Anticoagulation dilemma in a patient with nephrotic syndrome and bleeding of unknown origin: A case-based approach to risk-benefit decision-making Free

Introduction: Nephrotic syndrome is associated with a hypercoagulable state due to urinary loss of anticoagulant proteins and increased hepatic synthesis of clotting factors. As a result, anticoagulation is initiated even in the absence of a confirmed thrombotic event, particularly when additional risk factors are present. However, in patients with complex comorbidities, including chronic kidney disease and gastrointestinal bleeding, anticoagulation poses significant clinical dilemmas. This case describes a 72-year-old woman with nephrotic syndrome and multiple comorbid conditions who presented with symptomatic anemia and was found to have bleeding of unkown origin. The case illustrates the nuanced balance between thrombotic risk and bleeding risk in determining the appropriateness of ongoing anticoagulation therapy.

Case Presentation: A 72-year-old female with a past medical history of chronic kidney disease (CKD), nephrotic syndrome, hypoalbuminemia, peripheral arterial disease with intermittent claudication, recent right occipital cerebrovascular accident (03/31/2025), presented for symptomatic anemia. Patient had been on apixaban (Eliquis) secondary to nephrotic syndrome. On presentation, her hemoglobin was 5.2 g/dL. She received four units of packed red blood cells, one dose of Venofer 200 mg, and was started on pantoprazole 40 mg IV twice daily. Laboratory evaluation revealed hypoalbuminemia with normal total protein, consistent with her known nephrotic syndrome. Imaging with a non-contrast CT abdomen and a nuclear medicine gastrointestinal bleeding scan did not demonstrate active hemorrhage. EGD showed a normal esophagus, stomach, and duodenum with nonspecific background gastric inflammation. Colonoscopy revealed nonspecific colitis and background ischemic changes in the ascending colon, with incomplete visualization due to colonic atony and redundancy. No definitive source of bleeding was identified. Apixaban was initially held on admission due to the degree of anemia. After endoscopic evaluation, it was briefly restarted; however, a subsequent drop in hemoglobin to 7.7 g/dL prompted re-evaluation of anticoagulation safety. The patient's hemoglobin stabilized at 8.4 g/dL after cessation of Apixaban for a second time. Given the absence of confirmed thrombotic history, normal total protein despite hypoalbuminemia, recent significant gastrointestinal bleeding, and a HAS-BLED score of 3, the risk-benefit profile was carefully reviewed. Nephrology was consulted and supported discontinuation of anticoagulation. A shared decision-making discussion was held with the patient, who understood the risks and was agreeable to stopping apixaban. Follow-up with cardiology, nephrology, and hematology was arranged to reassess anticoagulation need longitudinally.

Discussion: Nephrotic syndrome is characterized by massive proteinuria, usually greater than 3.5g in 24 hours, hypoalbuminemia, and edema. Multiple hemostatic abnormalities arise in Nephrotic Syndrome, resulting in a hypercoagulable state. There is an imbalance between natural anticoagulant and procoagulant activity resulting in higher risk of thrombosis. There is urinary loss of antithrombic proteins including antithrombin III, protein S, and Protein C and, simultaneously, there's a procoagulant effect as synthesis of fibrinogen, factors V, VII, VIII, and X are increased in response to hypoalbuminemia. Apixaban is used do to predictable pharmacokinetics and lack of need for routine monitoring. Nephrotic syndrome alters drug pharmacokinetics through hypoalbuminemia and impaired renal clearance, potentially resulting in increased bleeding risk. In this case, the use of Apixaban posed a diagnostic and therapeutic dilemma as cessation of anticoagulation could result in a thrombotic event and continuing the medication could result in life threatening bleeding.

Conclusion: This case highlights the complexities of anticoagulation management in patients with nephrotic syndrome. Despite the indication for anticoagulation, the absence of a documented thrombotic event, stabilization of hemoglobin following Apixaban cessation, and a moderate bleeding risk favored cessation of therapy. Multidisciplinary input and shared decision-making were essential in aligning the treatment plan with the patient's evolving clinical status and preferences. Longitudinal follow-up with subspecialists is crucial to reassess thrombotic risk and guide future anticoagulation decisions.