Risk-stratified perioperative tranexamic acid utilization for total hip and knee arthroplasty: Analysis of trends of the past decade

European Guidelines on perioperative venous thromboembolism prophylaxis: Executive summary.

The efficacy of tranexamic acid (TXA) in reducing blood loss and transfusion requirements in total hip and knee arthroplasty has been well established in small controlled clinical trials and meta-analyses. The purpose of the current study was to determine the risks and benefits of TXA use in routine orthopaedic surgical practice on the basis of data from a large, statewide arthroplasty registry. From April 18, 2013, to September 30, 2014, there were 23,236 primary total knee arthroplasty cases and 11,489 primary total hip arthroplasty cases completed and registered in the Michigan Arthroplasty Registry Collaborative Quality Initiative (MARCQI). We evaluated the association between TXA use and hemoglobin drop, transfusion, length of stay (LOS), venous thromboembolism (VTE), readmission, and cardiovascular events by fitting mixed-effects generalized linear and mixed-effects Cox models. We used inverse probability of treatment weighting to enhance causal inference. For total hip arthroplasty, TXA use was associated with a smaller drop in hemoglobin (mean difference = -0.65 g/dL; 95% confidence interval [CI] = -0.60 to -0.71 g/dL), decreased odds of blood transfusion (odds ratio [OR] = 0.72; 95% CI = 0.60 to 0.86), and decreased readmissions (OR = 0.77; 95% CI = 0.64 to 0.93) compared with no TXA use. There was no effect on VTE (hazard ratio [HR] = 0.91; 95% CI = 0.62 to 1.33), LOS (incident rate ratio [IRR] = 1.00; 95% CI = 0.97 to 1.03), or cardiovascular events (OR = 0.85; 95% CI = 0.47 to 1.52). For total knee arthroplasty, TXA was associated with a smaller drop in hemoglobin (mean difference = -0.68 g/dL; 95% CI = -0.64 to -0.71 g/dL) and one-fourth the odds of blood transfusion (OR = 0.26; 95% CI = 0.21 to 0.31). There was an association with decreased risk of VTE within 90 days after surgery (HR = 0.56; 95% CI = 0.42 to 0.73), slightly decreased LOS (IRR = 0.93; 95% CI = 0.92 to 0.95), and no association with readmissions (OR = 0.90; 95% CI = 0.79 to 1.04) or cardiovascular events (OR = 1.12; 95% CI = 0.74 to 1.71). In routine orthopaedic surgery practice, TXA use was associated with decreased blood loss and transfusion risk for both total knee and total hip arthroplasty, without evidence of increased risk of complications. TXA use was also associated with reduced risk of readmission among total hip arthroplasty patients and reduced risk of VTE among total knee arthroplasty patients, and did not have an adverse effect on cardiovascular complications in either group. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Primary total hip arthroplasty (THA) procedures continue to increase. On the basis of data from 2000 to 2014, the frequency of THA in the U.S. is projected to grow to 635,000 procedures per year by 20301. The majority of implants from these procedures are expected to last >20 years. A study of 94,292 total hip replacements from the Finnish Arthroplasty Registry noted a survivorship of 58% at 25 years2. THA complications (especially periprosthetic joint infection [PJI] and dislocation), as well as perioperative management to optimize short stays and outpatient THA while minimizing perioperative complications, continue to draw heavy attention. Implant Design and Related Outcomes In a study evaluating 2016 data from the American Joint Replacement Registry (AJRR) compared with other national registries, the authors found that cementless stem fixation combined with the use of ceramic and 36-mm heads was the current preference in the U.S., while other registries indicated that cemented implants and metal and 32-mm heads were most commonly used3. Cemented Versus Cementless Implants There is evidence that cemented implants outperform cementless counterparts in elderly patients when early complication rates are compared. On the basis of the recent Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR) annual report, Tanzer et al. reported that, among patients >75 years of age who underwent THA, those treated with the best-performing cementless femoral stems had more early revisions (<30 days postoperatively) compared with those treated with the best-performing cemented implants4. These early revisions were mainly attributable to the risk of revision for fracture or loosening. This difference disappeared after 90 days following surgery4. Bearing Surfaces Metal-on-Polyethylene (MoP) Studies show better long-term survival with a metal-on-highly-cross-linked-polyethylene (HXLPE) articulation compared with metal-on-conventional, non-cross-linked polyethylene (CPE) in younger patients5-7. In a retrospective review of 101 hips in 84 patients ≤50 years of age, with a duration of follow-up of 15 to 20 years, cobalt-chromium (CoCr)-on-CPE showed a high rate of wear-related revision (13 of 101, 12.9%)5. In contrast, the authors of another report noted excellent 15-year survivorship and functional outcome with no wear-related revision in a cohort of 82 patients (89 hips) ≤50 years of age with CoCr-on-HXLPE6. An observational study from the AOANJRR showed that hips in which XLPE was used (199,131 procedures) had a significantly lower revision rate at 16 years following THA for osteoarthritis compared with hips in which CPE was used (41,171 procedures), regardless of the head material7. Ceramic-on-Ceramic (CoC) or Ceramic-on-Polyethylene (CoP) Clicking or squeaking continues to be present in a small percentage of patients who undergo THA with CoC components. In 1 report, audible noise was present in 6.4% of hips (48 of 749) following THA with use of fourth-generation alumina CoC bearings, although no patient underwent revision for clicking or squeaking8. The selection of CoP recently surpassed MoP as the most popular bearing surface used in THA in the U.S.9. Metal-on-Metal (MoM) A study from Korea demonstrated an acceptable rate of aseptic loosening (cup, 10.5%; stem, 6.1%) in a cohort of 114 hips treated with THA using 28-mm MoM components; the average follow-up was 20 years (range, 17 to 23 years)10. Nonetheless, the use of an MoM articulation continues to decline secondary to persistent concerns for metal debris-induced adverse local tissue reactions. Surface Treatment The authors of a prospective multicenter study reported that, at the 5-year follow-up, titanium alloy (Ti6Al4V) acetabular shells with a porous titanium coating (PTC) had a higher percentage of gaps/radiolucency compared with plasma-sprayed (PS) acetabular shells from the same manufacturer (23% versus 5%). Patients in the PTC group had more patient-reported pain, although none underwent revision for loosening11. Short Versus Standard Stems In a randomized double-blinded study, persistent mid-thigh pain was much more prevalent among patients with a short Collum Femoris Preserving (CFP) stem (LINK) (19%) compared with a