Semin Thromb Hemost 2024; 50(01): 008-025
DOI: 10.1055/s-0043-1761487
Review Article

Evolution of Hemostasis Testing: A Personal Reflection Covering over 40 Years of History*

1   Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Sydney Centres for Thrombosis and Haemostasis, NSW Health Pathology, Westmead Hospital, Westmead, NSW Australia
2   School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga Wagga, New South Wales, Australia
3   School of Medical Sciences, Faculty of Medicine and Health, University of Sydney, Westmead Hospital, Westmead, New South Wales, Australia
› Author Affiliations

Abstract

There is no certainty in change, other than change is certain. As Seminars in Thrombosis and Hemostasis celebrates 50 years of publication, I felt it appropriate to reflect on my own 40-year plus scientific career. My career in the thrombosis and hemostasis field did not start until 1987, but the subsequent 35 years reflected a period of significant change in associated disease diagnostics. I started in the Westmead Hospital “coagulation laboratory” when staff were still performing manual clotting tests, using stopwatches, pipettes, test tubes, and a water bath, which we transported to the hospital outpatient department to run our weekly warfarin clinic. Several hemostasis instruments have come and gone, including the Coag-A-Mate X2, the ACL-300R, the MDA-180, the BCS XP, and several StaR Evolution analyzers. Some instruments remain, including the PFA-100, PFA-200, the AggRAM, the CS-5100, an AcuStar, a Hydrasys gel system, and two ACL-TOP 750s. We still have a water bath, but this is primarily used to defrost frozen samples, and manual clotting tests are only used to teach visiting medical students. We have migrated across several methodologies in the 45-year history of the local laboratory. Laurel gel rockets, used for several assays in the 1980s, were replaced with enzyme-linked immunosorbent assay assays and most assays were eventually placed on automated instruments. Radio-isotopic assays, used in the 1980s, were replaced by an alternate safer method or else abandoned. Test numbers have increased markedly over time. The approximately 31,000 hemostasis assays performed at the Westmead-based laboratory in 1983 had become approximately 200,000 in 2022, a sixfold increase. Some 90,000 prothrombin times and activated partial thromboplastic times are now performed at this laboratory per year. Thrombophilia assays were added to the test repertoires over time, as were the tests to measure several anticoagulant drugs, most recently the direct oral anticoagulants. I hope my personal history, reflecting on the changes in hemostasis testing over my career to date in the field, is found to be of interest to the readership, and I hope they forgive any inaccuracies I have introduced in this reflection of the past.

* Dedicated to the memory of Prof Jerry Koutts (1944-2013), who facilitated my start in this field.




Publication History

Article published online:
02 February 2023

© 2023. Thieme. All rights reserved.

Thieme Medical Publishers, Inc.
333 Seventh Avenue, 18th Floor, New York, NY 10001, USA

