Gulraj S. Matharu, Michael R. Whitehouse.
Response/Recommendation: There is no formal risk stratification system available for predicting major bleeding events following orthopaedic procedures. A recent consensus statement limited to patients on chronic oral anticoagulation undergoing specific surgical procedures does stratify the risk of bleeding events (high, low/moderate, and minimal).
Strength of Recommendation: Consensus.
Rationale: Bleeding is a common adverse consequence following elective and trauma orthopaedic procedures. Major blood loss can occur which may result in further surgery, cardiopulmonary morbidity, infection, coagulopathy, hypothermia, increased hospital stays and costs, or even mortality1-3. Allogeneic blood transfusions may be required to manage major blood loss, but are also associated with risks including viral transmission and incompatibility4. Blood loss after orthopaedic surgery is multifactorial, and likely related to a number of patients, surgeon, and procedural factors. Two large cohort studies compromising a total of almost 4,500 patients reported the risk of major bleeding after orthopaedic surgery to be up to 5.4%5,6. The frequent use of chemical venous thromboembolism (VTE) prophylaxis for many orthopaedic procedures may also increase the risk of major bleeding7.
If the risk of major bleeding following orthopaedic procedures could be reliably predicted preoperatively and/or intraoperatively, then it may be possible to implement strategies to reduce blood loss and associated adverse events. We performed a systematic review of the literature (see Appendix for search strategy) to answer the research questions “Is there a risk stratification system for predicting major bleeding events following orthopaedic procedures?”
Presently there is no general formal risk stratification system available for predicting major bleeding events following orthopaedic procedures. Additionally, many of the studies concerning major bleeding following orthopaedic procedures explore surgical risk factors and do not discuss the impact of anticoagulant agents for VTE prophylaxis.
A recent consensus statement from the International Society on Thrombosis and Haemostasis does stratify the risk of procedural bleeding in a subset of patients on chronic oral anticoagulation pre-operatively into three groups (high, low/moderate, and minimal). The risk stratification is limited due to being based solely on the specific surgical procedure performed8. High bleeding risk orthopaedic procedures, defined as a 30 – day risk of major bleeding greater than 2%, include (i) major orthopaedic surgery, including shoulder replacement, (ii) major surgery with extensive tissue injury, (iii) spinal surgery, and (iv) any major operation lasting greater than 45 minutes. Low/moderate bleeding risk orthopaedic procedures, defined as a 30 – day risk of major bleeding of up to 2%, include arthroscopy, foot, and hand surgery. No orthopaedic procedure is defined within the minimal bleeding risk category. In a cohort of 3,082 patients undergoing hip, knee, or spine surgery which were predominantly elective, Oberweis et al., identified the procedure type as an independent predictor of major bleeding6. Multivariate analysis showed that spinal surgery was associated with the highest risk of major bleeding, with the risk of major bleeding being 81% and 65% lower in patients undergoing knee and hip surgery respectively compared to spinal surgery.
A number of studies have investigated predictors of major bleeding following specific elective and trauma orthopaedic procedures. In these studies, the outcomes assessed were most frequently blood transfusion requirements and/or the volume of blood loss measured in a variety of ways. Importantly, as a result of the increased risk of VTE following many orthopaedic procedures, patients are administered VTE prophylaxis to lower their risk. However, these anticoagulant agents are associated with an increased risk of major bleeding events in the postoperative period. Several studies have highlighted the differences in major bleeding event risk across prophylactic agents.(Anderson et al., 2018; Beyer-Westendorf et al., 2012; Jacob et al., 2014; Lassen et al., 2012; Lindquist et al., 2018; Nurmohamed et al., 1992).
