David L. McGlasson, MS, MLS(ASCP)

A few months ago, I posted on LinkedIn that I noticed at recent conferences and journal articles that blood coagulation factors were sometimes referred to in Euro-Arabic numbers (E-A), 0 through 9, instead of Roman numerals.  For example, “F8” was written instead of “FVIII”.  And sometimes they are used interchangeably. I received many comments and suggestions from many laboratorians who are dealing with this issue.

In my literature searches I have not been able to determine if this practice has been officially proposed as a change by any standardization committee. I was trying to picture the coagulation cascade in E-A numerals.  How would you order an anti-Factor Xa (anti-FXa)?  Would you order an anti-F10a assay?

A few years ago, I described a real-world scenario performing PT/INR, APTT, fibrinogen and D-dimer assays when I got the request for a Factor X (FX) level from the surgical ICU unit. Immediately I suspected this to be an incorrect request since true FX deficiencies are rare. I was sure that the ordering physician wanted an anti-Xa assay for heparin measurement. I inquired, “Does the patient have vitamin K deficiency, ingested old style rat poison, overdose of warfarin or is there some other coagulation problem? What kind of anticoagulant drug are you monitoring?” The voice on the other end of the line said the subject was on heparin and they needed a Factor X, pronouncing it “Factor Ex”, level stat. I was able to figure out that they really wanted a chromogenic anti-Factor Xa (anti-Xa) level, a test used to measure heparin. I asked what type of heparin the patient was receiving: “Are they on unfractionated heparin (UFH) or on a low molecular weight heparin (LMWH) such as enoxaparin?” The voice said, “I don’t know they are getting some type of heparin.” So, we determined that an anti-Xa assay was needed.

This occurred despite the Laboratory and Pharmacy departments sending many communications on how to order this assay when the physicians wanted a test to quantitate the amount of heparinoids present.  We also told the unit to list the type of heparin to be measured.  At the time the laboratory had to use specific calibrators for each type of heparin instead of using a single calibration system for determining heparin measurements.1,2 However, to this day we still get the anti-FXa test used for monitoring heparinoids confused with a FX assay.

It gets more confusing because the FX assay can be performed by a clotting or chromogenic assay and has nothing to do with monitoring heparin.  It is primarily used when determining levels of warfarin when the International Normalized Ratio (INR) is unreliable such as when a patient has interfering antiphospholipid antibodies.

Now some individuals are changing their numerical system from Roman numerals to E-A numerals to identify coagulation Factors I – XIII.

In the mid-1950s it became apparent that a standardized unification needed to be established to name coagulation factor proteins. Sometimes different laboratories identified the same factor and gave them different identifications. For example, FVII had thirteen different names in 1954. FVIII had at least eight names.  FIX was identified by six different names and FX by two names. Some of these are still used today. Chaos reigned at the time.

The Nomenclature of Blood Clotting Factors details how in 1954 the International Committee for the Nomenclature of Blood Clotting Factors was formed with a primary objective to develop a standardized set of scientific terminology for the coagulation factors referred to in the literature.

The committee that was assembled worked until 1963 to establish FI – FXIII nomenclature.  They decided Roman numerals were the preferred identifiers. Each factor had been defined as separate and distinct by specific, physical, biochemical, chemical, and physio-pathological properties.  They also came up with the idea to use a synonym for each factor4.

Factor I Fibrinogen
Factor II Prothrombin
Factor III Thromboplastin
Factor IV Calcium
Factor V Ac-Globulin, pro-accelerin
Factor VII Proconvertin, Spca
Factor VIII Antihemophilic Factor
Factor IX Plasma thromboplastin component-PTC
Factor X Stuart-Prower Factor
Factor XI Plasma thromboplastin antecedent-PTA

 

Clotting factor number Clotting factor name Function Plasma half-life (h) Plasma concentration (mg/L)
I Fibrinogen Clot formation 90 3000
II Prothrombin Activation of I, V, VII, VIII, XI, XIII, protein C, platelets 65 100
III TF Co factor of VIIa
IV Calcium Facilitates coagulation factor binding to phospholipids
V Proacclerin, labile factor Co-factor of IX-tenase complex 15 10
VI Unassigned
VII Stable factor, proconvertin Activates X: Forms tenase complex with factor VIII 5 0.5
VIII Antihaemophilic factor A Co-facotr of IX-tenase complex 10 0.1
IX Antihaemophilic factor B or Christmas factor Prothrombinase complex with factor V: Activates factor II 25 5
X Stuart-Prower factor Activates factor II 40 10
XI Plasma thromboplastin antecendent Activates factor IX 45 5
XII Hageman factor Activates factor XI, VII and prekallikrein
XIII Fibrin-stabilising factor Crosslinks fibrin 200 30
XIV Prekallikrein (F Fletcher) Serine protease zymogen 35
XV HMWK- (F Fitgerald) Co factor 150
XVI vWf Binds to VIII, mediates platelet adhesion 12 10 μg/mL
XVII Antithrombin III Inhibits IIa, Xa, and other proteases 72 0.15-02 mg/mL
XVIII Heparin cofactor II Inhibits IIa 60
XIX Protein C Inactivates Va and VIIIa 0.4
XX Protein S Cofactor for activated protein C

HMWK – High molecular weight kininogen; vWf – Von Willebrand factor; TF – Tissue factor

 

In the table above from Palta S., Palta A., and Saroa R, Overview of the Coagulation System, the authors attached Roman numerals to all components of most of the coagulation factors.  As you can see, they added XIV though XX for even the naturally occurring anticoagulants.5  This is the only article I could find that used any Roman numerals past FXIII.

