Reduced ADAMTS13 activity in delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.
The pathogenesis of delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (SAH) remains unknown. Besides vasospasm, microthrombosis might have an important function. As in patients with thrombotic thrombocytopenic purpura an A Disintegrin And Metalloprotease with ThromboSpondin repeats-13 (ADAMTS13) deficiency leads to higher concentrations of large von Willebrand factor (vWF) multimers resulting in microthrombosis, our purpose was to compare ADAMTS13 and vWF in patients with and without DCI after aneurysmal SAH. We measured ADAMTS13 activity, vWF antigen, vWF propeptide, and vWF ristocetin cofactor activity in plasma at standard intervals. Thirty-one patients were included. Eleven patients (35%) developed DCI. No differences were observed in baseline characteristics between patients with and without DCI. Patients with DCI had a stronger decrease in ADAMTS13 activity, and a more profound increase in vWF antigen, vWF propeptide, and vWF activity in the first few days after the hemorrhage (P-values for difference in polynomial time trend 0.0001, 0.020, 0.004, and 0.188, respectively). No indication of correlation between vWF antigen and ADAMTS13 was found (r=-0.027, P=0.736). Our results suggest that microthrombosis has a role in the pathogenesis of DCI, as a result of decreased ADAMTS13 activity and endothelium dysfunction.
Vergouwen
Mervyn D I
MD
Department of Neurology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. m.d.vergouwen@amc.uva.nl
Bakhtiari
Kamran
K
van Geloven
Nan
N
Vermeulen
Marinus
M
Roos
Yvo B W E M
YB
Meijers
Joost C M
JC
D051722:ADAM Proteins / Q000172:deficiency / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000201:enzymology*; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D055503:Protein Multimerization; D013345:Subarachnoid Hemorrhage / Q000150:complications*; D013927:Thrombosis / Q000209:etiology; D013997:Time Factors; D014841:von Willebrand Factor / Q000032:analysis
D014841:von Willebrand Factor; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human