ms_08768480190V1.

FXI
Factor XI

cobas t 511
08768480190 54 System‑ID 07 2003 5
cobas t 711

English Reagent handling

System information The reagent in the cassette has been assembled into a ready‑for‑use unit
(cobas t pack).
Short name ACN (application code number) All information required for correct operation is available via the cobas link.
FXI 28430 Storage and stability
Intended use Store at 2‑8 °C.
Human plasma immuno‑depleted of Factor XI for the quantitative Store the cobas t pack upright.
determination of Factor XI activity in citrated plasma, based on the activated The unopened cobas t pack is stable up to the stated expiration date.
partial thromboplastin time (aPTT) assay, on the indicated cobas t
analyzers. Stability of the opened cobas t pack:
Summary on the cobas t analyzer for each vial: 8 hours after
Factor XI (FXI) is a 160 kDa homodimeric glycoprotein of 607 amino acids. reconstitution
Deficiency of FXI is called Hemophilia C. FXI is the zymogen of a serine
protease that is activated (FXIa) either by FXIIa or by thrombin, to form Do not freeze.
FXIa as feedback activation after the initial thrombin generation via the Specimen collection and preparation
FVIIa/TF pathway, or autocatalytically by FXIa.1,2 Only the specimens listed below were tested and found acceptable:
In addition to its role in activating FIX, FXIa also displays antifibrinolytic 3.2 % citrated human plasma
activity by indirectly promoting the activation of thrombin-activatable Use standard sampling tubes made of plastic or siliconized glass. Strictly
fibrinolysis inhibitor (TAFI), leading to reduced fibrinolysis and enhanced observe the ratio of blood (9 parts) to sodium citrate solution 0.11 M
clot stability.3 (1 part).7,8
Thus, FXI plays a dual role by both, helping to generate thrombin and The sample types listed were tested with a selection of sample collection
downregulating fibrinolysis. This is also consistent with findings of variable tubes that were commercially available at the time of testing, i.e. not all
bleeding phenotypes in FXI deficient patients, which are largely FXI available tubes of all manufacturers were tested. Sample collection systems
independent so that e.g. a more pronounced FVIIa/TF response or low from various manufacturers may contain differing materials which could
fibrinolytic activity could compensate for low FXI:C (clotting assay) levels.4 affect the test results in some cases. When processing samples in primary
Test principle tubes (sample collection systems), follow the instructions of the tube
FXI activity is determined with an aPTT‑type assay. In order to make FXI manufacturer.
activity rate‑limiting, the patient plasma is diluted and added to a factor Centrifuge 15 minutes at 2500 g or such that the platelet count is
FXI‑deficient human plasma, with a residual FXI activity < 1 % of the norm, < 10000 platelets/μL and assay samples within the given stability period.
whereas all other coagulation factors are present at levels typically > 50 %
of the norm. The resulting clotting time is interpreted using a calibration Stability:
curve, obtained with dilutions of a calibrator plasma mixed with FXI‑deficient at 15 ‑ 25 °C 4 hours
human plasma. The extent of aPTT correction is proportional to FXI activity
in the sample, which is determined quantitatively from the calibration curve. at -20 °C (± 5 °C) 28 days
Reagents - working solutions Frozen plasma aliquots should be thawed within 5 minutes at 37 °C in a
waterbath, homogenized by carefully mixing without foam formation. Assay
cobas t pack thawed samples within 2 hours. Do not refreeze samples.
R2 Lyophilized Factor XI immunodepleted human plasma Materials provided
R2 is in position A, B and C. See “Reagents – working solutions” section.
Precautions and warnings Materials required (but not provided)
For in vitro diagnostic use for health care professionals. Exercise the ▪ 07575297190, Global Cal, 5 x 1 mL
normal precautions required for handling all laboratory reagents.
▪ 07539355190, Con N, 20 x 1 mL
Infectious or microbial waste:
Warning: handle waste as potentially biohazardous material. Dispose of ▪ 07539665190, Con P, 20 x 1 mL
waste according to accepted laboratory instructions and procedures. ▪ 07153589190, aPTT, 600T
Environmental hazards: ▪ 07154984190, CC 25mM, 50 mL
Apply all relevant local disposal regulations to determine the safe disposal.
▪ 07155042190, Owren B, 50 mL
Safety data sheet available for professional user on request.
All human material should be considered potentially infectious. All products ▪ General laboratory equipment
derived from human blood are prepared exclusively from the blood of ▪ Distilled or deionized water
donors tested individually and shown to be free from HBsAg and antibodies • cobas t coagulation analyzer. See User Assistance of the analyzer
to HCV and HIV. The testing methods use assays that have been approved concerned for additionally required materials.
by the FDA or that are in compliance with the legal rules applicable to
placing in vitro diagnostic medical devices for human use on the market in Assay
the European Union. For optimum performance of the assay follow the directions given in this
However, as no testing method can rule out the potential risk of infection document. Refer to the appropriate User Assistance for analyzer‑specific
with absolute certainty, the material should be handled with the same level assay instructions.
of care as a patient specimen. In the event of exposure, the directives of the The performance of applications not validated by Roche is not warranted
responsible health authorities should be followed.5,6 and must be defined by the user.
Avoid foam formation in all reagents and sample types (specimens,
calibrators and controls). Calibration
For calibration, use calibrator as listed in the "Materials required (but not
provided)" section.