A great article that deals with this is called Laboratory Test Names Matter.6   It discusses the issues that health care providers have trying to decode laboratory test names that adhere to standardized rules6.

Some institutions are using a different identification system for these coagulation factor proteins.  Many Laboratory Information Systems (LIS) have opted to use the E-A numbers for test ordering with more test information.3

So, I started out with the issue of problems ordering an anti-FXa assay for measuring heparin and I am kind of ending with that note.

I checked with different laboratories that had both the Cerner and Epic LIS systems and found that they could be adapted or programmed to use either the Arabic or Roman numeral nomenclature. The Hamilton Regional Laboratory Medicine Program (HRLMP) guidelines did that in some instances as seen in the table below.

We need to get some standardization accomplished, CLOTTERS!

Table: Example of coagulation cascade with suggested testing using Euro-Arabic numbers 

Hamilton Regional Laboratory Medicine Program (HRLMP) Laboratory Test Information Guide, Provided by: Karen A. Moffat  BEd, MSc, ART, FCSMLS(D), Technical Specialist, Special Coagulation, HRLMP, Associate Professor, Division of Hematology and Thromboembolism, Department of Medicine, McMaster University Associate Member, Department of Pathology and Molecular Medicine, McMaster University.

 

Factor II Assay Biological F2, F2B, Prothrombin level
Factor II ECHIS F2E
Factor IX Assay Factor 9
Factor IX Inhibitor Factor IX Inhibitor – Human (Bethesda)
Factor IX PEGylated Rebinyn, N9-GP
Factor V Assay F5
Factor V Leiden Genetic Testing genotyping, FV, PCR, F5
Factor VII Assay F7
Factor VIII Assay Factor VIII:C for Hemophilia, Factor VIII:C, Factor 8, F8
Factor VIII Chromogenic 2 stage factor VIII assay, Chromogenic FVIII
Factor VIII Inhibitor Factor VIII Inhibitor – Human (Bethesda)
Factor VIII Inhibitor Chromogenic
Factor VIII Jivi Jivi
Factor X Assay F10
Factor XI Assay F11
Factor XII Assay F12
Factor XIII Activity Factor XIII Functional
Factor XIII Panel
Factor XIII Screen Urea Clot Solubility

 

This is an example of a Laboratory Information System HIS/LIS that has moved primarily to EU-Arabic numbers.  This is an effort to minimize clinician ordering errors.  Their hematologists and hemophilia clinic have supported this endeavor.

Let me know your opinion on their format – submit your comments at diapharma.com.

 

Example of coagulation cascade with suggested testing using Arabic numbers.

Laboratory Testing of the Coagulation Protein System

COAGULATION NOMENCLATURE

Contribution from Dr. Eric Salazar, MD. UT Health, Associate Professor, Pathology and Laboratory Services, San Antonio, TX. Oral presentation on DOAC reversal. Clot Club Seminar power point slide. Adapted by Dr. Wayne Chandler, MD. Retired. Pathologist at Houston Methodist. Houston Methodist St. Louis University School of Medicine. Bellaire, Texas, United States with permission. Reproduced with permission from

 

REFERENCES

  1. McGlasson DL. Monitoring Unfractionated Heparin and Low Molecular Weight Heparin Anticoagulation with an anti-Xa Chromogenic Assay using a Single Calibration Curve. Lab Medicine. 2005;36(5):297-299.
  2. McGlasson DL et al: Effects of Pre-analytical Variables on the anti-FXa Chromogenic Assay when Monitoring Unfractionated Heparin and Molecular Weight Heparin Anticoagulation.  Blood Coagulation and Fibrinolysis. 2005;16(3):173-176.
  3. Jaques LB. Nomenclature for Blood Clotting Factors. Canad. M. A. J. 1960;82:1327-1330.
  4. Wright IS. The Nomenclature of Blood Clotting Factors. Canad .M.A.J. 1962;373-374.
  5. Palta S., Palta A., and Saroa R. Overview of the coagulation system. Indian J of Anaesthesia. 2014;58(5):515-523.
  6. Carter AB, Berger AL, Schreiber R. Laboratory Test Names Matter.: A Survey on What Works and What Doesn’t for Orders and Results. 2023. Arch Pathol Lab Med doi10.5858/arpa.2021-0314-OA.

 

ML-00-01126Rev01