full-profile wedge-tapered Alloclassic Zweymüller stem (Zimmer) (7%) at medium-term follow-up. Both cohorts, however, had a high percentage of varus malalignment (14% and 16%, respectively), and the results may not be generalizable to other cementless designs12. The association between periprosthetic femoral fracture and length/geometry of cementless implants was also studied. In a cohort study of 5,090 consecutive, direct-anterior primary THAs performed at a single institution, the incidence of periprosthetic fracture using femoral components with 4 variations in length and geometry was evaluated13. All stems were of a single-taper wedge design from the same manufacturer, with 1 of 4 configurations: full-length, standard profile; full-length, reduced distal profile; short-length, standard profile; and short-length, reduced distal profile. There was a trend toward a higher risk of periprosthetic fracture in the short-length-with-standard-profile group13. It is unclear whether the same trend would hold using other surgical approaches. Head Size In a study using data from the Nordic Arthroplasty Register Association database and including 186,231 patients who underwent MoP THA with use of a 28, 32, or 36-mm head, the authors found that the risk of dislocation was reduced with the use of 32 versus 28-mm heads, although the overall revision risk remained similar. Surprisingly, transitioning from 32 to 36-mm heads was associated with a higher risk of revision for all causes, including the risk of dislocation14. It appeared that 32-mm heads would be the optimal choice for MoP THA. Dual-Mobility Constructs Modular dual-mobility constructs employ a CoCr articular surface liner that locks into an outer shell of titanium. A systematic review of mid-term studies of dual-mobility constructs supports their efficacy in reducing the incidence of dislocation after both primary and revision THA15. The wear rate for contemporary dual-mobility constructs using an HXLPE design showed substantially larger magnitudes of initial head penetration and wear than those reported for HXLPE in fixed-bearing couples (twice the rate)16. It approaches a steady state after 2 years, making it comparable with traditional fixed bearings; future studies should address the long-term outcomes16. A propensity score-matched study showed that patients with a dual-mobility construct had a lower risk of revision due to dislocation, although there was no difference in the overall risk of revision between the dual-mobility construct group and the MoP/CoP group. The authors speculated that selection bias may have been present, as the dual-mobility construct group also showed a higher risk of revision due to infection17. Patient Factors in Relation to Outcomes Medical Comorbidities Dialysis dependence was demonstrated to be an independent risk factor for 30-day adverse events, intensive care unit (ICU) care, longer length of stay, and rehabilitation needs in patients undergoing total joint arthroplasty (TJA)18. Patients with hepatitis C who received interferon or direct antiviral agents prior to THA appeared to have fewer postoperative complications, especially PJI19. Dorr Type In a matched comparative study, a higher incidence of femoral stem-related complications (mainly periprosthetic femoral fractures) was observed when using double-tapered wedge stems in Dorr type-A compared with type-B femora20. A study correlating proximal femoral morphology and leg length after THA showed that patients with a Dorr type-A femur and a high femoral cortical index (FCI, defined as the ratio of cortical width minus endosteal width to the cortical width at a level 100 mm below the tip of the lesser trochanter on an anteroposterior radiograph of the hip) were at increased risk of leg lengthening while patients with a Dorr type-C femur and a low FCI had an increased probability of shortening21. Body Mass Index (BMI) Several studies showed a higher risk of complications (up to 3 times) among THA patients classified as morbidly obese compared with normal controls22-24. In particular, researchers in the U.K. reported on, to our knowledge, the largest longitudinal cohort study to date analyzing the influence of BMI on THA outcomes (>410,000 patients)25. Patients who were morbidly obese (BMI of 40 to 60 kg/m2) had the highest probability of revision at 10 years (twice that of the underweight group), while 90-day mortality was significantly higher for the underweight group compared with those with normal BMI. Milder obesity (BMI of 25 to 40 kg/m2) seemed to have a protective effect against mortality25. In another study, patients classified as super obese (BMI of ≥45 kg/m2) had a greater risk of reoperation and readmission and greater 90-day costs compared with the nonobese cohort, but they had comparable quality-of-life improvements26. Patients classified as morbidly obese who underwent bariatric surgery prior to TJA showed a reduced comorbidity burden at the time of TJA, with reduced post-TJA complications; however, the risk of revision was not reduced27. While obesity seems to be a major negative predictor of adverse outcomes, some argue that THA is still cost-effective for morbidly obese and super obese groups and recommend against a cutoff threshold to avoid unnecessary loss of health-care access28. Preoperative Opioid Use Opioid use within 3 months preceding THA was an independent predictor of early revision, while obesity and anxiety/depression were also shown to predict early failure of treatment29. Significantly higher 30-day readmission and revision rates were observed among THA/TKA (total knee arthroplasty) patients with a history of long-term preoperative opioid use30. In another study, patients who used opioids preoperatively tended to have significantly lower patient-reported outcome scores and longer hospital stays, and were more likely to be discharged to a rehabilitation facility31. Tobacco Use In a recent study, smokers had a significantly higher risk of deep infection and reoperation after revision THA compared with nonsmokers, and the risk was higher than for primary THA32. The authors of a systematic review and meta-analysis found that former tobacco users had a significantly lower risk of wound complications and PJI compared with current smokers. Smoking cessation counseling prior to total joint arthroplasty is strongly advocated33. A history of smoking was also recently tied to increased risk of nerve injury in patients undergoing THA34. Surgical Approach The optimal surgical approach in primary THA remains controversial. A systematic review and meta-analysis of prospective studies showed less pain and better reported function through 90 days postoperatively for the direct anterior approach compared with the posterior approach35. However, when comparing early revision rates (<5 years from index primary surgery), the direct anterior approach was associated with a significantly higher rate of early revision due to femoral loosening compared with the posterior