Dosage of i.v. brinase in man based on brinase inhibitor capacity and coagulation studies.
In 17 patients a total of 148 brinase infusions were given. All patients but two had anticoagulant treatment (dicoumarol or heparin) during the brinase series. Dosage of brinase was based on determination of brinase inhibitor capacity in plasma (azocollagen technique) prior to infusion of the enzyme. Iv infusion of brinase lowered inhibitors in plasma. Good correlation was found between expected lowering and measured inhibitor values after brinase infusion. The stipulated safety margin for brinase inhibitor capacity could be maintained. alpha 1-antitrypsin showed irregular changes and alpha 2-macroglobulin values were decreased by iv infusions of brinase. Fibrinogen values were somewhat lowered after iv brinase infusion. Values for fibrinogen degradation products increased and the ethanol gelation test became positive. Thrombotest values were lowered and the activated partial thromboplastin time was prolonged in patients receiving dicoumarol and iv heparin respectively. Changes in other coagulation parameters were insignificant. In two patients transient renal failure was recorded, laboratory data indicated intravascular coagulation as a possible cause. None of these two patients were on anticoagulant treatment. One patient developed a haematoma of the forefoot during massive iv heparin treatment during a series of iv infusions of brinase. Bleeding complications due to brinase treatment were not observed.
D001157:Arterial Occlusive Diseases / Q000188:drug therapy*; D001777:Blood Coagulation / Q000187:drug effects; D001798:Blood Proteins / Q000187:drug effects; D001954:Brinolase / Q000008:administration & dosage* / Q000009:adverse effects / Q000037:antagonists & inhibitors; D006801:Humans; D007262:Infusions, Intravenous; D010447:Peptide Hydrolases / Q000008:administration & dosage*
D001798:Blood Proteins; D010447:Peptide Hydrolases; D001954:Brinolase