Use of Apixaban for Venous Thromboembolism Prophylaxis in an Older Hemodialysis Patient After Total Knee Replacement: A Case Report

Introduction

Total knee arthroplasty (TKA) is a highly successful orthopedic procedure that relieves pain and restores function in patients with end-stage knee osteoarthritis. It is commonly performed for degenerative, post-traumatic, or inflammatory joint conditions, providing consistent improvements in quality of life [1,2]. However, these surgeries can be associated with complications such as periprosthetic fracture, wound complications, periprosthetic joint infection, and venous thromboembolism (VTE) [2,3]. Among these, VTE is one of the most significant postoperative risks.

To reduce its occurrence, anticoagulant prophylaxis is essential. Available agents include vitamin K antagonists (eg, warfarin), low-molecular-weight heparin (LMWH), and direct oral anticoagulants (DOACs) such as rivaroxaban, apixaban, edoxaban, dabigatran, and betrixaban [3,4]. In patients with end-stage renal disease (ESRD) who are on hemodialysis (HD), unfractionated heparin (UFH) and warfarin are the standard prophylactic options [4,5]. However, the use of unfractionated heparin and warfarin in patients with ESRD who are on hemodialysis is associated with significant challenges. Subcutaneous heparin requires frequent injections and careful preparation and handling, which can reduce adherence and increase the risk of injection-site complications such as hematoma, while warfarin therapy is complicated by multiple drug–drug and drug–food interactions, frequent INR monitoring, and a higher risk of major bleeding in dialysis patients [4–6].

Apixaban is a reversible inhibitor of factor Xa widely used for VTE treatment, stroke prevention in atrial fibrillation, and postoperative thromboprophylaxis after hip or knee surgery in the general population [5,7]. Moreover, Apixaban with 2.5 mg twice daily dosing has fewer practical challenges, with oral administration that avoids injections, more predictable pharmacokinetics, and fewer drug–drug and drug–food interactions, thereby simplifying anticoagulation management compared with heparin and warfarin [8]. However, no published studies have evaluated apixaban specifically for postoperative VTE prophylaxis after TKA in hemodialysis patients, which is an important gap in the literature [4,5,9,10].

Case Report

A 78-year-old Saudi woman with a past medical history of end-stage renal disease (ESRD) who was on regular hemodialysis (Sunday, Tuesday, Thursday), type 2 diabetes mellitus, hypertension, hypothyroidism, and advanced bilateral knee osteoarthritis was admitted on September 6, 2025 for an elective right total knee replacement (TKR) due to severe osteoarthritic pain and functional limitation. She had previously undergone a hysterectomy and denied any known drug allergies. Her long-term medications included amlodipine 5 mg once daily, furosemide 40 mg once daily, levothyroxine 100 μg once daily, NovoMix insulin 30 units twice daily, and desloratadine 5 mg as needed. She had limited mobility, using an assistive device for short-distance ambulation.

On admission, she appeared well, oriented, and hemodynamically stable. Her vital signs showed blood pressure of 170/100 mmHg, pulse 78 bpm, temperature 36.7°C, and SpO2 98% on room air. Her weight was 55.9 kg and her height was 153 cm. Physical examination revealed mild bilateral lower-limb edema, consistent with her renal disease. Cardiopulmonary and abdominal examinations were unremarkable. The musculoskeletal examination showed significant right-knee deformity and tenderness with restricted range of motion, consistent with end-stage osteoarthritis.

On September 8, she underwent a right total knee arthroplasty under standard anesthesia. The intraoperative course was uneventful, with blood loss around 50 ml and no anesthesia complications. Mechanical prophylaxis was applied to the contralateral limb using pneumatic compression and anti-embolism stockings.

Postoperative management included unfractionated heparin units subcutaneously 5000 unit every 12 h for thromboprophylaxis, intravenous fluids (dextrose 5% in 0.45% NaCl at 50 mL/h), insulin via sliding scale, tramadol and paracetamol for pain control, ondansetron as needed, and continuation of levothyroxine 100 μg daily. Electrolytes and renal function were closely monitored due to ESRD. On the next day (September 9), she received her first dose of UFH. Her hemoglobin dropped from 127 g/L (bassline) to 103 g/L, then to 86 g/L on postoperative day 2. This drop was attributed to perioperative blood loss as per the Internal Medicine (IM) team on postoperative day 3 (Table 1). There was no evidence of active bleeding (no hematemesis, no hemoptysis, and no melena). The plan formed by the IM team was to transfuse 1 unit of packed red blood cells prior to the dialysis session. She remained clinically stable, with SpO2 98% on room air and no signs of active bleeding, chest pain, or dyspnea. Liver and renal profiles were unchanged. By postoperative day 6 (September 14), the wound was clean and dry. She was cleared for discharge after coordination with her dialysis schedule.