approach, while the posterior approach demonstrated a higher incidence of early revision due to instability36. A Dutch joint-registry study showed small improvements in the 3-month postoperative patient-reported outcome measure (PROM) for the direct anterior and posterolateral approaches compared with the direct lateral and anterolateral approaches37. Regardless of the different approaches, there are minimal differences in gait mechanics at early or late follow-up38. The long-term prognosis of lateral femoral cutaneous nerve (LFCN) neuropathy was also investigated. One study found that approximately 11% of patients had persistent LFCN neuropathic symptoms even at 6 to 8 years after direct anterior THA, and the most common presentation was numbness (37%). This, however, did not affect hip functional scores39. Complications There is substantial variation in reported THA complication rates among national databases and joint registries. The American College of Surgeons National Surgical Quality Improvement Program (NSQIP) tends to show the lowest rate of complications40. Medical Complications A study of 10-year Hospital Episode Statistics data from the U.K. including 540,623 THAs showed that postoperative medical complications decreased year-after-year despite a steady rise in the average Charlson Comorbidity Index score. The only 2 exceptions were lower respiratory tract infection and renal failure, which continued to rise41. Venous Thromboembolism (VTE) and Anticoagulation A systematic review found that industry-funded studies assessing thromboprophylaxis reported fewer patients with pulmonary embolism (PE), major bleeding, and mortality compared with nonfunded studies42. A cross-sectional study in 5 countries found that the rate of in-hospital VTE after hip arthroplasty was 0.16% in Canada, 1.41% in France, 0.84% in New Zealand, 0.66% in the U.S. (California), and 0.37% in Switzerland, while the benchmark was 0.58%. French data showed a higher rate, potentially because of the systematic use of ultrasound, which could result in the over-detection of deep venous thrombosis (DVT) but not PE43. A retrospective analysis of the NSQIP data set from 2008 to 2016 demonstrated that the risk of DVT was not associated with obesity in patients undergoing THA. The risk of PE, however, was found to be elevated in THA patients whose BMI was ≥35 kg/m2. The authors concluded that, since current pharmacologic anticoagulation regimens can reduce the DVT rate but have not been demonstrated to affect the rate of PE or death, the data do not support increased DVT anticoagulation in THA patients who are obese but without other VTE risk factors44. Dislocation Spinopelvic pathology dominated the literature on THA dislocation, with important research focused on spine-pelvis-hip radiographs in the sagittal plane and the related functional safe zone45-52. It has been proposed that the spinopelvic relationship be categorized according to 4 groups, as assessed at the preoperative evaluation (1A: normal alignment, normal mobility; 1B: normal alignment, stiff spine; 2A: flatback deformity, normal spine; 2B: flatback deformity, stiff spine). Special attention should be paid to the 2B population, for whom surgeons may consider using a dual-mobility construct with targeted 30° of anteversion relative to the functional pelvic plane (based on standing, rather than supine, anteroposterior pelvic radiography)45. A modified classification system was recently proposed on the basis of supine anteroposterior pelvic, standing anteroposterior pelvic, and sitting and standing lateral spinopelvic radiographs46. The classification system adds a hyperlordosis spinal alignment category (pelvic incidence-lumbar lordosis [PI-LL] mismatch of <–10°) and suggests a new risk assessment tool incorporating sagittal spinal alignment (coded as a number) and spine mobility/stiffness (coded as a letter) to use in revision THA. This new assessment tool was validated in a group of 222 patients who underwent revision hip replacement for recurrent instability. Results for 111 patients who were evaluated using the new spinal function assessment were compared with a matched group of 111 patients who were not evaluated using the system. The dislocation rate was 3% among patients who had the new presurgical assessment compared with 16% for those who did not46. Patients undergoing THA with a history of lumbar spinal fusion (LSF) had a >100% increased risk of dislocation compared with those who had LSF 5 years after THA53. Another study found that fusion to the sacrum as well as multiple levels of lumbar involvement dramatically increased the risk of dislocation in primary THA54. Although there was no increased perioperative spike of dislocation in patients undergoing LSF following an otherwise stable THA, 1 study demonstrated that this population had a sustained elevated risk of dislocation (0.7% per year) compared with those without LSF (0.4% risk per year)55. PJI The past decade saw tremendous effort and focus on preventing PJI in patients undergoing TJA. Current unadjusted 1-year and 5-year risks of PJI following THA were found to be 0.69% and 1.09%, respectively. After adjustment, however, there was no detectable decline in the risk of PJI over time56. Once PJI is confirmed, the 1-year weighted mortality rate was noted to be 4.22%, and 5-year mortality, 21.12%, highlighting the devastating consequence of PJI57. A PJI consortium (International Consensus on Orthopedic Infections) recently published a guideline for comprehensive hip and knee PJI diagnosis, prevention, and treatment58-65. With the new evidence-based and validated PJI criteria in 2018, PJI diagnosis now consists of a scoring system for minor criteria in both preoperative and intraoperative diagnosis66. One recent study found that there is no difference in treatment success as defined by the Delphi criteria between patients meeting minor-only criteria and those meeting a major criterion of PJI diagnosis67. Another PJI scoring model assigns relative weights to the various risk factors for PJI following TJA. A previous open surgical procedure, drug abuse, a revision procedure, and human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) were deemed the most influential factors68. A positive association between postoperative urinary tract infection and PJI after THA or TKA was established in a population-based, retrospective cohort study of 113,061 patients (≥66 years old). No association was found between acute postoperative urinary retention and PJI69. Debate continues regarding the merits of 1-stage versus 2-stage revision for PJI. In a recent Danish study, the authors reported an encouraging 91% infection-free survival rate at a minimum of 2 years of follow-up when using 1-stage cementless revision in the treatment of patients with chronic periprosthetic hip joint infection70. In another study, about 30% of revisions had an increase in the vancomycin minimum inhibitory concentration (MIC) between 2 stages, raising