Abstract
Congenital and acquired fibrinogen disorders often have heterogeneous clinical phenotypes
and are challenging from a laboratory perspective. Fibrinogen determination using
the Clauss method remains the gold standard, while the reproducibility and significance
of the thrombin time and the reptilase time are limited. Molecular testing for causative
mutations in fibrinogen genes is now recommended to confirm the diagnosis of congenital
fibrinogen disorders. Research assays are used to evaluate alterations to fibrin formation
and properties of plasma and purified fibrinogen-derived clots, characterized by fiber
thickness, the number of branches, and pore sizes. Fibrin clot permeability (permeation,
porosity) using a hydrostatic pressure system represents the most commonly used method
for evaluating fibrin network density. Reduced clot permeability, which denotes the
reduced size of an average pore in the network, results in tighter fibrin networks,
typically associated with impaired susceptibility to lysis, leading to a thrombotic
tendency. Biophysical properties of fibrin clots are largely assessed using rheometry,
with atomic force microscopy and nanorheology being increasingly used in disease states.
Thromboelastography and thromboelastometry, a simple modification of rheometry, have
been used, mainly in intensive care units, for more than 50 years. Given growing evidence
for altered fibrin clot properties in diseases with elevated risk of venous and arterial
thromboembolism and in some bleeding disorders, further work on standardization and
validation of the assessment of fibrin clot characteristics is needed. This review
summarizes the current methods used to evaluate fibrinogen abnormalities in both diagnostic
and research laboratories.
Keywords fibrinogen - fibrin - permeability - thromboelastography - rheometry
