Low-dose aspirin protocol for venous thromboembolism prevention after total knee arthroplasty: A large Middle Eastern cohort

INTRODUCTION

After total knee arthroplasty (TKA), venous thromboembolic complications, such as deep vein thrombosis (DVT) and pulmonary embolism (PE) continue to contribute substantially to postoperative morbidity.^[1] Effective chemical prophylaxis is therefore a cornerstone of perioperative care, aimed at reducing the incidence of these potentially life-threatening complications while maintaining an acceptable safety profile. Conventionally, chemical prophylaxis includes low-molecular-weight heparin, warfarin, and direct Factor Xa inhibitors. While these medications are effective in reducing thromboembolic events, their use is concomitant with increased risk of hemorrhage, higher cost, and difficulties related to monitoring the doses.^[2] Consequently, there has been a growing interest in potentially safer alternatives, including low-dose aspirin. Over the past decade, numerous reports have confirmed the safety profile of thromboprophylaxis after primary TKAs.^[3-6] The latest international consensus meeting on venous thromboembolism (ICM-VTE) endorsed the use of low-dose aspirin for all patients due to its safety profile compared with other potent anticoagulants.^[2] Furthermore, the American College of Chest Physicians guidelines and the American Society of Hematology have endorsed aspirin as an alternative for venous thromboembolism (VTE) prophylaxis after total joint arthroplasty.^[7,8]

While much of the existing literature has been generated from Western populations, data regarding the safety and clinical outcomes of aspirin prophylaxis in Middle Eastern populations, specifically the Saudi population, remain limited. Differences in demographics, comorbidities, lifestyle factors, and healthcare practices may influence both thrombotic risk and bleeding profiles, underscoring the importance of evaluating prophylactic strategies within local populations. Furthermore, large-scale studies assessing aspirin safety in regional cohorts are limited. To address this gap, the present study aims to investigate the safety profile of low-dose aspirin for thromboprophylaxis in a large cohort of Saudi patients, including more than 1,000 TKAs. The primary outcomes assessed are the occurrence of thromboembolic events, while secondary outcomes include bleeding complications, gastrointestinal adverse events, and other medical complications. By examining these outcomes in the Saudi population, this study seeks to provide clinically relevant evidence to inform local practice patterns and contribute to the ongoing global discussion on the role of aspirin in thromboprophylaxis after TKA.

MATERIALS AND METHODS

A retrospective investigation was conducted at a single tertiary hospital in Saudi Arabia. Institutional ethical approval was obtained before initiating the study, and the STROBE reporting guidelines were followed. The study evaluated patients who underwent primary TKA and received low-dose aspirin as VTE prophylaxis. All consecutive primary TKA procedures (n = 1167 knees) during the study period (January 2022–January 2026) were screened for eligibility. The minimum follow-up period for inclusion was 6 weeks post-surgery. Individuals who were on chronic anticoagulants before surgery or had an aspirin allergy were excluded from the study. After applying these criteria, 16 procedures were excluded, and that left 1151 TKAs (961 patients) to be included. Of these, 190 patients had staged bilateral TKAs.

All procedures were carried out by one fellowship-trained arthroplasty surgeon, which helped ensure consistency in surgical technique, perioperative management, and postoperative care. Patient information was obtained from a prospectively stored hospital database and electronic medical files. Demographic and medical information collected included the American Society of Anesthesiologists (ASA) physical status, sex, age, and body mass index. Medical comorbidities, such as previous DVT, history of stroke, history of cancer, diabetes, hypertension, coronary artery disease, and smoking, were also recorded. Post-operative complications were systematically documented throughout the follow-up period. All suspected VTE events were diagnosed using Doppler ultrasonography for DVTs and pulmonary angiography for PEs. Doppler ultrasonography was performed only when clinically indicated based on symptoms suggestive of thromboembolic disease, such as a positive Homans’ sign, calf tenderness, and leg or thigh swelling. Routine Doppler ultrasonography for all patients was not performed.

