane-associated assembly of activated factor IX (FIXa), activated factor VIII (FVIIIa), phosphatidylserine and ionized calcium (calcium) and is responsible for the activation of factor X. Similarly, the prothrombinase complex consists of a complex of activated factor X (FXa), activated factor V (FVa), phosphatidylserine and ionized calcium and is responsible for the activation of prothrombin to thrombin.
Image of 24.4
24.4 Basic platelet reaction. This is the sequence of signalling events that occurs during platelet activation. The reaction is initiated when an agonist binds to its specific receptor on the platelet plasma membrane. Receptors for ADP, thromboxane A, thrombin, adrenaline (epinephrine), serotonin and prostaglandins E and I are coupled to messengers called glycoproteins (GPs); receptors for IgG, the collagen receptor GPVI and C-type lectin-like receptor 2 are FcγR-linked. Upon activation, GPs trigger activation of phospholipase A (eicosanoid or arachidonate pathway) or phospholipase Cβ (phospholipid pathway). In the eicosanoid pathway, phospholipase A catalyses the release of arachidonic acid from phospholipids (especially phosphatidylcholine) in the platelet membrane; leading to the synthesis of prostaglandin endoperoxides and thromboxane A. Thromboxane A plays a critical role in platelet recruitment and granule secretion. The phospholipid pathway is activated by both GP- and FcγR-coupled receptors. The FcγR-linked platelet receptors contain an immunoreceptor tyrosine-based activation motif (ITAM) similar to the primary signalling domain of classical immunoreceptors. Following agonist binding, the ITAM domain is phosphorylated; Syk (a tyrosine kinase) binds to the phosphorylated ITAM domain of the FcγR chain and triggers phospholipase Cγ activation. Activated phospholipase C (γ or β) in turn hydrolyses phosphatidylinositol 4, 5-bisphosphate to diacylglycerol and inositol 1, 4, 5-triphosphate (IP). Diacylglycerol activates protein kinase C, which, through secondary messengers, leads to platelet aggregation, shape change, and secretion. Inositol triphosphate increases cytosolic calcium concentrations by promoting calcium release from the dense tubular system and entry of extracellular ionized calcium. The increased intracellular calcium has several effects, including shape change, granule secretion and activation of the fibrinogen receptor, GPIIb-IIIa. Although these two pathways of platelet activation are illustrated as relatively distinct from one another, they do interact with, and amplify, each other. For example the inositol triphosphate-mediated increase in intracellular calcium concentration also leads to activation of phospholipase A (eicosanoid pathway). Platelets contain the enzyme adenylate cyclase (AC), which regulates intraplatelet levels of cyclic AMP (cAMP). Activation of GP-coupled receptors signals either activation or inhibition of AC (pathway not shown). When adrenaline, for example, binds to its GP-coupled receptor, it leads to inhibition of AC and decreased platelet cAMP, which in turn promotes calcium release from the dense tubular system and leads to increased platelet reactivity. When prostacyclin (PGI) released by vascular endothelial cells binds to its GP-linked receptor it signals activation of AC and increased levels of cAMP, which act to inhibit platelet reactivity. This is an important non-thrombotic effect of normal vascular endothelium.
Image of 24.6
24.6 Schematic illustration of primary haemostasis. The intact endothelium prevents platelet adherence by acting as a physical barrier and releasing inhibitors of platelet function, including prostacyclin (PGI) and nitric oxide (NO). These substances inhibit platelet function by increasing platelet concentrations of cyclic adenosine monophosphate and cyclic guanosine monophosphate, respectively. When the endothelium is disrupted, platelets adhere to the exposed subendothelium. Under conditions of high shear, platelets adhere through an interaction between GPIb-IX and von Willebrand factor (vWF). Under conditions of low shear, platelets adhere, through integrin receptors, to collagen, laminin and fibronectin in the subendothelial matrix. Adhesion activates platelets through the basic platelet reaction, resulting in shape change, the release reaction and thromboxane A (TXA) generation. This culminates in platelet recruitment, further platelet activation and aggregation. Platelet aggregation occurs when fibrinogen binds to its receptor, GPIIIb-IIIa, on the platelet membrane. Consequently, the primary platelet plug is produced by a fused mass of platelets. Platelet procoagulant activity (PF3) becomes available (through translocation of phosphatidylserine to the outer leaflet of the platelet membrane) upon platelet activation and promotes secondary haemostasis, resulting in the formation of fibrin. Fibrin solidifies the primary platelet plug, forming a stable thrombus.
Image of 24.12
24.12 Spontaneous epistaxis in a Great Pyrenees dog with Glanzmann’s thrombasthenia. (Courtesy of Dr M Boudreaux)
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error