title: Prevention of in vitro fibrinogenolysis during laboratory monitoring of thrombolytic therapy with streptokinase or APSAC.
abstract: In the present study, we systematically investigated aprotinin, epsilon-aminocaproic acid (EACA) and tranexamic acid as inhibitors of fibrinogen breakdown and of the generation of fibrinogen degradation products (FgDP). The experimental setting very closely imitated the conditions in practice when collecting blood from patients receiving thrombolytic therapy with streptokinase or APSAC. The minimal concentration of aprotinin required to completely inhibit fibrinogen breakdown and FgDP generation was 200 KIU/ml blood. This was sufficient even at the highest concentrations of streptokinase and APSAC expected to occur in patients (300 U/ml and 46 nM, respectively). However, 200 KIU/ml aprotinin heavily interfered in the determinations of plasminogen and alpha 2-antiplasmin. Relatively low concentrations of EACA (200 mM) and tranexamic acid (35 mM) were sufficient to prevent FgDP generation, but they interfered in the Clauss assay of fibrinogen. A non-interfering concentration of EACA (7 mM) allowed the inhibition of lower concentrations of APSAC (20 nM) and streptokinase. We conclude that at least 200 KIU aprotinin per ml blood is necessary to effectively inhibit in vitro fibrinogenolysis under circumstances likely to be met in clinical practice during thrombolytic therapy.
authors.affiliation: Department of Clinical Laboratories, Catharina Hospital, Eindhoven, The Netherlands.
authors.forename: J J
authors.initials: JJ
authors.lastname: Hoffmann
authors.forename: M
authors.initials: M
authors.lastname: Vijgen
mesh_terms: D015119:Aminocaproic Acid / Q000494:pharmacology; D016255:Anistreplase / Q000097:blood* / Q000627:therapeutic use; D007611:Aprotinin / Q000008:administration & dosage / Q000494:pharmacology; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism*; D005341:Fibrinolysin / Q000378:metabolism; D006801:Humans; D010958:Plasminogen / Q000378:metabolism; D013300:Streptokinase / Q000097:blood* / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D014148:Tranexamic Acid / Q000494:pharmacology; D000511:alpha-Macroglobulins / Q000378:metabolism
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D000511:alpha-Macroglobulins; C024668:plasmin-alpha(2)-macroglobulin complex; D014148:Tranexamic Acid; D016255:Anistreplase; D005340:Fibrinogen; D010958:Plasminogen; D007611:Aprotinin; D013300:Streptokinase; D005341:Fibrinolysin; D015119:Aminocaproic Acid