Efficacy and Safety of Tranexamic Acid in Major Non-Cardiac Surgeries at High Risk for Transfusion: A Systematic Review and Meta-Analysis

Houston, Brett L.; Uminski, Kelsey; Mutter, Thomas C; Rimmer, Emily; Houston, Donald S.; Menard, Chantalle; Garland, Allan; Ariano, Robert E.; Tinmouth, Alan; Abou‐Setta, Ahmed M; Rabbani, Rasheda; Neilson, Christine; Rochwerg, Bram; Turgeon, Alexis F.; Falk, Jamie; Breau, Rodney H.; Fergusson, Dean; Zarychanski, Ryan

doi:10.1016/j.tmrv.2019.10.001

Cited by 33 publications

(32 citation statements)

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“…contributed equally to this work. DOI: 10.1159/000511230 dergoing major surgery reduces the need for red blood cell transfusions [4][5][6][7][8][9][10][11]. It is known that hyperfibrinolysis is associated with increased mortality in severely injured patients [12,13].…”

Section: Introductionmentioning

confidence: 99%

“…Intravenous administration of tranexamic acid (TXA) is highly recommended for treatment and prophylaxis of hyperfibrinolysis [1, 2], not least due to the fact that alternatives like aprotinin and ε-aminocaproic acid are not widely available or have very restricted indications [3, 4]. TXA administration to trauma patients and/or those undergoing major surgery reduces the need for red blood cell transfusions [4-11]. It is known that hyperfibrinolysis is associated with increased mortality in severely injured patients [12, 13].…”

Section: Introductionmentioning

confidence: 99%

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Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry

Kämmerer

Groene

Sappel

et al. 2020

Transfus Med Hemother

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Introduction: Tranexamic acid (TXA) is the standard medication to prevent or treat hyperfibrinolysis. However, prolonged inhibition of lysis (so-called “fibrinolytic shutdown”) correlates with increased mortality. A new viscoelastometric test enables bedside quantification of the antifibrinolytic activity of TXA using tissue plasminogen activator (TPA). Materials and Methods: Twenty-five cardiac surgery patients were included in this prospective observational study. In vivo, the viscoelastometric TPA test was used to determine lysis time (LT) and maximum lysis (ML) over 96 h after TXA bolus. Additionally, plasma concentrations of TXA and plasminogen activator inhibitor 1 (PAI-1) were measured. Moreover, dose effect curves from the blood of healthy volunteers were performed in vitro. Data are presented as median (25–75th percentile). Results: In vivo TXA plasma concentration correlated with LT (r = 0.55; p < 0.0001) and ML (r = 0.62; p < 0.0001) at all time points. Lysis was inhibited up to 96 h (LTTPA-test: baseline: 398 s [229–421 s] vs. at 96 h: 886 s [626–2,175 s]; p = 0.0013). After 24 h, some patients (n = 8) had normalized lysis, but others (n = 17) had strong lysis inhibition (ML <30%; p < 0.001). The high- and low-lysis groups differed regarding kidney function (cystatin C: 1.64 [1.42–2.02] vs. 1.28 [1.01–1.52] mg/L; p = 0.002) in a post hoc analysis. Of note, TXA plasma concentration after 24 h was significantly higher in patients with impaired renal function (9.70 [2.89–13.45] vs.1.41 [1.30–2.34] µg/mL; p < 0.0001). In vitro, TXA concentrations of 10 µg/mL effectively inhibited fibrinolysis in all blood samples. Conclusions: Determination of antifibrinolytic activity using the TPA test is feasible, and individual fibrinolytic capacity, e.g., in critically ill patients, can potentially be measured. This is of interest since TXA-induced lysis inhibition varies depending on kidney function.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry

Kämmerer

Groene

Sappel

et al. 2020

Transfus Med Hemother

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“…For antifibrinolytic SSPLT, we formulated tranexamic acid (TA)-containing thermosensitive PEGylated DPPC and DPPC:lysoPC liposomes [ 16 ] that are envisaged to target to laser-induced thrombi and release TA upon a mild hyperthermic stimulus [ 17 ] using near-infrared light [ 9 , 11 , 14 ]. TA is a potent antifibrinolytic drug used clinically to deter heavy bleeding during e.g., surgery [ 18 , 19 ] through its inhibition of the enzyme (plasmin) responsible for thrombolysis [ 20 ]. To date our group has demonstrated that non-encapsulated TA reduces laser-induced thrombus breakdown in hamsters (manuscript in preparation).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Assessment of Thermosensitive Liposomes for the Treatment of Port Wine Stains by Antifibrinolytic Site-Specific Pharmaco-Laser Therapy

