title: Non-surgical bleeding in patients with ventricular assist devices could be explained by acquired von Willebrand disease.
abstract: OBJECTIVE
  Outcomes after ventricular assist device (VAD) implantation have significantly improved during the last decade. However, bleeding episodes remain a serious complication of VAD support. This cannot be explained by the individual anticoagulation regimen alone in several cases, but may be symptomatic of acquired von Willebrand disease (VWD). The leading finding in acquired VWD (AVWD) is the loss of large multimers which results in diminished binding to collagen and to the platelets. We, therefore, analysed patients with two VAD types for laboratory parameters of VWD and compared them with patients after heart transplantation (HTX).
  
  
  METHODS
  Seven patients with a HeartMate II left-ventricular assist device and five patients who received a Thoratec biventricular assist device were included in this study. Eight HTX recipients served as controls. Analysis included international normalized ratio (INR), partial thromboplastin time (PTT), platelet count, von Willebrand factor (VWF) antigen, collagen binding capacity, ristocetin cofactor activity, the ratios of the latter two to the VWF antigen and presence of large VWF multimers.
  
  
  RESULTS
  The VAD and HTX groups did not differ with regard to age or time-point of analysis after surgery. INR and number of platelets were comparable in both groups, PTT was prolonged in VAD patients. Both VAD and HTX patients had elevated but comparable amounts of VWF antigen. However, large multimers were missing in all of 10 tested VAD patients. In contrast, five of six tested HTX recipients displayed normal multimer pattern. Indeed, collagen binding capacity and ristocetin cofactor activity (which measures binding of VWF to platelets) were lower in VAD patients compared to HTX recipients. Impaired coagulation associated with VADs was also reflected by the diminished ratios of collagen binding capacity and ristocetin cofactor activity to VWF antigen. A pathologic collagen binding ratio was found in all 10 tested VAD patients and one of the eight HTX patients, a reduced ristocetin cofactor activity ratio in 10 of 12 VAD and one of eight HTX patients.
  
  
  CONCLUSIONS
  Non-surgical postoperative bleeding after VAD implantation could be explained by an AVWD. Several pharmacologic treatment options (tranexamic acid, desmopressin, VWF-factor VIII concentrate, recombinant factor VIIa) may arise from our data. Improved VAD design could prevent this problem in the future.
authors.affiliation: Department of Clinical Chemistry, University Medical Center Freiburg, Freiburg, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Geisen
authors.forename: Claudia
authors.initials: C
authors.lastname: Heilmann
authors.forename: Friedhelm
authors.initials: F
authors.lastname: Beyersdorf
authors.forename: Christoph
authors.initials: C
authors.lastname: Benk
authors.forename: Michael
authors.initials: M
authors.lastname: Berchtold-Herz
authors.forename: Christian
authors.initials: C
authors.lastname: Schlensak
authors.forename: Ulrich
authors.initials: U
authors.lastname: Budde
authors.forename: Barbara
authors.initials: B
authors.lastname: Zieger
mesh_terms: D000328:Adult; D000368:Aged; D005260:Female; D006353:Heart-Assist Devices / Q000009:adverse effects*; D006470:Hemorrhage / Q000209:etiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011474:Prosthesis Design; D013997:Time Factors; D018754:Ventricular Dysfunction / Q000150:complications / Q000601:surgery*; D014842:von Willebrand Diseases / Q000150:complications*; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D014841:von Willebrand Factor