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Trauma Induced Coagulopathy pp 403–418Cite as

Anti-fibrinolytics

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Abstract

The fibrinolytic system, driven by the plasminogen activator family of proteases, is widely known for its capacity to degrade fibrin and facilitate clot removal but also has a number of unrelated effects in the central nervous system (CNS). In the context of severe trauma, this system can be hyper-activated to varying extents and this is frequently observed in trauma-induced coagulopathy and is associated with poor outcome. Anti-fibrinolytic drugs including tranexamic acid (TXA) are currently used successfully in elective surgery and gynaecology to reduce bleeding complications. TXA, however, has been uniquely tested in recent years for its efficacy in patients who are bleeding or at risk of bleeding early after trauma. Administered within 3 h post injury, TXA reduced all-cause mortality and mortality due to bleeding, whereas later administration was surprisingly deleterious, but this may be explained by a counterintuitive effect of TXA on plasminogen under certain conditions. Moreover, while the trauma field has widely embraced the use of TXA, questions about its thromboembolic potential and the applicability for different subpopulations of trauma patients as well as the potential non-fibrinolytic consequences of plasmin blockade still remain and will be further assessed in ongoing clinical trials.

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Abbreviations

aPC:

Activated protein C

ATC:

Acute traumatic coagulopathy

CSF:

Cerebrospinal fluid

EACA:

ε-Aminocaproic acid

ICH:

Intracranial haemorrhage

ISS:

Injury severity score

LY30:

Percent clot lysis 30 min after maximum amplitude of the clot has been reached assessed with thromboelastography

PAI-1:

Plasmin activator inhibitor 1

PAI-2:

Plasmin activator inhibitor 2

TAFI:

Thrombin activatable fibrinolysis inhibitor

TBI:

Traumatic brain injury

TEG:

Thromboelastography

tPA:

Tissue-type plasminogen activator

TXA:

Tranexamic acid

uPA:

Urokinase-type plasminogen activator

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Authors and Affiliations

  1. Molecular Neurotrauma and Haemostasis, Australian Centre for Blood Diseases, Central Clinical School, Monash University, Level 4 Burnet Building, 89 Commercial Road, Melbourne, 3004, VIC, Australia

    Dominik F. Draxler M.D. & Robert L. Medcalf Ph.D.

  2. National Trauma Research Institute, Melbourne, Australia

    Russell L. Gruen M.B.B.S., Ph.D., F.R.A.C.S.

Authors
  1. Dominik F. Draxler M.D.
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  2. Robert L. Medcalf Ph.D.
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  3. Russell L. Gruen M.B.B.S., Ph.D., F.R.A.C.S.
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Correspondence to Robert L. Medcalf Ph.D. .

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Editors and Affiliations

  1. Dept of Surgery & Trauma Research Center, Univ of Colorado School of Medicine, Aurora, Colorado, USA

    Eduardo Gonzalez

  2. Dept of Surgery & Trauma Research Center, Univ of Colorado School of Medicine, Aurora, Colorado, USA

    Hunter B. Moore

  3. Dept of Surgery & Trauma Research Center, Univ of Colorado Sch of Med&Denver Healt, Denver, Colorado, USA

    Ernest E. Moore

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Draxler, D.F., Medcalf, R.L., Gruen, R.L. (2016). Anti-fibrinolytics. In: Gonzalez, E., Moore, H., Moore, E. (eds) Trauma Induced Coagulopathy. Springer, Cham. https://doi.org/10.1007/978-3-319-28308-1_25

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