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ms_08768480190V1.0

FXI
Factor XI

Calibration frequency: full calibration must be performed Limit of Quantitation (LoQ) = 1.00 %
▪ after lot change of aPTT reagent or FXI-deficient plasma The Limit of Quantitation was determined in accordance with the CLSI
(Clinical and Laboratory Standards Institute) EP17‑A2 requirements.14
▪ every 6 months when using a specific aPTT reagent and FXI-deficient
plasma lot combination The Limit of Quantitation is defined as the lowest analyte concentration in a
sample that can be reproducibly measured with an intermediate precision
▪ as required following quality control procedures. CV of ≤ 20 %.
Traceability: This method has been standardized against the NIBSC
International plasma standard SSC/ISTH Secondary Coagulation Standard. Expected values
73.4 % ‑ 149 %
Quality control
These values correspond to the 2.5th and 97.5th percentiles of results
Controls are required for checking the accuracy and reproducibility of the obtained from a total of 200 human plasma samples.
results.
Each laboratory should investigate the transferability of the expected values
For quality control, use control kits as listed in the "Materials required (but to its own patient population and if necessary determine its own reference
not provided)" section. ranges.
The control intervals and limits should be adapted to each laboratory’s
individual requirements. It is recommended to perform quality control Specific performance data
always after lot calibration and subsequently at least every 8 hours Representative performance data on the analyzers are given below.
(corresponding to the reagent stability after reconstitution). Values obtained Results obtained in individual laboratories may differ.
should fall within the defined limits. Each laboratory should establish Precision
corrective measures to be taken if values fall outside the defined limits.
Repeatability and intermediate precision were determined using human
Follow the applicable government regulations and local guidelines for samples and controls in accordance with the CLSI (Clinical and Laboratory
quality control. Standards Institute) EP05 requirements (2 aliquots per run, 2 runs per day,
Calculation 21 days).15 The following results were obtained:
The cobas t analyzers automatically calculate the analyte activity of each Repeatability Intermediate
sample.
precision
Conversion factor: 100 % = 1 IU/mL.9,10
Sample Mean SD CV SD CV
Limitations - interference (%) (%) (%) (%) (%)
The effect of the following endogenous substances and pharmaceutical
compounds on assay performance was tested. No impact on results was Con N 88.9 1.70 1.9 2.60 2.9
observed up to the listed concentrations. Con P 33.9 0.595 1.8 1.03 3.0
Endogenous substances Plasma 1 6.61 0.157 2.4 0.224 3.4
Compound Concentration Plasma 2 20.6 0.321 1.6 0.538 2.6
Conjugated bilirubin 15 mg/dL Plasma 3 43.8 0.891 2.0 1.25 2.9
Unconjugated bilirubin 45 mg/dL Plasma 4 69.5 1.12 1.6 2.01 2.9
Hemoglobin 500 mg/dL Plasma 5 131 2.40 1.8 3.38 2.6
Intralipid 1000 mg/dL Method comparison
Criterion: Recovery within (±10 %) of the initial value. A comparison of the FXI assay on the cobas t 711 analyzer (y) with an
The impact of lipemia, hemoglobin and bilirubin was tested according to automated coagulation assay (x) gave the following correlation:
Glick.11 Number of samples measured: 120
Drugs: No interference was found at therapeutic concentrations using Deming16
common drug panels except for heparin.12,13
The fibrinolytic action of streptokinase alters the clotting time and thus the y = 1.027x + 0.00715
FXI activity. The presence of fondaparinux and direct thrombin inhibitors r = 0.997
such as argatroban, bivalirudin and dabigatran, or factor Xa inhibitors, such
as edoxaban, rivaroxaban, and apixaban, in the sample influences the The FXI activities using the FXI reagent were between 1.02 and 143 %.
assay results (reduced FXI activity) which can be of clinical importance. References
No significant interference was observed up to an oritavancin (Orbactiv) 1 Bolton-Maggs PH. Factor XI deficiency--resolving the enigma?
concentration of 15 mg/L. Hematology Am Soc Hematol Educ Program. 2009:97-105.
For diagnostic purposes, the results should always be assessed in 2 Emsley J, McEwan PA, Gailani D. Structure and function of factor XI.
conjunction with the patient’s medical history, clinical examination and other Blood. 2010 Apr 1;115(13):2569-77.
findings.
3 Bouma BN, Meijers JC. Fibrinolysis and the contact system: a role for
Extra wash cycle: The use of special wash steps is mandatory when factor XI in the down-regulation of fibrinolysis. Thromb Haemost. 1999
certain test combinations are run together on cobas t analyzers. Refer to Aug;82(2):243-50.
the latest version of the carry over evasion list found with the CLEAN and
Deproteinizer Method Sheets and the User Assistance for further 4 Wheeler AP, Gailani D. Why factor XI deficiency is a clinical concern.
instructions. Where required, special wash/carry over evasion cycles must Expert Rev Hematol. 2016 Jul;9(7):629-37.
be implemented prior to reporting results with this test. 5 Occupational Safety and Health Standards: Bloodborne pathogens.
Limits and ranges (29 CFR Part 1910.1030). Fed. Register.
Measuring range 6 Directive 2000/54/EC of the European Parliament and Council of
1.00‑150 % 18 September 2000 on the protection of workers from risks related to
exposure to biological agents at work.
For samples with concentrations > 150 up to 250 % FXI activity, the rerun
function decreases the sample volume by a factor of 5 and the results are 7 CLSI Document H21-A5, Vol.28, No.5, 2008. Collection, transport, and
automatically multiplied by this factor. processing of blood specimens for testing plasma-based coagulation
Lower limits of measurement assays and molecular hemostasis assays; approved guideline, 5th
edition.

