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 Table of Contents  
LETTER TO EDITOR
Year : 2016  |  Volume : 7  |  Issue : 4  |  Page : 148-149

Low fibrinogen levels: How to maximize accuracy when using an optically derived method


Department of Blood Sciences, Pathology Laboratory, General Hospital, Jersey, UK

Date of Web Publication18-Jan-2017

Correspondence Address:
Sergio Gama
Department of Blood Sciences, Pathology Laboratory, General Hospital, Gloucester Street, St. Helier, Jersey JE1 3QS
UK
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1658-5127.198512

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How to cite this article:
Gama S. Low fibrinogen levels: How to maximize accuracy when using an optically derived method. J Appl Hematol 2016;7:148-9

How to cite this URL:
Gama S. Low fibrinogen levels: How to maximize accuracy when using an optically derived method. J Appl Hematol [serial online] 2016 [cited 2020 Jun 1];7:148-9. Available from: http://www.jahjournal.org/text.asp?2016/7/4/148/198512

Sir,

Fibrinogen is an important coagulation factor synthesized in the hepatocyte. It is a major plasma protein with normal levels between 1.5 and 4.0 g/L.[1],[2] It is crucial that low levels of fibrinogen be accurately detected, because they are associated with an increased risk of bleeding due to impaired primary and secondary hemostasis.[3] Replacement therapy is usually required when plasma fibrinogen levels drop below 1.0 g/L in bleeding patients.[4]

A number of different tests may be used to assess the fibrinogen levels. The fibrinogen Clauss assay and the derived fibrinogen test are two of the most widely available tests when using automated methods, and laboratories usually combine one of these tests with the prothrombin time (PT) and activated partial thromboplastin time as part of a coagulation screen test set for general screening of hemostasis. The fibrinogen Clauss assay is a clotting-based functional assay that measures the clotting time after adding a high concentration of thrombin, whereas the derived fibrinogen test result is extrapolated when running a PT assay (at no extra cost) in several coagulation platforms using optical endpoint detection systems such as the Werfen IL (Werfen, MA, USA) and Sysmex analyzers (Sysmex Corporation, Kobe, Japan), which may explain why it is still widely used worldwide despite some reports showing it may overestimate the fibrinogen levels in a variety of clinical settings.[5],[6] The fibrinogen Clauss assay is perhaps the most well established fibrinogen assay, and it is the method of choice in clinical laboratories in the UK.[2] This report aims to establish the levels at which a functional assay must be performed to ensure that low fibrinogen results are accurately identified in laboratories that use a derived fibrinogen method for screening fibrinogen levels.

Samples referred for coagulation screen test were tested over a 3-month period. A total of 1875 venous blood samples collected into 2.7 mL anticoagulated BD vacutainer tubes containing 0.109 mol/3.2% tri-sodium citrate (BD, Oxford, UK), spun at 4000 rpm for 4 min prior to analysis, were screened for fibrinogen levels (as per local policy) using the PT-derived fibrinogen method on the Werfen IL ACL TOP 500 coagulation analyzer (Werfen, MA, USA). Samples showing a derived fibrinogen level of <3.0 g/L were immediately tested by the fibrinogen Clauss assay. Both tests were performed on fresh blood samples within 4 h of collection. Specimens showing evidence of hemolysis or lipemia as well as under- or overfilled specimens were rejected as per local policy. The statistical analysis of the data was performed using the Statistical Package for the Social Sciences version 16.0 (SPSS, Chicago, IL, USA) and probability (P) < 0.05 was considered significant.

