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Hamostaseologie 2022; 42(06): 381-389
DOI: 10.1055/a-1945-9490
Review Article

Reference Intervals in Coagulation Analysis

Jens Müller
1   Institute of Experimental Hematology and Transfusion Medicine, University Hospital Bonn, Bonn, Germany
,
Martin Büchsel
2   Institute of Clinical Chemistry and Laboratory Medicine, Medical Center, Faculty of Medicine, University of Freiburg, Freiburg, Germany
,
Michael Timme
3   Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany
,
Urban App
4   Siemens Healthcare GmbH, Eschborn, Germany
,
Wolfgang Miesbach
5   Medical Clinic 2, Institute of Transfusion Medicine, University Hospital Frankfurt, Frankfurt, Germany
,
Ulrich J. Sachs
6   Department of Thrombosis and Hemostasis, Giessen University Hospital, Giessen, Germany
7   Institute for Clinical Immunology and Transfusion Medicine, Justus Liebig University, Giessen, Germany
,
Michael Krause
8   Center of Hemostasis, MVZ Labor Dr. Reising-Ackermann und Kollegen, Leipzig, Germany
,
Ute Scholz
8   Center of Hemostasis, MVZ Labor Dr. Reising-Ackermann und Kollegen, Leipzig, Germany
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Abstract

Blood coagulation analysis is characterized by the application of a variety of materials, reagents, and analyzers for the determination of the same parameter, or analyte, by different laboratories worldwide. Accordingly, the application of common reference intervals, that, by definition, would represent a “range of values (of a certain analyte) that is deemed normal for a physiological measurement in healthy persons,” is difficult to implement without harmonization of procedures. In fact, assay-specific reference intervals are usually established to allow for the discrimination of normal and abnormal values during evaluation of patient results. While such assay-specific reference intervals are often determined by assay manufacturers and subsequently adopted by customer laboratories, verification of transferred values is still mandatory to confirm applicability on site. The same is true for reference intervals that have been adopted from other laboratories, published information, or determined by indirect data mining approaches. In case transferable reference intervals are not available for a specific assay, a direct recruiting approach may or needs to be applied. In comparison to transferred reference interval verification, however, the direct recruiting approach requires a significantly higher number of well-defined samples to be collected and analyzed. In the present review, we aim to give an overview on the above-mentioned aspects and procedures, also with respect to relevant standards, regulations, guidelines, but also challenges for both, assay manufacturers and coagulation laboratories.

Zusammenfassung

Die Gerinnungsdiagnostik ist durch die Anwendung verschiedenster Reagenzien und Assays zur Bestimmung einzelner Analyten gekennzeichnet. Dementsprechend bedarf die Anwendung übergreifender, generischer Referenzintervalle, die per Definition einen “Wertebereich (eines bestimmten Analyten), der für eine physiologische Messung bei gesunden Personen als normal angesehen wird,” darstellen würden, einer entsprechenden Harmonisierung von Testverfahren. Somit werden in der Regel Assay-spezifische Referenzintervalle festgelegt, um eine Unterscheidung zwischen normalen und abnormalen Messwerten im Rahmen der Analyse von Patientenproben zu ermöglichen. Während entsprechende Referenzintervalle häufig von den Testherstellern ermittelt und anschließend von den anwendenden Laboren übernommen werden, bleibt eine Verifizierung der übertragenen Werte obligatorisch, um deren Anwendbarkeit vor Ort zu bestätigen. Das gleiche gilt für Referenzintervalle, die aus Veröffentlichungen oder von anderen Labors übernommen, oder aber durch indirekte (Data-Mining) Verfahren ermittelt wurden. Falls für einen bestimmten Assay keine übertragbaren Referenzintervalle verfügbar sind, kann (oder muss) ein direktes Rekrutierungsverfahren angewandt werden. Im Vergleich zur Verifizierung von übertragenen Referenzintervallen erfordert dieser direkte Ansatz jedoch eine wesentlich höhere Anzahl an zu analysierenden Proben gesunder Probanden. In der hier vorliegenden Arbeit soll ein Überblick über die vorgenannten Aspekte und Verfahren der Erhebung von Referenzintervallen geben werden. Dies auch im Hinblick auf einschlägige Normen, Vorschriften und Richtlinien, aber auch bezüglich der hiermit verbundenen Herausforderungen sowohl für Hersteller als auch Labore.