All procedures were performed with standardized operative and perioperative protocols, including pre-operative antibiotics and 2 g of tranexamic acid (1 g before tourniquet use and 1 g at the time of skin closure). The majority of patients in this cohort underwent spinal anesthesia. Only 13 (1.1%) of 1151 procedures were performed under general anesthesia, based on the anesthesiologist’s or cardiologist’s recommendations and, in some cases, on the patient’s request. The use of a tourniquet was routine, and tourniquet time was recorded for each case. Following surgery, as part of the aspirin VTE prevention protocol, all patients were mobilized on the same day as the procedure to reduce postoperative complications, including thromboembolic events. During their hospital stay, patients also received mechanical thromboprophylaxis with pneumatic compression devices. Pain management was achieved using a multimodal analgesia protocol, which typically included a combination of pharmacologic agents designed to minimize opioid consumption and facilitate early mobilization. All patients received low-dose aspirin for VTE prophylaxis (100 mg twice daily for 1 month) and started approximately 8 hours after surgery. All patients received 1 tablet of a proton pump inhibitor daily for 1 month to provide gastrointestinal protection during the prophylaxis period.

Primary outcomes were the occurrences of DVT and PE. Secondary study outcomes included the occurrence of bleeding complications, sudden death, gastrointestinal adverse events, myocardial infarction, stroke, and return to the operating room for any cause. All complications were identified through clinical documentation, hospital records, and follow-up assessments.

Patients were followed according to a standardized postoperative protocol. Routine clinical follow-up visits were conducted at 1 week, 6 weeks, and 6 months post-operatively. During these visits, patients were evaluated for surgical recovery, complications, and any clinical signs or symptoms suggestive of thromboembolic or medical events. Additional investigations were performed when clinically indicated.

RESULTS

A total of 1151 knees in 961 patients underwent primary TKA and received aspirin as venous VTE prophylaxis. Of these, 961 were single TKAs, and 190 staged bilateral TKAs. Basic demographics are shown in Table 1, and the ASA score is shown in Table 2. Eighty-one percent of the knees (n = 937) were in females, and 19% (n = 214) were in males.

The most common comorbidities [Table 3] were hypertension (35.4%) and diabetes mellitus (31.6%). Other comorbidities included coronary artery disease (4.9%), thyroid disorder (4.7%), previous stroke (0.9%) and previous history VTE (0.3%) (but not on anticoagulants before surgery), rheumatoid arthritis (2.3%), history of cancer (1.7%), asthma (3%), chronic obstructive pulmonary disease (0.4%) and smoking (1%).

All patients underwent TKAs with no intraoperative complications. The mean tourniquet time was 63.3±11.5 minutes (range 35–91).

Post-operative complications were rare [Table 4]. There was no post-operative documented DVT or post-operative bleeding. However, there was a confirmed post-operative PE in one patient that occurred on post-operative day 2 and was diagnosed through computed tomographic pulmonary angiography. This patient had no prior medical history other than controlled diabetes and hypertension. This patient was fully anticoagulated and had no subsequent events. There was one post-operative death on day 10 post-surgery. It was a sudden death at home, and the exact reason for the death is unknown. This patient was healthy and only had a prior history of superficial thrombophlebitis one year before the surgery, and was not on any anticoagulants before surgery. Although the exact cause of death could not be determined, PE or a cardiovascular event could not be definitively excluded. In addition, one patient experienced a postoperative stroke, and two patients developed myocardial infarction during the post-operative period. One patient had a deep infection 5 weeks post-surgery and was treated with debridement and polyethylene exchange, as well as intravenous antibiotics. She had no recurrence at the 2-year follow-up. Four patients had gastrointestinal irritations, and two of them required temporary readmissions for intravenous hydration.

DISCUSSION

The present study demonstrates that aspirin provides effective thromboprophylaxis following TKA with extremely low rates of thromboembolic complications. In our cohort of 1151 knees, only one confirmed PE and one mortality occurred, and no cases of symptomatic post-operative DVT were identified. The occurrence of unexplained post-operative mortality could be attributed to PE or a cardiovascular event. Although staged bilateral arthroplasty may theoretically increase thromboembolic risk, no symptomatic VTE complications were observed within this subgroup in our cohort. Cardiovascular complications, including stroke and myocardial infarction, were uncommon (0.09–0.17%) and within a comparable incidence as reported in the literature. In a recent study^[9] of a large cohort of patients (more than 32,000 subjects), those receiving low-dose aspirin had a lower incidence of cardiovascular complications (0.1–0.2%) than those receiving other anticoagulants (0.2–0.3%). Furthermore, no post-operative bleeding events were observed. Taken together, these results suggest that aspirin can serve as a well-tolerated pharmacological option for thromboprophylaxis after TKA. The occurrence of VTE events observed in the present study is consistent with the reported literature. Published series report low rates of thromboembolic events and mortality after TKA, ranging from approximately 0.2–1.6%.^[9-12] These authors found comparable protection against thromboembolic events when aspirin was compared with stronger anticoagulants, while maintaining a more favorable safety profile. Our findings, therefore, add further support to the growing body of evidence advocating aspirin as an effective prophylactic agent after total joint arthroplasty.

