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Fibrinolysis, Antifibrinolytic Agents, and Perioperative Considerations

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Essentials of Blood Product Management in Anesthesia Practice

Abstract

Fibrinolysis is an integral component of hemostasis that acts to regulate fibrin formation. Its actions are counterbalanced by the coagulation process, maintaining against excess clot formation or hemorrhage. Excessive release of plasmin through surgery or other means can result in a pathophysiological state characterized by bleeding, inflammation, and coagulopathy. Measurement of this fibrinolytic activity is often done in the clinical setting using viscoelastic testing; however, there is no gold standard. The antifibrinolytics tranexamic acid, epsilon-aminocaproic acid, and aprotinin act to reduce bleeding and transfusion requirements in the perioperative setting. Despite widespread concerns for thromboembolic complications, data has shown their relative safety. Tranexamic acid has been the most widely studied and utilized agent and is well tolerated with minimal side effects. The concern for seizure activity, particularly associated with cardiac surgery, has been diminished with appropriate dosing of tranexamic acid. The popularity of tranexamic acid in trauma is based on the CRASH-2 study, but the controversy surrounding fibrinolytic shutdown has limited its use in many centers. Orthopedics, liver surgery and transplantation, obstetrics, neurosurgery, and pediatric surgery have all extensively studied and implemented tranexamic acid to reduce blood loss and transfusion requirements.

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Abbreviations

A2AP:

Alpha-2-antiplasmin

ACT:

Activated clotting time

APTT:

Activated partial thromboplastin time

ATC:

Acute traumatic coagulopathy

BART:

Blood conservation using antifibrinolytics in a randomized trial

CABG:

Coronary artery bypass graft

CPB:

Cardiopulmonary bypass

CRASH:

Clinical randomization of an antifibrinolytic in significant hemorrhage

EACA:

Epsilon-aminocaproic acid

FDA:

Food and drug administration

GABA/A:

Gamma-aminobutyric acid type A

INR:

International normalized ratio

IV:

Intravenous

LY30:

Lysis measurement 30 minutes

MATTERs:

Military application of tranexamic acid in trauma emergency resuscitation study

PAI-1:

Plasminogen activator inhibitor-1

PAI-2:

Plasminogen activator inhibitor-2

PATCH:

Prehospital antifibrinolytics for traumatic coagulopathy and hemorrhage

PPH:

Postpartum hemorrhage

RCT:

Randomized control trial

ROTEM:

Rotational thromboelastometry

SAH:

Subarachnoid hemorrhage

TAFI:

Thrombin-activated fibrinolysis inhibitor

TBI:

Traumatic brain injury

TEG:

Thromboelastography

THA:

Total hip arthroplasty

TKA:

Total knee arthroplasty

tPA:

Tissue plasminogen activator

TXA:

Tranexamic acid

ULTRA:

Ultra-early tranexamic acid after subarachnoid hemorrhage

uPA:

Urokinase plasminogen activator

WHO:

World health organization

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Authors and Affiliations

  1. NYU Langone Health, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York, NY, USA

    Aaron N. Primm

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  1. Aaron N. Primm
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Correspondence to Aaron N. Primm .

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Editors and Affiliations

  1. NYU-Grossman School of Medicine, Department of Anesthesiology, New York, NY, USA

    Corey S. Scher

  2. Departments of Anesthesiology and Pharmacology Toxicology, and Neurosciences, Louisiana State University School of Medicine-Shreveport, Shreveport, LA, USA

    Alan David Kaye

  3. Department of Anesthesiology and Perioperative Medicine, Milton S. Hershey Medical Center, Penn State College of Medicine, Hershey, PA, USA

    Henry Liu

  4. NYU Grossman School of Medicine, Department of Anesthesiology, Perioperative Care and Pain Medicine, New York, NY, USA

    Seth Perelman

  5. NYU-Grossman School of Medicine, Department of Anesthesiology, New York, NY, USA

    Sarah Leavitt

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Primm, A.N. (2021). Fibrinolysis, Antifibrinolytic Agents, and Perioperative Considerations. In: Scher, C.S., Kaye, A.D., Liu, H., Perelman, S., Leavitt, S. (eds) Essentials of Blood Product Management in Anesthesia Practice. Springer, Cham. https://doi.org/10.1007/978-3-030-59295-0_5

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