Abstract
Objective
This study aimed to explore the efficacy and safety of intravenous tranexamic acid (TXA) for reducing perioperative blood loss and allogeneic blood transfusions in revision hip arthroplasty.
Methods
TXA was routinely administered as an intravenous preoperative dose in all the revision hip arthroplasty cases in our institution from December 2012. We retrospectively reviewed 803 patients who underwent revision hip arthroplasty from January 2008 to September 2018. These patients were divided into 2 groups based on whether they received intravenous TXA (n=482; 231 men and 251 women; mean age: 63.27±11.73 years) or not (n=321; 159 men and 162 women; mean age: 63.91±11.69 years). The 2 groups were compared in terms of estimated intraoperative blood loss, visible blood loss, hidden blood loss, the rate and volume of allogeneic blood transfusions, and the incidence of symptomatic venous thromboembolism. The patients were also compared depending on whether they underwent total hip revision, isolated acetabular revision, or isolated femoral revision.
Results
Regardless of the type of revision involved, the patients who received TXA showed significantly lower estimated intraoperative blood loss, visible blood loss, hidden blood loss, and allogeneic blood transfusion rate and volume (all p values were less than 0.001). Use of TXA was not associated with significant changes in the incidence of postoperative symptomatic venous thromboembolism (p=0.911). Similar results were obtained with subgroups of patients who underwent different types of revision surgeries, except hidden blood loss (p=0.994) of patients in the isolated femoral revision subgroup.
Conclusion
The administration of intravenous TXA can safely and effectively reduce the perioperative blood loss and allogeneic blood transfusions in revision hip arthroplasty.
Level of Evidence
Level III, Therapeutic study
Keywords: Tranexamic acid, Hip revision, Blood loss, Blood transfusion, Arthroplasty
Introduction
Total hip arthroplasty (THA) is an important method to treat non-infective end-stage diseases of the hip joint. Although THA technology is maturing, the increasing number of procedures has also led to an increase in the number of revision hip arthroplasties, such as a result of fracture around the prosthesis; loosening or dislocation of the prosthesis; infection; and wearing-out of the polyethylene liner (1). One study estimated that the number of revision hip arthroplasties in the United States will increase by 137% from 2005 to 2030 (2). Revision hip arthroplasty can lead to a greater blood loss than primary THA because it takes longer and often requires an enlarged incision, removal of the original prosthesis, and cleaning of the medullary cavity and acetabulum to facilitate the placement of the new prosthesis (3, 4). Simultaneously, hidden blood loss can be high when hemolysis activates the fibrinolytic system, and a large amount of blood enters the interstitial spaces (5). Estimated intraoperative blood loss in revision hip arthroplasty can be as great as 2000 ml, and rates of allogeneic blood transfusions can reach 45% (6). Substantial blood loss during revision hip arthroplasty can lead to anemia, poor prognosis, and even hemorrhagic shock, whereas transfusion itself increases the risk of infectious diseases, acute lung injury, and fever (7). Therefore, perioperative blood management of patients undergoing revision hip arthroplasty should be optimized to reduce the perioperative blood loss and the incidence of venous thrombus embolism (VTE) to promote early rehabilitation. It poses a challenge for joint surgeons.
At present, hemorrhage during revision hip arthroplasty cannot be controlled effectively by autologous blood transfusion or intraoperatively controlled hypotensive anesthesia (8). However, tranexamic acid (TXA) may be a good choice. TXA, a synthetic derivative of the amino acid lysine, is widely used as an antifibrinolytic agent to reduce the blood loss during primary THA. It inhibits the conversion of plasminogen to plasmin, preventing dissolution of the platelet plug and promoting clot maintenance and hemostatics (9). Several studies have shown that TXA can significantly reduce the blood loss and the rate of allogeneic blood transfusion in primary THA, without increasing the risk of VTE, including deep vein thrombosis (DVT) and pulmonary embolism (PE) (10, 11). Relatively few studies, most of them involving small samples, have examined whether TXA can reduce the perioperative blood loss in revision hip arthroplasty. To address this question, we retrospectively analyzed the clinical data of more than 800 patients undergoing revision hip arthroplasty at our medical center. We compared some safety and efficacy outcomes between those who received intravenous TXA and those who did not. We wished to determine whether intravenous TXA can reduce the perioperative blood loss and allogeneic blood transfusions, which may help guide the clinical practice.
