Thrombogenicity

Biomaterials with Low Thrombogenicity. Poly(ethylene oxide) exhibits extraordinary inertness toward most proteins and biological macromolecules. The polymer is therefore used in bulk and surface modification of biomaterials to develop antithrombogenic surfaces for blood contacting materials. Such modified surfaces result in reduced concentrations of ceU adhesion and protein adsorption when compared to the nonmodifted surfaces. 

Acute coronary syndromes most often result from a physical disruption of the fibrous cap, either frank cap fracture or superficial endothelial erosion, allowing the blood to make contact with the thrombogenic material in the lipid core or the subendothelial region of the intima. This contact initiates the formation of a thrombus, which can lead to a sudden and dramatic blockade of blood flow through the affected artery. If the thrombus is nonocclusive or transient, it may either be clinically silent or manifest as symptoms characteristic of unstable angina. Importantly, if collateral vessels have previously formed, for example, due to chronic ischemia produced by multi vessel disease, even total occlusion of one coronary artery may not lead to an acute myocardial infarction. 

The cell layer lining blood vessels. It is now well established that endothelial cells not only maintain a non-thrombogenic surface in the blood vessels, but also... 

The design of bioeompatible (blood compatible) potentiometric ion sensors was described in this chapter. Sensing membranes fabricated by crosslinked poly(dimethylsiloxane) (silicone rubber) and sol gel-derived materials are excellent for potentiometric ion sensors. Their sensor membrane properties are comparable to conventional plasticized-PVC membranes, and their thrombogenic properties are superior to the PVC-based membranes. Specifically, membranes modified chemically by neutral carriers and anion excluders are very promising, because the toxicity is alleviated drastically. The sensor properties are still excellent in spite of the chemical bonding of neutral carriers on membranes. 

Factor IX Replacement Hemophilia B therapy may include recombinant (produced via transfection of mammalian cells with the human factor IX gene) or plasma-derived (concentrate from pooled plasma) factor IX (see Table 64-2). Guidelines for choosing the factor-concentrate formulation for hemophilia B are similar to the guidelines for hemophilia A. However, older-generation factor IX concentrates containing other vitamin K-dependent proteins (e.g., factors II, VII, and IX), called prothrombin complex concentrates (PCCs), have been associated with thrombogenic side effects. Consequently, these products are not first-line treatment for hemophilia B.11... 

Clotting cascade A series of enzymatic reactions by clotting factors leading to the formation of a blood clot. The clotting cascade is initiated by several thrombogenic substances. Each reaction in the cascade is triggered by the preceding one, and the effect is amplified by positive feedback loops. 

Clotting factor Plasma proteins found in the blood that are essential to the formation of blood clots clotting factors circulate in inactive forms, but are activated by their predecessor in the clotting cascade or a thrombogenic substance. Each clotting factor is designated by a Roman numeral (e.g., factor VII) and by the letter a when activated (e.g., factor Vila). 

Thromhogenic Relating to thrombogen causing thrombosis or coagulation of the blood. 

There is also another group of polyphenolic compounds, thus far only known through their biological activity as thrombogenic haptens.69... 

Ferrario JB, Deleon IR, Tracy RE. 1985b. Evidence for toxic anthropogenic chemicals in human thrombogenic coronary plaques. Arch Environ Contain Toxicol 14 529-234. 

Esmon N. L., Smirnov M. D., Esmon C. T. Thrombogenic mechanisms of antiphospholipid antibodies. Thromb Haemost 1997 78,79-82. 

MJ. Berrocal, I.H.A. Badr, D. Gao, and L.G. Bachas, Reducing the thrombogenicity of ion-selective electrode membranes through die use of a silicone-modified segmented polyurethane. Anal. Chem. 73, 5328-5333 (2001). 

C. Espadas-Torre and M.E. Meyerhoff, Thrombogenic properties of untreated and poly(ethylene oxide)-modified polymeric matrices useful for preparing intraarterial ion-selective electrodes. Anal. Chem. 67, 3108-3114 (1995). 

Sefton, M. V., Sawyer, A., Gorbet, M., Black, J. P., Cheng, E., Gemmell, C., and Pottinger-Cooper, E., Does surface chemistry affect thrombogenicity of surface modified polymers . J. Biomed. Mater. Res. 55, 447 459 (2001a). 

Simultaneously, activation of the extrinsic coagulation cascade occurs as a result of exposure of blood to the thrombogenic lipid core and endothelium, which are rich in tissue factor. This pathway ultimately leads to the formation of a fibrin clot composed of fibrin strands, cross-linked platelets, and trapped red blood cells. 

Valvular heart disease with thrombogenic complications (e.g., pulmonary hypertension, atrial fibrillation, history of endocarditis)... 

Thrombogenic mutations (e.g., factor V Leiden, protein C or S deficiency, antithrombin III... 

Table 9.2. Factors affecting thrombogenicity in coronary heart disease [from Badimon etal. (1999)] ...

Ferraccioli, G. and Gremese, E., Thrombogenicity of TNFa in rheumatoid arthritis defined through biological probes TNFa blockers, Autoimm. Rev., 3, 261, 2004. 

Hydrophobic polymer materials that slowly release N O can be used on the surface of medical devices. Many medical devices suffer from the surface adhesion of blood platelets. To minimize this thrombogenic effect, blood thinners such as heparin, coumarin, and aspirin are often used. However, systemic administration of antiplatelet agents could increase the risk of uncontrolled bleeding elsewhere in the body. In contrast, biocompatible polymer films would solve this problem [153]. It is possible to create polymeric surfaces that mimic the inner surface of a blood vessel by... 

Smith et al. (S34, S35) did not detect a relationship between Lp(a) and plasminogen in eluates from human atherosclerotic lesions and thrombi. They concluded that the thrombogenicity of Lp(a) is caused by an accumulation of Lp(a) rather than a displacement of plasminogen by Lp(a). 

MaUat, Z, Hugel, B., Ohan, J., Leseche, G., Freyssinet, J.M., and Tedgui, A., 1999, Shed membrane microparticles with procoagulant potential in human atherosclerotic plaques a role for apoptosis in plaque thrombogenicity, Circulation 99 348-353. 

The fatal complications caused by toxin-LR in mice are unusual. Toxin-LR is a potent thrombogenic agent. Generally, such agents bring about symptoms of illness within a few minutes of injection of a lethal dose. However, toxin-LR produces no overt signs of illness until about one-half hour has elapsed. Moreover, pretreatment of mice with known antithrombotic agents does not affect the lethality of the toxin. 

One molecule of lepirudin binds to one molecule of thrombin and thereby blocks the thrombogenic activity of thrombin. As a result, all thrombin-dependent coagulation assays are affected (eg, aPTT values increase in a dose-dependent fashion). Pharmacokinetics ... 

---