Johannes J M L Hoffmann1, Oliver Kops. 1. Department of Clinical Laboratories, Catharina Hospital, P.O. Box 1350, Eindhoven, ZA 5602, The Netherlands. hans.hoffmann@cze.nl
Abstract
INTRODUCTION: Laboratory monitoring of the hemostatic system during thrombolytic therapy requires that the fibrinolytic activity generated in vivo be immediately inhibited at blood collection in order to prevent artificial results as a consequence of degradation of clotting proteins. For most thrombolytic drugs efficient inhibitors have been described, but not yet for the new thrombolytic agent, desmoteplase, which is vampire bat salivary plasminogen activator. Therefore, we investigated the effect of aprotinin and D-Phe-Pro-Arg-chloromethylketone (PPACK) on desmoteplase-induced fibrinolysis. MATERIALS AND METHODS: We added desmoteplase in pharmacological concentrations to blood samples supplemented with aprotinin, PPACK or both. Fibrinolytic activity was assessed by measuring degradation products of fibrin and fibrinogen, plasmin-antiplasmin complex, thrombin-antithrombin complex, fibrinogen and some overall clotting assays. RESULTS: Desmoteplase caused in vitro activation of plasminogen with concomitant degradation of fibrin and fibrinogen. Aprotinin completely inhibited these effects, whereas PPACK gave only partial inhibition. Neither inhibitor prevented plasminogen activation and thus significant generation of plasmin-antiplasmin complex was observed. CONCLUSION: Blood collection for hemostatic analyses in clinical studies with desmoteplase requires addition of aprotinin (final concentration 250 KIU/mL) in order to prevent in vitro artifacts.
INTRODUCTION: Laboratory monitoring of the hemostatic system during thrombolytic therapy requires that the fibrinolytic activity generated in vivo be immediately inhibited at blood collection in order to prevent artificial results as a consequence of degradation of clotting proteins. For most thrombolytic drugs efficient inhibitors have been described, but not yet for the new thrombolytic agent, desmoteplase, which is vampire bat salivary plasminogen activator. Therefore, we investigated the effect of aprotinin and D-Phe-Pro-Arg-chloromethylketone (PPACK) on desmoteplase-induced fibrinolysis. MATERIALS AND METHODS: We added desmoteplase in pharmacological concentrations to blood samples supplemented with aprotinin, PPACK or both. Fibrinolytic activity was assessed by measuring degradation products of fibrin and fibrinogen, plasmin-antiplasmin complex, thrombin-antithrombin complex, fibrinogen and some overall clotting assays. RESULTS: Desmoteplase caused in vitro activation of plasminogen with concomitant degradation of fibrin and fibrinogen. Aprotinin completely inhibited these effects, whereas PPACK gave only partial inhibition. Neither inhibitor prevented plasminogen activation and thus significant generation of plasmin-antiplasmin complex was observed. CONCLUSION: Blood collection for hemostatic analyses in clinical studies with desmoteplase requires addition of aprotinin (final concentration 250 KIU/mL) in order to prevent in vitro artifacts.
Authors: P W Koppert; W Kuipers; B Hoegee-de Nobel; E J Brommer; J Koopman; W Nieuwenhuizen Journal: Thromb Haemost Date: 1987-02-03 Impact factor: 5.249
Authors: S J Gardell; L T Duong; R E Diehl; J D York; T R Hare; R B Register; J W Jacobs; R A Dixon; P A Friedman Journal: J Biol Chem Date: 1989-10-25 Impact factor: 5.157
Authors: Gabriel T Liberatore; André Samson; Christopher Bladin; Wolf-Dieter Schleuning; Robert L Medcalf Journal: Stroke Date: 2003-02 Impact factor: 7.914