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Immunity Role of Platelets
Besides haemostasis, platelets also appear to have a role in the immune system.38 Low grade inflammatory conditions are associated with a high mean platelet volume (MPV).36 Platelets can also be classified as natural inflammatory cells. They have the ability to aggregate/gather around microorganisms, and to assist with the removal from the blood.38 In the presence of infection, platelets become activated and their production is increased by certain inflammatory mediators, such as interleukin 6.36 Platelets aggregate with leukocytes in areas of ischemia/reperfusion injury.34 The activated platelets interact with and signal to other inflammatory cells, such as leukocytes, and release their granules in high concentrations. Approximately 0.26 to 7.6% of HIV infected patients will have venous thromboembolism and activated platelets have been suggested as the etiology.38 Several chemokines are stored in very significant amounts in alpha granules in the platelet cytoplasm which possess virucidal and suppressive activity against HIV37. Activated platelets release cytokines such as IL-1-β, IL-7, IL-8, platelet activating factor (PAF) and transforming growth factor (TGF)-β.38 The chemokines released activates leukocytes, specifically
neutrophils and monocytes. P-selectin, a cell adhesion molecule, mediated by thrombin, is expressed on activated platelets which increase the platelet’s adhesion to endothelial cells and to neutrophils. Activated platelets release a pro-inflammatory-mediator CD40 ligand which induces the production of IL-6, IL-8 and the synthesis of tissue factor.36 Platelets therefore play a role in surveillance and amplifying the immune response during viral infections. However, platelets and cytokines, such as IL-18, can also cause dysregulation of the immune response to HIV.38
Red Blood Cells (Erythrocytes)
Platelets are influenced by physical and chemical properties of red blood cells (RBCs). RBCs can release ADP and therefore has prothrombotic properties by activating platelets resulting in a prothrombotic state. RBCs may stimulate platelet granule release which will recruit additional platelets into the developing thrombus. The interaction between platelets and RBCs are initiated by platelet activation. As the platelets become activated, the coagulation pathways are stimulated resulting in fibrin network trapping more platelets and RBCs. The interaction of activated platelets with RBCs therefore has a positive feedback on the coagulation system.47 Fibrinogen expresses binding sites for the membrane receptors of cells involved in inflammation. Fibrinogen enhances adhesion of the RBCs by binding to the erythrocyte membrane.47 Red blood cells aggregation thereby increases in the presence of fibrinogen. The erythrocyte sedimentation rate (ESR) is a marker of inflammation. Since inflammation can increase the concentration of fibrinogen, the ESR can assess fibrinogen levels indirectly.27 Red blood cell membranes appear smooth in non-pregnant females and granular in pregnant females, it is possible that the same appearance may be present in HIV patients who are also hypercoagulable.47
Chapter 1: Introduction
1.1) Introduction
1.2) Hypothesis and Objectives
Chapter 2: Literature review
2.1) Cells and plasma proteins in the blood
2.2) Platelets
2.3) Platelet recruitment pathway
2.4) Thrombocytopenia
2.5) Immunity Role of Platelets
2.6) Antiretrovirals and Platelets
2.7) Ultrastructure of Platelets
2.8) Red Blood Cells (Erythrocytes)
2.9) Fibrin
2.10) Coagulation models and monitoring
2.11) Inflammatory-coagulation link
2.12) Fibrin and Iron
2.13) Microparticles/microvesicles
2.14) Deep Vein Thrombosis (DVT) 36
2.15) Screening tests for deep vein thrombosis
2.16) Relevance and Motivation
Chapter 3: Methodology
3.1) Study Design
3.2) Research Site
3.3) Subjects and Patient selection
3.4) Materials and Methods
3.5) Ethical Considerations
3.6) Financing
Chapter 4: Haematological markers
Introduction
Chapter objectives
Materials and Methods
Results
Discussion
Conclusion
Chapter 5: Viscoelastic, Light microscopy and ultrastructural properties
Introduction
Chapter objectives
Materials and Methods
Results
TEG
Light Microscopy
Scanning electron microscopy
Discussion
Conclusion
Chapter 6: Viscoelastic and ultrastructural properties of platelet poor plasma
Introduction
Chapter objectives
Materials and Methods
Results
Scanning electron microscopy
Discussion
Conclusion