Despite the increasing international acceptance of aspirin as thromboprophylaxis after arthroplasty, its use remains relatively limited in many institutions across the Middle East. This reluctance is often related to historical interpretations of earlier clinical guidelines and concerns raised by certain studies. For instance, the recent CRISTAL randomized trial reported higher rates of symptomatic VTE with aspirin than with enoxaparin.^[13] However, several methodological limitations were identified in the interpretation of this study.^[14] The authors utilized a relatively low dose of aspirin (100 mg once per day and started one day after surgery) for a short duration of therapy (14 days only), and baseline differences between treatment groups were present. Nearly 15% of patients assigned to the enoxaparin group remained on antiplatelet therapy, effectively receiving dual prophylaxis. In addition, most of the difference in VTE events was related to distal DVT rather than PE or proximal DVT, which may have limited clinical significance. These methodological limitations significantly affect the CRISTAL trial’s conclusion. On the other hand, there is overwhelming evidence supporting the safety of aspirin and its ability to reduce the risk of post-operative bleeding, hematomas, infections, and overall mortality compared with potent anticoagulants after joint arthroplasty.^[9,12,15-18] These were contributing factors to the rising adoption of aspirin after hip and knee arthroplasty in North America and have recently expanded to include orthopedic trauma patients.^[2,19,20] From a regional perspective, published data on aspirin use after TKA in the Middle East remain limited. A prospective Saudi study of 242 TKA patients included only 29 aspirin-treated patients and reported that the aspirin group had the best overall post-operative complication and recovery profile, while rivaroxaban had the highest DVT incidence.^[21] It is important to note that the favorable outcomes observed in our cohort and others likely reflect a multimodal strategy, including aspirin prophylaxis, early mobilization, and mechanical compression devices rather than aspirin alone. To our knowledge, the present study represents the largest cohort from the Middle East evaluating aspirin prophylaxis following TKA and, therefore, provides important regional data supporting its safety profile.

An additional important observation in this study is the effectiveness of aspirin even among patients with recognized thromboembolic risk factors, including those with a history of malignancy or previous DVT. Despite the presence of these risk factors in our cohort, none of the patients experienced VTE. Our observations are also consistent with recent reports suggesting that high-risk arthroplasty patients may still be suitable candidates for aspirin prophylaxis. Verhey et al.^[22] reported that a prior history of VTE should not be considered an absolute contraindication to aspirin prophylaxis, while Ludwick et al.^[11] demonstrated similarly low complication rates in patients with prior thromboembolic disease. Furthermore, Tan et al.^[10] showed that escalation to stronger anticoagulation does not necessarily translate into fewer thromboembolic events in high-risk patients. Taken together, these findings support the view that aspirin may represent a reasonable prophylactic strategy across a broad range of patient risk profiles while minimizing post-operative complications associated with potent anticoagulants.

Several limitations should be acknowledged. First, the retrospective nature of the analysis leaves the study vulnerable to selection bias. Second, because the data came from one center, the findings may not be fully generalizable to other practice settings. Third, only symptomatic thromboembolic events were captured in the present study. Routine postoperative duplex ultrasonography screening was not performed; therefore, asymptomatic DVT events may have gone undetected, and the true incidence of asymptomatic DVT remains unknown. Finally, the retrospective single-arm design limits direct comparison with alternative thromboprophylaxis regimens and precludes conclusions regarding comparative efficacy or superiority in this patient population. Nevertheless, the study includes a large cohort with detailed clinical follow-up, providing valuable data regarding aspirin use after TKA in our region.

CONCLUSION

In this large cohort of Saudi patients undergoing primary TKA, aspirin prophylaxis was associated with very infrequent rates of thromboembolic complications and no documented post-operative bleeding. These results support the growing body of evidence that aspirin is a safe, effective, and practical option for thromboprophylaxis after TKA, including among patients with thromboembolic risk factors. Moreover, this study provides regional observational data that may help inform future prospective studies and local practice discussions regarding thromboprophylaxis after TKA.