Elsevier

Thrombosis Research

Volume 131, Issue 1, January 2013, Pages e6-e11
Thrombosis Research

Regular Article
Duration of Postoperative Fibrinolysis after Total Hip or Knee Replacement: A Laboratory Follow-up Study

https://doi.org/10.1016/j.thromres.2012.11.006Get rights and content

Abstract

Introduction

Hyperfibrinolysis is observed during and immediately after major orthopedic surgery. The kinetics and duration of this phase should be defined to adjust the duration of antifibrinolytic treatment with tranexamic acid (TXA).

Objective

We aimed to quantify the duration of postoperative fibrinolysis and to assess the biological impact of TXA administration.

Materials and Methods

Fourteen patients undergoing total hip replacement (THR) and 10 patients undergoing total knee replacement (TKR) with tourniquet were included in an observational, prospective, single-center study. Among these patients, 7 THR patients and 5 TKR patients received TXA (15 mg/kg IV intraoperatively, followed by continuous infusion of 15 mg/kg/h until end of surgery, then every 4 hours until 16 ± 2 hours after surgery). D-dimers, euglobulin lysis time (ELT), and thrombin generation time (TGT) were measured prior to surgery as well as 6, 18 and 24 hours (H) after.

Results

No significant difference in ELT was observed between the groups. In contrast, D-dimers significantly increased postoperatively in patients not treated with TXA (p < 0.001), while such an increase was prevented in patients receiving TXA, as measured at H0, H6, H18 and H24 after THR, and at H6 and H18 after TKR (p < 0.001). No significant between-group change in TGT, was observed (peak thrombin and endogenous thrombin potential) all along the study.

Conclusion

This study shows that fibrinolysis peaked 6 hours after end of surgery and maintained about 18 hours after surgery, as evidenced by an increase in D-dimers. When administered for up to 16 ± 2 hours after surgery, TXA reduced postoperative fibrinolysis.

Introduction

A hyperfibrinolytic phase, leading to increase bleeding is observed during and immediately after major orthopedic surgery. In the wake of stimuli such as vascular hypoxia, hypotension, or cytokine circulation, the endothelium releases tissue plasminogen activator, which in turn catalyzes the conversion of plasminogen to plasmin, resulting in the breakdown of fibrin and the destruction of blood clots [1]. Postoperative fibrinolysis may vary in duration and intensity depending on surgery type and whether a tourniquet is applied. Eriksson et al. showed that in 10 cases of total hip replacement (THR), fibrinolysis activation began at implantation [2], [3]. After total knee replacement (TKR), the rate of fibrinolysis was higher with tourniquet and peaked after tourniquet release [4], [5]. Fibrinolysis in THR and TKR appears to decrease after day (D) 2 following surgery [2], [5], [6], [7], [8]. The exact kinetics of fibrinolysis in such interventions nonetheless requires further investigation.

Tranexamic acid (TXA) is a synthetic lysine analog and acts as an antifibrinolytic agent. It binds reversibly to the lysine binding site of plasminogen, inhibiting the binding to fibrin and the activation to plasmin. Its efficacy in limiting blood loss and transfusion after THR and TKR has been thoroughly demonstrated by several meta-analyses [9], [10], [11], [12], [13]. However, at this time, current guidelines do not recommend using TXA during THR and TKR, even if it is widely used because, optimal dosage and duration of treatment remain unknown. A bolus of 15 mg/kg appears to be sufficient and is most commonly used [10]. The few studies that have addressed postoperative fibrinolysis and the very short half-life of TXA (about 2 hours) stated that prolonged administration of TXA might further decrease blood loss after major orthopedic surgery [14]. Blood loss has been shown to be essentially postoperative, with 2/3 occurring postoperatively after THR and 4/5 after TKR with tourniquet [13], [15]. Single intraoperative administration of TXA has demonstrated less efficacy in limiting blood loss and transfusion than prolonged administration (10 mg/kg intraoperatively, then at hour (H) 3 after surgery) [15], [16]. Therefore, it seems appropriate to prolong TXA administration postoperatively in this type of surgery.

Notwithstanding the above, venous thromboembolic events have also been observed immediately after major orthopedic surgery [6], [8], and TXA might increase this risk. Some studies have sought to measure biomarkers of fibrinolysis and coagulation perioperatively in major orthopedic surgery. Reduced fibrinolytic marker activity may be associated with increased thrombotic risk [2], [17], but studies of TKR with tourniquet show conflicting results as to the effects of TXA on coagulation markers [18], [19], [20]. In clinical practice, various meta-analyses of TXA in orthopedic surgery have shown no increase in thrombotic or thromboembolic risk [10], [11], [21], [22].

Intraoperative TXA infusion sustained for up to 16 hours postoperatively may help limit blood loss and transfusion needs, as shown by preliminary studies [14], [15], [16]. Before the initiation of any randomized trials, the exact kinetics of postoperative fibrinolysis had to be further explored so as to determine the appropriate duration of antifibrinolytic TXA treatment without increasing the risk of thrombotic events. The objectives of this investigation were to quantify the duration of postoperative fibrinolysis and assess the impact of TXA administration after THR and TKR through a follow-up pilot laboratory study.

Section snippets

Patients and Study Design

This prospective observational study was performed in the orthopedic surgery unit of Cochin-Hôtel Dieu Hospital. Following the National regulations for this kind of observational study, Internal Review Board approval was not necessary. However, patients were informed during preoperative visits, and a signed informed consent was obtained.

A total of 14 patients undergoing THR and 10 patients undergoing TKR with tourniquet were included. The exclusion criteria were refusal to participate, arterial

Results

Thirty patients were initially enrolled, but 6 had to be excluded because of off-protocol events (no laboratory sample taken, TKR performed without tourniquet), resulting in a final study population of 24 patients. The study population was broken down into 2 THR groups, THR (n = 7) and THR-TXA (n = 7), and 2 TKR groups, TKR (n = 5) and TKR-TXA (n = 5). All patients underwent a femoral block combined with general anaesthesia.

Discussion

This study showed that the peak of fibrinolysis, as evidenced by an increase in DDE, occurred at 6 hours after surgery, but the hyperfibrinolytical state is maintained 18 hours. TXA administration for up to 16 ± 2 hours after surgery limited postoperative fibrinolysis.

ELT measures global fibrinolytic activity in inhibitor-free plasma by precipitation in an acid medium. The precipitate (coagulation factors, plasminogen, t-PA) is recalcified and clot lysis time is measured. Hyperfibrinolysis is

Conflict of Interest Statement

All authors declare no conflict of interest.

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