Materials and Methods
Patients
This study protocol was approved by the clinical trials and biomedical ethics committee of our institution, which waived the requirement for a written consent considering the retrospective nature of the study. Patients undergoing revision hip arthroplasty in our institution between January 2008 and September 2018 were eligible for inclusion. We excluded patients who had contraindications to TXA, including those with (1) coronary artery disease, (2) renal failure (serum creatinine > 200 mmol/L, creatinine clearance <50 mL/min, dialysis), (3) lifelong anticoagulant use or a history thereof (4) TXA sensitivity, (5) disseminated intravascular coagulation, (6) active thrombolytic events, or (7) thrombolytic events (myocardial infarction, cerebrovascular accident, DVT, and pulmonary embolus) within 1 year of the revision surgery. Patients were also excluded if they were treated with TXA in a way that deviated from the following practices at our hospital, which became standard from December 2012: TXA was routinely administered as an intravenous preoperative dose (15 mg/kg) in all the revision hip arthroplasty cases, and it was administered again intravenously at the point when the surgery exceeded 2 h. This is because of the approximate 2-h half-life of intravenous TXA (12). Patients were excluded if they underwent isolated femoral head and liner exchange because only a handful of such patients were treated during the enrollment period.
Group allocations
Patients were grouped according to their operation date, i.e., whether they received intravenous TXA or no TXA at all. They were further grouped according to the type of revision: (1) total hip revision (revision of both femoral and acetabular components), (2) isolated acetabular revision, and (3) isolated femoral revision.
Perioperative management
Between January 2008 and September 2018, all the revision hip arthroplasties were performed using posterolateral approach after general anesthesia by 5 experienced joint surgeons of our institution, and their experience were at the same level. During this period, no surgeons joined or quit. Patients received intravenous TXA (15 mg/kg) 5–10 min before the skin incision, and the same dose of TXA was administered again intravenously at the point when the surgery exceeded 2 h. After placement of the prosthesis, a drainage tube was placed before closing the incision. If the volume of drainage within 24 h after the surgery did not exceed 500 mL, the drainage tube was removed at 24 h after the surgery. Otherwise, the drainage tube was retained until 36 h after the surgery.
Perioperative physical and drug prophylaxis were used to prevent VTE. Patients were regularly trained in the ankle pump exercise and quadriceps femoris isometric contraction exercise. Low molecular weight heparin (0.2 mL) was administered at 12 h after the surgery and then 0.4 mL every 24 h afterwards until discharge to prevent VTE. Low molecular weight heparin was discontinued if there was significant wound bleeding or subcutaneous bleeding during hospitalization. Rivaroxaban (10 mg) was administered once a day for 2 weeks after discharge from the hospital to continue to prevent VTE. Celecoxib (200 mg) was administered twice daily to control postoperative pain for all the patients. If the patients were allergic to Celecoxib, they used Loxoprofen (60 mg) 3 times a day. In addition, if the patients were unable to tolerate the pain, 5 mg of morphine hydrochloride as rescue analgesic was injected subcutaneously.
The indications for postoperative allogeneic blood transfusion were (1) hemoglobin <70 g/L or (2) 70 g/L<hemoglobin<100 g/L in the presence of dizziness, palpitations, chest tightness, weakness, and other anemia symptoms.
Data collection
General demographic data were recorded, including gender, age, and body mass index (BMI). The duration of the surgery was also recorded. The following data were recorded from the electronic medical records: estimated intraoperative blood loss, postoperative drainage volume, autologous blood transfusion volume, allogeneic blood transfusion volume, hematocrit (HCT) within 1 day before the surgery and 72 h after the surgery.
Estimated intraoperative blood loss was calculated as follows:
Estimated intraoperative blood loss=the volume of liquid in the negative pressure aspirator - the volume of flushing saline + net weight gain of the gauze.
The preoperative weight of the dry gauze with exact specification was known. Thereafter, the circulating nurse weighed the used gauze with an electronic scale after the surgery. Finally, we got the net weight gain of the gauze.