concerns about the potential for the emergence of resistant organisms between the stages of a 2-stage revision71. Postoperative Urinary Retention Risk factors for postoperative urinary retention have been defined, including an age of >60 years, intraoperative fluid administration of >1,350 mL, and intraoperative of an of risk factors related to postoperative urinary retention are and should be Although the percentage probability of periprosthetic femoral fracture using cementless stems was demonstrated to be only at 10 years, this dramatically increased to at years after primary another study the incidence of periprosthetic femoral fracture in stems found that the incidence of periprosthetic femoral fracture continued to increase after the decade and the incidence of aseptic loosening in the decade A study using data from the national found that the annual incidence of periprosthetic femoral fracture in primary THAs increased from of to of the of to In the report, type-C 4 more than and they were more commonly in cemented The incidence of with MoP is and an average of 5 years to metal the ratio have been shown to be higher in MoP (range, or compared with MoM (range, to Another study a level of and a ratio of to be a cutoff threshold for important MoP The levels of and to decline by and 3 months after potential in the femoral nerve was observed in 17 of patients who underwent the direct anterior approach in THA when were against the anterior of the although this was The authors of another recent study of the anterior in a relative safe to the to avoid In a recent retrospective cohort study using the A data was found to be associated with significantly lower rates of dislocation and aseptic revision of the acetabular following primary The authors when their results because of potential by In a double-blinded study in the U.K. that patients undergoing THA or the use of with an and to show a in the rate of surgical infection Current and The past decade has a rise in the incidence of both outpatient and THA, according to a recent comparative and have been for or to be while also patient supports a trend toward better postoperative outcomes when hip replacement is performed by While the majority of primary THAs are performed at surgeons are the majority of these A more relationship was by a New data set of of the was associated with a 2 to increase in the risk of complications, mortality, and revision relative to while hospital was associated with a increase in complications and a 4 to increase in The opioid has has more attention in recent years. regarding opioid after joint replacement surgery show that to of patients continue opioid use even at 1 year have been to reduce opioid without of A study indicated that fewer compared with 90 was associated with a in opioid and decreased opioid without pain scores and patient-reported In a retrospective review of patients who underwent THA and TKA reported a history of those reported and including respiratory and In this study, no patient with a who was an adverse It was also found that, for the patients with a who were or no differences could be found in the rate of Use is now an of the THA to reduce loss and the risk of by including the American Association of and Surgeons and the American of Orthopaedic Surgeons state that no of or time of administration have been shown to A recent randomized study did that multiple postoperative of reduced loss compared with a single preoperative The of 1 preoperative of 2 by 3 postoperative of of loss in Smoking A study from the demonstrated that level of 8 within 1 of TJA could significantly rates of smokers It also to of patients who reported as continued smoking and as more than after surgery among those who and A from demonstrated that the administration of could to for among patients undergoing THA, by a in postoperative pain scores of was also in reducing opioid and The of use in patients with undergoing THA or TKA was recently in a retrospective study of 2 of patients in the group and in the patients who received were not found to have a significantly higher infection rate than to the that PJI is an this study have been with the of with a a mainly a spinal using significantly the length of of patients undergoing THA by 1 Postoperative Current evidence that the postoperative of and levels following THA in patients with a normal preoperative level is the should be by risk factors and Preoperative and levels of and 4 have been as below which should consider postoperative and It has been that consider the use of the in for THA including of patients with THA with a had significantly higher than those without a and among the THA with a was greater for those The of The a of recently published studies related to the system that received a higher of In to in this 4 other with a higher of to hip replacement are to this review after the standard with a about to in an evidence-based in this treatment and risk of or after total hip a cohort study from national Danish Joint This to the knowledge, the largest study using the Danish databases to address the association between perioperative treatment and postoperative 30-day PE, and from all among patients who underwent THA. A total of patients were the study from to among received perioperative and did After use was not found to significantly increase the risk of PE, or The authors were to the of using on patients with previous and other in this of on outcomes after primary and revision total hip at the a cohort study patients who underwent primary or revision THA from through A using 32 factors found in the medical including 17 and of was used to the study population as index of of to and of With to in-hospital complications, differences were found only for wound complications and the and with patients had a significantly higher risk of mortality ratio of dislocation, wound and reoperation within 90 days and 1 year after primary THA. The authors did not a association of with aseptic periprosthetic or prior bariatric surgery outcomes following total joint arthroplasty in the morbidly A This meta-analysis studies from to 2018, with a total of patients who underwent THA or underwent bariatric surgery prior to TJA and the patients with obesity as the group. The study found that bariatric surgery prior to TJA was associated with reduced risks of medical complications, length of stay, and The risks of wound infection or and the long-term risks of dislocation, periprosthetic and revision were not the THA and TKA bariatric surgery was associated with a in the risk of PJI after but not after THA. of of and on in the after total hip the randomized The and in is a Danish study the and of 4 regimens or after THA. The was 1 surgery and 6 for for a total of 4 of the on the postoperative and patients were in the The authors found that significantly reduced compared with in the after The surgical approach versus for the study cohort was not which have the postoperative for

What's New in Hip Replacement.

