In March 2019, OrthoBuzz covered a JBJS study by Rudasill et al. that found a progressively increasing risk of bleeding requiring transfusion among total knee arthroplasty (TKA) patients who had a preoperative International Normalized Ratio (INR) >1. (INR is a standardized measure of how long it takes blood to clot—the higher the number, the longer the clotting time.) These authors also found a significantly increased risk of infection in TKA patients with INR >1.5. and an increased risk of mortality within 30 days of surgery among those with an INR >1.25 to 1.5.
In the January 2, 2020 issue of JBJS, the same team of researchers report findings from a similarly designed NSQIP-based study of patients undergoing total hip arthroplasty (THA). The authors evaluated data from >17,500 patients who underwent a primary THA between 2005 and 2016 and who also had an INR value documented within 2 days prior to joint replacement. Rudasill et al. stratified these patients into 4 groups based on preoperative INRs: ≤1, >1 to <1.25, 1.25 to <1.5, and ≥1.5).
After adjustment, the authors found a significant, independent effect between increased preoperative INR and increased bleeding requiring transfusion and mortality. Specifically, bleeding risk became evident at INR ≥1.25, and patients with INR ≥1.5 were at a significantly increased risk of mortality. The length of hospital stay also increased significantly as INR class increased.
The authors suggest that “current INR targeting [INR <1.5 for elective orthopaedic surgery] may not be strict enough to minimize adverse outcomes for patients undergoing primary total hip arthroplasty.” While admitting that these findings are not likely to change the day-to-day practice of orthopaedic surgeons, the authors say they “may influence preoperative risk stratification for those patients with elevated INR.”
An elevated International Normalized Ratio (INR)—a standardized gauge for how long it takes blood to clot—is rarely a good sign when someone is about to undergo an elective orthopaedic procedure. This is especially true for larger surgeries such as total hip or knee arthroplasty, in which there are already concerns about perioperative bleeding. Excessive surgery-related blood loss can lead to wound complications, increased length of hospital stay, and higher mortality rates. But what precisely constitutes an “elevated” INR? While some recommendations suggest that elective procedures be performed only when a patient’s INR is ≤1.5, the evidence supporting this recommendation, especially in the setting of total knee arthroplasty (TKA), is sparse at best.
In the March 20, 2019 issue of The Journal, Rudasill et al. use the National Surgical Quality Improvement Program (NSQIP) database to help define what “elevated” should mean in the context of TKA. They evaluated data from >21,000 patients who underwent a TKA between 2010 and 2016 and who also had an INR level reported within one day before their joint replacement. They stratified these patients based on their INR levels (≤1, >1 to 1.25, >1.25 to 1.5, and >1.5). Using multivariate regression analysis to adjust for patient demographics and comorbidities, the authors found a progressively increasing risk of bleeding requiring transfusion for each group with an INR >1 (odds ratios of 1.19, 1.29 and 2.02, respectively). Relative to patients with an INR of ≤1, Rudasill et al. also found a significantly increased risk of infection in TKA patients with an INR >1.5 (odds ratio 5.34), and an increased risk of mortality within 30 days of surgery among patients with an INR >1.25 to 1.5 (odds ratio 3.37). Lastly, rates of readmission and the length of stay were significantly increased in patients with an INR >1.25.
While there are certainly weaknesses inherent in using the NSQIP dataset, this study is the first to carefully evaluate the impact of slight INR elevations on post-TKA morbidity and mortality. While I was not surprised that increasing INR levels were associated with increased bleeding events, I was impressed by the profound differences in length of stay, infection, and mortality between patients with an INR ≤1 and those with an INR >1.25. I agree with the authors’ conclusion that “current guidelines for a target INR of <1.5 should be reconsidered for patients undergoing TKA.” Further, based on the risks highlighted in this study, prospective or propensity matched cohort studies should be performed to help determine whether anyone with an INR >1 should undergo a TKA.
Chad A. Krueger, MD
JBJS Deputy Editor for Social Media