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Continuous thrombin infusion leads to a bleeding phenotype in sheep.
Jolanta M Siller-Matula1, Ingrid Miller, Manfred Gemeiner
1Department of Cardiology, Medical University of Vienna, Austria. jolanta.siller-matula@meduniwien.ac.at
Thrombosis Research
|February 1, 2012
Summary
Protracted intravenous thrombin infusion in sheep revealed significant anti-coagulant and anti-platelet effects, including decreased fibrinogen and platelets, alongside lung hemorrhage. This establishes a new large animal model for studying thrombin in vivo.
Area of Science:
- Biochemistry
- Physiology
- Pharmacology
Background:
- Thrombin plays a key role in coagulation and hemostasis.
- Thrombin possesses multiple, less understood functions beyond coagulation.
- Establishing a large animal model is crucial for in vivo thrombin research.
Purpose of the Study:
- To develop and validate an ovine (sheep) model for studying thrombin's effects in vivo.
- To investigate the systemic effects of prolonged thrombin infusion in a large animal model.
Main Methods:
- Continuous intravenous infusion of thrombin in Austrian Mountain Sheep over five hours.
- Dose escalation study (0.0004-0.42 IU/kg/min) and dose verification study (0.42 IU/kg/min vs. saline).
- Analysis included proteomic analysis, coagulation tests, and platelet function assays.
Main Results:
- Thrombin infusion significantly decreased fibrinogen levels (75%) and platelet counts (36%).
- Coagulation tests showed prolonged thrombin time and activated partial thromboplastin time.
- Predominant anti-coagulant and anti-platelet effects observed, including reduced clot firmness and platelet aggregation, with lung hemorrhage as a notable outcome.
Conclusions:
- Protracted intravenous thrombin infusion in sheep provides a novel experimental model.
- This model allows for the in vivo study of thrombin's diverse effects in a large animal species.
- The model demonstrates thrombin's complex role, including anti-coagulant and anti-platelet activities.
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