Molecular Aspects of Pathophysiology of Platelet Receptors

Receptor is a dynamic instrumental surface protein that helps to interact with specific molecules to respond accordingly. Platelet is the smallest in size among the blood components, but it plays many pivotal roles to maintain hemostasis involving its surface receptors. It (platelet) has cell adhesion receptors (e.g., integrins and glycoproteins), leucine-rich repeats receptors (e.g., TLRs, glycoprotein complex, and MMPs), selectins (e.g., CLEC, P-selectin, and CD), tetraspanins (e.g., CD and LAMP), transmembrane receptors (e.g., purinergic—P2Y and P2X1), prostaglandin receptors (e.g., TxA2, PGH2, and PGI2), immunoglobulin superfamily receptors (e.g., FcRγ and FcεR), etc. on its surface. The platelet receptors (e.g., glycoproteins, protease-activated receptors, and GPCRs) during platelet activation are over expressed and their granule contents are secreted (including neurotransmitters, cytokines, and chemokines) into circulation, which are found to be correlated with different physiological conditions. Interestingly, platelets promote metastasis through circulation protecting from cytolysis and endogenous immune surveillance involving several platelets receptors. The updated knowledge about different types of platelet receptors in all probable aspects, including their inter- and intra-signaling mechanisms, are discussed with respect to not only its (platelets) receptor type but also under different pathophysiological conditions.

Platelet Rich Fibrin (PRF) Application in Oral Surgery

Platelet rich fibrin (PRF) is an autologous biological product which becomes popular day by day and available in a wide variety of fields in medicine. Platelet concentrates which are introduced at the early 90s have evolved over the years. The use such autologous materials have become trendy in recent years to encounter demanding expectations of patients, improve treatment success and maximize patient comfort. Despite its increasing use in dentistry and oral surgery, the most indications and effects are still being discussed. PRF is easily accepted by patients because of its low cost, easy to receive, low donor morbidity, low postoperative complication and infection rate. This biomaterial may be a solution for patients who have strong negative beliefs about the use of allografts and xenografts or who are afraid of complications during the grafting procedure. The objectives of these technologies are to use their synergistic effect to improve the hard and soft tissue regeneration. PRF in oral surgery are used for alveolar bone reconstruction, dental implant surgery, sinus augmentation, socket preservation, osteonecrosis, oroantral fistula closure, struggling with oral ulcers, preventing swelling and edema constitution. This chapter aims to review the clinical applications of platelets in oral surgery and the role of molecular components in tissue healing.

MicroRNAs in Platelets: Should I Stay or Should I Go?

In this chapter, we discuss different topics always using the microRNA as the guiding thread of the review. MicroRNAs, member of small noncoding RNAs family, are an important element involved in gene expression. We cover different issues such as their importance in the differentiation and maturation of megakaryocytes (megakaryopoiesis), as well as the role in platelets formation (thrombopoiesis) focusing on the described relationship between miRNA and critical myeloid lineage transcription factors such as RUNX1, chemokines receptors as CRCX4, or central hormones in platelet homeostasis like TPO, as well as its receptor (MPL) and the TPO signal transduction pathway, that is JAK/STAT. In addition to platelet biogenesis, we review the microRNA participation in platelets physiology and function. This review also introduces the use of miRNAs as biomarkers of platelet function since the detection of pathogenic situations or response to therapy using these noncoding RNAs is getting increasing interest in disease management. Finally, this chapter describes the participation of platelets in cellular interplay, since extracellular vesicles have been demonstrated to have the ability to deliver microRNAs to others cells, modulating their function through intercellular communication, redefining the extracellular vesicles from the so-called “platelet dust” to become mediators of intercellular communication.

Rapid Cytoreduction by Plateletapheresis in the Treatment of Thrombocythemia

The objective of this chapter is to provide a systematic overview of current knowledge regarding therapeutic apheresis—primarily therapeutic plateletapheresis (TP)—and to summarize evidence-based practical approaches related to cytapheresis treatment of “hyperthrombocytosis” or “extreme thrombocytosis” (ETC). Our results of platelet (Plt) quantitative/qualitative analyses and evaluation of efficacy of apheresis systems/devices—on the basis of Plt removal and in vivo Plt depletion—will be presented. Our preclinical researches confirmed that in Plt concentrates, the initial ratio of discoid shapes was 70%, spherical 20%, and less valuable (dendritic/balloonized) shapes 10%—with morphological score of platelets (MSP = 300–400). After storage, the ratio of discoid and spherical shapes was decreased, while the less valuable ones progressively increased (MSP = 200). Electron microscopy has shown discoid shapes with typical ultrastructural properties. Spherical shapes with reduced electron density and peripheral location of granules/organelles were detected. Also, dendritic shapes with cytoskeletal “rearrangement,” membrane system integrity damages, and pseudopodia formations were documented. Our clinical study demonstrated that TP was useful in ETC treatment and should help prevention of “thrombo-hemorrhagic” events—until chemotherapy, antiplatelet drugs, and other medication take effect. During TP treatment, Plt count and morphology/ultrastructure were examined. Plt functions by multiplate analyzer were evaluated. We concluded that intensive TP was an effective, safe, and rapid cytoreductive treatment for ET.