Visible blood loss is the sum of estimated intraoperative blood loss and postoperative drainage volume.
Hidden blood loss was calculated as follows. First, the patient’s blood volume (PBV) was calculated according to the formula (13):
PBV (mL) = [k1×height (m) 3+k2 × weight (kg) +k3] × 1000, where k1=0.3669, k2=0.03219, and k3=0.6041 for male patients, whereas k1=0.3561, k2=0.03308, and k3=0.1833 for female patients. Next, the Gross equation was used to calculate hidden blood loss based on HCT:
Hidden blood loss=PBV×2×(preoperative HCT - HCT of postoperative 72 h)/(preoperative HCT + HCT of postoperative 72 h) + autologous blood transfusion volume + allogeneic blood transfusion volume - visible blood loss.
Meanwhile, the safety data were collected in the form of postoperative symptomatic VTE (e.g., symptomatic DVT and symptomatic PE). When the patients suffered from suspected DVT symptoms, such as lower extremity pain, swelling, circumference change, and positive Homans’ sign during hospitalization, the double lower extremity deep vein ultrasonography was performed. If the results were positive, it was defined as symptomatic DVT. When the patients suffered from chest tightness, chest pain, hemoptysis, and decreased oxygen saturation during hospitalization, the blood coagulation indicator test and blood gas analysis were performed, and computed tomography pulmonary angiography was also performed. If the results were positive, it was defined as symptomatic PE. All the patients were required to return to the outpatient department of our medical center for suture removal 3 weeks after discharge. Therefore, we followed postoperative symptomatic VTE until 3 weeks after discharge.
Statistical analysis
Statistics were calculated using Statistical Package for the Social Sciences version 25 (IBM SPSS Corp.; Armonk, NY, USA). All the data are presented as means and standard deviations, unless otherwise indicated. Intergroup differences in continuous demographic and clinical variables (e.g., age, estimated intraoperative blood loss, and allogeneic blood transfusion volume) were assessed for significance using student’s t test for 2 independent samples. Student-Newman-Keuls test was used for the comparison of multiple samples. Intergroup differences in the categorical variables (e.g., symptomatic VTE occurrence) were assessed using Pearson’s Chi-squared test or Fisher’s exact probabilities test. Differences associated with p<0.05 were considered significant.
Results
A total of 957 patients who underwent revision hip arthroplasties between January 2008 and September 2018 in our institution were assessed for eligibility, of whom 154 did not meet the eligibility criteria. Therefore, we collected data from 803 eligible patients, including 321 patients treated before December 2012 who did not use TXA, as well as 482 patients treated after December 2012 who received intravenous TXA as per routine practice at our hospital. The grouping composition of patients is listed in Table 1. In the early analyses, we found that the volume of blood loss varied among the 3 subtypes of revision surgery. The difference was significant in the case of estimated intraoperative blood loss (Table 1).
Table 1.
The components of revision
| The components of revision | TXAa (n) | No-TXAb (n) | Total (n, %) | Estimated intraoperative blood loss (mL) |
|---|---|---|---|---|
| Total hip revision | 342 | 255 | 597 (74.35) | 735.33±522.38c,d |
| Isolated acetabular revision | 72 | 36 | 108 (13.45) | 442.31±270.43 |
| Isolated femoral revision | 68 | 30 | 98 (12.20) | 576.22±418.99a |
TXA: Patients used tranexamic acid
No-TXA: Patients who did not use tranexamic acid
P < 0.05 compared with the isolated acetabular revision subgroup
P < 0.05 compared with the isolated femoral revision subgroup. Student-Newman-Keuls test was used for the comparison
Among all the patients regardless of the revision type, patients who used TXA or not did not differ significantly in age, gender, BMI or duration of surgery (Table 2). Patients who used TXA showed significantly lower values for the following parameters: estimated intraoperative blood loss, visible blood loss, hidden blood loss, and rate and volume of allogeneic blood transfusions (all p values were less than 0.001). Patients who used TXA or not did not differ significantly in the incidence of symptomatic VTE during the follow-up period (p=0.911).
Table 2.
