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Review
. 2021 Jan-Feb;71(1):65-75.
doi: 10.1016/j.bjane.2020.12.007. Epub 2020 Dec 25.

Perioperative hyperfibrinolysis - physiology and pathophysiology

David Silveira Marinho  1
Affiliations
Review

Perioperative hyperfibrinolysis - physiology and pathophysiology

David Silveira Marinho. Braz J Anesthesiol. 2021 Jan-Feb.

Abstract

Introduction and objectives: The role of the anesthesiologist in the perioperative management of hemostasis has attracted increasing attention. The fibrinolytic system participates in hemostasis, removing clots after repair of the vascular injury. Over the past two decades, several studies have assessed the efficacy and safety of antifibrinolytic agents in reducing perioperative bleeding and transfusion requirements. Some of the conditions that seem to benefit from antifibrinolytic drugs involve trauma, postpartum hemorrhage, cardiac surgery, spine surgery, knee or hip arthroplasty, urological and gynecological surgery, among others. However, there are currently few publications focusing on the perioperative features of fibrinolytic system, which will be the subject of the present review.

Content and conclusions: Fibrinolytic physiology, its relationship with the clot structure and its perioperative behavior are described. Pathophysiological mechanisms related to anesthesiology clinical practice and their possible perioperative scenarios are addressed according to a suggested classification. This article aims to provide anesthesiologists with a broader understanding of the normal functioning of fibrinolysis, the mechanisms of possible deviations from normality in the perioperative period, the pathophysiological rationale supporting the current indications of antifibrinolytics, and some recent outcomes obtained with their use.

Keywords: Blood clotting disorders; Fibrinolysis; Hemostasis.

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Figures

Figure 1
Figure 1
Physiological activators and inhibitors of fibrinolysis. Tissue plasminogen activator (t-PA); Plasminogen Activator Inhibitor 1 (PAI-1); α2-antiplasmin (α2-AP); Thrombin-activatable Fibrinolysis Inhibitor (TAFI).
Figure 2
Figure 2
Early events of coagulation and fibrinolysis. Plasminogen (PLG); Tissue plasminogen activator (t-PA).
Figure 3
Figure 3
Formation of a ternary complex between plasminogen, t-PA and fibrin.
Figure 4
Figure 4
Dynamic action of t-PA and plasmin on fibrin mesh. A: Arrows indicate peptide bonds (formed by lysine and another amino acid) close to the plasmin molecule; B: Cleavage of several peptide bonds by a single plasmin molecule; C: Lysine residues originated from the cleaved peptide bond become exposed and offer a new binding site for several other plasminogen molecules, starting a positive feedback. Plasminogen (PLG); Plasmin (PLI); Tissue plasminogen activator (t-PA).
Figure 5
Figure 5
Control of fibrinolysis by inhibitors’ action after detachment of t-PA and plasmin from the fibrin mesh surface. A: After completing the fibrin mesh breakdown, plasmin and t-PA are released into the surrounding plasma, where they are captured by their inhibitors (α2-AP and PAI-1, respectively). B: Although it does not restore the fibrin fragmented points, TAFI removes the newly exposed lysine residues, preventing additional plasminogen molecules from binding and intensifying fibrinolysis and blocking the positive feedback described previously. Plasmin (PLI); Tissue plasminogen activator (t-PA); Plasminogen Activator Inhibitor 1 (PAI-1); α2-antiplasmin (α2-AP); Thrombin-Activatable Fibrinolysis Inhibitor (TAFI).
Figure 6
Figure 6
Classification proposed for fibrinolysis.
See this image and copyright information in PMC

References

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