title: Thrombolysis using consecutive high dose bolus and infusion of alteplase in a patient with acute massive pulmonary embolism.
abstract: We describe the successful use of a novel dosage regimen of alteplase in a 77-year-old man with massive acute pulmonary embolism in the presence of a relative contraindication (recent cranial surgery). An intravenous alteplase bolus of 50 mg was administered, followed 40 min later by a 50 mg infusion over 2 h. Pulmonary arteriography showed a considerable increase in intraluminal filling of thrombotically occluded vessels as a result of alteplase administration, and was accompanied by marked clinical improvement. Peak alteplase plasma concentration after the bolus was 5.5 micrograms/ml, and the steady state concentration during infusion was 0.52 micrograms/ml. Detailed monitoring of haemostasis parameters showed elevated endogenous fibrinolytic activity at baseline, very high levels of fibrin degradation products during treatment resulting from lysis of an extensive thrombus mass, moderate fibrinogenolysis compared to fibrinolysis, long plasma half-lives of fibrin(ogen) degradation products (9.2-11.0 h), and increased thrombin generation. There were no bleeding side-effects. The regimen combines the advantages of rapid onset (bolus) and maintained potency (infusion) of thrombolytic effect in pulmonary embolism.
authors.affiliation: Medizinische Klinik II, Kreiskrankenhaus, Detmold, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Tebbe
authors.forename: E
authors.initials: E
authors.lastname: Seifried
authors.forename: J
authors.initials: J
authors.lastname: Carlsson
authors.forename: P
authors.initials: P
authors.lastname: Tanswell
mesh_terms: D000368:Aged; D000990:Antithrombin III / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D005340:Fibrinogen / Q000378:metabolism; D005342:Fibrinolysis; D006801:Humans; D008297:Male; D010447:Peptide Hydrolases / Q000378:metabolism; D011655:Pulmonary Embolism / Q000097:blood / Q000000981:diagnostic imaging / Q000188:drug therapy*; D011859:Radiography; D013917:Thrombin / Q000378:metabolism; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D005340:Fibrinogen; D010447:Peptide Hydrolases; D013917:Thrombin; D010959:Tissue Plasminogen Activator