Contact system dependent fibrinolytic activity in vivo: observations in healthy subjects and factor XII deficient patients.
The contribution of activation of the contact system to activation of the fibrinolytic system in vivo was investigated in healthy volunteers and in factor XII deficient patients. The plasminogen activating activity in normal plasma was only partially blocked (for 77%) with specific antibodies to tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). The residual activity could be quenched by a monoclonal antibody that inhibits factor XII activity and was not present in patients with a factor XII deficiency. The formation of plasmin upon the DDAVP stimulus as reflected by circulating plasmin-alpha 2-antiplasmin (PAP) complexes was lower in factor XII deficient patients than in healthy volunteers. These results indicate that in vivo the plasminogen activating activity is partially dependent on activation of the contact system. This fibrinolytic activity is impaired in factor XII deficient patients which may explain the occurrence of thromboembolic complications in these patients.
Levi
M
M
Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, University of Amsterdam, The Netherlands.
Hack
C E
CE
de Boer
J P
JP
Brandjes
D P
DP
Büller
H R
HR
ten Cate
J W
JW
D000328:Adult; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004797:Enzyme-Linked Immunosorbent Assay; D005174:Factor XII / Q000032:analysis / Q000378:metabolism*; D005175:Factor XII Deficiency / Q000097:blood*; D005342:Fibrinolysis / Q000187:drug effects; D006801:Humans; D012016:Reference Values; D010959:Tissue Plasminogen Activator / Q000097:blood; D014568:Urokinase-Type Plasminogen Activator / Q000097:blood
D005174:Factor XII; D010959:Tissue Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator; D003894:Deamino Arginine Vasopressin