The antifibrinolytic and anti‐inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial

Wang, Deren; Luo, Zeyu; Yu, Zhanxia; Liu, L.-X.; Chen, C.; Meng, Wenxia; Yu, Qing; Pei, Fuxing; Zhou, Zongke; Zeng, Wei‐Nan

doi:10.1111/jth.14316

Cited by 44 publications

(68 citation statements)

References 52 publications

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“…In one recent study with oral TXA (ref. 3 ), the plasma levels of TXA after oral administration achieved the threshold for the haemostatic effect (10 mg/L) at 10, 14, 18 and 22 h after surgery, and for all of the examined modes (i.e., 1, 2, 3 or 4 doses). A similar arrangement as in our study was also used by Zhang et al, who observed D-dimer and FDP pre-operatively, respectively on the 1 st and 3 rd post-operative day after intravenous, combined and topical administration of TXA.…”

Section: Discussionmentioning

confidence: 85%

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Monitoring of fibrinolytic system activity with plasminogen, D-dimers and FDP in primary total knee arthroplasty (TKA) after topical, intravenous or combined administration of tranexamic acid

Lošťák¹,

Gallo²,

Slavík³

et al. 2020

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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Aim. We assessed various ways of tranexamic acid (TXA) administration on the fibrinolytic system. Blood loss, transfusions, drainage and haematoma were secondary outcomes. Methods. In this prospective study, we examined 100 patients undergoing primary total knee arthroplasty (TKA) between June and November 2018. Patients were randomly assigned to 4 groups according to the following TXA regimens: 1) loading dose 15 mg TXA/kg single intravenous administration applied at initiation of anesthesia (IV1); 2) loading dose 15 mg TXA/kg + additional dose 15 mg TXA/kg 6 h after the first application of TXA (IV2); 3) IV1 regime in combination with a local wash of 2 g of TXA in 50 mL of saline (COMB); 4) topical administration of 2 g of TXA in 50 mL of saline (TOP). Results. Systemic fibrinolysis interference was insignificant in all of the regimens; we did not detect significant differences between IV1, IV2 and COMB in the monitored parameters within the elapsed time after the TKA; IV regimes had the lowest total drainage blood loss; the lowest blood loss was associated with the IV1 and IV2 regimens (IV1, IV2 < COMB < TOP); the lowest incidence of haematomas was in patients treated with TXA topically (i.e., in COMB + TOP). Conclusion. The largest antifibrinolytic effect was associated with intravenous administration of TXA. In terms of blood loss, intravenously administered TXA can interfere with the processes associated with the formation of the fibrin plug more efficiently than the simple washing of wound surfaces with TXA.

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Section: Discussionmentioning

confidence: 85%

“…At higher concentrations, TXA can also directly inhibit plasmin activity 1,2 . It is also believed that TXA has an anti-inflammatory effect (inhibition of plasmin-mediated complement, monocyte and neutrophil inhibition) 3 . Compared with other antifibrinolytics, the effect of TXA is more potentiated by factor X (ref.…”

Section: Introductionmentioning

confidence: 99%

Monitoring of fibrinolytic system activity with plasminogen, D-dimers and FDP in primary total knee arthroplasty (TKA) after topical, intravenous or combined administration of tranexamic acid

Lošťák¹,

Gallo²,

Slavík³

et al. 2020

Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub

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“…In one study of orthopedic surgery patients, intravenous TXA administration both before and after surgery led to increased levels of circulating proinflammatory molecules, such as TNF-α, IL-1β, and IL-6 (38). Conversely, in another cohort of orthopedic surgery patients followed up to 48 h, it was found that an increased number of post-operative oral doses of TXA suppressed IL-6 levels (39). Moreover, prophylactic TXA use in cardiac surgery patients was shown to have an "immune-enhancing" effect, as leukocytes from patients receiving TXA had decreased expression of immunosuppressive surface markers (LAP and PD-L1), and increased expression of immune-activating markers (CD83 and CCR7) (40).…”