 
  • References

  • 1 Case RM, Conigrave AD, Favaloro EJ, Novak I, Thompson CH, Young JA. The role of buffer anions and protons in secretion by the rabbit mandibular salivary gland. J Physiol 1982; 322: 273-286
  • 2 Bradstock KF, Favaloro EJ, Kabral A. et al. Human myeloid differentiation antigens identified by monoclonal antibodies: expression on leukemic cells. Pathology 1985; 17 (03) 392-399
  • 3 Bradstock KF, Favaloro EJ, Kabral A, Kerr A, Hughes WG, Musgrove E. Myeloid progenitor surface antigen identified by monoclonal antibody. Br J Haematol 1985; 61 (01) 11-20
  • 4 Bradstock KF, Kerr A, Kabral A, Favaloro EJ, Hewson JW. Coexpression of p165 myeloid surface antigen and terminal deoxynucleotidyl transferase: a comparison of acute myeloid leukaemia and normal bone marrow cells. Am J Hematol 1986; 23 (01) 43-50
  • 5 Bradstock KF, Favaloro EJ, Kabral A. et al. Standardization of monoclonal antibodies for use in autologous bone marrow transplantation for common acute lymphoblastic leukemia. Pathology 1986; 18 (02) 197-205
  • 6 Favaloro EJ, Bradstock KF, Kamath S, Dowden G, Gillis D, George V. Characterization of a p43 human thymocyte antigen. Dis Markers 1986; 4 (04) 261-270
  • 7 Zola H, Potter A, Neoh SH. et al. Evaluation of a monoclonal IgM antibody for purging of bone marrow for autologous transplantation. Bone Marrow Transplant 1987; 1 (03) 297-301
  • 8 Bradstock KF, Stevens M, Bergin M. et al. Transplantation of monoclonal antibody-purged autologous bone marrow for treatment of poor risk common acute lymphoblastic leukemia. Aust N Z J Med 1987; 17 (03) 283-289
  • 9 Favaloro EJ, Bradstock KF, Grimsley A, Henniker A, Kamath S. Further studies on the heterogeneity of antigens recognised by CD-1 monoclonal antibodies: distribution of epitopes and analysis of serological binding patterns. Immunol Cell Biol 1987; 65 (Pt 6): 517-527
  • 10 Favaloro EJ, Bradstock KF, Kabral A, Grimsley P, Berndt MC. Characterization of monoclonal antibodies to the human myeloid-differentiation antigen, ‘gp67’ (CD-33). Dis Markers 1987; 5 (04) 215-225
  • 11 Kabral A, Bradstock KF, Grimsley P, Favaloro EJ. Immunophenotype of clonogenic cells in myeloid leukaemia. Leuk Res 1988; 12 (01) 51-59
  • 12 Favaloro EJ, Bradstock KF, Kabral A, Grimsley P, Zowtyj H, Zola H. Further characterization of human myeloid antigens (gp160,95; gp150; gp67): investigation of epitopic heterogeneity and non-haemopoietic distribution using panels of monoclonal antibodies belonging to CD-11b, CD-13 and CD-33. Br J Haematol 1988; 69 (02) 163-171
  • 13 Yi D, Gergis M, Hsu J. et al. Next-generation chimeric antigen receptor T-cells. Hematol Oncol Stem Cell Ther 2022; 15 (03) 117-121
  • 14 Pasqui DM, Latorraca CDOC, Pacheco RL, Riera R. CAR-T cell therapy for patients with hematological malignancies. A systematic review. Eur J Haematol 2022; 109 (06) 601-618
  • 15 Al-Haideri M, Tondok SB, Safa SH. et al. CAR-T cell combination therapy: the next revolution in cancer treatment. Cancer Cell Int 2022; 22 (01) 365
  • 16 Favaloro EJ, Moraitis N, Koutts J, Exner T, Bradstock KF. Expression of normal haemopoietic antigens on vascular endothelial cells. Tissue Antigens 1989; 33: 341
  • 17 Favaloro EJ, Moraitis N, Koutts J, Exner T, Bradstock KF. Endothelial cells and normal circulating haemopoietic cells share a number of surface antigens. Thromb Haemost 1989; 61 (02) 217-224
  • 18 Favaloro EJ, Moraitis N, Bradstock K, Koutts J. Co-expression of haemopoietic antigens on vascular endothelial cells: a detailed phenotypic analysis. Br J Haematol 1990; 74 (04) 385-394
  • 19 Brown JE, Bosak JO. An ELISA test for the binding of von Willebrand antigen to collagen. Thromb Res 1986; 43 (03) 303-311
  • 20 Favaloro EJ. Collagen binding assay for von Willebrand factor (VWF:CBA): detection of von Willebrands Disease (VWD), and discrimination of VWD subtypes, depends on collagen source. Thromb Haemost 2000; 83 (01) 127-135
  • 21 Favaloro EJ, Grispo L, Exner T, Koutts J. Development of a simple collagen based ELISA assay aids in the diagnosis of, and permits sensitive discrimination between type I and type II, von Willebrand's disease. Blood Coagul Fibrinolysis 1991; 2 (02) 285-291
  • 22 Exner T, Rickard KA, Kronenberg H. A sensitive test demonstrating lupus anticoagulant and its behavioural patterns. Br J Haematol 1978; 40 (01) 143-151
