The amount of plasminogen, tissue-type plasminogen activator and plasminogen activator inhibitor type 1 in human thrombi and the relation to ex-vivo lysibility.
Thrombolytic therapy successfully reopens obstructed blood vessels in the majority of cases. However, it is not known why a substantial amount of thrombi are resistant to lysis by a fibrinolytic agent. In vitro studies have demonstrated that tissue-type plasminogen activator (t-PA) and plasminogen incorporated in the clot (during formation) increase lysibility. To test whether lysibility of in vivo formed human thrombi is related to their composition, we studied 25 venous thrombi obtained at autopsy and 21 arterial thrombi obtained during embolectomy. Plasminogen activator inhibitor-1 (PAI-1) antigen was measured in a phosphate-buffered saline (PBS) extract of each thrombus; t-PA antigen and plasminogen antigen were determined in a 6 M urea extract of the thrombus, representing bound proteins. Lysibility was measured as weight reduction during 8 h of incubation in PBS containing streptokinase (SK) 100 U/ml, corrected for spontaneous lysis, reflected by weight loss in PBS without SK. In addition, lysibility in SK was compared with lysibility in urokinase (UK) 100 U/ml and in t-PA 200 U/ml. Spontaneous lysis amounted to 29 +/- 5% (mean +/- SEM) and 33 +/- 5% in venous and arterial thrombi, respectively, and inversely correlated with the PAI-1 content of thrombi (r = -0.43, p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
Potter van Loon
B J
BJ
Westeinde Hospital, Dept. of Internal Medicine, Den Haag, The Netherlands.
Rijken
D C
DC
Brommer
E J
EJ
van der Maas
A P
AP
D006801:Humans; D066298:In Vitro Techniques; D010958:Plasminogen / Q000378:metabolism*; D015849:Plasminogen Inactivators / Q000378:metabolism*; D015912:Thrombolytic Therapy; D013924:Thrombophlebitis / Q000188:drug therapy / Q000378:metabolism; D013927:Thrombosis / Q000188:drug therapy / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000378:metabolism*
D015849:Plasminogen Inactivators; D010958:Plasminogen; D010959:Tissue Plasminogen Activator