Abstract
For the monitoring of unfractionated heparin therapy (UFH) there are numerous pre-analytical, analytical and biological variables associated with the use of activated partial thromboplastin time (APTT), so the traditional range of 1.5-2.5 times the baseline value can lead to inadequate heparinization, resulting in thrombosis. Guidelines recommend to obtain the heparin therapeutic range (HTR) with ex vivo samples from patients under continuous heparin infusion therapy, measuring heparinemia by anti-Xa assay, since when in vitro UFH spiked plasmas are used, an overestimation of the therapeutic range is noted. The objective of this study was to compare the results of HTR obtained using ex vivo samples and in vitro heparin spiked normal plasma samples. HTR for ex vivo samples resulted in 56-87 sec by anti-Xa assay. For in vitro spiked samples HTR was 55-127 sec. Using an alternative in vitro protocol correlating the APTT with UFH concentration between 0.2 and 0.4 IU/ ml, the HTR was 55-85 sec. The results also showed that there is an overestimation of HTR with the in vitro protocol especially at high concentrations, whereas the lower value of the range does not have significant differences when we compared both methods. Laboratories that do not have anti-Xa assay could obtain an estimate of the lower value of the HTR with an alternative protocol in vitro.
References
2. Lindahl U, Bäckström G, Höök M y col. Structure of the Antithrombin-Binding Site in Heparin. Proc Natl Acad Sci USA. 1979; 76: 3198–3202.
3. Oosta GM, Gardner WT, Beeler DL y col. Multiple Functional Domains of the Heparin Molecule. Proc Natl Acad Sci USA. 1981; 78:829–833.
4. Nakkache M, Martinuzzo M. Control de la terapia anticoagulante con heparina. Fundamentos para el manejo práctico en el laboratorio de hemostasia. Grupo Cooperativo Argentino de Hemostasia y Trombosis (Grupo CAHT). Segunda Edición. Cap 7. Pág 346-354.
5. Lane DA, Denton J, Flynn AM y col. Anticoagulant Activities of Heparin Oligosaccharides and Their Neutralization by Platelet Factor 4. Biochem J. 1984; 218: 725–732.
6. Adcock D, Moser K. Mechanism and Monitoring of Anticoagulant agents. An Algorithmic Approach to Hemostasis Testing. Second edition. CAP Press eBooks. Kandice Kottke-Marchant Editor. 2016; Cap 28: p 39-40.
7. Rosa CM, Burdet J. Monitoreo de la terapia con heparina no fraccionada: el APTT tradicional versus la heparinemia por anti-Xa. Hematología. 2017; 21(1): 86-92. http://www.sah.org.ar//revista/index.asp.
8. Kitchen S, Preston FE. The therapeutic range for heparin therapy: relationship between six activated partial thromboplastin time reagents and two heparin assays. Thromb Haemost.
1996 May; 75(5): 734-9.
9. Olson JD, Arkin CF, Brandt JT y col. College of American Pathologists Conference XXXI on laboratory monitoring of anticoagulant therapy: laboratory monitoring of unfractionated
heparin therapy. Arch Pathol Lab Med. 1998; 122:782-798.
10. College of American Pathologists (CAP). Heparin Therapeutic Range. HEM.23453. Phase I. Revised 07/29/2013.
11. Smythe MA, Priziola J, Dobesh P y col. Guidance for the practical management of the heparin anticoagulants in the treatment of venous thromboembolism. J Thromb Thrombolysis.
2016; 41: 165-186.
12. Marlar RA, Clement B, Gausman J. Activated partial thromboplastin time monitoring of unfractionated heparin therapy: issues and recommendations. Semin Thromb Hemost. 2016;
43(3): 253-260.
13. Marlar RA, Gausman JN. The effect of instrumentation and laboratory site on the accuracy of the APTT-based heparin therapeutic range. Int J Lab Hematol. 2012 Dec; 34(6): 614-20.
14. Vandiver JW, Vondracek TG. Antifactor Xa Levels versus Activated Partial Thromboplastin time for monitoring Unfractionated Heparin. Pharmacotherapy. 2012; 32(6):546-558.
15. McGlasson DL, Kaczor DA, Krasuski RA y col. Effects of pre-analytical variables on the anti-activated factor X chromogenic assay when monitoring unfractionated heparin and low molecular weight heparin anticoagulation. Blood Coagul Fibrinolysis. 2005 Apr; 16(3):173-6.
16. Guervill DJ, Rosenberg AF, Winterstein AG y col. Activated Partial Thromboplastin Time Versus Antifactor Xa Heparin Assay in Monitoring Unfractionated Heparin by Continuous
Intravenous Infusion. Ann Pharmacother. 2011; 45:861-8.
17. Lehman CM, Frank EL. Laboratory monitoring of heparin therapy: partial thromboplastin time or anti-Xa assay? Labmedicine.com. CE Update Jan 2009; 40: 47-51.
18. Eikelboom JW, Hirsh J. Monitoring unfractionated heparin with the aPTT: time for a fresh look. Thromb Haemost. 2006; 96:547-552.
19. Mariné L, Sánchez G, Vargas J.F. y col. Correlación de valores de TTPa con anti factor Xa para establecer rango terapéutico en tratamiento anticoagulante con heparina sódica. Rev. Med.
Chile. 2014;142: 1392-1397.
20. Byun J-H, Jang I-S, Kim JW y col. Establishing the heparin therapeutic range using aPTT and anti-Xa measurements for monitoring unfractionated heparin therapy. Blood Res. 2016; 51: 171-4.
21. Wayne, PA. CLSI. One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test; Approved Guideline. 2nd ed. CLSI document H47–A2. Clinical and Laboratory Standards Institute; 2008 20.
22. Olson JD. How to validate heparin sensitivity of the aPTT. CAP Today 2004; 18:72-78.
23. Price EA, Jin J, Nguyen H y col. Discordant aPTT and Anti-Xa values and Outcomes in Hospitalized Patients Treated with Intravenous Unfractionated Heparin. Ann Pharmacother- 2013; 47:151-158.
24. Cheluja MG, Lorenzón MV, D´Adamo A y col. Cálculo del rango terapéutico de APTT para el tratamiento con Heparina no Fraccionada. Poster Xº Congreso Argentino de Hemostasia y Trombosis del Grupo CAHT. 2016.
All material published in the journal HEMATOLOGÍA (electronic and print version) is transferred to the Argentinean Society of Hematology. In accordance with the copyright Act (Act 11 723), a copyright transfer form will be sent to the authors of approved works, which has to be signed by all the authors before its publication. Authors should keep a copy of the original since the journal is not responsible for damages or losses of the material that was submitted. Authors should send an electronic version to the email: revista@sah.org.ar
