Overview of platelet physiology: its hemostatic and nonhemostatic role in disease pathogenesis

Abstract

Platelets are small anucleate cell fragments that circulate in blood playing crucial role in managing vascular integrity and regulating hemostasis. Platelets are also involved in the fundamental biological process of chronic inflammation associated with disease pathology. Platelet indices like mean platelets volume (MPV), platelets distributed width (PDW), and platelet crit (PCT) are useful as cheap noninvasive biomarkers for assessing the diseased states. Dynamic platelets bear distinct morphology, where α and dense granule are actively involved in secretion of molecules like GPIIb , IIIa, fibrinogen, vWf, catecholamines, serotonin, calcium, ATP, ADP, and so forth, which are involved in aggregation. Differential expressions of surface receptors like CD36, CD41, CD61 and so forth have also been quantitated in several diseases. Platelet clinical research faces challenges due to the vulnerable nature of platelet structure functions and lack of accurate assay techniques. But recent advancement in flow cytometry inputs huge progress in the field of platelets study. Platelets activation and dysfunction have been implicated in diabetes, renal diseases, tumorigenesis, Alzheimer's, and CVD. In conclusion, this paper elucidates that platelets are not that innocent as they keep showing and thus numerous novel platelet biomarkers are upcoming very soon in the field of clinical research which can be important for predicting and diagnosing disease state.

Figure 1

Platelet-activation mechanisms and role of the P2Y₁₂ receptor. Platelet activation leads to dense-granule secretion of ADP, which activates P2Y₁₂, inducing amplification of aggregation, procoagulant, and proinflammatory responses (adapted from Storey, 2008 [7]).

Figure 2

Mechanism of vascular changes by platelet-derived microparticles (PMPs). PMPs activate monocytes by a reaction between P-selectin and PSGL-1 (P-selectin glycoprotein ligand-1). Activated monocytes induce expression on the cell surface of tissue factor (TF) and CD11b. Activated monocytes also induce release of monocyte-derived microparticles (MMPs). PMPs induce COX-2 production in endothelial cells. PMPs enhance expression of CD54 (ICAM-1) on the endothelial surface. Activated endothelial cells also induce release of endothelial cell-derived microparticles (EMPs), enhancing adhesion between endothelial cells and monocytes. Finally, monocytes induce migration of endothelial cells, resulting in vascular changes. Abbreviations: arachidonic acid (AA); protein kinase C (PKC); mitogen-activated protein kinase (MAPK) (adapted from Nomura, 2001 [8]).

Figure 3

Pathway illustrating hemostasis.

Figure 4

Thromboxane biosynthesis pathway.

Figure 5

After an injury in the vessel wall, activation of platelets begins to start. It involves its adhesion to the subendothelium surface. Interaction between receptors like GPIb-V-IX, GPIa-IIa, and subendothelial compounds like vWf and collagen triggers the release of platelet granule contents accelerating aggregate formation.

Figure 6

Diagram illustrating the role of von Willebrand factor (vWf) in platelet adhesion. High flow rates induce conformational changes in vWf allowing interaction of its A3 domain with matrix collagen. This induces a conformational change in the A1 domain, thereby allowing interaction with glycoprotein (GP) platelet receptor Ib-IX-V. This interaction stimulates calcium release, subsequent platelet activation, and subsequent conformational change of the fibrinogen receptor (GPIIb/IIIa), which can interact with fibrinogen and vWf to favor the interaction between platelets (platelet aggregation process). ADP indicates adenosine diphosphate; RGD and Arg-Gly-Asp are amino acid sequences (adapted from Badimon et al., 2009 [30]).

Figure 7

Flow cytometric detection of P-selectin in (a) diabetic patient and (b) nondiabetic patient (adapted from Saad et al., 2011 [34]).

Figure 8

The multifunctional platelet (adapted from Harrison, 2005 [44]).