<p>Unfractionated heparin (UFH) is used as an adjunct during thrombolytic therapy. However, its use is associated with many clinical limitations, such as the inability to inhibit fibrin-bound coagulation factors, increasing the potential for sustained procoagulant activity. We have developed a covalent conjugate of antithrombin (AT) and heparin (ATH) with superior anticoagulant properties to those of UFH. Some advantages of ATH include enhanced inhibition of surface-bound enzymes and its ability to reduce the overall size and mass of clots <em>in vivo</em>. However, the potential interactions of UFH or ATH with the components of the fibrinolytic pathway are not well understood. Therefore, our study utilized discontinuous second order rate constant (<em>k<sub>2</sub></em>) assays to determine rates of inhibition of plasmin (Pn) in the presence or absence of fibrin by AT+UFH <em>vs.</em> ATH. In addition, we monitored the rates of Pn generation in a system comprised of preformed fibrin clots with the aim of evaluating the inhibitory effect of AT+UFH or ATH in this more native system. The <em>k<sub>2 </sub></em>values for the inhibition of Pn without fibrin were 5.74x10<sup>6</sup>±0.278x10<sup>6</sup> and 6.39x10<sup>6</sup>±0.588x10<sup>6</sup> for AT+UFH and ATH, respectively (p=0.36). In the presence of fibrin, the <em>k<sub>2 </sub></em>values decreased to 1.45x10<sup>6</sup>±0.0971x10<sup>6</sup> for AT+UFH and 3.07x10<sup>6</sup>±0.192x10<sup>6 </sup>for ATH (<em>p</em></p> / Master of Science (MS)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/13086 |
| Date | 10 1900 |
| Creators | Chander, Ankush |
| Contributors | Chan, Anthony K.C., Medical Sciences (Blood and Cardiovascular) |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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