D Dimer ve Preanalitik Hata Kaynakları
Synopsis
In this chapter titled "D-Dimer and Sources of Preanalytical Error" from the book "Current Biochemistry Studies II," the biochemical formation processes of the D-dimer biomarker within the framework of hemostasis and fibrinolysis mechanisms, its clinical application areas, current measurement methods, and preanalytical variables determining the accuracy of test results are thoroughly examined. D-dimer, generated through the conversion of fibrinogen into cross-linked fibrin polymers by thrombin and factor XIIIa, followed by degradation via plasmin, serves as a fundamental clinical parameter in the diagnosis and monitoring of conditions such as deep vein thrombosis, pulmonary thromboembolism, disseminated intravascular coagulation, and acute aortic aneurysm. The study presents a comparative overview of ELISA, ELFA, chemiluminescent (CLIA), latex-based immunoturbidimetric, and point-of-care (POC) testing methods in terms of sensitivity, specificity, turn-around times, device automation, and sample types. Focusing on the preanalytical phase responsible for approximately 60-70% of total laboratory errors, the chapter details phlebotomy needle gauges, sodium citrate anticoagulant fill ratios, butterfly set and tourniquet application durations, sample transport via pneumatic tube systems, centrifugation speeds, and storage stability conditions. Furthermore, the impacts and tolerance limits of major spectrophotometric and biological interference sources—such as in vitro hemolysis, lipemia, and hyperbilirubinemia—on D-dimer test results are explained in accordance with international guidelines.
References
Linkins LA, Takach Lapner S. Review of d-dimer testing: Good, bad, and ugly. Int J Lab Hematol. 2017;39 Suppl 1:98-103.
Blomback B. Fibrinogen and fibrin--proteins with complex roles in hemostasis and thrombosis. Thromb Res. 1996;83(1):1-75.
Medved L, Nieuwenhuizen W. Molecular mechanisms of initiation of fibrinolysis by fibrin. Thromb Haemost. 2003;89(3):409-19.
Lip GY, Lowe GD. Fibrin D-dimer: A useful clinical marker of thrombogenesis? Clin Sci (Lond). 1995;89(3):205-14.
Favresse J, Lippi G, Roy PM, Chatelain B, Jacqmin H, Ten Cate H, et al. D-dimer: Preanalytical, analytical, postanalytical variables, and clinical applications. Crit Rev Clin Lab Sci. 2018;55(8):548-77.
Thachil J, Lippi G, Favaloro EJ. D-dimer testing: Laboratory aspects and current issues. Methods Mol Biol. 2017;1646:91-104.
Haase C, Joergensen M, Ellervik C, Joergensen MK, Bathum L. Age- and sex-dependent reference intervals for D-dimer: Evidence for a marked increase by age. Thromb Res. 2013;132(6):67680.
https://www.siemens-healthineers.com/tr/point-of-care-testing/featured-topics-in-poct/cardiac-featured-topics/d-dimer-testing (25.08.2021).
Riley RS, Gilbert AR, Dalton JB, Pai S, McPherson RA. Widely used types and clinical applications of D-dimer assay. Lab Med. 2016;47(2):90-102.
Greenberg CS, Devine DV, McCrae KM. Measurement of plasma fibrin D-dimer levels with the use of a monoclonal antibody coupled to latex beads. Am J Clin Pathol. 1987;87(1):94-100.
Adam SS, Key NS, Greenberg CS. D-dimer antigen: Current concepts and future prospects. Blood. 2009;113(13):2878-87.
Pittet JL, de Moerloose P, Reber G, Durand C, Villard C, Piga N, et al. Vidas D-dimer: Fast quantitative elisa for measuring D-dimer in plasma. Clin Chem. 1996;42(3):410-5.
Lippi G, Salvagno GL, Rossi L, Montagnana M, Franchini M, Guidi GC. Analytical performances of the D-dimer assay for the Immulite 2000 automated immunoassay analyser. Int J Lab Hematol. 2007;29(6):415-20.