Raath

Khakpour

et al. 2020

Pharmaceutics

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Antifibrinolytic site-specific pharmaco-laser therapy (SSPLT) is an experimental treatment modality for refractory port wine stains (PWS). Conceptually, antifibrinolytic drugs encapsulated in thermosensitive liposomes are delivered to thrombi that form in semi-photocoagulated PWS blood vessels after conventional laser treatment. Local release of antifibrinolytics is induced by mild hyperthermia, resulting in hyperthrombosis and complete occlusion of the target blood vessel (clinical endpoint). In this study, 20 thermosensitive liposomal formulations containing tranexamic acid (TA) were assayed for physicochemical properties, TA:lipid ratio, encapsulation efficiency, and endovesicular TA concentration. Two candidate formulations (DPPC:DSPE-PEG, DPPC:MPPC:DSPE-PEG) were selected based on optimal properties and analyzed for heat-induced TA release at body temperature (T), phase transition temperature (Tm), and at T > Tm. The effect of plasma on liposomal stability at 37 °C was determined, and the association of liposomes with platelets was examined by flow cytometry. The accumulation of PEGylated phosphocholine liposomes in laser-induced thrombi was investigated in a hamster dorsal skinfold model and intravital fluorescence microscopy. Both formulations did not release TA at 37 °C. Near-complete TA release was achieved at Tm within 2.0–2.5 min of heating, which was accelerated at T > Tm. Plasma exerted a stabilizing effect on both formulations. Liposomes showed mild association with platelets. Despite positive in vitro results, fluorescently labeled liposomes did not sufficiently accumulate in laser-induced thrombi in hamsters to warrant their use in antifibrinolytic SSPLT, which can be solved by coupling thrombus-targeting ligands to the liposomes.

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“…This may be associated with the more aggressive preoperative preparation and the application of tranexamic acid. Other studies have shown that not only patients with good basic conditions and fewer coexisting diseases but also patients with bleeding tendencies or blood coagulation disorders similar to SLE can also benefit from the use of TXA [20][21][22][23]. Therefore, we have reason to think that TXA can also reduce the perioperative blood loss of patients with SLE, thus reducing their blood transfusion rate.…”

Section: Discussionmentioning

confidence: 99%

Does systemic lupus erythematosus increase the risk of complications from total hip arthroplasty?

Cai

Ding

Rong

et al. 2021

BMC Musculoskelet Disord

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Background Patients with systemic lupus erythematosus are more likely to receive THA than the general population. However, it is controversial whether SLE increases the risk of complications from THA. The purpose of this retrospective study was to reassess the risks from THA in patients with SLE under the management model of enhanced recovery after surgery. Methods Patients with systemic lupus erythematosus diagnosed from December 2011 to December 2017 and treated with THA were compared with THA patients with osteoarthritis. The data were extracted from the medical record system of our department. The chi-square test and t-test were used for comparison. Results The postoperative blood loss in patients with SLE was significantly higher than that in the control group, and the postoperative hemoglobin (Hb) and hematocrit (Hct) in the control group were lower than those in the control group (P < 0.05). There was no significant difference in the rate of blood transfusion (9.733 vs 8.133 P = 0.3148) or other complications between the two groups (P > 0.05). Conclusion Well-controlled and well-managed SLE will not increase the risk of complications in THA, but can increase the amount of perioperative blood loss. Therefore, perioperative blood management is still essential in SLE patients.

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Efficacy and Safety of Tranexamic Acid in Major Non-Cardiac Surgeries at High Risk for Transfusion: A Systematic Review and Meta-Analysis

Cited by 33 publications

References 91 publications

Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry

Functional Testing for Tranexamic Acid Duration of Action Using Modified Viscoelastometry

In Vivo Assessment of Thermosensitive Liposomes for the Treatment of Port Wine Stains by Antifibrinolytic Site-Specific Pharmaco-Laser Therapy

Does systemic lupus erythematosus increase the risk of complications from total hip arthroplasty?

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