OC 20.1 - Use of global coagulation assays to predict spontaneous major bleeding in chronic kidney disease patients

Background: Chronic kidney disease (CKD) is associated with increased bleeding and cardiovascular disease (CVD) risks. Moreover, CVD management often involves antiplatelets and/or anticoagulation. Yet, there are no routine blood tests to predict bleeding risk.

Aims: To evaluate the use of global coagulation assays (GCA) in predicting risk of spontaneous major bleeding in CKD.

Methods: This was a prospective observational study, which recruited adult patients with CKD (estimated glomerular filtration rate (eGFR) < 30mL/min/1.73m2) between March 2017 and July 2021 at Northern Health, Australia. Exclusion criteria included therapeutic anticoagulation and/or active malignancy. At recruitment, baseline clinical data and blood tests for standard laboratory assays and GCAs (thromboelastography (TEG) on whole blood; overall haemostatic potential (OHP) and calibrated automated thrombogram (CAT) using platelet-poor plasma (PPP)) were collected. Patients were followed-up for median 3 years and clinical outcomes recorded. Major bleeding was defined as per ISTH-SSC guidelines.

Results: 87 patients were recruited (67.8% (n=59) male; median age 67 years) including 65 (74.7%) dialysis-dependent patients. Ten spontaneous major bleeding (sMB) events were recorded (11.5%; 3.0/100person-years). There were no significant differences in age, gender, coagulation studies (PT, APTT, vWF antigen), urea, renal function, dialysis-dependence, platelet count or antiplatelet use in patients with sMB and those without (Table1). Patients with sMB demonstrated lower endogenous thrombin potential (ETP, 1099.6 vs 1340.0nM.min, p=0.007 ) and OHP (7.7 vs 17.0, p= 0.035). When analysed in quartiles, the most hypocoagulable quartiles of ETP (HR 7.6;95%CI 1.9-29.2), OHP (HR 6.4;95%CI 1.6-24.7) and maximum amplitude (TEG) (HR 3.6;95%CI 1.0-12.4) were associated with sMB (Figure1).

Conclusion(s): In this pilot study, GCAs performed on PPP, particularly CAT and OHP, demonstrated association with spontaneous major bleeding in CKD patients, despite traditional surrogate markers being comparable. These findings suggest haemostatic dysfunction in CKD may also be influenced by platelet independent processes beyond the current understanding of platelet dysfunction.