Lippi G, Ippolito L, Russello T, Ponzo V, Salvagno GL, Guidi GC. Analytical performance of the new ACL AcuStar HemosIL D-dimer. Blood Coagul Fibrinolysis. 2012;23(2):164-7.
Helmersson-Karlqvist J, Karlsson B, Fredriksson A, Larsson A. Evaluation of the Alere D-dimer test for point of care testing. J Thromb Thrombolysis. 2014;38(2):250-2.
Plebani M. Errors in clinical laboratories or errors in laboratory medicine? Clin Chem Lab Med. 2006;44(6):750-9.
Plebani M. The detection and prevention of errors in laboratory medicine. Ann Clin Biochem. 2010;47(Pt 2):101-10.
Lippi G, Franchini M, Montagnana M, Salvagno GL, Poli G, Guidi GC. Quality and reliability of routine coagulation testing: Can we trust that sample? Blood Coagul Fibrinolysis. 2006;17(7):513-9.
Magnette A, Chatelain M, Chatelain B, Ten Cate H, Mullier F. Pre-analytical issues in the haemostasis laboratory: Guidance for the clinical laboratories. Thromb J. 2016;14:49.
Loeffen R, Kleinegris MC, Loubele ST, Pluijmen PH, Fens D, van Oerle R, et al. Preanalytic variables of thrombin generation: Towards a standard procedure and validation of the method. J Thromb Haemost. 2012;10(12):2544-54.
CLSI. Collection, transport, and processing of blood specimens for testing plasma-based coagulation assays and molecular hemostasis assays. CLSI document H21-A5. 5th ed. Wayne, PA: Clinical and laboratory standards institute; 2008.
Favaloro EJ, Funk DM, Lippi G. Pre-analytical variables in coagulation testing associated with diagnostic errors in hemostasis. Lab Med. 2012;43(2):1-10.
Schutgens RE, Haas FJ, Ruven HJ, Spannagl M, Horn K, Biesma DH. No influence of heparin plasma and other (pre)analytic variables on D-dimer determinations. Clin Chem. 2002;48(9):1611-3.
Lippi G, Salvagno GL, Guidi GC. No influence of a butterfly device on routine coagulation assays and D-dimer measurement. J Thromb Haemost. 2005;3(2):389-91.
Le Quellec S, Paris M, Nougier C, Sobas F, Rugeri L, Girard S, et al. Pre-analytical effects of pneumatic tube system transport on routine haematology and coagulation tests, global coagulation assays and platelet function assays. Thromb Res. 2017;153:7-13.
Wallin O, Soderberg J, Grankvist K, Jonsson PA, Hultdin J. Preanalytical effects of pneumatic tube transport on routine haematology, coagulation parameters, platelet function and global coagulation. Clin Chem Lab Med. 2008;46(10):1443-9.
Toulon P, Metge S, Hangard M, Zwahlen S, Piaulenne S, Besson V. Impact of different storage times at room temperature of unspun citrated blood samples on routine coagulation tests results. Results of a bicenter study and review of the literature. Int J Lab Hematol. 2017;39(5):458-68.
Salvagno GL, Lippi G, Bassi A, Poli G, Guidi GC. Prevalence and type of pre-analytical problems for inpatients samples in coagulation laboratory. J Eval Clin Pract. 2008;14(2):351-3.
Lippi G, Avanzini P, Zobbi V, Ippolito L. Influence of mechanical hemolysis of blood on two D-dimer immunoassays. Blood Coagul Fibrinolysis. 2012;23(5):461-3.
Lippi G, Plebani M, Favaloro EJ. Interference in coagulation testing: Focus on spurious hemolysis, icterus, and lipemia. Semin Thromb Hemost. 2013;39(3):258-66.
Türk Biyokimya Derneği. Koagülasyon testlerinde preanalitik evre kılavuzu. 2020-Ankara.
La’ulu SL, Dominguez CM, Roberts WL. Performance characteristics of the AxSYM D-dimer assay. Clin Chim Acta. 2008;390(1-2):148-51.