Comparison of all patients
| Group A (TXAa) | Group B (No-TXAb) | p | |
|---|---|---|---|
| Cases | 482 | 321 | |
| Age (years) | 63.27±11.73 | 63.91±11.69 | 0.446c |
| Gender (male/female) | 231/251 | 159/162 | 0.655d |
| BMIe (kg/m2) | 23.99±3.53 | 23.79±3.17 | 0.406c |
| Duration of surgery (min) | 119.43±23.95 | 122.17±22.41 | 0.099c |
| Estimated intraoperative blood loss (mL) | 479.94±346.68 | 971.65±536.39 | <0.001c |
| Visible blood loss (mL) | 839.12±508.33 | 1754.66±843.05 | <0.001c |
| Hidden blood loss (mL) | 590.25±550.84 | 1149.93±1044.73 | <0.001c |
| Allogeneic blood transfusion rate | 30.91% | 80.37% | <0.001c |
| Allogeneic blood transfusion volume (mL) | 273.96±546.09 | 1252.46±1169.97 | <0.001c |
| Symptomatic VTEf (cases/incidence) | 8 (1.66%) | 5 (1.56%) | 0.911d |
| Symptomatic PEg (cases) | 2 | 1 | |
| Symptomatic DVTh (cases) | 6 | 4 |
TXA: Patients used tranexamic acid;
No-TXA: Patients who did not use tranexamic acid; cStudent’s t test;
Pearson’s Chi-squared test;
BMI: Body mass index; fVTE: Venous thromboembolism;
VTE: Venous thromboembolism;
PE: Pulmonary embolism
hDVT: Deep vein thrombosis
In the total hip revision subgroup, the isolated acetabular revision subgroup, and the isolated femoral revision subgroup, patients who used TXA or not did not differ significantly in age, sex, BMI, or duration of surgery. As in the analysis of all patients, patients in these three subgroups showed significantly lower parameters if they used TXA: estimated intraoperative blood loss, visible blood loss, allogeneic blood transfusion rate, and allogeneic blood transfusion volume (Table 3). However, in the isolated femoral revision subgroup, patients who used TXA or not did not differ significantly in terms of hidden blood loss (p=0.994). Patients in the total hip revision subgroup and the isolated acetabular revision subgroup showed significantly lower hidden blood loss if they used TXA.
Table 3.
Comparison of the three subgroups
| Group A (TXAa) | Group B (No-TXAb) | p | |
|---|---|---|---|
| Total hip revision subgroup | |||
| Duration of surgery (min) | 127.51±18.91 | 128.31±18.52 | 0.610c |
| Estimated intraoperative blood loss (mL) | 516.64±375.68 | 1028.63±547.78 | <0.001c |
| Visible blood loss (mL) | 925.15±541.34 | 1837.82±820.01 | <0.001c |
| Hidden blood loss (mL) | 479.38±479.88 | 1205.21±1103.50 | <0.001c |
| Allogeneic blood transfusion rate | 31.58% | 84.71% | <0.001d |
| Allogeneic blood transfusion volume (mL) | 307.02±601.37 | 1315.65±1137.61 | <0.001c |
| Symptomatic VTEe (cases/incidence) | 6 (1.75%) | 4 (1.57%) | 0.883d |
| Symptomatic PEf (cases) | 1 | 1 | |
| Symptomatic DVTg (cases) | 5 | 3 | |
| Isolated acetabular revision subgroup | |||
| Duration of surgery (min) | 90.93±17.48 | 92.03±17.34 | 0.758c |
| Estimated intraoperative blood loss (mL) | 373.19±213.52 | 580.56±318.77 | 0.001c |
| Visible blood loss (mL) | 625.56±298.77 | 1048.33 ± 614.33 | <0.001c |
| Hidden blood loss (mL) | 432.31±275.06 | 1137.56±733.69 | <0.001c |
| Allogeneic blood transfusion rate | 12.50% | 55.56% | <0.001d |
| Allogeneic blood transfusion volume (mL) | 75.69±216.24 | 822.22±1097.88 | <0.001c |
| Symptomatic VTEe (cases/incidence) | 1 (1.39%) | 0 (0%) | 1.000h |
| Symptomatic PEg (cases) | 1 | 0 | |
| Symptomatic DVTg (cases) | 0 | 0 | |
| Isolated femoral revision subgroup | |||
| Duration of surgery (min) | 108.93±25.58 | 106.17±21.28 | 0.606c |
| Estimated intraoperative blood loss (mL) | 408.38±268.14 | 956.67±453.10 | <0.001c |
| Visible blood loss (mL) | 632.53±372.62 | 1895.33±892.71 | <0.001c |
