<p>The management of thrombosis in the presence of thrombocytopenia is challenging because the inherent risk of bleeding associated with anticoagulant use may increase due to low platelet counts. Guidelines regarding anticoagulant use in this situation are based mainly on expert opinions and anecdotal data. We developed an <em>in-vitro</em> model to study the effect of anticoagulants on plasma clot formation in the presence of low platelet counts. We used thromboelastography (TEG) to measure global viscoelastic properties of clot formation and scanning electron microscopy (SEM) to observe and quantify changes in the fibrin clot structure. Experiments were conducted in plasma with varying platelet concentrations from <10 >– 150 × 10<sup>9</sup>/L. Clotting was activated with tissue factor (TF) and calcium, in the presence of factor XIIa inhibitor, corn trypsin inhibitor. One of the following anticoagulants at therapeutic concentration was added to the mixture: unfractionated heparin (UFH), dalteparin, fondaparinux, rivaroxaban or dabigatran. We found clotting had different sensitivity to TF concentration depending on the anticoagulant present. Effects on TEG parameters varied at a fixed TF concentration with each anticoagulant. UFH had the greatest influence, delaying clotting significantly at low platelet counts. The factor-specific anticoagulants had the least impact on TEG parameters. SEM revealed that UFH had the greatest impact on clot structure. UFH caused significant increase in porosity and fibrin widths and had significantly less fibers when platelets decreased. In conclusion, this study may provide fundamental data to understand clot formation in the presence of anticoagulants at low platelet counts. At low platelets the anticoagulants can jeopardize clot formation, especially UFH. The mechanism of each anticoagulant may contribute to the variation in response to TF initiated clotting. AT-dependent anticoagulants compromised plasma clotting more than the newer factor specific anticoagulants, possibly related to the multiple, non-specific inhibition of coagulation factors.</p> / Master of Science (MSc)
| Identifer | oai:union.ndltd.org:mcmaster.ca/oai:macsphere.mcmaster.ca:11375/14052 |
| Date | 04 1900 |
| Creators | Gantioqui, Jorell |
| Contributors | Chan, Anthony K.C., Chan, Howard, Sheffield, William, Medical Sciences (Blood and Cardiovascular) |
| Source Sets | McMaster University |
| Detected Language | English |
| Type | thesis |
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