Article

Jurk K, Kehrel BE. Platelets: physiology and biochemistry

Department of Anaesthesiology and Intensive Care, Experimental and Clinical Haemostasis, University-Hospital Münster, Münster, Germany.
Seminars in Thrombosis and Hemostasis (Impact Factor: 3.88). 02/2005; 31(4):381-92. DOI: 10.1055/s-2005-916671
Source: PubMed

ABSTRACT

Platelets are specialized blood cells that play central roles in physiologic and pathologic processes of hemostasis, inflammation, tumor metastasis, wound healing, and host defense. Activation of platelets is crucial for platelet function that includes a complex interplay of adhesion and signaling molecules. This article gives an overview of the activation processes involved in primary and secondary hemostasis, for example, platelet adhesion, platelet secretion, platelet aggregation, microvesicle formation, and clot retraction/stabilization. In addition, activated platelets are predominantly involved in cross talk to other blood and vascular cells. Stimulated "sticky" platelets enable recruitment of leukocytes at sites of vascular injury under high shear conditions. Platelet-derived microparticles as well as soluble adhesion molecules, sP-selectin and sCD40L, shed from the surface of activated platelets, are capable of activating, in turn, leukocytes and endothelial cells. This article focuses further on the new view of receptor-mediated thrombin generation of human platelets, necessary for the formation of a stable platelet-fibrin clot during secondary hemostasis. Finally, special emphasis is placed on important stimulatory and inhibitory signaling pathways that modulate platelet function.

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Available from: Beate E Kehrel, Aug 23, 2015
    • "P latelets (PLTs) are key contributors to coagulation and wound healing, as well as providing a significant contribution to inflammation and innate immune responses ( Jurk and Kehrel 2005). Transfusion of platelet concentrates (PCs) is standard in the treatment of thrombocytopenia and severe trauma (Hunt 1998; Sahler and others 2012). "
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    ABSTRACT: The transfusion of platelet concentrates (PCs) is widely used to treat thrombocytopenia and severe trauma. Ex vivo storage of PCs is associated with a storage lesion characterized by partial platelet activation and the release of soluble mediators, such as soluble CD40 ligand (sCD40L), RANTES, and interleukin (IL)-8. An in vitro whole blood culture transfusion model was employed to assess whether mediators present in PC supernatants (PC-SNs) modulated dendritic cell (DC)-specific inflammatory responses (intracellular staining) and the overall inflammatory response (cytometric bead array). Lipopolysaccharide (LPS) was included in parallel cultures to model the impact of PC-SNs on cell responses following toll-like receptor-mediated pathogen recognition. The impact of both the PC dose (10%, 25%) and ex vivo storage period was investigated [day 2 (D2), day 5 (D5), day 7 (D7)]. PC-SNs alone had minimal impact on DC-specific inflammatory responses and the overall inflammatory response. However, in the presence of LPS, exposure to PC-SNs resulted in a significant dose-associated suppression of the production of DC IL-12, IL-6, IL-1α, tumor necrosis factor-α (TNF-α), and macrophage inflammatory protein (MIP)-1β and storage-associated suppression of the production of DC IL-10, TNF-α, and IL-8. For the overall inflammatory response, IL-6, TNF-α, MIP-1α, MIP-1β, and inflammatory protein (IP)-10 were significantly suppressed and IL-8, IL-10, and IL-1β significantly increased following exposure to PC-SNs in the presence of LPS. These data suggest that soluble mediators present in PCs significantly suppress DC function and modulate the overall inflammatory response, particularly in the presence of an infectious stimulus. Given the central role of DCs in the initiation and regulation of the immune response, these results suggest that modulation of the DC inflammatory profile is a probable mechanism contributing to transfusion-related complications.
    No preview · Article · Oct 2015 · Journal of interferon & cytokine research: the official journal of the International Society for Interferon and Cytokine Research
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    • "The relation between platelets and cancer progression suggests a possible role that extends beyond their hemostatic function [14,15]. More recently, platelets have been recognized as mediators of other regulatory functions in physiology such as angiogenesis, wound healing and immunomodulation [15]. "
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    ABSTRACT: Background Head and neck squamous cell carcinoma (HNSCC) mortality rates have not shown significant reduction in decades. Platelets are being implicated in having cancer-promoting roles, an observation supported by the adverse outcomes in many malignancies associated with thrombocytosis. However, the prognostic significance of platelet counts in HNSCC is unknown. Here, we comprehensively investigate the predictive value of platelet counts at diagnosis and post-diagnosis antiplatelet treatment in the overall survival of HNSCC patients.Methods The study population consists of 1051 pathologically confirmed HNSCC cases diagnosed between years 2000 and 2012 in a tertiary medical center. Platelet count was investigated as a predictor of survival by fitting Cox Proportional Hazards (CPH) regression models to generate Hazard Ratios (HR) and 95% confidence intervals (CI), while adjusting for age, sex, race, stage, treatment and smoking status. Finally, we evaluated the association between overall survival and antiplatelet medication intake after diagnosis.ResultsMultivariable analysis showed an increased death rate in patients with thromobocytosis [HR 2.37, 95% CI 1.60-3.50)] and high normal platelet counts [HR 2.20, 95% CI 1.58-3.05] compared to the reference middle normal group. Post-diagnosis treatment with antiplatelet medications was inversely associated with death rate [HR 0.76, 95% CI 0.58-0.99].Conclusions Higher platelet counts were associated with poorer prognosis in HNSCC patients, whereas antiplatelet agents were associated with better prognosis. Antiplatelet agents warrant evaluation in preclinical and clinical settings as a way to improve survival in HNSCC.
    Full-text · Article · Sep 2014 · Journal of Hematology & Oncology
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    • "Platelet can be activated via both native and exogenous molecules, including collagen, platelet-activating factor, calcium, serotonin, magnesium, thromboxane A2 (TXA2), adenosine diphosphate (ADP), adrenergic activity, oxidative stress, shear stress, physical as well as mental stress or chemical used, such as nicotine8687888990. The activated platelets express various surface markers like; glycoprotein receptor GPIIb/IIIa, p-selectin and CD40 ligand and secretes many pro-inflammatory and immune-modulators from their storage granules[87]. This process of paracrine secretion is termed " platelet bioactivity " and enables platelets to crosstalk with other platelets, endothelial cells as well as immune cell's9192. "
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    ABSTRACT: Management of osteoporotic fracture is challenging. In most clinical settings, skeletal regenerations are biologically optimized, but still many patients continue to experience delayed or impaired healing. Methods to enhance these healing processes, are needed to decrease patient’s agony, so that they can return to their work and regain their socioeconomic status in the community. Till this time, autologous bone grafting remain the standard procedure against which all new technologies are compared and analyzed.The success rate of union even after these grafts varies between 80-85% which further becomes decreased in case of repeated bone graft surgeries with donor site morbidities. Considering the concept that the healing of fracture started as soon as the formation of fracture clot, several investigators have suggested that degranulation of platelets at fracture clot elaborates the bioactive component, that aided the healing process. Because autologous platelet rich plasma products are safe and easy to prepare and administer, in this review, we reviewed the role of bioactive component released by activated platelet rich plasma in the fracture healing process and hypothesized that by combining the advantages of autologous bone grafts with autologous platelets concentrate, better and prompt results in orthopedic trauma managements can be obtained. We also observe that the use of these bioactive factors to enhance skeletal repair/healing represents the future of skeletal trauma management
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