Frequency and Risk Factors of Bleeding in Patients With Chronic Kidney Disease Receiving Anticoagulants

1-Introduction: Chronic kidney disease (CKD) is a significant global public health issue, closely linked to cardiovascular disease (CVD). Moreover, CKD is acknowledged as an independent risk factor for developing CVD and represents a heigh risk factor to thromboembolic disease in coronary and cerebral arteries also in the venous circulation that requires anticoagulation (1). According to the latest United States Renal Data System report, the prevalence of any CVD in CKD patients is nearly double that of the general population, at 69.8% compared to 34.8% (2). Also, if microalbuminuria is detected and glomerular filtration rate (eGFR) is less than \<60 mL/min/1.73m2, there is an increased risk of cardiovascular events, venous thrombosis and mortality (3).

On the other hand, patients with an eGFR of less than 60 mL/min/1.73m² have double the risk of atrial fibrillation (AF) and acute coronary syndrome (ACS) (4\&5). For dialysis-dependent CKD patients, the prevalence of AF is 11.6%, and within 12 months after kidney transplantation, the risk of AF occurrence rises to 35.6% per 1000 patient-years (6). Also, the risk of pulmonary venous thromboembolism (VTE) in CKD increases by 25%-30% is constant in all CKD stages, and typically characterizes the nephrotic syndrome (7).

Oral anticoagulant is an effective mean of reducing rate of ischemic stroke and systemic embolism in patient with AF in CKD patient and minimizing the morbidity and the mortality caused by venous thromboembolic disease (1). At the same time abnormalities in the platelet membrane and impaired platelet-vessel wall interaction put CKD patients at risk of bleeding significantly more than other patients of chronic disease (8).

The paradox in CKD is the association between the high thromboembolic risk and major hemorrhagic risk with declining kidney function. In CKD, managing the delicate balance between preventing thromboembolic events and avoiding hemorrhage poses significant challenges for anticoagulation treatment. This difficulty arises due to several factors:

• A higher need for anticoagulants in CKD patients.
• The absence of reliable risk scores for thromboembolic and hemorrhagic events specific to CKD patients.
• The risk-benefit ratio being influenced by numerous variables unique to this subgroup.
• Drugs bioavailability and pharmacokinetics are altered in this setting.
• A lack of consensus on recommendations for oral anticoagulation, particularly for patients in stages 4 and 5 of CKD (1).
• Randomized trials comparing direct oral anticoagulants (DOACs) and warfarin have excluded patients with creatinine clearance (CrCl) below 30 mL/min. Lack of high-quality evidence in CKD has led to differences in recommendations by various professional bodies adding on to this confusion (9). This has thus led to underutilization of DOACs in CKD patients (10) .

Due to the currently limited data, clinicians need practical clues for monitoring and optimizing the anticoagulant therapy. We try to explain the complex thrombotic-hemorrhagic state of CKD patients, and practical considerations for the management of anticoagulation in them with a focus on risk factors for bleeding.