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: G C G Hugenholtz, K Ruitenbeek, J Adelmeijer, I T A Pereboom, J C M Meijers, W van der Bij, R J Porte, M E Erasmus, T Lisman
• Journal: American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons (Am J Transplant) Vol. 15 Issue 7 Pg. 1958-66 (Jul 2015) ISSN: 1600-6143 [Electronic] United States
• PMID: 25846964 (Publication Type: Comparative Study, Journal Article)
• Copyright: © Copyright 2015 The American Society of Transplantation and the American Society of Transplant Surgeons.

Chemical References

• Hemostatics
• von Willebrand Factor
• ADAM Proteins
• ADAMTS13 Protein
• ADAMTS13 protein, human

Topics

• ADAM Proteins (blood)
• ADAMTS13 Protein
• Adult
• Case-Control Studies
• Coronary Artery Bypass
• Female
• Follow-Up Studies
• Graft Rejection
• Graft Survival
• Hemostatics
• Humans
• Lung Diseases (surgery)
• Lung Transplantation (adverse effects)
• Male
• Middle Aged
• Platelet Adhesiveness
• Postoperative Complications
• Prognosis
• Risk Factors
• Thrombosis (etiology, metabolism, pathology)
• von Willebrand Factor (metabolism)