Fibrinogen (Fb) mass spectrometry is useful in the diagnosis of Fb variants associated with familial hypofibrinogenaemia (quantitative Fb deficiency) and dysfibrinogenaemia (qualitative Fb deficiency).
Hypofibrinogenaemia is characterised by low antigenic Fb concentration (< 1.5 mg/mL) and can be caused by different Fb gene mutations. Mutations can affect transcription, mRNA processing, translation, polypeptide chain processing and assembly, export from the hepatocyte, or stability of the mature protein. Although heterozygosity for a mutation might reduce Fb levels below the normal range, they do not usually produce a significant clinical condition unless inherited in the homozygous, or compound heterozygous state. In this case, afibrinogenaemia may result and lead to a serious bleeding condition.
Classical dysfibrinogenaemia results from impairment of fibrin polymerisation. Dysfibrinogenaemia is associated with prolonged thrombin clotting times and low functional Fb but usually normal antigenic Fb concentration. Dysfibrinogenaemia is most likely caused by mutation in the region of the Fb gene that codes for functional domains involved in polymerisation.
Genetics - Molecular Pathology
Coagulation investigation (TCT, Clauss fibrinogen, antigenic fibrinogen).
Citrate plasma is required for coagulation testing (if needed) and Fb mass spectrometry.
EDTA whole blood is required for extraction of DNA. This test requires nucleated cells. Please do not centrifuge or freeze blood sample.
If storing blood tubes prior to delivery please refrigerate at 4 degrees (transport still at ambient temperature).
Blood tubes should be transported with several cold packs if not arriving within 4 hours of collection.
Ambient (8 - 24 degrees Celsius)
If overnight - Chilled (2 - 8 degrees Celsius)
Available coagulation testing results (TCT, Clauss fibrinogen, antigenic fibrinogen) and relevant clinical and family history should be provided with the referral.
Investigation of suspected hypofibrinogenaemia or dysfibrinogenaemia is initially by time-of-flight (TOF) mass spectrometry. Mass changes are used to identify variant fibrinogen A-alpha, B-beta, or gamma chain(s).
DNA sequencing of FGA/FGB/FGG genes is then performed to identify and/or confirm a mutation.
If coagulation testing is required as part of the investigation TCT and Clauss Fb will be measured by StaR Max using STA Liquid Fib and antigenic Fb measured by Siemens BNII using N antiserum fib.
$200 (Exclusive of GST)
The total cost for testing depends on the amount of analysis required.
Mass spectrometry analysis plus DNA sequencing of a single exon is approximately $475 (Exclusive of GST); if full sequencing of FGA, FGB, and FGG genes is required the cost is approximately $1000 (Exclusive of GST).
Coagulation testing results (TCT, Clauss fibrinogen, antigenic fibrinogen) and relevant clinical and family history should be provided with the referral.
If relevant coagulation testing results are not provided with the referral/have not been performed already this may be completed as part of the hypo/dysfibrinogenaemia investigation at our laboratory.
Depending on the abnormality detected by mass spectrometry, genetic analysis may also be required.
The combination of tests performed for hypo/dysfibrinogenaemia investigation will be at the discretion of the laboratory.
The 4 week turnaround time is for a full hypo/dysfibrinogenaemia investigation, including mass spectrometry and any subsequent genetic analysis required to establish a diagnosis.
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