Most studies investigating predictors of major bleeding following orthopaedic procedures have included patients undergoing primary total hip arthroplasty (THA) and total knee arthroplasty (TKA). Studies have reported an increased risk of blood transfusion following primary THA and TKA with a lower pre-operative hemoglobin concentration, lower patient body weight or body mass index (BMI), older age at surgery, female sex, longer operative times, and in patients with a history of cancer, coronary artery disease, or chronic obstructive pulmonary disease, and patients undergoing bilateral TKA6,9-19. Studies also found a reduced risk of allogeneic blood transfusion in patients receiving topical tranexamic acid following primary THA10, and in patients receiving re-infused blood collected from cell salvage following primary TKA20. Additionally, many studies have analyzed the impact VTE prophylaxis has in major bleeding events following joint procedures. Lindquist et al., retrospective cohort study, which analyzed the impact of VTE prophylaxis on major bleeding rates following TKA, found patients on aspirin (ASA) and enoxaparin to be associated with a lower major bleeding risk than patients on rivaroxaban. While Lassen et al., study comparing rivaroxaban and enoxaparin demonstrated no significant difference in postoperative bleeding events, Anderson et al., reported no difference between major bleeding events in patients undergoing total joint arthroplasty between ASA and rivaroxaban. Additionally, a study by Jacob et al., identified clopidogrel, an antiplatelet, to incur a greater bleeding risk postoperatively.
Revision THA and TKA are associated with increased blood loss compared with primary procedures9. In a cohort of 210 patients undergoing revision THA, independent predictors of allogeneic blood transfusion were low pre-operative hemoglobin concentration, low patient body weight, operating theatre blood loss, and the absence of perioperative cell salvage21. In another cohort of 146 revision THA, blood loss and transfusion risk were associated with patient factors, such as male sex, older age, low pre-operative hemoglobin concentration, and were also associated with surgical factors, including femoral component and dual-component revisions (compared with acetabular only revisions), and revision of cemented components22.
In studies assessing patients undergoing idiopathic scoliosis surgical correction, greater blood loss was associated with larger preoperative total Cobb angles, increasing number of vertebral levels fused, increasing number of screws inserted, and longer operative times23-25. One study of 311 patients undergoing posterior spinal instrumentation and fusion for adolescent idiopathic scoliosis reported that the variable most strongly associated with blood loss was the number of levels fused; the fusion of 12 or more levels had a probability of greater than 10% of major haemorrhage24.
Following 169 periacetabular osteotomies performed for acetabular dysplasia, longer duration of surgery correlated with increased blood loss, whilst other factors such as patient age, BMI, arthrotomy, and anesthesia used were not associated with blood loss26. Blood loss increased by 11.1% per hour of surgery.
In a cohort of 546 patients undergoing surgery for acute hip fracture, independent predictors of blood loss were type of surgery, pre-operative use of ASA, intra-operative hypotension, and gastrointestinal bleeding or ulceration27. In terms of the type of surgery performed, compared to dynamic hip screw, intramedullary nailing was associated with increased blood loss. The use of screw/pin fixation and the use of arthroplasty were both associated with reduced blood loss compared to dynamic hip screw fixation27.
In a study of 212 patients undergoing shoulder replacement for either trauma or elective indications, the predictors of blood transfusion were preoperative hemoglobin levels less than 12.15 g/dL, and postoperative day one hemoglobin levels less than 10.0 g/dL28.
While many of these focus on the importance of identifying risk factors for major bleeding events, most studies do not focus on the incidence of major bleeding as a result of differences in both patient risk factors and VTE prophylactic agents. Beyer-Westendort et al., analyzed the differences in the bleeding rates between rivaroxaban and fondaparinux in patients undergoing major orthopaedic surgery, identifying rivaroxaban to be associated with decreased bleeding risk. Additionally, Nurmohamed et al., meta-analysis found no significant difference between the risk of bleeding between low-molecular-weight heparin (LMWH) and standard heparin following orthopaedic surgery. Unfortunately, the literature of bleeding risk stratification is limited to discrete comparisons between a subset of anticoagulants. No study has been able to thoroughly investigate the risk for major bleeding events across the variety of anticoagulation agents available for patients undergoing orthopaedic surgery. Due to differences in patient demographics, it is important to identify the relationship between risk factors and clinical variables, such as VTE prophylaxis, to properly predict and stratify patient risk preoperatively.
Future research should focus on developing and validating a risk stratification system for predicting major bleeding events following both elective and trauma orthopaedic procedures that place a larger emphasis on VTE prophylactic agents. Any risk stratification system should consider patient and procedural factors as well as postoperative anticoagulation and should aim to be generalizable to the population of interest rather than limited subsets.
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