Studies on the functionality of fibrinogen during rt-PA therapy: results of three different methods of fibrinogen determination.

The conversion of soluble fibrinogen to insoluble fibrin is a crucial event in the process of haemostasis. In the present study three different methods were used for the determination of plasma fibrinogen levels in 12 patients with acute myocardial infarction during rt-PA therapy. Two methods were based on fibrin formation and thus measured 'functional' fibrinogen: a clotting rate assay according to the Clauss method and a photometric polymerization rate assay. Thirdly, fibrinogen antigen was measured with a new enzyme immunoassay (EIA) for immunologically intact fibrinogen. The levels of functional and intact fibrinogen were strikingly different: 4.1 g/l (Clauss) and 3.6 g/l (photometric) vs 2.6 g/l (EIA) at baseline, 2.2 g/l (54% of preinfusion value) and 2.1 g/l (59%) vs 2.1 g/l (81%) at 9, min, 5.7 g/l (146%) and 4.5g/l (130%) vs 2.7 g/l (106%) at 72 h. The rebound phenomenon exhibited by functional fibrinogen (130-150%) was not observed for levels of intact fibrinogen. A ratio was calculated of functional (Clauss method) to intact fibrinogen (EIA) for each individual patient and each time point. The mean ratio (n = 12 patients) was 1.6 at baseline, 1.0 at 90 min, and increased markedly between 8 and 24 h to a maximum of 2.1 (P < 0.01). Our data indicate that the functionality', i.e. the clotting rate per unit concentration of circulating fibrinogen, changed during acute myocardial infarction and subsequent thrombolytic therapy. This is in keeping with data from literature that the relative amount of fast clotting high molecular weight (HMW) fibrinogen of total fibrinogen was increased in the initial phase of acute myocardial infarction. Our data suggest that about 20% of HMW fibrinogen was either converted to low molecular weight (LMW') fibrinogen or degraded during rt-PA infusion. After 8 h circulating fibrinogen was fast clotting again and may well represent newly synthesized fibrinogen with a high portion of HMW fibrinogen. If this is indeed the case, the ratio between functional and immunologically intact fibrinogen may serve as an important index for the specific clotting activities of fibrinogen and for the selection of patients at high risk for early reocclusion.