Keywords

coagulation analysis - reference intervals - direct approach - indirect approach

Schlüsselwörter

Gerinnungsdiagnostik - Referenzintervalle - Direkter Ansatz - Indirekter Ansatz


Publikationsverlauf

Eingereicht: 01. September 2022

Angenommen: 09. September 2022

Artikel online veröffentlicht:
22. Dezember 2022

© 2022. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

  • References

  • 1 CLSI. Defining, Establishing, and Verifying Reference Intervals in the Clinical Laboratory; Approved Guideline. 3rd ed. CLSI EP28–A3. Wayne, Pennsylvania: Clinical and Laboratory Standards Institute; 2010
    Google Scholar
  • 2 Castellone DD. Establishing reference intervals in the coagulation laboratory. Int J Lab Hematol 2017; 39 (Suppl. 01) 121-127
    CrossrefPubMedGoogle Scholar
  • 3 Ozarda Y, Sikaris K, Streichert T, Macri J. IFCC Committee on Reference intervals and Decision Limits (C-RIDL). Distinguishing reference intervals and clinical decision limits - a review by the IFCC Committee on Reference Intervals and Decision Limits. Crit Rev Clin Lab Sci 2018; 55 (06) 420-431
    CrossrefPubMedGoogle Scholar
  • 4 Tate JR, Yen T, Jones GR. Transference and validation of reference intervals. Clin Chem 2015; 61 (08) 1012-1015
    CrossrefPubMedGoogle Scholar
  • 5 Farrell CL, Nguyen L. Indirect reference intervals: harnessing the power of stored laboratory data. Clin Biochem Rev 2019; 40 (02) 99-111
    PubMedGoogle Scholar
  • 6 Zierk J, Arzideh F, Haeckel R, Rascher W, Rauh M, Metzler M. Indirect determination of pediatric blood count reference intervals. Clin Chem Lab Med 2013; 51 (04) 863-872
    CrossrefPubMedGoogle Scholar
  • 7 Neufassung der Richtlinie der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen – Rili-BÄK. Dtsch Arztebl 2019;116(51–52): A-2422/B-1990/C-1930
    PubMedGoogle Scholar
  • 8 International Organization for Standardization. ISO 15189 Medical Laboratories - Requirements for Quality and Competence. 3rd ed. Geneva: The Organization; 2012
    Google Scholar
  • 9 Regulation (EU) 2017/746 of the European Parliament and of the Council of 5 April 2017 on in vitro diagnostic medical devices and repealing Directive 98/79/EC and Commission Decision 2010/227/EU. Offic J Eur Commun 2017; 117: 176-332
    PubMedGoogle Scholar
  • 10 Saris NE. The International Federation of Clinical Chemistry, IFCC Section (1978) no. 2. International Federation of Clinical Chemistry provisional recommendation on the theory of reference values (1978). Part 1. The concept of reference values. J Clin Chem Clin Biochem 1979; 17 (05) 337-339
    PubMedGoogle Scholar
  • 11 Solberg HE. International Federation of Clinical Chemistry. Scientific committee, Clinical Section. Expert Panel on Theory of Reference Values and International Committee for Standardization in Haematology Standing Committee on Reference Values. Approved recommendation (1986) on the theory of reference values. Part 1. The concept of reference values. Clin Chim Acta 1987; 165 (01) 111-118
    PubMedGoogle Scholar
  • 12 PetitClerc C, Solberg HE. International Federation of Clinical Chemistry (IFCC). Approved recommendation (1987) on the theory of reference values. Part 2. Selection of individuals for the production of reference values. Clin Chim Acta 1987; 170: S3-S12
    CrossrefPubMedGoogle Scholar
  • 13 Solberg HE, PetitClerc C. Approved recommendation (1988) on the theory of reference values. Part 3. Preparation of individuals and collection of specimens for the production of reference values. Clin Chim Acta 1988; 177 (03) S3-S11
    CrossrefPubMedGoogle Scholar
  • 14 Solberg HE, Stamm D. International Federation of Clinical Chemistry IFCC. IFCC recommendation – theory of reference values. Part 4. Control of analytical variation in the production, transfer and application of reverence values. Clin Chim Acta 1991; 202 (1-2): S5-S11
