title: Perioperative treatment of hemophilia A patients: blood group O patients are at risk of bleeding complications.
abstract: ESSENTIALS: Targeting of factor VIII values is a challenge during perioperative replacement therapy in hemophilia. This study aims to identify the extent and predictors of factor VIII underdosing and overdosing. Blood group O predicts underdosing and is associated with perioperative bleeding. To increase quality of care and cost-effectiveness of treatment, refining of dosing is obligatory.
  
  
  CONCLUSIONS
  
  
  
  BACKGROUND
  Perioperative administration of factor VIII (FVIII) concentrate in hemophilia A may result in both underdosing and overdosing, leading to respectively a risk of bleeding complications and unnecessary costs.
  
  
  OBJECTIVE
  This retrospective observational study aims to identify the extent and predictors of underdosing and overdosing in perioperative hemophilia A patients (FVIII levels < 0.05 IU mL(-1)).
  
  
  METHODS
  One hundred nineteen patients undergoing 198 elective, minor, or major surgical procedures were included (median age 40 years, median body weight 75 kg). Perioperative management was evaluated by quantification of perioperative infusion of FVIII concentrate and achieved FVIII levels. Predictors of underdosing and (excessive) overdosing were analyzed by logistic regression analysis. Excessive overdosing was defined as upper target level plus ≥ 0.20 IU mL(-1).
  
  
  RESULTS
  Depending on postoperative day, 7-45% of achieved FVIII levels were under and 33-75% were above predefined target ranges as stated by national guidelines. A potential reduction of FVIII consumption of 44% would have been attained if FVIII levels had been maintained within target ranges. Blood group O and major surgery were predictive of underdosing (odds ratio [OR] 6.3, 95% confidence interval [CI] 2.7-14.9; OR 3.3, 95% CI 1.4-7.9). Blood group O patients had more bleeding complications in comparison to patients with blood group non-O (OR 2.02, 95% CI 1.00-4.09). Patients with blood group non-O were at higher risk of overdosing (OR 1.5, 95% CI 1.1-1.9). Additionally, patients treated with bolus infusions were at higher risk of excessive overdosing (OR 1.8, 95% CI 1.3-2.4).
  
  
  CONCLUSIONS
  Quality of care and cost-effectiveness can be improved by refining of dosing strategies based on individual patient characteristics such as blood group and mode of infusion.
authors.affiliation: Department of Pediatric Hematology, Erasmus University Medical Center - Sophia Children's Hospital Rotterdam, Rotterdam, the Netherlands.
authors.forename: H C A M
authors.identifier: http://orcid.org/0000-0003-4988-0582
authors.initials: HC
authors.lastname: Hazendonk
authors.affiliation: Department of Pediatric Hematology, Erasmus University Medical Center - Sophia Children's Hospital Rotterdam, Rotterdam, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Lock
authors.affiliation: Hospital Pharmacy - Clinical Pharmacology, Academic Medical Center Amsterdam, Amsterdam, the Netherlands.
authors.forename: R A A
authors.initials: RA
authors.lastname: Mathôt
authors.affiliation: Department of Hematology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Meijer
authors.affiliation: Department of Pediatric Hematology, Academic Medical Center Amsterdam, Amsterdam, the Netherlands.
authors.forename: M
authors.initials: M
authors.lastname: Peters
authors.affiliation: Department of Hematology, Radboud University Medical Center, Nijmegen, the Netherlands.
authors.forename: B A P
authors.initials: BA
authors.lastname: Laros-van Gorkom
authors.affiliation: Department of Thrombosis and Hemostasis, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: F J M
authors.initials: FJ
authors.lastname: van der Meer
authors.affiliation: Netherlands Hemophilia Patient Society (NVHP), Nijkerk, the Netherlands.
authors.forename: M H E
authors.initials: MH
authors.lastname: Driessens
authors.affiliation: Department of Hematology, Erasmus University Medical Center Rotterdam, Rotterdam, the Netherlands.
authors.forename: F W G
authors.initials: FW
authors.lastname: Leebeek
authors.affiliation: Department of Pediatric Hematology, Academic Medical Center Amsterdam, Amsterdam, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Fijnvandraat
authors.affiliation: Department of Pediatric Hematology, Erasmus University Medical Center - Sophia Children's Hospital Rotterdam, Rotterdam, the Netherlands.
authors.forename: M H
authors.initials: MH
authors.lastname: Cnossen
mesh_terms: D000017:ABO Blood-Group System; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects*; D001780:Blood Coagulation Tests; D016063:Blood Loss, Surgical / Q000517:prevention & control*; D016009:Chi-Square Distribution; D002648:Child; D002675:Child, Preschool; D003029:Coagulants / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004334:Drug Administration Schedule; D054796:Drug Dosage Calculations; D016903:Drug Monitoring; D005169:Factor VIII / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D006467:Hemophilia A / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D007263:Infusions, Parenteral; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009426:Netherlands; D016017:Odds Ratio; D019990:Perioperative Care / Q000379:methods*; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D012189:Retrospective Studies; D012307:Risk Factors; D016896:Treatment Outcome
chemical_list: D000017:ABO Blood-Group System; D003029:Coagulants; D005169:Factor VIII
keywords: ABO blood group system; factor VIII; hemophilia A; perioperative period; surgery