Title
Levels of functional versus intact fibrinogen in 140 patients with acute myocardial infarction treated with Reteplase
Author
Müller, M.M.
Eilbrück, D.
Grünewald, M.
Ziesche, S.
Mohren, M.
Neuhaus, K.-L.
Hombach, V.
Nieuwenhuizen, W.
Seifried, E.
Gaubius Instituut TNO
Publication year
1996
Abstract
Reteplase, the novel K2P-deletion mutant of t-PA, was administered in a dose-finding multicenter study (GRECO) to 140 patients (pts) with acute myocardial infarction (AMI). 40 pts (group A) received an 18 mg (10 Megaunits (MU)) i.V. single bolus of Reteplase and 100 subsequent pts (Group B) were treated with a 27 mg (15 MU) i.v. single bolus. Fibrinogen (fbg) was measured using two different methods before (pre) and 2, 4, 8 and 24 h after Reteplase: the first fbg method was a clotting rate assay according to the Clauss method (functional fbg), the second an enzyme immunoassay (EAI) for immunologically intact fbg. In 10 out of the group B pts (group C; 27 mg) changes of fbg levels were measured in very close intervals until 18 days (dl8) after thrombolysis. Results: The levels of functional (Clauss) and intact (EIA) fbg differed significantly at each time point: A (Clauss/EIA; median values; [g/1]): Pre: 2.8/3.5; 2 h: 1.7/2.7 (60%/77% of the pre-bolus value of each method); 4 h: 1.7/2.7 (62%/76%); 8 h: 1.5/2.6 (54%/74%); 24 h: 2.2/3.0 (79%/86%) (p<0.001 between Clauss and EIA at any time of sampling). B: Pre: 2.6/3.2; 2 h: 1.0/2.1 (37%/66%); 4 h: 0.9/2.2 (36%/69%); 8 h: 1.0/2.2 (37%/69%); 24 h: 1.6/2.4 (63%/75%) (p<0.0005). C: Pre: 2.7/3.1; 30 min.: 1.6/2.5; 60 min.: 1.3/2.4; 2 h: 1.2/2.3; 4 h: 1.2/2.2 (44%/69%); 8 h: 1.3/2.2; 24 h: 1.8/2.5; 48 h: 2.8/2.7; 72 h: 4.1/3.6; d6: 4.7/3.8 (173%/123%); d9: 4.5/3.9 (167%/126%); d!2: 4.1/3.5; d!5: 3.9/3.2; d!8: 4.0/3.4 (p<0.05; exception: 48 h: not significant). Conclusions: The levels of functional (Clauss) fbg showed lower nadirs and higher rebound levels (C) compared to the intact (EAI) fbg levels. Lower nadirs measured by the Clauss method might reflect the disturbance of this method by fibrin(ogen) degradation products. Higher rebound levels of functional fbg (Clauss) might indicate newly synthesized fast clotting HMW (high molecular weight) fbg and therefore a risk factor for reocclusions in AMI pts treated with thrombolytic agents. In contrast to our previous studies in rt-PAtreated AMI pts, the pretreatment ratio of functional (Clauss) to intact (EAI) fbg here was <0.9 in groups A, B and C compared to 1.6 in the rt-PA study. © Pearson Professional Ltd 1996.
Subject
Biology
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TNO identifier
233655
ISSN
0268-9499
Source
Fibrinolysis, 10 (SUPPL. 1), 39-40
Article number
Abstract 127
Document type
article