title: Different Heparin Contents in Prothrombin Complex Concentrates May Impair Blood Clotting in Outpatients With Ventricular Assist Devices Receiving Phenprocoumon.
abstract: OBJECTIVE
  Prothrombin complex concentrates (PCCs) are used to rapidly reverse anticoagulation by oral vitamin K antagonists. They differ in the content of clotting factors, endogenous anticoagulants, and heparin. The authors hypothesized that PCCs' specific heparin content may compromise the hemostatic effect.
  
  
  METHODS
  Prospective ex-vivo investigation.
  
  
  METHODS
  University hospital.
  
  
  METHODS
  Venous blood samples were obtained from 8 patients with implanted ventricular assist devices who also were receiving phenprocoumon.
  
  
  METHODS
  Four different 4-factor PCCs were added to patient blood to attain a calculated increase in prothrombin time by 20%, 40%, and 60% greater than baseline in paired experiments.
  
  
  RESULTS
  Clotting was measured using thromboelastometry and endogenous thrombin potential. Two heparin-containing PCCs prolonged the clotting times in a concentration-dependent manner compared with baseline (p<0.01) and compared with PCCs containing significantly less or no heparin (p<0.01). The PCCs containing low or no heparin enhanced the area under the curve of thrombin generation and peak thrombin several fold relative to the heparin-containing PCCs (p<0.01). One of the PCCs containing heparin even decreased peak thrombin generation by ~90% compared with baseline (p<0.01). PCC with low or no heparin shortened the lag phase (p<0.01), whereas 1 heparin containing PCC prolonged the lag phase by 66% (p<0.01).
  
  
  CONCLUSIONS
  Physicians should be aware of the differences in heparin contents. Extrapolation of results from one agent to other PCC preparations may be difficult. Patients with an implanted left ventricular assist device and anticoagulated with vitamin-K antagonists could benefit from the use of PCC with low heparin content when surgery or bleeding requires emergency reversal. Further clinical studies are warranted.
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia and Intensive Care.
authors.forename: Alessia
authors.initials: A
authors.lastname: Felli
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia and Intensive Care.
authors.forename: Petra
authors.initials: P
authors.lastname: Zeidler
authors.affiliation: Department of Clinical Pharmacology, Vienna, Austria.
authors.forename: Bernd
authors.initials: B
authors.lastname: Jilma
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia and Intensive Care.
authors.forename: Philipp
authors.initials: P
authors.lastname: Opfermann
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia and Intensive Care.
authors.forename: Caroline
authors.initials: C
authors.lastname: Holaubek
authors.affiliation: Department of Cardiac Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Daniel
authors.initials: D
authors.lastname: Zimpfer
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia and Intensive Care.
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Wadowski
authors.affiliation: Division of Cardiothoracic and Vascular Anesthesia and Intensive Care.
authors.forename: Barbara
authors.initials: B
authors.lastname: Steinlechner
mesh_terms: D000328:Adult; D000553:Ambulatory Care / Q000379:methods*; D000925:Anticoagulants / Q000008:administration & dosage / Q000737:chemistry*; D001777:Blood Coagulation / Q000187:drug effects* / Q000502:physiology; D001779:Blood Coagulation Factors / Q000008:administration & dosage / Q000737:chemistry*; D001780:Blood Coagulation Tests / Q000379:methods; D004339:Drug Compounding; D005260:Female; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006493:Heparin / Q000008:administration & dosage / Q000737:chemistry*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010644:Phenprocoumon / Q000008:administration & dosage*; D011446:Prospective Studies; D011517:Prothrombin Time / Q000379:methods
chemical_list: D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates; D006493:Heparin; D010644:Phenprocoumon
keywords: coumarin; heparin; prothrombin complex concentrate; thromboelastography; ventricular assist device