During the period of this audit, 1875 clotting screen samples were tested and a total of 135 samples showed a derived fibrinogen level of <3.0 g/L. [Table 1] shows the fibrinogen results obtained per method in the latter group, and the number of samples with low fibrinogen levels (<1.5 g/L) per method.
Table 1: Fibrinogen levels estimated by various methods, and number of samples showing low fibrinogen levels

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We found 0.72 ± 0.02 g/L [95% confidence interval (CI) 0.67–0.77] difference between the two methods (P < 0.001, Student’s t-test) at the lower end of fibrinogen results (group of samples showing derived fibrinogen <3.0 g/L). Nineteen patients presenting with low fibrinogen levels showed normal results by the derived fibrinogen method (52.8% of all patients with low fibrinogen level tested). On the basis of the range of samples tested, there was potential for falsely normal fibrinogen results being reported in about 1% of all clotting screens processed when using the derived fibrinogen method alone for screening of fibrinogen levels.

Our data show that using a derived fibrinogen cut-off level of 2.27 g/L allowed for approximately 95% of low fibrinogen results to be identified when using a screening model that consisted of a derived fibrinogen method as a first-line screening test supported by a Clauss assay for confirmation of abnormal results. An alternative approach (and perhaps the most effective option) is to run the derived test internally only with a reflex test automatically set-up to measure fibrinogen levels by a functional assay when the screening revealed a derived fibrinogen level of <2.27 g/L. This would address the recommendations set in the British Committee for Standards in Haematology guidelines because the derived method would be supported by a functional assay before a diagnosis or a management decision was made. This model may not be accurate in patients with dysfibrinogenemia as it may give normal results when tested by the derived fibrinogen method;[7] although only approximately 250 patients with dysfibrinogenemia have been reported in the literature, the majority of them were asymptomatic[8] and, therefore, less likely to pose a significant risk. A provision should be made to test all bleeding patients by a functional assay regardless of the derived fibrinogen result.

The suggested testing models may assist laboratories in identifying patients who may be at increased risk of bleeding due to low fibrinogen levels, which could otherwise be missed if testing centers were to stop screening for fibrinogen levels to reduce costs as a result of not being able to afford to offer a fibrinogen functional assay (or other suitable tests such as a sensitive thrombin clotting time) as part of routine clotting screens.

Acknowledgements

The author wishes to thank Justin Daws and Ian Burch for their technical assistance and valuable suggestions.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Hantgan R, Francis C, Marder V. Fibrinogen structure and physiology. In: Colman RW, Hirsh J, Marder VJ, Salzman EW, editors. Hemostasis and Thrombosis: Basic Principles & Clinical Practice. Philadelphia: JB Lippincott; 1994. p. 277-300.  Back to cited text no. 1
    
2.
Mackie IJ, Kitchen S, Machin SJ, Lowe GD. Guidelines on fibrinogen assays. Br J Haematol 2003;121:396-404.  Back to cited text no. 2
    
3.
Lowe GD, Rumley A, Mackie IJ. Plasma fibrinogen. Ann Clin Biochem 2004;41:430-40.  Back to cited text no. 3
    
4.
O’Shaughnessy DF, Atterbury C, Bolton Maggs P, Murphy M, Thomas D, Yates S et al. British Committee for Standards in Haematology, Blood Transfusion Task Force. Guidelines for the use of fresh-frozen plasma, cryoprecipitate and cryosupernatant. Br J Haematol 2004;126:11-28.  Back to cited text no. 4
    
5.
Lawrie AS, McDonald SJ, Purdy G, Mackie IJ, Machin SJ. Prothrombin time derived fibrinogen determination on Sysmex CA-6000. J Clin Pathol 1998;51:462-6.  Back to cited text no. 5
    
6.
Chitolie A, Mackie IJ, Grant D, Hamilton JL, Machin SM. Inaccuracy of the ’derived’ fibrinogen measurement. Blood Coagul Fibrinolysis 1994;5:955-7.  Back to cited text no. 6
    
7.
Miesbach W, Schenk J, Alesci S, Lindhoff-Last E. Comparison of the fibrinogen Clauss assay and the fibrinogen PT derived method in patients with dysfibrinogenemia. Thromb Res 2010;126:428-33.  Back to cited text no. 7
    
8.
Haverkate F, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on fibrinogen. Thromb Haemost 1995;73:151-61.  Back to cited text no. 8
    



 
 
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