Disorders of
fibrinogen are usually caused by genetic mutations that result in low
protein levels (hypofibrinogenemia) or an abnormal molecule (dysfibrinogenemia). However, environmental and plasma factors can have an acquired effect on its expression or function. For example,
antibodies can bind
fibrinogen and/or
fibrin to interfere with polymerization and inhibit coagulation. The objective here was to determine the cause of dysfibrinogenemia in a 63-year-old man. Despite a low functional
fibrinogen concentration and prolonged thrombin time, no inherited
fibrinogen abnormality could be detected after extensive
protein analysis and gene sequencing. Thus, electrophoresis methods and
fibrinogen binding studies were used to establish the cause of the acquired dysfibrinogenemia. An
immunoglobulin lambda light chain was found to bind
fibrinogen as a monomer. It had no significant effect on fibrinopeptide release, but caused substantial defects in all other stages of
thrombin-catalyzed
fibrin polymerization. Binding to
fibrinogen also seemed to prevent the light chain from being filtered through the kidneys, causing only low levels of it in the urine. Once in the urine, the lambda chain lost its anti-
fibrinogen activity, apparently due to dimerization. The 63-year-old patient acquired dysfibrinogenemia from a monoclonal production of lambda light chain that bound and inhibited the function of
fibrinogen. At age 64.5 he was diagnosed with
monoclonal gammopathy of undetermined significance, explaining the abnormal
immunoglobulin chain production. This case was particularly unusual in that the inhibition of
fibrin polymerization was caused by a single
immunoglobulin light chain, rather than by a whole antibody molecule.