Fibrinogen Reference Range in Adolescents
Authors: Wakeman Lisa J , Munro Roger C , Williams Rhys , Davies Bruce , Baker Julien , Al-Ismail Saad , Thomas Non 
Published: April 2020

Abstract
Introduction: Elevated fibrinogen levels are well recognized as an independent risk factor for cardiovascular events in adults. Current research highlights the need to understand the mechanisms that influence fibrinogen levels in adolescents in order to elucidate its role in early onset ischaemic heart disease in young people. Depressed levels of fibrinogen are observed in a range of pathological conditions including acquired and congenital hypo- and afibrinogenaemias, consumptive coagulopathies, carcinoma and liver disease. Appropriate determination of the status of fibrinogen levels in patients is vital in identifying fibrinogen as a risk factor for cardiovascular events and in the investigation of coagulopathy. Ascertaining the meaningful status of the fibrinogen level in a patient relies on comparison with a reference range determined by the same methodology using an analogous population from which the patient originates. We present a reference range for Clauss fibrinogen determination in adolescents aged 12–14 years using the Sysmex CA-1500 coagulometer (Sysmex Corp., Kobe; Japan).
Methodology: Blood samples for fibrinogen determination were collected from 240 adolescent schoolchildren aged between 12 and 14 years (M=119; F=121). All of the children were healthy with no apparent underlying pathology. Early morning samples were collected into siliconised glass BD Vacutainers containing tri-sodium citrate (Ref: 367691) and analysed within 4 hours of collection. Fibrinogen determination was performed using Dade-Behring thrombin and Owrens Veronal buffer reagents. Calibration of the Clauss fibrinogen assay was performed using NIBSC WHO International reference plasma for human fibrinogen (product number 98/612).
Results: Fibrinogen results for males and females were examined for normality using Anderson-Darling and Kolmogorov-Smirnov tests. Results were found to be normally distributed and reference ranges constructed using the arithmetic mean +/− 1.96SDs. Male and female results were examined using the two-sample T- test for gender differences where p&lt;0.05 indicates a statistically significant difference. Fibrinogen data from the adolescent group (Table) were compared with 209 healthy adults (F=151; M=58: aged 21–55 years for both gender) tested in the same way.
N Mean (g/l) SD Ref Range (g/l) Two sample test for gender difference (p) Adolescents Male 119 2.66 0.464 1.76 – 3.58 0.76 Female 121 2.67 0.467 1.76 – 3.59 Total sample 240 2.67 0.465 1.76 – 3.58 Adults Male 58 2.71 0.672 1.37 – 4.05 &lt;0.05 Female 151 2.99 0.653 1.68 – 4.29 Total sample 209 2.93 0.663 1.60 – 4.30
Conclusion: Reference ranges for Clauss fibrinogen for school children aged 12–14 years (1.8–3.6g/l) determined using the Sysmex CA-1500 coagulometer differ from the reference range for the healthy adult population (1.6–4.3g/l) determined using the same analyzer and methodology. No statistically significant difference was observed between adolescent male and female cohorts in contrast to significant gender differences observed within the healthy adult population. Reference ranges described in our study show the upper limit in adolescents to be lower than in the healthy adult population. The meaningful assessment of fibrinogen as a risk factor for cardiovascular events in young people should take cognizance of the age specific reference interval. The use of an appropriate, robust reference range for young people is essential in evaluating the influence of contributory risk factors for cardiovascular disease such as diet, body mass and exercise. Assessment of haemostatic function and investigations of coagulopathies in adolescents should be undertaken with reference to age specific ranges where available. This study was approved by the LREC and informed consent was obtained from parents/guardians.