Abnormal whole-blood viscoelastic test results in patients with bleeding disorder of unknown cause

Bleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion in patients with a clinically relevant bleeding tendency. Although patients with BDUC often display bleeding phenotypes similar to those with other established mild-to-moderate bleeding disorders, global assays to identify BDUC or predict bleeding severity are lacking. Diagnostic utility of nonactivated rotational thromboelastometry (ROTEM) in patients with BDUC and its association with bleeding severity and risk of future bleeding were assessed. In total, 464 patients with BDUC from the Vienna Bleeding Biobank were compared with 100 age-matched healthy controls. ROTEM was performed within 1 hour of sampling. The assessed parameters included clotting time (CT), clot formation time, maximum clot firmness, maximal lysis (ML), and area under the curve (AUC). Overall, we observed a delayed clot formation process with reduced lysis potential resulting in a larger ROTEM-AUC in patients with BDUC. Compared with controls, patients with BDUC exhibited prolonged CT (median, 634.0 vs 617.5 s; P < .001), lower ML (15% vs 16%; P = .007), and higher ROTEM-AUC (5729.5 vs 4890.5 s × mm; P < .001). Among tested clinical parameters, including age, sex, blood group O, hemoglobin, platelets, fibrinogen, and factor VIII, and von Willebrand factor, hemoglobin levels were the strongest determinant of ROTEM variation. ROTEM parameters, especially ROTEM-AUC, exhibited meaningful discrimination between patients with BDUC and controls (receiver operating characteristic [ROC] AUC, 0.752; extreme gradient boosting model ROC-AUC, 0.812). However, ROTEM parameters did not correlate with bleeding scores. In conclusion, nonactivated ROTEM revealed altered clot formation and fibrinolytic profiles in BDUC and could distinguish patients with BDUC from healthy individuals.