Comparison of plasma fibrinogen by Clauss, prothrombin time-derived, and immunonephelometric assays in a general population: implications for risk stratification by thirds of fibrinogen

There is strong evidence from meta-analyses of prospective epidemiological studies that increasing plasma fibrinogen levels are associated with increasing risk of ischaemic heart disease. It has been suggested that categorization of plasma fibrinogen by thirds of the population distribution be added to cardiovascular risk prediction equations. However, the heterogeneity of plasma fibrinogen and the resulting discrepancies between commonly performed assays may lead to differences in both mean levels and distributions, and in categorizations of populations by thirds. We therefore compared three commonly performed routine fibrinogen assays in a random population sample of 1373 men and women aged 25-64 years in the fourth World Health Organization MONICA survey in north Glasgow. The two assays of clottable fibrinogen (von Clauss and prothrombin time derived) showed similar mean values and distributions, whereas the immunonephelometric assay showed lower mean values. There was significant disagreement between all three assays in categorization of thirds of population fibrinogen distribution (kappa statistic, 0.64 von Clauss versus prothrombin time derived, 0.46 von Clauss versus immunonephelometric, and 0.51 prothrombin time derived versus immunonephelometric). We conclude that further standardization of plasma fibrinogen assays is desirable for ischaemic heart disease risk stratification, and that further studies of the causes and clinical significance of discrepancies between fibrinogen assays in the general population are indicated. (C) 2003 Lippincott Williams Wilkins.