Upon discharge, the clinical pharmacist was consulted for the choice of prophylactic anticoagulant as the patient was ready for discharge. The duration was determined by the primary consultant to be for total of 35 days. The plan given by the clinical pharmacist was to initiate apixaban 2.5 mg orally every 12 h, starting 10–12 h after the last heparin dose, for postoperative thromboprophylaxis for 29 days (Timeline, Figure 1). Warfarin was avoided because its initiation would require prolonged hospitalization to achieve a therapeutic INR, as well as frequent follow-up for INR monitoring, in addition to its well-known clinical complications. Subcutaneous UFH was avoided due to the unavailability of ready-to-use dosage forms or multidose vials.

Given her chronic renal impairment, a detailed counseling session provided her with information regarding signs of bleeding, medication adherence, and follow-up. Administration of apixaban was advised to be every 12 h, at the same time each day. However, because she was receiving hemodialysis at an external facility, precise timing relative to dialysis sessions could not be consistently guaranteed.

At the follow-up appointment on October 22 (almost 1 week after the end of apixaban therapy), the patient remained in stable condition. She reported continuing hemodialysis at an external facility and confirmed that she had discontinued apixaban after completing 29 days of therapy. She denied any symptoms suggestive of minor or major bleeding.

Discussion

Postoperative venous thromboembolism (VTE) is a common and serious complication following total knee replacement, and pharmacologic prophylaxis is recommended for all patients [2,3]. In patients with ESRD on hemodialysis, anticoagulant selection is challenging because of altered drug clearance, increased bleeding risk, and exclusion from pivotal DOAC trials [5,9].

Unfractionated heparin and warfarin remain standard prophylactic agents used for dialysis patients, whereas LMWH can accumulate due to renal clearance [4,7]. Apixaban offers advantages – fixed dosing, oral administration, and no INR monitoring – but its use postoperatively in dialysis patients remains off-label, with data limited to pharmacokinetic studies and observational cohorts focused on atrial fibrillation or VTE treatment [5,10,11].

In this case, apixaban was selected because the patient was an older adult, required ongoing dialysis at an external center, and frequent hospital visits were impractical [4,5]. The dose of apixaban was recommended without adjustment, based on a pharmacokinetic study that found only modest increase in area under the curve (AUC) of apixaban in ESRD and limited drug clearance after hemodialysis [5]. Moreover, anti-FXa activity was not planned to be measured because apixaban exhibits predictable pharmacokinetics even in patients with ESRD, and current guidelines do not recommend routine monitoring outside exceptional circumstances such as bleeding, overdose, or urgent surgery [5,9].

Warfarin was avoided due to higher bleeding risk, drug interactions, and the need for extended monitoring. The patient tolerated apixaban without complications, aligning with pharmacokinetic data showing modestly increased exposure in ESRD and minimal removal by hemodialysis [5,9].

Despite this positive outcome, our findings cannot be generalized and bleeding events associated with apixaban in patient with ESRD cannot be ruled out [12]. Prospective studies and larger clinical investigations are needed to define optimal dosing and compare apixaban with UFH or warfarin in dialysis patients undergoing major orthopedic surgery [9–11].

Conclusions

This case demonstrates that apixaban can be a feasible postoperative VTE prophylaxis option in carefully selected patients with ESRD who are on hemodialysis undergoing total knee arthroplasty. Although UFH remains the standard agent used in this population, practical limitations and patient-specific factors led to choosing apixaban in this case. The patient tolerated treatment well, with no bleeding or thromboembolic complications. While this positive outcome aligns with limited data suggesting acceptable safety in dialysis patients, apixaban use in this setting remains off-label. Larger studies are needed to guide evidence-based anticoagulation strategies for postoperative VTE prevention in ESRD patients.