November 2024: Does your coagulation laboratory need help?
by Donna Castellone • November 05, 2024
Coagulation is complex enough in itself, but there are also many other rules and standards that need to be followed. There are also regulations from governing agencies and possibly from your state. The difference between standards and guidelines is that standards require strict adherence (uses must) where guidelines offer recommendations and are not always mandatory (uses may). Guidelines are developed by peers and are evidence based. Some may even use a grading system to demonstrate how important are certain recommendations.
Where do you go to get answers? How do I create a coagulation laboratory that provides quality results, that are reproducible and the optimum results to provide to the clinician for both diagnosis and treatment of coagulopathies. Here is a directory of several of the guidelines that can be used and accessed for the coagulation laboratory.
Pre-Analytical:
International Council for Standardization in Haematology (ICSH) recommendations for processing of blood samples for coagulation testing
Steve Kitchen, Dorothy M Adcock, Ray Dauer, Ann-Helen Kristoffersen, Giuseppe Lippi, Ian Mackie, Richard A Marlar, Sukesh Nair
The International Council for Standardization in Hematology (ICSH) provides this guidance to aid in laboratories processing citrated blood samples throughout the world. The guidance includes: sample transport (including pneumatic tube systems), clots, centrifugation, primary tube storage and stability, interfering substances (haemolysis, icterus, lipemia), secondary aliquot transport, storage and processing, as well a preanalytical variables for platelet function testing. Recommendations are based on published data in peer reviewed literature and expert opinion.
To Access: https://onlinelibrary.wiley.com/doi/10.1111/ijlh.13702
https://www.icsh.org/publications
Collection, Transport, and Processing of Blood Specimens for Testing Plasma-Based Coagulation Assays, 6th Edition, CLSI H21. 2024
CLSI H21 provides procedures for collecting, transporting, and storing blood, processing blood specimens, storing plasma for coagulation testing, and general recommendations for performing the tests. Coagulation samples are susceptible to preexamination errors which can include those resulting from specimen collection and mixing, storage, transport, patient variability and exogenous interferences.
To Access information for purchasing: https://clsi.org/standards/products/hematology/documents/?page=12&sort=FriendlyCode&sortdir=asc&subcat=&area=Documents
International Council for Standardisation in Haematology (ICSH) recommendations for collection of blood samples for coagulation testing
Robert C. Gosselin, CLS, Donna Castellone, MS, MASCP, MT (ASCP) SH, Akbar Dorgalaleh, PhD, Kieron Hickey, Giuseppe Lippi, MD, Karen Moffat, BEd, MSc, ART, FCSMLS(D), Rebecca O’Toole, MSc, Joe Rigano, BAppSci (MLS) (Dis), FAIMS
15 November 2023 Seminars in Thrombosis & Hemostasis Vol. 50 No. 8/2024
Laboratories should determine the performance of new reagents to ensure there is no significant shift in reagent performance or reporting of patient data. This guidance comes from ICSH to provide assistance in evaluating and verifying the performance of new lots of reagents used for coagulation testing. Recommendations are based on GLP, regulatory recommendations, scientific publications and expert opinions.
To Access: https://www.thieme-connect.com/products/ejournals/pdf/10.1055/s-0043-1776405.pdf
TESTING:
Guidelines on the laboratory aspects of assays used in haemostasis and thrombosis
Peter Baker, Sean Platton, Claire Gibson, Elaine Gray, Ian Jennings, Paul Murphy, Mike Laffan, On behalf of British Society for Haematology, Haemostasis and Thrombosis Task Force
14 June 2020 British Journal of Hematology
This guideline is intended to help clinical laboratories perform high quality valid assays for the basic procoagulants and anticoagulants as part of a routine diagnostic service.
To Access: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.16776?msockid=01e56ca7a40a674a2e307f25a5806637
CLSI H47: One-Stage Prothrombin Time (PT) Test and Activated Partial Thromboplastin Time (APTT) Test, 3rd Edition
This document provides guidelines for performing the PT and APTT tests in the clinical laboratory, for reporting results, and for identifying sources of error. It describes the principles and procedures for the routine PT and aPTT using citrated plasma. These are important screening tests used in the evaluation of disorders of coagulation. This guideline is to improve test reproducibility through standardization of techniques.
