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Chapter 13
Biomaterials and Thrombosis
| Question | Answer |
|---|---|
| Two main mechanisms of blood coagulation | Intrinsic Extrinsic |
| What is the final product of both mechanisms of blood coagulation? | The conversion of fibrinogen to fibrin, the main constituent of the blood clot. |
| Why are substances that bind calcium (called calcium chelators) effective anticoagulants? | Calcium is required for almost all reactions in each cascade. |
| How is the intrinsic pathway initiated? | 1. By trauma to blood itself 2. Exposure of blood to ECM molecules in a damaged vessel wall. |
| Intrinsic pathways are important around biomaterials if... | ...the surface of the biomaterial is negatively charged, where initiation occurs by adsorption of Factor XII protein to the surface. |
| How is the extrinisic pathway initiated? | By the release of tissue factor (TF) from macrophages and endothelial cells after exposure to inflammatory mediators (IL-1 and TNF-alpha) |
| What converts prothrombin into the active enzyme Thrombin? | Factor Xa. This process is now a part of the Common Pathway, the part of the cascade system both intrinsic and extrinsic pathways lead to. |
| What is the importance of Thrombin? | As a procoagulant: cleaves fibrinogen, resulting in the creation of fibrin monomer and fibrinopeptides A and B |
| Why are fibrin monomers important? | They polymerize to form long fibrin fibers, the basis of the blood clot. |
| Why are fibrinopeptides A and B important? | Act as chemotaxis for neutrophils. |
| Importance of Factor V (A substrate of thrombin) | When converted to Factor Va it accelerates the conversion of prothrombin into thrombin to speed clotting. |
| Importance of Factor XIII (A substrate of thrombin) | Acts in the presence of calcium to covalently crosslink fibrin chains |
| What is considered a mature thrombus (blood clot)? | The meshwork of fibrin encasing platelets, adhesive proteins, and other bioactive factors. |
| Hemocompatibility tests in vitro | Interaction time is important Static - test material is exposed to freshly drawn whole blood and the time for thrombus formation is recorded. Dynamic - test similar to static but involve controlled flow regimes |
| Quantifiable parameters of dynamic in vitro tests | Coagulation time Amount of adhered platelets Mass of adherent thrombus Amount of platelet granule release |
| Major limitation of in vitro experiments | The use of anticoagulants affects the recorded coagulation time Control materials must be tested at the same time and with same blood as experimental material |
| Hemocompatibility tests in vivo | Assessment is similar to that of in vitro Not completely productive because of the differences between animal species and humans |
| Choices that exist when choosing an in vivo experiment | 1. Choice of animal 2. Length of study and choice of time points 3. Inclusion of proper control materials |
| Concerns about direct in vivo testing | It is difficult to control or measure blood flow conditions in animal models Variations in tissue trauma during implantation can affect the results of the experiments |
| How to improve in vivo testing | Use shunts and perform test ex vivo. Material is in tubular form and placed as an extension in a shunt that connect an arterty to a vein or vice verse. |
| Advantage/Distadvantage of shunts | Advantage: easily controlled flow native blood may be useed shunt can remain for several months Disadvantage: does not replicate an implant procedure. |
Created by:
digitaleyes
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