Section: Introductionmentioning

confidence: 99%

The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

et al. 2020

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Background: The hemostatic properties of tranexamic acid (TXA) are well described, but the immunological effects of TXA administration after traumatic injury have not been thoroughly examined. We hypothesized TXA would reduce monocyte activation in bleeding trauma patients with severe injury. Methods: This was a single center, double-blinded, randomized controlled trial (RCT) comparing placebo to a 2 g or 4 g intravenous TXA bolus dose in trauma patients with severe injury. Fifty patients were randomized into each study group. The primary outcome was a reduction in monocyte activation as measured by human leukocyte antigen-DR isotype (HLA-DR) expression on monocytes 72 h after TXA administration. Secondary outcomes included kinetic assessment of immune and hemostatic phenotypes within the 72 h window post-TXA administration. Results: The trial occurred between March 2016 and September 2017, when data collection ended. 149 patients were analyzed (placebo, n = 50; 2 g TXA, n = 49; 4 g TXA, n = 50). The fold change in HLA-DR expression on monocytes [reported as median (Q1-Q3)] from pre-TXA to 72 h post-TXA was similar between placebo [0.61 (0.51-0.82)], 2 g TXA [0.57 (0.47-0.75)], and 4 g TXA [0.57 (0.44-0.89)] study groups (p = 0.82). Neutrophil CD62L expression was reduced in the 4 g TXA group [fold change:

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“…Recently, Maniar et al [9] have investigated the serum levels of IL-6 and CRP in the hours and days immediately postoperatively to understand their normal trajectory. However, with the promotion of enhanced recovery after surgery (ERAS), many methods have been used to minimize surgical trauma and reduce inflammation [3,10]. Little is known of the normal curve in the hours and days of CRP and IL-6 immediately postoperatively under an ERAS scenario.…”

Section: Introductionmentioning

confidence: 99%

Normal trajectory of Interleukin-6 and C-reactive protein in the perioperative period of total knee arthroplasty under an enhanced recovery after surgery scenario

Huang¹,

Huang²,

Wang³

et al. 2020

BMC Musculoskelet Disord

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Background: We designed the current study to understand the normal trajectories of interleukin-6 (IL-6) and Creactive protein (CRP) in the immediate hours and days after primary total knee arthroplasty (TKA) under the management of an enhanced recovery after surgery (ERAS) protocol and examined whether one or the other returned to normal more quickly. Methods: In this prospective cross-sectional study, we examined the plasma IL-6 and CRP levels in 100 patients undergoing primary TKA at the following time points: 12 h preoperatively as well as postoperatively 12 h, 48 h, 3 days and 2 weeks. Patients were followed up for 1 year to monitor the postoperative complications, especially the infection. Results: IL-6 peaked at 48 h postoperatively. Then IL-6 started to decline at 3 days postoperatively and went back to baseline level at 2 weeks (p = 0.950). CRP peaked at 3 days postoperatively. At 2 weeks, CRP declined to a normal range, without being significantly different from the baseline level (p = 0.816). Conclusion: We found that under the ERAS scenario, the postoperative peak of IL-6 and CRP was deferred compared with previous studies. Compared to IL-6, CRP showed a gradual rise after surgery. Both of these two biomarkers returned to normal under the ERAS scenario. Future multiple-center studies with larger sample size can help define the thresholds of IL-6 and CRP for periprosthetic joint infection (PJI) early diagnosis. With these reference data, a clinician can make a quicker decision to perform aspiration to diagnose early PJI and benefits more patients.

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The antifibrinolytic and anti‐inflammatory effects of multiple doses of oral tranexamic acid in total knee arthroplasty patients: a randomized controlled trial

Cited by 44 publications

References 52 publications

Monitoring of fibrinolytic system activity with plasminogen, D-dimers and FDP in primary total knee arthroplasty (TKA) after topical, intravenous or combined administration of tranexamic acid

Monitoring of fibrinolytic system activity with plasminogen, D-dimers and FDP in primary total knee arthroplasty (TKA) after topical, intravenous or combined administration of tranexamic acid

The Immunologic Effect of Early Intravenous Two and Four Gram Bolus Dosing of Tranexamic Acid Compared to Placebo in Patients With Severe Traumatic Bleeding (TAMPITI): A Randomized, Double-Blind, Placebo-Controlled, Single-Center Trial

Normal trajectory of Interleukin-6 and C-reactive protein in the perioperative period of total knee arthroplasty under an enhanced recovery after surgery scenario

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