To Access for purchase: https://clsi.org/standards/products/hematology/documents/?page=2&sort=FriendlyCode&sortdir=asc&subcat=&area=Documents
International Council for Standardization in Haematology Field Study Evaluating Optimal Interpretation Methods for Activated Partial Thromboplastin Time and Prothrombin Time Mixing Studies
Robert C. Gosselin, CLS; Gary W. Moore, BSc, DBMS; Geoffrey W. Kershaw, FAIMS; Silmara Montalvão, PhD;, Dorothy M. Adcock, MD
This guidance document aids laboratories in defining an optimal method for determining correction or noncorrection of plasma mixing tests. When the prothrombin time (PT) and activated partial thromboplastin time (APTT) are prolonged is often evaluated using a mixing test with normal plasma. Failure to correct ("noncorrection") prolongation upon mixing is attributed to an inhibitor, whereas “correction” points to factor deficiency(ies). The document covers and suggest the most suitable methods for interpreting PT and aPTT mixing studies.
To Access: https://doi.org/10.5858/arpa.2023-0030-OA
International council for standardisation in haematology recommendations on fibrinogen assays, thrombin clotting time and related tests in the investigation of bleeding disorders
Ian Mackie, Alessandro Casini, Marlien Pieters, Rajiv Pruthi, Chris Reilly-Stitt, Atsuo Suzuki,
20 November 2023, International Journal of Laboratory Hematology
This guidance is from the ICSH that focuses on tests and assays for the determination of fibrinogen function particularily in bleeding disorders. This includes the thrombin time, Clauss fibrinogen assays, PT derived fibrinogen, viscoelastic POC testing, and reptilase time. Fibrinogen antigen assays should be used in the investigation of functional abnormalities as well as to confirm congenital disorders. Recommendations are based on published literature and expert opinion and should supplement local regulation and standards.
To access: https://onlinelibrary.wiley.com/doi/10.1111/ijlh.14201
CLSI H48: Determination of Coagulation Factor Activities Using the One-Stage Clotting Assay, 2nd Edition
This guidance document provides laboratories information to optimize factor assay testing by minimizing variation in preexamination, examination, and post examination processes. It identifies good laboratory practices related to analyzer and reagent performance, reference intervals, lot-to-lot validation, quality assurance, and quality control issues. Standardizing assay performance provides patients with the best outcomes with regard to both diagnosis and treatment.
To Access for purchase: https://clsi.org/standards/products/hematology/documents/?page=2&sort=FriendlyCode&sortdir=asc&subcat=&area=Documents
Guidelines for laboratory diagnosis of factor XIII deficiency
Dorgalaleh, Akbar; Tabibian, Shadi; Hosseini, Soudabeh; Shamsizadeh, Morteza
Blood Coagulation & Fibrinolysis 27(4):p 361-364, June 2016.
This is an extremely rare hemorrhagic disorder (incidence of one/two million). Various laboratory approaches can be used including screening and diagnosis of the disorder in countries with a relatively high rate of FXIIID and recurrent mutation(s) with a simple polymerase chain reaction-restriction fragment length polymorphism analysis or polymerase chain reaction-sequencing for detection of one or a few specific mutations. FXIII activity should be used to screen suspected FXIIID patients; more specific tests such as molecular analysis should be used for confirmation. This study suggests a simple, reliable and flexible algorithm for early diagnosis of FXIIID, and may, with one-time diagnosis of FXIIID, reduce the rate of morbidity and mortality in patients with the disorder.
ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease
Paula D. James, Nathan T. Connell, Barbara Ameer, Jorge Di Paola, Jeroen Eikenboom, Nicolas Giraud, Sandra Haberichter, Vicki Jacobs-Pratt, Barbara Konkle, Claire McLintock, Simon McRae, Robert R. Montgomery, James S. O’Donnell, Nikole Scappe, Robert Sidonio, Jr, Veronica H. Flood, Nedaa Husainat, Mohamad A. Kalot, Reem A. Mustafa
CLINICAL GUIDELINES| January 12, 2021 Blood Adv (2021) 5 (1): 280–300.