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FXI
Factor XI

8 CLSI Document H3-A6. Procedures for the collection of diagnostic

blood specimens by venipuncture; approved standard - Sixth Edition,
vol. 27, No. 26, 2007.
9 Bristow AF, Barrowcliffe T, Bangham DR. Standardization of biological
medicines: the first hundred years, 1900-2000. Notes Rec R Soc Lond.
2006 Sep 22;60(3):271-89.
10 Hubbard AR. International biological standards for coagulation factors
and inhibitors. Semin Thromb Hemost. 2007 Apr;33(3):283-9.
11 Glick MR, Ryder KW, Jackson SA. Graphical Comparisons of
Interferences in Clinical Chemistry Instrumentation.
Clin Chem 1986;32:470-475.
12 Breuer J. Report on the Symposium “Drug effects in Clinical Chemistry
Methods”. Eur J Clin Chem Clin Biochem 1996;34:385-386.
13 Sonntag O, Scholer A. Drug interference in clinical chemistry:
recommendation of drugs and their concentrations to be used in drug
interference studies. Ann Clin Biochem 2001;38:376-385.
14 CLSI Document EP17-A2. Evaluation of Detection Capability for
Clinical Laboratory Measurement Procedures. Vol. 32, No. 8, 2012.
Approved standard, 2nd Edition.
15 CLSI Document EP05-A3. Evaluation of Precision of Quantitative
Measurement Procedures. Vol. 24, No. 25, 2014. Approved guideline,
3rd Edition.
16 Martin RF. General Deming Regression for Estimating Systematic Bias
and its Confidence Interval in Method Comparison Studies. Clinical
Chemistry 2000;46(1):100-104.
A point (period/stop) is always used in this Method Sheet as the decimal
separator to mark the border between the integral and the fractional parts of
a decimal numeral. Separators for thousands are not used.
For further information, please refer to the appropriate User Assistance for
the relevant analyzer and Method Sheets of all necessary components.
Any serious incident that has occurred in relation to the device shall be
reported to the manufacturer and the competent authority of the Member
State in which the user and/or the patient is established.
Symbols
Roche Diagnostics uses the following symbols and signs in addition to
those listed in the ISO 15223‑1 standard (for USA: see [Link] for
definition of symbols used):
Contents of kit
Analyzers/Instruments on which reagents can be used
Reagent
Calibrator
Volume for reconstitution
GTIN Global Trade Item Number

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