Haematological management of major bleeding associated with direct oral anticoagulants – UK experience

The lack of antidotes for activated factor X-inhibitor direct oral anticoagulants (DOACs) means that management of bleeding consists largely of existing supportive therapies. This study aimed to: (i) examine the relative frequency of DOAC-related major bleeding in relation to DOAC prescriptions over the study period; (ii) describe the presentation and haematological management of DOAC-related major bleeding; and (iii) evaluate the association between the use of prothrombin-complex-concentrate (PCC) and in-hospital mortality. Over a 3-year period, 32 UK hospitals submitted data on haematological management of DOAC-related bleeding. Data consisted of 421 episodes (67%, 21%, 11% and 1% on rivaroxaban, apixaban, dabigatran and edoxaban respectively) of major bleeding on DOACs. The proportion of major bleeds on DOACs and DOAC prescriptions increased throughout the study. Overall, 44% and 37% of patients presented with gastrointestinal bleeding and intracranial haemorrhage (ICH) respectively. Drug concentrations were seldom measured. Compared to no PCC, there was a borderline evidence that receiving low dose PCC (≤25 iu/kg) was associated with better outcomes in terms of mortality (sub-distribution hazard ratio: 0·15; 95% confidence interval: 0·02-1·19; P = 0·07): but this was not the case for higher doses. DOAC concentrations are seldom measured. There was no evidence of benefit for PCC on in-hospital mortality.