title: Intracranial haemorrhage in patients treated with direct oral anticoagulants.
abstract: BACKGROUND
  Direct oral anticoagulants (DOAC) are increasingly used for the prevention and treatment of thromboembolic events. However, only little evidence is available regarding the management of patients who are treated with DOAC and present with potentially life-threatening intracranial haemorrhage. Herein, we describe our experience with respective patients treated at our institution.
  
  
  METHODS
  We retrospectively analysed all consecutive patients with DOAC intake and intracranial haemorrhage treated at our institution from 09/2011 to 03/2015. Patient characteristics were analysed with specific focus on results of laboratory studies, treatment modalities and patient outcomes. Findings were compared between survivors (SV) and non-survivors (NSV) on day 30 after admission.
  
  
  RESULTS
  A total of 55 patients were identified. The 30-day mortality rate in this patient cohort was 20.0%. Neurosurgical procedures were carried out in 37 patients (67%). Median values of international normalized ratio (INR) did not differ significantly between SV (1.11) and NSV (1.09). Renal function was significantly lower in NSV (median serum creatinine: 115μmol/l) than in SV (median serum creatinine: 69μmol/l; p<0.05) and all patients with serum creatinine levels >125μmol/l died during in-hospital treatment. Pro-haemostatic therapy with prothrombin complex concentrates (PCC) had no effect on INR in repeated measurements.
  
  
  CONCLUSIONS
  Our experience demonstrates that successful neurosurgical management of patients with intracranial haemorrhage and DOAC intake is feasible. However, drastic deterioration was observed in some patients, particularly when impaired renal function was present. The role of pro-haemostatic therapy with PCC is unclear. These findings underscore the urgent need of improving treatment modalities for these patients.
authors.affiliation: Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Electronic address: christopher.beynon@med.uni-heidelberg.de.
authors.forename: Christopher
authors.initials: C
authors.lastname: Beynon
authors.affiliation: Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Oliver W
authors.initials: OW
authors.lastname: Sakowitz
authors.affiliation: Pharmacy Department, Heidelberg University Hospital, Heidelberg, Im Neuenheimer Feld 670, 69120 Heidelberg, Germany.
authors.forename: Dominic
authors.initials: D
authors.lastname: Störzinger
authors.affiliation: Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Berk
authors.initials: B
authors.lastname: Orakcioglu
authors.affiliation: Department of Neuroradiology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Radbruch
authors.affiliation: Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Potzy
authors.affiliation: Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.
authors.forename: Andreas W
authors.initials: AW
authors.lastname: Unterberg
mesh_terms: D000284:Administration, Oral; D017677:Age Distribution; D000368:Aged; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects*; D015984:Causality; D015897:Comorbidity; D005260:Female; D006801:Humans; D015994:Incidence; D020300:Intracranial Hemorrhages / Q000139:chemically induced* / Q000401:mortality*; D008297:Male; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D015996:Survival Rate; D013923:Thromboembolism / Q000401:mortality* / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants
keywords: Anticoagulation; Haemostasis; Intracerebral haemorrhage; Trauma