Association Between Tranexamic Acid and Decreased Periprosthetic Joint Infection Risk in Patients Undergoing Total Hip and Knee Arthroplasty: A Systematic Review and Meta-Analysis of Over 2 Million Patients

<h3>Background and Aims</h3> The use of tranexamic acid (TXA) has reduced rates of perioperative blood transfusion for total hip arthroplasty (THA) and total knee arthroplasty (TKA)¹. While oral rather than intravenous (IV) dosing of TXA at the time of surgery may simplify perioperative protocols and reduce costs, it is not clear whether oral TXA is as effective as IV TXA in reducing blood loss and transfusion rates. <h3>Methods</h3> This randomized controlled trial compared the use of one preoperative dose of oral TXA (1,950mg) to one preoperative dose of IV TXA (1,000mg) in THA (N=200) and TKA (N=200). Consecutive patients undergoing primary THA or TKA under regional anesthesia with sedation were enrolled. The primary outcome was calculated blood loss (CBL). Secondary outcomes were transfusions and complications, including cardiac events and venous thromboembolism. The study was designed as a non-inferiority trial with an intention-to-treat analysis. <h3>Results</h3> Oral TXA was non-inferior to IV TXA (p&lt;0.001). Mean CBL values were 842.21 mL versus 860.45 mL for THA and 798.48 mL versus 878.13 mL for TKA in the oral and IV arms, respectively. There was one postoperative transfusion, which occurred in the IV TXA arm of the study. There was no difference in complication rates between the two arms of the study. <h3>Conclusions</h3> Oral TXA can be feasibly administered in the preoperative setting prior to THA or TKA and is non-inferior to IV TXA with respect to CBL and transfusion rates in this setting.

IntroductionPatients undergoing total hip arthroplasty (THA) and total knee arthroplasty (TKA) are considered to have a symptomatic venous thromboembolism (VTE) risk of 1.0%–1.5% despite thromboprophylaxis. Fast-track treatment protocols have substantially lowered the VTE risk in most patients. Hence, the majority of patients may be unnecessarily exposed to the burden and risk of thromboprophylaxis. On the contrary, there are still patients with a high VTE risk who develop VTE despite thromboprophylaxis. Thus, tailored thromboprophylaxis treatment may potentially reduce both VTE and bleeding risk.Methods and analysisThe DISTINCT (inDividual, targeted thrombosIS prophylaxis versus the standard ‘one-size-fits-all’ approach in patients undergoing Total hIp or total kNee replaCemenT) trial is a national, multicentre, randomised, multiarm, open-label trial. The main objective is to study whether tailored thromboprophylaxis reduces the occurrence of symptomatic VTE (primary outcome) and major bleeding (primary safety outcome) within 90 days after THA/TKA in comparison with standard thromboprophylaxis. Patients with a low, intermediate or high predicted VTE risk (based on the Thrombosis Risk Prediction following total hip and knee arthroplasty score (TRiP(plasty) score)) will be included in the DISTINCT-1, DISTINCT-2 or DISTINCT-3 studies, respectively. In the DISTINCT-1 trial, 3478 patients will be randomly allocated to receive either in-hospital thromboprophylaxis or standard prophylaxis. In the DISTINCT-2 cohort study, 2500 patients will receive standard prophylaxis. In the DISTINCT-3 trial, 4100 patients will be randomly allocated to receive either 6 weeks of high-dose thromboprophylaxis or standard prophylaxis. Standard prophylaxis consists of a low dose of any approved thromboprophylactic agent for 4 weeks. We hypothesise that (1) the efficacy of in-hospital only thromboprophylaxis is non-inferior in preventing VTE and equally safe compared with standard prophylaxis in patients with a low VTE risk (DISTINCT-1) and (2) prolonged high-dose thromboprophylaxis is superior in preventing VTE as compared with standard prophylaxis in patients with a high VTE risk (DISTINCT-3). Patients with intermediate VTE risk will be observed to evaluate VTE and bleeding rates (DISTINCT-2).Ethics and disseminationThe protocol has been approved by the Medical Research Ethics Committee Leiden-Den Haag-Delft, EU-trial-number 2023-510186-98. Study results will be disseminated through peer-reviewed journals and during international conferences.Trial registration numberNCT06581965.

