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Fibrinogen concentrate in dilutional coagulopathy: a dose study in pigs

Authors

  • Judith Martini,

    Corresponding author
    1. Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    2. Clinical Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    3. Department of Paediatrics, Medical University Innsbruck, Innsbruck, Austria
    4. US Army Institute of Surgical Research, Fort Sam Houston, Texas
    • Address reprint requests to: Judith Martini, Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Anichstrasse 35, 6020 Innsbruck, Austria; e-mail: Judith.Martini@uki.at; Judith.Martini@i-med.ac.at.

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  • Sonja Maisch,

    1. Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    2. Clinical Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    3. Department of Paediatrics, Medical University Innsbruck, Innsbruck, Austria
    4. US Army Institute of Surgical Research, Fort Sam Houston, Texas
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  • Lisa Pilshofer,

    1. Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    2. Clinical Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    3. Department of Paediatrics, Medical University Innsbruck, Innsbruck, Austria
    4. US Army Institute of Surgical Research, Fort Sam Houston, Texas
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  • Werner Streif,

    1. Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    2. Clinical Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    3. Department of Paediatrics, Medical University Innsbruck, Innsbruck, Austria
    4. US Army Institute of Surgical Research, Fort Sam Houston, Texas
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  • Wenjun Martini,

    1. Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    2. Clinical Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    3. Department of Paediatrics, Medical University Innsbruck, Innsbruck, Austria
    4. US Army Institute of Surgical Research, Fort Sam Houston, Texas
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  • Dietmar Fries

    1. Clinical Department of Anesthesiology and General Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    2. Clinical Department of General and Surgical Intensive Care Medicine, Medical University Innsbruck, Innsbruck, Austria
    3. Department of Paediatrics, Medical University Innsbruck, Innsbruck, Austria
    4. US Army Institute of Surgical Research, Fort Sam Houston, Texas
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  • This study was supported in part by LFB, Paris, France.

Abstract

Dilutional coagulopathy can be reversed with fibrinogen concentrate. Effects of different fibrinogen dosages on clot function are not defined; high doses may increase the risk of thromboemboembolism. This study investigated the effect of six fibrinogen dosages on coagulation profile and blood loss in coagulopathic pigs.

Forty-two pigs underwent a 60% hemodilution (HD) with hydroxyethylstarch (HES 130/0.4). After a standardized bone injury, animals randomly received 37.5, 75, 150, 300, 450 or 600 mg/kg fibrinogen (FGTW, LFB) or 500 ml of saline. Four hours later, a standardized liver injury was performed. Animals were then observed for two hours or until death. Blood loss was measured after death; Hemodynamic and coagulation parameters (thromboelastometry) were measured at baseline (BL), after HD, 15’, 1, 2, 4 hours after fibrinogen administration and 2 hours after liver injury or right before the animals’ death. Occurrence of thrombosis was examined in histological slides of internal organs. Statistical significance was set at p < 0.05.

Doses of 150 mg/kg fibrinogen and higher reversed dilutional coagulopathy: Maximum clot firmness (MCF) was decreased after hemodilution (36 ± 3 mm vs. 65 ± 4 mm at BL, p < 0.05) and returned to BL after fibrinogen administration (69 ± 5 mm). Blood loss was significantly decreased with increased fibrinogen dosages: 42 ± 19 (sham), 34 ± 14 (75 mg/kg), 29 ± 13 (150 mg/kg), 28 ± 10 ml/kgbw (600 mg/kg).

Fibrinogen (150-600 mg/kg) normalized clot firmness and decreased blood loss. No signs of hypercoagulability or thromboembolism were detected after high dosages.

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