Inhibition of desmoteplase-induced fibrinolytic activity in vitro.
BACKGROUND
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.


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.


CONCLUSIONS
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.
Hoffmann
Johannes J M L
JJ
Department of Clinical Laboratories, Catharina Hospital, P.O. Box 1350, Eindhoven, ZA 5602, The Netherlands. hans.hoffmann@cze.nl
Kops
Oliver
O
D007611:Aprotinin / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005342:Fibrinolysis / Q000187:drug effects / Q000502:physiology*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006801:Humans; D010314:Partial Thromboplastin Time; D010960:Plasminogen Activators / Q000494:pharmacology*
D005343:Fibrinolytic Agents; C069588:salivary plasminogen activator alpha 1, Desmodus rotundus; D007611:Aprotinin; D010960:Plasminogen Activators