These evidence-based guidelines of the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF), and the World Federation of Hemophilia (WFH) are intended to support patients, clinicians, and other health care professionals in their decisions about VWD diagnosis. Key recommendations of these guidelines include the role of bleeding-assessment tools in the assessment of patients suspected of VWD, diagnostic assays and laboratory cutoffs for type 1 and type 2 VWD, how to approach a type 1 VWD patient with normalized levels over time, and the role of genetic testing vs phenotypic assays for types 2B and 2N. Future critical research priorities are also identified.
To Access: https://ashpublications.org/bloodadvances/article/5/1/280/474888
International Council for Standardization in Haematology recommendations for laboratory measurement of factor VIII and FIX type I inhibitors
Piet Meijer, Flora Peyvandi, Guy Young, Rajiv Pruthi, Silmara de Lima Montalvão, Steve Kitchen, International Journal of Laboratory Hematology
Guidance from the ICSH on recommendations on the measurement of FVIII, and Factor IX inhibitors. It includes screening for inhibitors, assay principle, sample requirements, testing requirements, and interpretation, QA, interferences and recent developments.
To Access: https://onlinelibrary.wiley.com/doi/10.1111/ijlh.14109
Guidance from the Scientific and Standardization Committee for lupus anticoagulant/antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis
Update of the guidelines for lupus anticoagulant detection and interpretation
Katrien M. J. Devreese, Philip G. de Groot, Bas de Laat, Doruk Erkan, Emmanuel J. Favaloro, Ian Mackie, Marta Martinuzzo, Thomas L. Ortel, Vittorio Pengo, Jacob H. Rand, Armando Tripodi, Denis Wahl, Hannah Cohen.
Journal of Thrombosis and Hemostasis, 2020
This guidance document is from the International Society on Thrombosis and Haemostasis Scientific and Standardization Committee and focuses on methodological aspects of lupus anticoagulant (LA) testing including how to handle testing in anticoagulated patients and the timing of testing. Accurate assessment of LA is essential for diagnosis and management of APS patients. It is a complex analysis that includes preanalytical conditions and interpretation. The guidance herein will focus on aspects of methodology, choice of assays, cutoff values, calculation and interpretation of results, and timing of testing in relation to thrombosis and pregnancy, with the emphasis on practical guidance for laboratory scientists and clinicians.
To Access: https://islh.org/web/downloads/2020-LAC-guidance-JTH-16859413.pdf
CLSI H60: Laboratory Testing for the Lupus Anticoagulant; Approved Guideline, 1st Edition
This document provides guidance and recommendations regarding the proper collection and handling of the specimen; descriptions and limitations of screening and confirmatory assays, and mixing tests used to identify lupus anticoagulant (LA); determination of cutoff values and calculations associated with the various assays; and interpretation of test results in an LA panel.
To Access for purchase: https://clsi.org/standards/products/hematology/documents/?page=2&sort=FriendlyCode&sortdir=asc&subcat=&area=Documents
American Society of Hematology 2023 guidelines for management of venous thromboembolism: thrombophilia testing
Saskia Middeldorp, Robby Nieuwlaat, Lisa Baumann Kreuziger, Michiel Coppens, Damon Houghton, Andra H. James, Eddy Lang, Stephan Moll, Tarra Myers, Meha Bhatt, Chatree Chai-Adisaksopha, Luis E. Colunga-Lozano, Samer G. Karam, Yuan Zhang, Wojtek Wiercioch, Holger J. Schünemann, Alfonso Iorio, Blood Adv (2023) 7 (22): 7101–7138.
These evidence-based guidelines from the American Society of Hematology (ASH) intend to support decision making about thrombophilia testing. The panel agreed on 23 recommendations regarding thrombophilia testing and associated management. Nearly all recommendations are based on very low certainty in the evidence due to modeling assumptions.
