Inflammation-associated ADAMTS13 deficiency promotes formation of ultra-large von Willebrand factor.
In a prospective, longitudinal study, we investigated the association between decreased ADAMTS13 activity and impaired hemostasis, as well as organ dysfunctions in patients with systemic inflammation due to extracorporeal cardiopulmonary circuit or with severe sepsis. Similar to negative acute phase proteins, ADAMTS13 activity declined stepwise according to the extent of inflammatory responses. A marked imbalance between ADAMTS13 activity and VWF antigen level was associated with the appearance of ultra-large VWF multimers in plasma, with organ dysfunction and lethality. Our data support the view that systemic inflammation results in an ADAMTS13 deficiency which activates hemostasis.
Bockmeyer
Clemens L
CL
Department of Anaesthesiology and Intensive Care Medicine, University Hospital, Friedrich-Schiller-University, Erlanger Allee 101, D-07747 Jena, Germany.
Claus
Ralf A
RA
Budde
Ulrich
U
Kentouche
Karim
K
Schneppenheim
Reinhard
R
Lösche
Wolfgang
W
Reinhart
Konrad
K
Brunkhorst
Frank M
FM
D051722:ADAM Proteins / Q000172:deficiency* / Q000502:physiology*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D000941:Antigens / Q000737:chemistry; D001792:Blood Platelets / Q000378:metabolism; D005260:Female; D006487:Hemostasis; D006801:Humans; D007249:Inflammation; D008297:Male; D008875:Middle Aged; D018805:Sepsis / Q000175:diagnosis; D018746:Systemic Inflammatory Response Syndrome / Q000097:blood* / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000175:diagnosis; D014841:von Willebrand Factor / Q000737:chemistry*
D000941:Antigens; D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human