Introduction 
Prediction of major bleeding in patients with pulmonary embolism (PE) is challenging. The recently developed VTE-BLEED score helps to predict major bleeding in patients on stable anticoagulation treated with warfarin and the non-vitamin K-dependent oral anticoagulants (NOACs) edoxaban and dabigatran. However, since the VTE-BLEED score has not yet been validated in a real-world cohort of PE patients and regarding its ability to predict early major bleeding, we investigated its prognostic performance in PE patients included in the prospective ongoing Pulmonary Embolism Registry Göttingen (PERGO) and the influence of early major bleeding on in-hospital and long-term outcomes.

Methods 
Consecutive PE patients prospectively included in PERGO between September 2008 and November 2016 were eligible for the present analysis; patients treated with thrombolysis were excluded. The VTE-BLEED and the HASBLED score were calculated post-hoc; in-hospital major bleeding was defined using the ISTH definition.

Results 
Overall, 522 patients (median age, 69 [IQR, 56-78] years, 53% female) were included in the present analysis; major bleeding occurred in 18 (3.5%) patients. The area under the curve for predicting in-hospital major bleeding was higher for the VTE-BLEED score (0.69, 95% CI 0.58-0.80) as compared to the HASBLED score (0.54, 95% CI 0.48-0.69). Patients classified as high-risk (≥2 points) by the VTE-BLEED score (n=305; 58 %) had a major bleeding rate of 4.9% compared to 1.4% (n=217; 42%) classified as low-risk (OR 3.7, 95% CI 1.1-13; sensitivity 83%, specificity 42%). The HASBLED score failed to predict major bleeding (OR 1.1, 95% CI 0.4-2.9). During the observation period, the use of unfractionated heparin (UFH) as initial treatment and the rate of major bleeding decreased over time (Figure 1). Interestingly, initial treatment with UFH tended to be associated with an increased risk of major bleeding (OR 2.7, 95% CI 0.9-8.2) (Figure 1). In-hospital major bleeding was not associated with an increased odds-ratio of in-hospital mortality (OR 3.4, 95% CI 0.7-15.8) but was identified as an independent predictor of 1-year mortality (HR 3.2, 95% CI 1.5-6.6). Using Kaplan Meier analysis, in-hospital major bleeding was associated with a decreased probability of 1-year survival (log rank p<0.001); especially in patients with cancer (1-year mortality 100%). Patients classified as at high risk by the VTE-BLEED score had an increased risk for in-hospital (OR 6.8, 95% CI 1.6 29.6) and 1-year overall mortality (HR 3.6, 95% CI 2.3-5.5).

Conclusion 
The VTE-BLEED score identified PE patients at risk for in-hospital major bleeding, in-hospital and 1-year mortality. Therefore, the VTE-BLEED score might help to guide therapeutic decision making in patients with acute PE.