Biochemistry and measurement of fibrinogen

Fibrinogen is a large heterogeneous family of closely related molecules consisting of three pairs of non-identical polypeptide chains: two A alpha-, two B beta- and two gamma-chains, held together by disulphide bridges. The heterogeneity of fibrinogen is due to heterogeneities in all three chains. Four main types of assay are used to determine fibrinogen:clotting rate (Clauss), clottable protein, precipitation and immunological assays. Heterogeneities may differ from person to person and may affect the apparent fibrinogen concentrations in different assays. A further complicating factor was, until recently, the lack of an international fibrinogen standard. The ratio of Clauss:enzyme immunoassay (EIA) for high + low molecular weight fibrinogen decreases during therapy for acute myocardial infarction and increases again after thrombolytic therapy to above normal values. Furthermore, high molecular weight fibrinogen tends to clot more easily than low molecular weight fibrinogen. This suggests that high molecular weight fibrinogen might be associated with increased thrombotic risk. Fibrinogen assessed by a functional assay (Clauss) alone is strongly associated with ischaemic heart disease. Although not proven, it is conceivable that a fibrinogen with a Clauss:EIA ratio of > 1 has an even stronger association in epidemiological studies.