    CrossrefPubMedGoogle Scholar
  • 15 Solberg HE. International Federation of Clinical Chemistry (IFCC). Approved recommendation (1987) on the theory of reference values. Part 5. Statistical treatment of collected reference values. Determination of reference limits. Clin Chim Acta 1987; 170: S13-S32
    CrossrefPubMedGoogle Scholar
  • 16 Dybkœr R, Solberg HE. International Federation of Clinical Chemistry (IFCC). Approved recommendation (1987) on the theory of reference values. Part 6. Presentation of observed values related to reference values. Clin Chim Acta 1987; 170: S33-S42
    CrossrefPubMedGoogle Scholar
  • 17 Campbell C, Caldwell G, Coates P. et al. Consensus statement for the management and communication of high risk laboratory results. Clin Biochem Rev 2015; 36 (03) 97-105
    PubMedGoogle Scholar
  • 18 Asadollahi K, Hastings IM, Beeching NJ, Gill GV. Laboratory risk factors for hospital mortality in acutely admitted patients. QJM 2007; 100 (08) 501-507
    CrossrefPubMedGoogle Scholar
  • 19 Ozarda Y. Reference intervals: current status, recent developments and future considerations. Biochem Med (Zagreb) 2016; 26 (01) 5-16
    CrossrefPubMedGoogle Scholar
  • 20 CLSI and IFCC. C28–A3 Document; Defining, Establishing and Verifying Reference Intervals in the Clinical Laboratory: Approved Guideline. 3rd ed. 2008; 28: 1-76
    PubMedGoogle Scholar
  • 21 Ceriotti F, Hinzmann R, Panteghini M. Reference intervals: the way forward. Ann Clin Biochem 2009; 46 (Pt 1): 8-17
    CrossrefPubMedGoogle Scholar
  • 22 Directive 98/79/EC of the European Parliament and of the Council of 27 October 1998 on in vitro diagnostic medical devices. . Offic J Eur Commun 1998:L331/1–L331/37
    PubMedGoogle Scholar
  • 23 ISO 134585:2016. Medical devices – Quality management systems
    PubMed
  • 24 DIN EN 13612:2002–08. Performance Evaluation of In Vitro Diagnostic Medical Devices. Beuth. Accessed September 25, 2022 at: https://dx.doi.org/10.31030/9220711
    PubMed
  • 25 ISO 17511:2020. In Vitro Diagnostic Medical Devices – Requirements for Establishing Metrological Traceability of Values Assigned to Calibrators, Trueness Control Materials and Human Samples. Beuth. ICS 11.100.10.
    PubMed
  • 26 Solberg HE. A guide to IFCC recommendations on reference values. J Int Fed Clin Chem 1993; 5 (04) 162-165
    PubMedGoogle Scholar
  • 27 CLSI EP17–A2; Evaluation of Detection Capability for Clinical Laboratory Measurement Procedures; Approved Guideline. 2nd ed. Wayne, PA: Clinical and Laboratory Standards Institute; 2012
    Google Scholar
  • 28 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the full-term infant. Blood 1987; 70 (01) 165-172
    CrossrefPubMedGoogle Scholar
  • 29 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80 (08) 1998-2005
    CrossrefPubMedGoogle Scholar
  • 30 Appel IM, Grimminck B, Geerts J, Stigter R, Cnossen MH, Beishuizen A. Age dependency of coagulation parameters during childhood and puberty. J Thromb Haemost 2012; 10 (11) 2254-2263
    CrossrefPubMedGoogle Scholar
  • 31 Flanders MM, Crist RA, Roberts WL, Rodgers GM. Pediatric reference intervals for seven common coagulation assays. Clin Chem 2005; 51 (09) 1738-1742
    CrossrefPubMedGoogle Scholar
  • 32 Klarmann D, Eggert C, Geisen C. et al. Association of ABO(H) and I blood group system development with von Willebrand factor and Factor VIII plasma levels in children and adolescents. Transfusion 2010; 50 (07) 1571-1580
    CrossrefPubMedGoogle Scholar
  • 33 Andrew M, Paes B, Milner R. et al. Development of the human coagulation system in the healthy premature infant. Blood 1988; 72 (05) 1651-1657
    CrossrefPubMedGoogle Scholar
  • 34 Toulon P. Developmental hemostasis: laboratory and clinical implications. Int J Lab Hematol 2016; 38 (Suppl. 01) 66-77
