D-dimer levels enhance the discriminatory capacity of bleeding risk scores for predicting in-hospital bleeding events in acute pulmonary embolism

Introduction: Bleeding is a major complication of anticoagulation in acute pulmonary embolism (APE) while estimating individual bleeding risk remains challenging. Elevated D-dimer levels (DD) have been shown to predict bleeding events. Objectives: (1) direct comparison of the capacity of bleeding risk prediction scores (VTE-BLEED, RIETE, HASBLED, HEMORR(2)HAGES) to prognosticate in-hospital bleeding events in the acute phase of APE in a real-life population of APE patients;(2) augmentation of the discriminative capacity of fore mentioned scores with DD. Materials: Post-hoc analysis of a prospective observational study. DD levels were measured using the VIDAS Ddimer Exclusion test. Receiver operating characteristic curves, areas under the curve (AUC) for bleeding prediction were calculated for scores and DD. Bleeding scores + DD were compared using an established index quantifying the reclassification of patients (net reclassification index, NRI). Results: 310 APE patients were included. 35(11.3%) bleeding events occurred (hematomas, GI, urinary tract, retroperitoneal, uterine, CNS, respiratory tract): 17 major (MB) and 18 clinically-relevant non-major bleedings (CRNMB), none were fatal. All scores had satisfactory AUCs (0.754-0.767), except HAS-BLED (AUC = 0.512; 0.455-0.569). DD were higher in patients with bleeding events (29,911 ng/ml vs. 4805 ng/ml, p = .031), AUC 0.621(0.520-0.721), p = .02. DD = 5750 ng/ml was characterized by OR = 2.3(95%CI 1.05-5.0) for all bleeding events. Adding DD improved the discriminatory capacity of tested scores in the non-high risk of bleeding category, NRI 0.07-03. Conclusions: Of the tested scores RIETE, HEMORR 2 HAGES, VTE-BLEED performed best at identifying APE patients at risk of in-hospital bleeding complications. DD levels may predict in-hospital bleeding events and may improve identifying patients classified as non-high risk who experience bleeding complications.