To describe a single institution's experience after initiation of a protocol in which all primary total hip arthroplasty (THA) and total knee arthroplasty (TKA) patients were administered intravenous tranexamic acid (TXA) intraoperatively to decrease perioperative blood loss. A retrospective review of medical records at a single institution from February 2012 to April 2014. The TXA treatment group was compared to a control group. We reviewed intraoperative blood loss, preoperative hemoglobin (Hb) levels, postoperative day 0 to 2 Hb levels, transfusion rates, postoperative venous thromboembolism, and other complication rates. 259 patients underwent either TKA (165) or THA (94). 121 received perioperative intravenous TXA and 138 did not. There was a statistically decreased rate of allogeneic blood transfusion (0 vs. 10, p = 0.003) as well as a higher postoperative day 2 Hb level (10.8 ± 1.1 vs. 10.2 ± 2.6 g/dL, p = 0.02) in the treatment group. There was no statistical difference in any variable measured in the THA group, though there was a trend toward higher postoperative Hb levels at all-time points measured. Intravenous TXA is a safe and effective drug to decrease perioperative blood loss and allogeneic transfusion in THA and TKA. There was no increased risk of venous thromboembolism or other complications in our review.

Objectives: The aim of this study is to compare blood loss from IV (intravenous) TXA (tranexamic acid) to PO (oral) TXA in THA (total hip arthroplasty) and TKA (total knee arthroplasty) at UHSJMC (University Hospitals St. John Medical Center). The primary endpoint is to compare the hemoglobin change (g/dL) in patients using IV versus PO TXA after THA or TKA. The secondary endpoints are to compare the amount of blood loss (mL), amount of transfusions (units), and length of stay (days). Methodology: This is a retrospective chart review of patients who receive IV or PO TXA during a THA or TKA. Inclusion criteria are patients receiving IV TXA between September 1, 2018 and February 28, 2019 or patients receiving PO TXA between September 1, 2019 and February 29, 2020 for a THA or TKA. Patients will be excluded if they are less than 18 years old; patients who have a history of cognitive/psychosocial impairment, dementia, or language barrier, have had a deep vein thrombosis or pulmonary embolism within the past twelve months; have a history of deep vein thrombosis or pulmonary embolism being treated with anticoagulation; known congenital thrombophilia; or cardiac stent or ischemic stroke within one year. Primary endpoint will be analyzed using a standard independent T-test comparing mean change in hemoglobin. Secondary endpoints will be analyzed using descriptive statistics. Results: A total of 357 patients were reviewed for inclusion in the study with a total of 289 patients enrolled, 257 in the IV group and 32 in the PO group. There were 107 THA and 150 TKA included in the IV TXA group. There were 18 THA and 14 TKA included in the PO TXA group. The primary outcome of change in hemoglobin was -2.721 ± 1.04 g/dL for the IV TXA group and -2.513 ± 1.09 g/dL for the PO TXA group (p < 0.001). The secondary outcome of blood loss was 189.35 ± 180.2 mL for the IV TXA group and 89.69 ± 70.7 mL for the PO TXA group (p < 0.001). The secondary endpoint of length of stay was 2.02 ± 1.05 days for the IV TXA group and 1.84 ± 1.05 days for the PO TXA group (p < 0.001). Only one patient received a blood transfusion of 2 units during this study therefore statistical tests could not be performed. A post hoc analysis was preformed comparing THA to TKA. Hemoglobin change, length of stay, and transfusions were non-inferior to each other but amount of blood loss was significantly more for THA versus TKA (p < 0.001). Conclusion: With the ease of use of PO tablets, possible cost savings, and longer half-life, the use of PO TXA may be more beneficial for select patients. Future studies with larger sample sizes, randomization, and lack of surgeon variability are still needed.

» Despite many patients traveling by air for total hip arthroplasty (THA) and total knee arthroplasty (TKA), there are limited data to guide recommendations for air travel after these procedures.» It is unknown whether the timing of postoperative air travel contributes to the risk of developing venous thromboembolism (VTE) after THA and TKA.» The existing limited data do not suggest a difference in VTE risk between those who did and did not travel by air after THA and TKA surgery, mostly within 7 days.» As more patients travel by air seeking THA and TKA, there is an increasing need for a thorough evaluation of associated risks. This assessment should account for patient-specific risk factors, duration of air travel, and the timing of flights in relation to the postoperative period to ensure optimal safety and outcomes.» There is no consensus on the ideal VTE prophylaxis for patients who travel by air after THA and TKA. However, long-haul flights (>4 hours) are associated with a higher VTE risk and are likely to require stronger prophylactic measures.» Some airlines and regulatory agencies may enforce regulations for passengers who travel by air soon after THA and TKA. Patients may be asked to present proof of medical clearance from the treating surgeon before boarding the airplane in addition to being on appropriate VTE prophylaxis.