    CrossrefPubMedGoogle Scholar
  • 35 Delbrück C, Haferland I, Scholz K. et al. Hämophilie-A-Patienten und Konduktorinnen für Hämophilie A. Steigt die FVIII-Aktivität mit dem Lebensalter?. [Does FVIII activity increase with age in patients with haemophilia A and carriers of haemophilia A?] Hamostaseologie 2011; 31 (Suppl. 01) S24-S28
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 36 Robert-Ebadi H, Robin P, Hugli O. et al. Impact of the age-adjusted D-dimer cutoff to exclude pulmonary embolism: a multinational prospective real-life study (the RELAX-PE Study). Circulation 2021; 143 (18) 1828-1830
    CrossrefPubMedGoogle Scholar
  • 37 Nah EH, Kim S, Cho S, Cho HI. Complete blood count reference intervals and patterns of changes across pediatric, adult, and geriatric ages in Korea. Ann Lab Med 2018; 38 (06) 503-511
    CrossrefPubMedGoogle Scholar
  • 38 Achila OO, Semere P, Andemichael D. et al. Biochemistry reference intervals for healthy elderly population in Asmara, Eritrea. BMC Res Notes 2017; 10 (01) 748
    CrossrefPubMedGoogle Scholar
  • 39 Huber KR, Mostafaie N, Stangl G. et al. Clinical chemistry reference values for 75-year-old apparently healthy persons. Clin Chem Lab Med 2006; 44 (11) 1355-1360
    CrossrefPubMedGoogle Scholar
  • 40 Siennicka A, Kłysz M, Chełstowski K. et al. Reference values of D-dimers and fibrinogen in the course of physiological pregnancy: the potential impact of selected risk factors - a pilot study. BioMed Res Int 2020; 2020: 3192350
    CrossrefPubMedGoogle Scholar
  • 41 Szecsi PB, Jørgensen M, Klajnbard A, Andersen MR, Colov NP, Stender S. Haemostatic reference intervals in pregnancy. Thromb Haemost 2010; 103 (04) 718-727
    Google Scholar
  • 42 Kourlaba G, Relakis J, Kontodimas S, Holm MV, Maniadakis N. A systematic review and meta-analysis of the epidemiology and burden of venous thromboembolism among pregnant women. Int J Gynaecol Obstet 2016; 132 (01) 4-10
    CrossrefPubMedGoogle Scholar
  • 43 Fu M, Liu J, Xing J. et al. Reference intervals for coagulation parameters in non-pregnant and pregnant women. Sci Rep 2022; 12 (01) 1519
    CrossrefPubMedGoogle Scholar
  • 44 Baboolall U, Zha Y, Gong X, Deng DR, Qiao F, Liu H. Variations of plasma D-dimer level at various points of normal pregnancy and its trends in complicated pregnancies: a retrospective observational cohort study. Medicine (Baltimore) 2019; 98 (23) e15903
    CrossrefPubMedGoogle Scholar
  • 45 Zhang GM, Zhang W, Zhang GM. Age-specific reference intervals for PT, aPTT, fibrinogen and thrombin time for parturient women. Thromb Haemost 2019; 119 (06) 894-898
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 46 Tang J, Lin Y, Mai H. et al. Meta-analysis of reference values of haemostatic markers during pregnancy and childbirth. Taiwan J Obstet Gynecol 2019; 58 (01) 29-35
    CrossrefPubMedGoogle Scholar
  • 47 Klajnbard A, Szecsi PB, Colov NP. et al. Laboratory reference intervals during pregnancy, delivery and the early postpartum period. Clin Chem Lab Med 2010; 48 (02) 237-248
    CrossrefPubMedGoogle Scholar
  • 48 Harris EK. Effects of intra- and interindividual variation on the appropriate use of normal ranges. Clin Chem 1974; 20 (12) 1535-1542
    CrossrefPubMedGoogle Scholar
  • 49 Shou W, Chen Q, Wu W, Cui W. Biological variations of lupus anticoagulant, antithrombin, protein C, protein S, and von Willebrand factor assays. Semin Thromb Hemost 2016; 42 (01) 87-92
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 50 Chen Q, Shou W, Wu W. et al. Biological and analytical variations of 16 parameters related to coagulation screening tests and the activity of coagulation factors. Semin Thromb Hemost 2015; 41 (03) 336-341