| Hidden blood loss (mL) | 669.47±478.16 | 668.34±668.06 | 0.994c |
| Allogeneic blood transfusion rate | 47.06% | 73.33% | 0.016d |
| Allogeneic blood transfusion volume (mL) | 317.65±448.28 | 1231.67±1431.45 | 0.002c |
| Symptomatic VTE (cases/incidence) | 1 (1.47%) | 1 (3.33%) | 0.521h |
| Symptomatic PE (cases) | 0 | 0 | |
| Symptomatic DVT (cases) | 1 | 1 | |
TXA: Patients used tranexamic acid;
No-TXA: Patients who did not use tranexamic acid;
Student’s t test;
Pearson’s Chi-squared test;
VTE: Venous thromboembolism;
PE: Pulmonary embolism;
DVT: Deep vein thrombosis;
Fisher’s exact probabilities test
In the three subgroups, patients who used TXA showed no significant differences from those who did not use the drug in the incidence of symptomatic VTE during the follow-up period.
Discussion
It is very important to control the blood loss during revision hip arthroplasty, which is more complex and traumatic than primary THA. The abundant blood supply in tissues surrounding the hip inevitably leads to bleeding during the surgery, and removal of the primary prosthesis and re-expansion of the femoral bone marrow cavity can aggravate hemorrhage in the femoral medullary cavity. Revision hip arthroplasty is also accompanied by a large amount of hidden blood loss, mainly due to hemolysis and collection of the blood in the joint cavity or exudative interstitial fluid (5).
To reduce the influence of surgical techniques, surgeon’s experience, and the equipment, we included cases only from the last 10 years. There were no significant differences in the general demographic data and the duration of surgery for all groups of patients. This indicated that the comparability of our included patients was satisfactory.
TXA, already well supported as an antifibrinolytic agent that safely and effectively reduces the perioperative blood loss and the rate of blood transfusions in primary THA may provide similar benefits in the revision setting (14). However, relevant studies involve relatively small populations (15–17). In this large retrospective study, we found that the administration of intravenous TXA can safely and effectively reduce the perioperative blood loss and allogeneic blood transfusions in patients undergoing revision hip arthroplasty. Use of TXA was associated with significantly lower estimated intraoperative blood loss, visible blood loss, hidden blood loss, and allogeneic blood transfusion rate and volume. At the same time, the use of TXA did not substantially alter the incidence of postoperative symptomatic VTE. Our results are consistent with several studies demonstrating the efficacy of TXA in revision hip arthroplasty (14–16). In theory, the use of TXA can reduce the incidence of related adverse events, shorten the hospitalization, accelerate the recovery, and reduce the medical expenses by reducing the need for allogeneic blood transfusion (18).
In our study, the clinical benefits of intravenous TXA did not vary substantially with the subtype of revision surgery. One exception is that the use of TXA did not significantly reduce the hidden blood loss in patients undergoing isolated femoral revision. One potential explanation is that the rate of autologous blood transfusion was relatively high for patients who used TXA in this subgroup, and hemolysis might occur during the filtration process, contributing to hidden blood loss. Another explanation for this result is the small sample size of this subgroup. Further studies with larger sample sizes should be conducted to verify this finding.