Update This article was updated on February 6, 2019, because of a previous error. On page 105, in the subsection titled “Outcomes and Design” the sentence that had read “Furthermore, in a retrospective review, Houdek et al. 48 , at a mean follow-up of 8 years, demonstrated improved survivorship of 9,999 metal-backed compared with 1,645 all-polyethylene tibial components, over all age groups and most BMI categories” now reads “Furthermore, in a retrospective review, Houdek et al. 48 , at a mean follow-up of 8 years, demonstrated inferior survivorship of 9,999 metal-backed compared with 1,645 all-polyethylene tibial components, over all age groups and most BMI categories.” An erratum has been published: J Bone Joint Surg Am. 2019 Mar 20;101(6):e26.

BackgroudIntravenous tranexamic acid (TXA) has been shown to reduce blood loss in patients undergoing total joint arthroplasty without systemic complications. There is limited evidence of its effectiveness in revision procedures. This study evaluated intravenous TXA effect on blood loss, transfusion rates, and length of hospital stay in revision joint replacement.MethodsOne-hundred revision total joint arthroplasty patients were retrospectively reviewed [44 revision total hip arthroplasty (THA) and 54 revision total knee arthroplasty (TKA)] who underwent surgery from 2013 to 2016. Fifty-four revision joint patients (23 THA and 31 TKA) received intravenous TXA intra-operatively, while 46 revision joint patients (23 THA/TKA) did not. Primary outcome measures were blood loss, transfusion rates, and length of hospital stay.ResultsThe mean blood loss difference between revision THA patients who received TXA vs. not receiving TXA was 180ml in revision THA patients (p < .005). Mean length of hospital stay was 6 days in non-TXA vs. 3 days in TXA patients (p < .001). Eighteen patients received transfusions in the non-TXA revision TKA group compared to nine patients in the TXA revision TKA group (p < .001). Average length of hospital stay was 5 days in the non-TXA revision TKA group compared to 3 days in the TXA revision TKA group (p < .003). There was no increased risk of thromboembolic complications in TXA groups for either procedure.ConclusionsIntravenous TXA reduced length of hospital stay in both revision cohorts, decreased blood loss in revision THA and decreased the rate of transfusion in revision TKA without an increase in thromboembolic complications.Level of EvidenceLevel III (Case-control study)

What's New in Hip Replacement.

This issue of TRANSFUSION features two clinical trials on the use of tranexamic acid (TXA) in joint replacement surgery. The first study examines the use of TXA for reducing autologous blood transfusion in total knee or hip replacement surgery.1 The second study reports the effect of TXA on allogeneic blood transfusion for two-staged bilateral total knee replacement surgery.2 The first study is a double-blinded randomized placebo controlled trial in which Oremus and colleagues1 compared TXA with placebo to evaluate the efficacy of TXA to reduce autologous transfusion of shed blood in unilateral primary total knee or hip replacement. Ninety-eight primary hip or primary knee replacement patients were randomly allocated to receive an intraoperative intravenous (IV) dose of 1 g of TXA or placebo 15 minutes before skin incision for total hip replacement or 15 minutes before tourniquet release for total knee replacement. After 3 hours, a second dose of 1 g of TXA or an equivalent volume of placebo (saline) was administered IV. The minimum volume of retransfusion was set at 250 mL and a transfusion trigger of hemoglobin (Hb) level of less than 8 or 8 to 10 g/dL with symptoms of anemia. Only 10.2% in the TXA group versus 85.7% in the placebo group received autologous transfusion. The TXA group had a 75% lower requirement for autologous transfusion than the placebo group. The median total external blood loss during the first 24 hours was 320 mL (80-930 mL) in the TXA group versus 970 mL (100-2600 mL) in the placebo group. This study also examined the safety profile of TXA by measuring hemodynamic changes during administration of TXA and performed postoperative screening for deep vein thrombosis (DVT). Clinical assessment for DVT was performed three times a day and ultrasonography, fibrinogen, and D-dimer measurements were performed in suspected cases. The authors did not find any difference in hemodynamic changes or DVT between both groups. In addition, there was no difference in blood loss between the total knee replacement and total hip replacement surgery. This study provides evidence that using TXA with a restrictive transfusion trigger policy can potentially replace the use of an autologous drain system. This protocol can avoid the autologous blood transfusion related complications such as febrile reactions and possible retrograde infection. The use of closed suction drainage for joint replacement surgery is controversial and there is practice variation in whether surgical drains are used. Although the use of a drain is based on individual or institutional practice, evidence has shown that the use of a closed system suction drainage increases the total blood loss after joint replacement surgery.3 At the same time, a recent meta-analysis has confirmed that autologous shed blood transfusion is an effective method to reduce allogeneic blood transfusion.4 Other techniques used to reduce the blood loss are clamping the drain, retrograde injection of TXA through the drain, and closure without a drain.5 The current study by Oremus and coworkers suggests that TXA could potentially eliminate the need for surgical drains and autologous shed blood transfusion. The cost-effectiveness of using TXA rather than autologous transfusion of shed blood was not analyzed in this study, although the cost of TXA may be lower. Overall this well-designed randomized controlled trial shows the efficacy of TXA on reducing autologous shed blood transfusion. The second study is a retrospective study in which Kelley and coworkers2 determined the effect of TXA on blood transfusion in patients undergoing bilateral total knee replacement staged 3 days apart. Transfusion rates were compared between patients who did not receive TXA (before the routine use of TXA) and after the institution of TXA for bilateral total knee replacement. The TXA group received 1 g of TXA IV 15 minutes before incision and 1 g IV before tourniquet release. The main findings were the TXA group had lower mean blood loss than