Jordyn A. Moore¹ and Richard I. King¹
Specialist Biochemistry, Canterbury Health Laboratories, Health NZ

Fibrinogen is a 340 kDa glycoprotein made up of three polypeptide chains (Aα, Bβ and γ). The three polypeptide chains assemble into dimers to form the circulating fibrinogen molecule. Time-of-flight (TOF) mass spectrometry coupled with reversed phase chromatography enables detection of the three intact fibrinogen chains in a top-down mass spectrometry approach. The detailed structural information provided by this technique can be used for identification of fibrinogen variants in plasma. This enables screening and diagnosis of congenital dysfibrinogenaemia and hypofibrinogenaemia variants, which are caused by mutation of fibrinogen genes (FGA, FGB and FGG). Affected patients manifest different clinical pictures, with some clinically silent, while others show bleeding or thrombosis. Dysfibrinogenaemia is characterised by functional abnormalities of fibrinogen (qualitative), while hypofibrinogenaemia results from reduced levels of circulating fibrinogen (quantitative). The most common dysfibrinogenaemia variant is AαArg16His, which is a structural defect impairing cleavage of fibrinopeptide A by thrombin. We present a case of this variant to illustrate the laboratory workflow, which involves coagulation testing, TOF mass spectrometry and genetic analysis, highlighting the effectiveness of TOF mass spectrometry for screening these disorders.

Jordyn is the Scientific Officer in charge of TOF mass spectrometry for hypo/dysfibrinogenaemia cases. Jordyn routinely performs, interprets, reports and authorises this testing. Jordyn will collate the case information and assemble the poster. Richard is the Pathologist in charge of hypo/dysfibrinogenaemia cases. Richard routinely authorises this testing. Richard has reviewed the abstract and will review the poster.