title: Identification of acquired coagulation disorders and effects of target-controlled coagulation factor substitution on the incidence and severity of spontaneous intracranial bleeding during veno-venous ECMO therapy.
abstract: BACKGROUND
  Intracranial haemorrhage is a redoubtable complication during extracorporeal membrane oxygenation (ECMO) therapy. The underlying mechanisms of haemorrhagic diathesis are still not completely understood. This study was performed to evaluate a coagulation protocol for the regular analysis of acquired coagulation disorders and the systematic substitution of coagulation factors to reach predefined target values. We hypothesised that using this strategy would lead to the identification of acquired bleeding disorders which cannot be monitored with standard coagulation tests and that substitution of the respective factors in a target-controlled approach could have an impact on the incidence and severity of intracranial haemorrhage.
  
  
  METHODS
  A protocol for the analysis of acquired coagulation disorders and the subsequent administration of associated factor concentrates was introduced. Previously, coagulation management was mainly based on clinical bleeding signs as the trigger for the administration of blood products. In this investigation, nineteen consecutive patients before (control group) and twenty consecutive patients after the implementation of the protocol (intervention group) have been included in the study.
  
  
  RESULTS
  Eighty-eight percent of the patients developed factor XIII deficiency, 79% acquired von Willebrand syndrome, 40% fibrinogen deficiency and 54% of the patients showed a decline in platelet count >20% within the first 24 hours of ECMO therapy. In 6 out of 19 (31%) patients in the control group and in 2 patients out of 20 (10%) in the intervention group, intracranial haemorrhage was detected. Whilst 5 of 6 patients in the control group died because of fatal bleeding, both of the patients in the intervention group recovered with a favourable neurologic outcome.
  
  
  CONCLUSIONS
  Veno-venous ECMO therapy leads to thrombocytopenia, factor XIII and fibrinogen deficiency as well as acquired von Willebrand syndrome. The implementation of a coagulation protocol including a standardized determination and target-controlled substitution of coagulation factors may have a beneficial impact on the incidence and severity of intracranial haemorrhage.
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Freiburg University Medical Centre, Freiburg, Germany Johannes.kalbhenn@uniklinik-freiburg.de.
authors.forename: J
authors.initials: J
authors.lastname: Kalbhenn
authors.affiliation: Department of Anaesthesiology, Critical Care and Emergency Medicine, St. Josef's Hospital Freiburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Wittau
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Freiburg University Medical Centre, Freiburg, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Schmutz
authors.affiliation: Department of Paediatrics and Adolescent Medicine, Laboratory for Haemostaseology, Freiburg University Medical Centre, Freiburg, Germany.
authors.forename: B
authors.initials: B
authors.lastname: Zieger
authors.affiliation: Department of Anaesthesiology and Critical Care Medicine, Marienhospital, Stuttgart, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Schmidt
mesh_terms: D000328:Adult; D000368:Aged; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000209:etiology*; D001779:Blood Coagulation Factors / Q000008:administration & dosage*; D016022:Case-Control Studies; D015199:Extracorporeal Membrane Oxygenation / Q000009:adverse effects*; D005260:Female; D005858:Germany / Q000453:epidemiology; D006470:Hemorrhage / Q000453:epidemiology / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012720:Severity of Illness Index; D015996:Survival Rate; D014680:Veins / Q000503:physiopathology*; D055815:Young Adult
chemical_list: D001779:Blood Coagulation Factors
keywords: ARDS; ECMO; bleeding; coagulopathy; factor XIII; fibrinogen; intracranial haemorrhage; von Willebrand syndrome