We performed the subgroup analysis according to the type of revision surgery because studies suggest that the various types are associated with the differences in perioperative blood loss and blood transfusion volume, and they have come to conflicting conclusions about which revision types are worse in these outcomes. A retrospective study found that revision of both femoral and acetabular components was associated with the greatest blood loss with no significant difference between isolated femoral or acetabular component revision (19). In contrast, another study found that revision of the femoral component was associated with the greatest blood loss, followed by total hip revision group and revision of the acetabular component (20). Other studies found that isolated acetabular revision was associated with the highest blood loss (15), or that blood loss followed the trend: major revision (deep infection, periprosthetic femoral fracture, combined femoral and acetabular revision) > isolated femoral revision > isolated acetabular revision > isolated femoral head, and liner exchange (21). In our sample, total hip revision was associated with the greatest blood loss, followed by isolated femoral component revision, and finally by isolated acetabular component revision. As a result, we conducted further analyses separately for patients who underwent each of these three types of revision surgeries. Despite these discrepancies in the literature, our data suggest that intravenous TXA can provide substantial clinical benefit for all types of revision hip arthroplasties.
One potential disadvantage of using TXA in the revision hip arthroplasty is that because it inhibits the fibrinolytic system, it may increase the risk of VTE, at least in principle (22). However, this work as well as the previous study involving tens of thousands of patients suggests that this is not the case (23, 24). Studies also suggest that this is not the case when TXA is used in primary THA (25, 26). In conclusion, TXA used in revision hip arthroplasty is safe and does not increase the risk of VTE.
Our study examined only intravenous TXA. It may be worthwhile investigating the safety and efficacy of topical or combined topical-intravenous administration, which has been reported in other hip surgeries (27, 28) but rarely for revision hip arthroplasty. Topical administration may be a safe alternative for patients with contraindications to intravenous administration. In addition, the best regimen of TXA is still unclear. A recent study reported that intraoperative infusion regimen (10 mg/kg TXA perioperative intravenous infusion starting 15 min before the surgery until the closure of the wound, and 5 mg/kg additional intravenous dose was administered 12 h after the surgery) of TXA is more effective than the divided-dose regimen (total dose of 10 mg/kg intravenous TXA divided into 2 doses: 15 min before tourniquet inflation and 15 min before tourniquet deflation) for total knee arthroplasty patients (29).
Although our study involves a relatively large sample and takes into account the potential variations with types of revision surgeries, our conclusions should be interpreted with caution in light of several limitations. First, the patients in our study were divided into 2 groups according to their date of surgery. Although we included cases only from the last 10 years, the revision surgeries of the control group were performed more than 6 years from the time we did this retrospective study. The surgical tools and surgical sets, which are used for arthroplasty surgery, are renewed in recent years, which might have played a role in the results of the perioperative blood loss. Second, although our institution has clear standards for blood transfusion, postoperative blood transfusion was decided by the duty physician. Different physicians may have different judgments, which may contribute to variations in the volume and rate of allogeneic blood transfusions. Third, the retrospective design is open to biases that would be reduced with a prospective design. Additionally, our follow-up was limited to the short follow-up period, limiting our ability to detect the incidence of symptomatic VTE beyond 3 weeks after discharge.
In conclusion, the administration of intravenous TXA can safely and effectively reduce the perioperative blood loss and allogeneic blood transfusions in revision hip arthroplasty.
HIGHLIGHTS.
The administration of intravenous TXA can effectively reduce the perioperative blood loss and allogeneic blood transfusions in revision hip arthroplasty.
Intravenous TXA used in revision hip arthroplasty is safe and does not increase the risk of VTE.
The clinical benefits of intravenous TXA did not vary substantially with the subtype of revision hip arthroplasty, including total hip revision, isolated acetabular revision, and isolated femoral revision.
Footnotes
Ethics Committee Approval: Ethics committee approval was received for this study from the Clinical Trials and Biomedical Ethics Committee of Sichuan University West China Hospital.
Informed Consent: The Clinical Trials and Biomedical Ethics Committee of Sichuan University West China Hospital waived the requirement for a written informed consent considering the retrospective nature of the study.
Author Contributions: Concept - P.K.; Design - P.K., Q.W.; Supervision – P.K.; Data Collection and/or Processing - Q.W., R.Y., D.L., Z.Y.; Analysis and/or Interpretation - D.L.; Literature Search - Q.W., R.Y.; Writing Manuscript - Q.W., R.Y; Critical Review - Q.W., R.Y.
Conflict of Interest: The authors have no conflicts of interest to declare.
Financial Disclosure: The authors declared that this study has received no financial support.
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