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 51 Banfi G, Del Fabbro M. Biological variation in tests of hemostasis. Semin Thromb Hemost 2009; 35 (01) 119-126
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 52 Xu P, Zhou Q, Xu J. Reference interval transference of common clinical biomarkers. Scand J Clin Lab Invest 2021; 81 (04) 264-271
    CrossrefPubMedGoogle Scholar
  • 53 CLSI. Measurement Procedure Comparison and Bias Estimation Using Patient Samples; Approved Guideline - Third Edition. CLSI EP09. Wayne, Pennsylvania: Clinical and Laboratory Standards Institute; 2018
    Google Scholar
  • 54 Lykkeboe S, Nielsen CG, Christensen PA. Indirect method for validating transference of reference intervals. Clin Chem Lab Med 2018; 56 (03) 463-470
    CrossrefPubMedGoogle Scholar
  • 55 Sikaris KA, Yen T. CALIPER: supporting the steps forward in paediatric laboratory measurement. Clin Biochem 2013; 46 (13-14): 1195-1196
    CrossrefPubMedGoogle Scholar
  • 56 Zierk J, Ganslandt T, Rauh M, Metzler M, Strasser E. Data mining of reference intervals for coagulation screening tests in adult patients. Clin Chim Acta 2019; 499: 108-114
    CrossrefPubMedGoogle Scholar
  • 57 Haeckel R, Wosniok W, Arzideh F. A plea for intra-laboratory reference limits. Part 1. General considerations and concepts for determination. Clin Chem Lab Med 2007; 45 (08) 1033-1042
    CrossrefPubMedGoogle Scholar
  • 58 Jones GRD, Haeckel R, Loh TP. et al; IFCC Committee on Reference Intervals and Decision Limits. Indirect methods for reference interval determination - review and recommendations. Clin Chem Lab Med 2018; 57 (01) 20-29
    CrossrefPubMedGoogle Scholar
  • 59 Weber GM, Kohane IS. Extracting physician group intelligence from electronic health records to support evidence based medicine. PLoS One 2013; 8 (05) e64933
    CrossrefPubMedGoogle Scholar
  • 60 Poole S, Schroeder LF, Shah N. An unsupervised learning method to identify reference intervals from a clinical database. J Biomed Inform 2016; 59: 276-284
    CrossrefPubMedGoogle Scholar
  • 61 Hoffmann RG. Statistics in the practice of medicine. JAMA 1963; 185: 864-873
    CrossrefPubMedGoogle Scholar
  • 62 Bhattacharya CG. A simple method of resolution of a distribution into gaussian components. Biometrics 1967; 23 (01) 115-135
    CrossrefPubMedGoogle Scholar
  • 63 Hoffmann G, Lichtinghagen R, Wosniok W. Ein einfaches Verfahren zur Schätzung von Referenzintervallen aus routinemäßig erhobenen Labordaten Simple estimation of reference intervals from routine laboratory data. J Lab Med 2015; 39 (06) 389-402
    PubMedGoogle Scholar
  • 64 Holmes DT. Correct implementation of the Hoffmann method. Clin Biochem 2019; 70: 49-50
    CrossrefPubMedGoogle Scholar
  • 65 Oosterhuis WP, Modderman TA, Pronk C. Reference values: Bhattacharya or the method proposed by the IFCC?. Ann Clin Biochem 1990; 27 (Pt 4): 359-365
    CrossrefPubMedGoogle Scholar
  • 66 Wosniok W, Haeckel R. A new indirect estimation of reference intervals: truncated minimum chi-square (TMC) approach. Clin Chem Lab Med 2019; 57 (12) 1933-1947
    CrossrefPubMedGoogle Scholar
  • 67 Kairisto V, Poola A. Software for illustrative presentation of basic clinical characteristics of laboratory tests – GraphROC for Windows. Scand J Clin Lab Invest Suppl 1995; 222: 43-60
    CrossrefPubMedGoogle Scholar
  • 68 Arzideh F, Wosniok W, Gurr E. et al. A plea for intra-laboratory reference limits. Part 2. A bimodal retrospective concept for determining reference limits from intra-laboratory databases demonstrated by catalytic activity concentrations of enzymes. Clin Chem Lab Med 2007; 45 (08) 1043-1057
    CrossrefPubMedGoogle Scholar
  • 69 Gindler EM. Calculation of normal ranges by methods used for resolution of overlapping Gaussian distributions. Clin Chem 1970; 16 (02) 124-128
    CrossrefPubMedGoogle Scholar