To Access: https://doi.org/10.1182/bloodadvances.2023010177
https://ashpublications.org/bloodadvances/article/7/22/7101/495845/American-Society-of-Hematology-2023-guidelines-for
Recommendations for clinical laboratory testing for protein C deficiency, for the subcommittee on plasma coagulation inhibitors of the ISTH
Peter C. Cooper, Anna Pavlova, Gary W. Moore, Kieron P. Hickey, Richard A. Marlar, Journal of Thrombosis and Hemostasis RECOMMENDATIONS AND GUIDELINES: Volume 18, Issue 2, p271-277 February 2020
This guideline looks at Protein C deficiency both inherited and acquired, as well as the difference in testing methods and best practices. Pre-analytical variables in the specimen affect measurement of PC, and can be assay-dependent; for example, a partially clotted sample will have falsely raised PC level by chromogenic assay but reduced level by clotting-based assay. Direct oral anticoagulants falsely raise PC level in the clotting-based assay but the standard chromogenic assay is unaffected.
Diagnosis and management of heparin-induced thrombocytopenia: Third edition
Deepa J. Arachchillage, Jecko Thachil, Julia A. M. Anderson, Peter Baker, Anthony Poles, Steve Kitchen, Mike Laffan, the BSH Committee, 28 December 2023
This guideline includes functional assays in the diagnosis of heparin-induced thrombocytopenia (HIT), when to use direct-acting oral anti-coagulants, and the role of intravenous (IV) immunoglobulins and plasma exchange in the management of HIT and spontaneous HIT.
To Access: https://onlinelibrary.wiley.com/doi/full/10.1111/bjh.19180
Measurement of heparin, direct oral anti-coagulants and other non-coumarin anti-coagulants and their effects on haemostasis assays: A British Society for Haematology Guideline
Peter Baker, Sean Platton, Deepa J. Arachchillage, Steve Kitchen, Jignesh Patel, Renu Riat, Keith Gomez, the BSH Committee
It provides recommendations based on the body of literature produced since the previous guidance published in 2014. Direct factor (F)XIa- and direct FXIIa-inhibiting anti-coagulants are at various stages of development but not yet licensed, so are not discussed in this guideline. The recent guidelines from the International Society of Thrombosis and Haemostasis Scientific Standardization Committee (ISTH/SSC) on the nomenclature to be used when describing non-vitamin K anti-coagulation3 are followed.
To Access: https://doi.org/10.1111/bjh.19729
https://onlinelibrary.wiley.com/doi/10.1111/bjh.19729
CLSI H58 Platelet Function Testing by Aggregometry, 1st Edition
This document provides concrete, standard procedures for using aggregometry to assess platelet function in patient specimens with the intent to achieve greater uniformity of results. Descriptions of light transmission aggregometry, whole blood impedance aggregometry, and shear-flow technologies are provided so both long-time and new users may establish consistent, reproducible platelet function testing programs in their laboratory
To Access for purchase: https://clsi.org/standards/products/hematology/documents/?page=2&sort=FriendlyCode&sortdir=asc&subcat=&area=Documents
CLSI H59: Quantitative D-dimer for the Exclusion of Venous Thromboembolic Disease, 1st Edition
This document provides guidelines regarding the use of D-dimer in exclusion of venous thromboembolism (VTE) including a description of the value of clinical determination of the pretest probability of VTE; the proper collection and handling of the specimen; assays used for D-dimer analysis; determination of the threshold for exclusion of VTE; interpretation of test results; and aspects of regulatory and accreditation requirements.
To Access for purchase: https://clsi.org/standards/products/hematology/documents/?page=2&sort=FriendlyCode&sortdir=asc&subcat=&area=Documents
POST-ANALYTICAL
ICSH Recommendations for Hemostasis Critical Values, Tests, and Reporting
Robert C. Gosselin, Dorothy Adcock, Akbar Dorgalaleh, Emmanuel J. Favaloro, Giuseppe Lippi, João M. Pego, Irene Regan, Virginie Siguret
22 October 2019, Semin Thromb Hemost 2020; 46(04): 398-409
This guidance from ICSH was developed by an international committee of clinical and laboratory experts. It was developed to provide guidance for identifying coagulation tests that have potential patient risk based on analysis, test result and patient presentations, thresholds for critical results and acceptable reporting and documenting systems as well as developing laboratory policies.
To Access: https://www.thieme-connect.de/products/ejournals/html/10.1055/s-0039-1697677
CONCLUSIONS:
Using guidance documents can be an important tool in the laboratory's testing and quality process. Being able to reference best practices and expert opinion will be important in ensuring optimum procedures, protocols and performance. This all translates into better patient care.