Severe Hemorrhage Associated With Oral Anticoagulants

Abstract

Background: Few data have been published to date on outcomes after the common clinical experience of severe hemorrhage in orally anticoagulated patients.

Methods: A prospective, multicenter observational study was carried out to investigate outcomes and management in a series of consecutive patients who sustained a severe hemorrhage under treatment with vitamin K antagonists (VKA) or direct oral anticoagulant drugs (DOAC). The primary endpoint was in-hospital death up to and including day 30 after hospital admission. The secondary endpoints were the duration of bleeding, in-hospital death due to hemorrhage (as defined by the study physician examining the patient's records), the use of antagonists, the extent of supportive measures used to stop the hemorrhage, and an assessment of causality. Consecutive patients were recruited until a predefined number of patients was reached in both groups.

Results: Among 193 patients with severe hemorrhage, 97 had been taking a VKA, and 96 had been taking a DOAC. 13.0 % (95% confidence interval [8.6; 18.5]; 25/193) of the overall group patients died in the first 30 days after hospital admission, including 17.5% ([10.6; 26.6]; 17/97) in the VKA group and 8.3% ([3.7; 15.8]; 8/96) in the DOAC group (p = 0.085). The median duration of bleeding was 19.8 hours in the VKA group and 27.8 hours in the DOAC group (p = 0.632). The in-hospital mortality due to hemorrhage was higher in the VKA group than in the DOAC group (15.5% [15/97] versus 4.2% [4/97]; p = 0.014). Only the use of prothrombin complex concentrates (PCCs) lowered the median duration of hemorrhage in the two patient groups. In 35% (68/193) of the patients, the hemorrhage was caused by an external influence, most commonly a fall.

Conclusion: The in-hospital mortality was higher among patients treated with VKA than among patients treated with DOAC, although the difference failed to reach statistical significance.

Figure 1

Cumulative incidence curves of hospital mortality up to and including day 30 after hospital admission (two-sided log-rank test taking into account the time to death: p = 0.053). 17.5% (17/97) of patients died in the VKA group compared to 8.3 % (8/96) in the DOAC group.

Figure 2

The box plots show a comparison of duration of bleeding in patients treated with or without PCC. a) VKA-treated patients; b) DOAC-treated patients (p values: Mann-Whitney U test) DOAC, direct oral anticoagulants; PCC, prothrombin complex concentrates; VKA, vitamin K antagonists; CNS, central nervous system

eFigure 1

Cumulative incidence curves of bleeding-associated in-hospital mortality up to and including day 30 after hospital admission (Gray test: p = 0.008)

eFigure 2

Comparison of treatments between the VKA and DOAC groups a) shows box plots of the percentages of patients treated in each group (p values: Fisher‘s exact test). b) shows box plots of the total doses of antidotes administered as well as the quantity of red blood cell concentrates and platelet concentrates administered within 30 days after hospital admission (p values: Mann-Whitney U test). DOAC, direct oral anticoagulants; VKA, vitamin K antagonists