title: Development of a Hyperactive Primary Hemostatic System During Off-Pump Lung Transplantation Resulting From an Unbalance Between von Willebrand Factor and Its Cleaving Protease ADAMTS13.
abstract: An unbalance between the platelet-adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off-pump lung transplantation. We analyzed plasma of 10 patients and distinguished lung transplantation-specific effects from those generally accompanying open-chest surgeries by comparing results with 11 patients undergoing off-pump coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for reference values. VWF antigen levels as well as the VWF ristocetin cofactor activity/VWF antigen ratio increased during lung transplantation and after CABG surgery. An increase in VWF propeptide levels was paralleled by a decrease in ADAMTS13 activity. This was more pronounced during lung transplantation. Similarly, the capacity of plasma to support platelet aggregation under shear flow conditions in vitro was more increased during lung transplantation. The proportion of high molecular weight VWF multimers was elevated in both groups without evidence for ultra-large VWF. VWF's collagen binding activity remained unchanged. In conclusion, a hyperactive primary hemostatic system develops during lung transplantation resulting both from a pronounced (functional) increase of the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet thrombosis within the allograft.
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: G C G
authors.initials: GC
authors.lastname: Hugenholtz
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: K
authors.initials: K
authors.lastname: Ruitenbeek
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: J
authors.initials: J
authors.lastname: Adelmeijer
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: I T A
authors.initials: IT
authors.lastname: Pereboom
authors.affiliation: Department of Plasma Proteins, Sanquin Research, Amsterdam, the Netherlands.|Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands.
authors.forename: J C M
authors.initials: JC
authors.lastname: Meijers
authors.affiliation: Department of Pulmonary Diseases, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: W
authors.initials: W
authors.lastname: van der Bij
authors.affiliation: Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University of Medical Center Groningen, Groningen, the Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Porte
authors.affiliation: Department of Cardiothoracic Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.
authors.forename: M E
authors.initials: ME
authors.lastname: Erasmus
authors.affiliation: Surgical Research Laboratory, Department of Surgery, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands.|Section of Hepatobiliary Surgery and Liver Transplantation, Department of Surgery, University of Groningen, University of Medical Center Groningen, Groningen, the Netherlands.
authors.forename: T
authors.initials: T
authors.lastname: Lisman
mesh_terms: D051722:ADAM Proteins / Q000097:blood*; D000071120:ADAMTS13 Protein; D000328:Adult; D016022:Case-Control Studies; D001026:Coronary Artery Bypass; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection; D006085:Graft Survival; D006490:Hemostatics; D006801:Humans; D008171:Lung Diseases / Q000601:surgery*; D016040:Lung Transplantation / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D010973:Platelet Adhesiveness; D011183:Postoperative Complications; D011379:Prognosis; D012307:Risk Factors; D013927:Thrombosis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D006490:Hemostatics; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human