Procoagulant Platelets

There are two well-known subpopulations of activated platelets: pro-aggregatory and procoagulant. Procoagulant platelets represent a subpopulation of activated platelets, which are morphologically and functionally distinct from pro-aggregatory ones. Although various names have been used to describe these platelets in the literature (CoaT, CoaTed, highly activated, ballooned, capped, etc.), there is a consensus on their phenotypic features including exposure of high levels of phosphatidylserine (PSer) on the surface; decreased aggregatory and adhesive properties; support of active tenase and prothrombinase complexes; maximal generation by co-stimulation of glycoprotein VI (GPVI) and protease-activated receptors (PAR). In this chapter, morphologic and functional features of procoagulant platelets, as well as the mechanisms of their formation, will be discussed.

Thrombocytopenia in Neonates

Thrombocytopenia defined as platelet count below 150,000/μL is not an uncommon event at the neonatal intensive care unit (NICU). In our region we calculated a prevalence of nearly 2 of 1000 live births. Early-onset neonatal thrombocytopenia (NT) occurring within the first 72 hours of life is more common than late-onset NT. Preterm infants are affected more often than term infants and bacterial infection is the most common diagnosis associated with NT. There are a lot of maternal, perinatal, and neonatal causes associated with NT and complications include bleedings with potentially life-threatening intracranial hemorrhage. Alloimmune thrombocytopenia (NAIT) often presents with severe thrombocytopenia (<30,000/μL) in otherwise healthy newborns and needs careful evaluation regarding HPA-1a antigen status and HLA typing. Platelet transfusions are needed in severe NT and threshold platelet counts might be at ≤25,000/μL irrespective of bleeding or not. Immune mediated NT recovers within 2 weeks with a good prognosis when there happened no intracranial hemorrhage. This short review gives an overview on etiology and causes of NT and recommendations regarding platelet transfusions.

Bleeding Disorders Associated with Abnormal Platelets: Glanzmann Thrombasthenia and Bernard-Soulier Syndrome

Platelets, the smallest cells in the blood, are associated with hemostasis, bowel formation, tissue remodeling, and wound healing. Although the prevalence of inherited platelet disorders is not fully known, it is a rare disease group and is encountered in approximately between 10000 and 1000000. Glanzmann thrombasthenia (GT) and Bernard-Soulier syndrome (BSS) are more frequently observed in inherited platelet disorders. In GT, the platelet aggregation stage due to deficiency or dysfunction of the platelet GPIIb/IIIa complex cannot take place. BSS is a platelet adhesion disorder due to the absence or abnormality of GPIb/IX complex on the platelet surface. If there is bleeding after easy bruising, mucous and oral cavities, menorrhagia, tooth extraction, tonsillectomy, or other surgical interventions, inherited platelet dysfunction should be considered if the platelet count is normal while the bleeding time is long. Firstly, other causes should be investigated by making differential diagnosis of GT and BSS. In this chapter, the definition, etiology, historical process, epidemiology, genetic basis, pathophysiology, clinical findings, diagnosis, differential diagnosis, and the follow-up and treatment approach of GT and BSS will be reviewed according to the current medical literature.

Platelet Imaging

The knowledge gained through imaging platelets has formed the backbone of our understanding of their biology in health and disease. Early investigators relied on conventional light microscopy with limited resolution and were primarily able to identify the presence and basic morphology of platelets. The advent of high resolution technologies, in particular, electron microscopy, accelerated our understanding of the dynamics of platelet ultrastructure dramatically. Further refinements and improvements in our ability to localize and reliably identify platelet structures have included the use of immune-labeling techniques, correlative-fluorescence light and electron microscopy, and super-resolution microscopies. More recently, the expanded development and application of intravital microscopy in animal models has enhanced our knowledge of platelet functions and thrombus formation in vivo, as these experimental systems most closely replicate native biological environments. Emerging improvements in our ability to characterize platelets at the ultrastructural and organelle levels include the use of platelet cryogenic electron tomography with quantitative, unbiased imaging analysis, and the ability to genetically label platelet features with electron dense markers for analysis by electron microscopy.