the non-TXA group (373.8 ± 264.6 mL vs. 871.6 ± 457.7 mL, respectively). The blood transfusion rate was lower (43.1% vs. 71.4%) in the TXA group and the amount of allogeneic blood transfusion was lower (0.64 ± 0.84 units vs. 1.53 ± 1.30 units) in the TXA group. In addition, the TXA group had significantly higher Hb level on Day 1 and Day 2 with each stage of total knee replacement. Otherwise there was no difference in postoperative complications including infection, venous thromboembolism, reoperation, hematoma, or pre- and postoperative Knee Society score and range of movement. Since this study was retrospective, routine screening for venous embolism was not done. The transfusion trigger was 9 g/L for the first surgery and 8 g/L for the second surgery. These two studies add to the growing literature supporting the efficacy of TXA for reducing blood loss6, 7 and blood transfusion in joint replacement surgery. Surgical trauma and the use of a tourniquet have been shown to activate fibrinolysis. TXA is a lysine analog that helps to prevent fibrinolysis in conditions that promote fibrinolysis. TXA is relatively inexpensive, easy to administer, and more cost-effective than transfusion and other blood conservation techniques. Existing studies in the orthopedic surgical literature have not shown an increase in adverse events such as thromboembolic complications with the use of TXA for joint replacement surgery. Although the study designs differ, both current studies used the same total dose of TXA and used closed suction drain systems. The total dose of TXA used in both studies was 2 g, but the timing of administration was different. The timing of administration and dosage of TXA have varied in previous studies. A recent study found a preoperative and intraoperative IV dose of TXA was more effective than a single dose of TXA given intraoperatively or an intraoperative dose followed by a postoperative dose.8 These authors also concluded that a single dose with local application was more effective than a single dose administered IV.8 The optimal dose, timing of administration, mode of administration, and duration of treatment have not been determined. A recent systematic review and meta-analysis concluded that the effect of TXA on blood loss varied with the timing of administration of TXA, but the extent of this variation was small, and the authors questioned the clinical importance of this variation.9 The authors also found a lack of a dose–response relationship of TXA, with a total dose of about 14 mg/kg (approx. 1 g) appearing to be sufficient. However, these authors did not specifically examine joint replacement surgery, but included different types of surgery. Most of the blood loss in total knee replacements occurs during the first few hours after surgery.10 A recent pharmacokinetic study showed that peak fibrinolytic activity occurred at 6 hours from the incision time for both total hip and total knee replacement, and the fibrinolysis activity persisted for 18 hours.11 This finding supports a multiple dose regime or a postoperative infusion as the most effective way to reduce blood loss with use of TXA in joint replacement surgery. However, this protocol must be balanced with the high risk for DVT in this patient population. These studies support the use of TXA to reduce blood loss and transfusion in joint replacement surgery. The optimal timing, dose, duration of treatment, and route of administration of TXA, however, remain uncertain. There is a need for more pharmacokinetics studies to optimize the use of TXA to reduce blood loss and blood transfusion, while minimizing any potential adverse effects in joint replacement surgery. These studies should be encouraged by the transfusion medicine community since TXA appears to be a useful pharmacologic alternative to transfusion in orthopedic surgery. None.

This study involved a meta-analysis of 36 published studies to examine the efficacy of intravenous (IV) and intra-articular (IA) tranexamic acid (TXA) in reducing blood loss, drain output, thromboembolic complications, and hospital stay following total hip and total knee arthroplasty. This study also evaluated whether treatment with a combination of both IA and IV TXA has an effect on these outcomes. Lastly, this study attempted to analyze the method and technique of TXA administration in order to establish a best practice for its use in reducing overall blood loss in arthroplasty procedures. MEDLINE, Embase, and the Cochrane Library database were screened. Studies comparing IV TXA with IA TXA or with combined IV and IA TXA were included. Data including total blood loss, drain output, thromboembolic complications, and hospital stay, where available, were analyzed using meta-analysis with fixed effects. Results are presented as the standardized mean difference (SMD), and meta-regression was employed to explore plausible demographic contributions to heterogeneity. Twenty-eight randomized controlled trials, 3 prospective cohort studies, and 5 retrospective cohort studies with 5,499 patients were included in this review. IA administration during total knee arthroplasty showed a significant advantage in terms of total blood loss (SMD = -0.14, 95% confidence interval [CI] = -0.027 to -0.02, I = 78.2%) and drain output (SMD = -0.30, 95% CI = -0.43 to -0.18). There was no significant difference between IV and IA administration in total hip arthroplasty. Combined IA plus IV TXA was associated with a significant reduction in blood loss versus IV TXA alone in both total knee arthroplasty and total hip arthroplasty. IV TXA dosing varied, as 14 (39%) of the studies used a weight-based approach while 22 (61%) used a standard dose. Twenty-seven (96%) of 28 studies of IA administration used standard dosing while 1 study followed a weight-based protocol. There was no difference in symptomatic thromboembolic complications, with overall rates in total knee arthroplasty and total hip arthroplasty of 1.0% and 1.0% for IV administration and 1.1% and 0.3% for IA administration, respectively. There was no difference in length of hospital stay for IV versus IA TXA administration. IA TXA, either alone or in conjunction with IV TXA, reduces total blood loss and/or drain output in total knee arthroplasty and total hip arthroplasty. Optimal methodology remains to be clarified; however, there are substantial economic benefits of utilizing either IV or IA TXA, with greater cost benefits when using IA TXA. Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.