  • 23 Exner T. Comparison of two simple tests for the lupus anticoagulant. Am J Clin Pathol 1985; 83 (02) 215-218
  • 24 Exner T. The laboratory diagnosis of lupus anticoagulants. Arch Pathol Lab Med 1990; 114 (01) 8-9
  • 25 Exner T, Papadopoulos G, Koutts J. Use of a simplified dilute Russell's viper venom time (DRVVT) confirms heterogeneity among ‘lupus anticoagulants’. Blood Coagul Fibrinolysis 1990; 1 (03) 259-266
  • 26 Exner T, Triplett DA, Taberner D, Machin SJ. SSC Subcommittee for the Standardization of Lupus Anticoagulants. Guidelines for testing and revised criteria for lupus anticoagulants. Thromb Haemost 1991; 65 (03) 320-322
  • 27 Lee LD, Baden HP, Cheng CK. Rocket immunoelectrophoresis in the presence of denaturing agents. J Immunol Methods 1978; 24 (1-2): 155-162
  • 28 Mohammed A, Mehrabani PA, Coombs R, Molesworth L, Favaloro EJ. The MDA-180 coagulation analyser: a laboratory evaluation. Pathology 1997; 29 (02) 176-183
  • 29 Kundu SK, Heilmann EJ, Sio R, Garcia C, Davidson RM, Ostgaard RA. Description of an in vitro platelet function analyzer–PFA-100. Semin Thromb Hemost 1995; 21 (Suppl. 02) 106-112
  • 30 Mammen EF, Alshameeri RS, Comp PC. Preliminary data from a field trial of the PFA-100 system. Semin Thromb Hemost 1995; 21 (Suppl. 02) 113-121
  • 31 Favaloro EJ, Facey D, Henniker A. Use of a novel platelet function analyzer (PFA-100) with high sensitivity to disturbances in von Willebrand factor to screen for von Willebrand's disease and other disorders. Am J Hematol 1999; 62 (03) 165-174
  • 32 De Luca M, Facey DA, Favaloro EJ. et al. Structure and function of the von Willebrand factor A1 domain: analysis with monoclonal antibodies reveals distinct binding sites involved in recognition of the platelet membrane glycoprotein Ib-IX-V complex and ristocetin-dependent activation. Blood 2000; 95 (01) 164-172
  • 33 Favaloro EJ, Mohammed S, McDonald J. Validation of improved performance characteristics for the automated von Willebrand factor ristocetin cofactor activity assay. J Thromb Haemost 2010; 8 (12) 2842-2844
  • 34 Sadler JE, Budde U, Eikenboom JCJ. et al; Working Party on von Willebrand Disease Classification. Update on the pathophysiology and classification of von Willebrand disease: a report of the Subcommittee on von Willebrand Factor. J Thromb Haemost 2006; 4 (10) 2103-2114
  • 35 Favaloro EJ, Lloyd J, Rowell J. et al. A cross-over, multi-centre study to compare pharmacokinetics of two factor concentrates (Biostate® and AHF (High Purity)) in people with von Willebrand disorder. Thromb Haemost 2007; 97 (06) 922-930
  • 36 Favaloro EJ, Mohammed S. Evaluation of a von Willebrand factor three test panel and chemiluminescent-based assay system for identification of, and therapy monitoring in, von Willebrand disease. Thromb Res 2016; 141: 202-211
  • 37 Favaloro EJ, Oliver S. Evaluation of a new commercial von Willebrand factor multimer assay. Haemophilia 2017; 23 (04) e373-e377
  • 38 Lippi G, Sanchis-Gomar F, Favaloro EJ, Lavie CJ, Henry BM. Coronavirus disease 2019-associated coagulopathy. Mayo Clin Proc 2021; 96 (01) 203-217
  • 39 Lippi G, Favaloro EJ. D-dimer is associated with severity of coronavirus disease 2019 (COVID-19): a pooled analysis. Thromb Haemost 2020; 120 (05) 876-878
  • 40 Thachil J, Favaloro EJ, Lippi G. D-dimers-“Normal” levels versus elevated levels due to a range of conditions, including “D-dimeritis,” inflammation, thromboembolism, disseminated intravascular coagulation, and COVID-19. Semin Thromb Hemost 2022; 48 (06) 672-679
  • 41 Favaloro EJ, Lay M, Mohammed S, Vong R, Pasalic L. Pathology utilisation during COVID-19 outbreaks beyond viral testing: routine coagulation and D-dimer testing. Pathology 2022; S0031-3025 (22) 00138-6
  • 42 Favaloro EJ, Mohammed S, Vong R. et al. Verification of the ACL top 50 family (350, 550 and 750) for harmonization of routine coagulation assays in a large network of 60 laboratories. Am J Clin Pathol 2021; 156 (04) 661-678
  • 43 Favaloro EJ, Mohammed S, Vong R. et al. A multi-laboratory assessment of congenital thrombophilia assays performed on the ACL TOP 50 family for harmonisation of thrombophilia testing in a large laboratory network. Clin Chem Lab Med 2021; 59 (10) 1709-1718
  • 44 Favaloro EJ, Mohammed S, Vong R. et al. A multi-laboratory assessment of lupus anticoagulant assays performed on the ACL TOP 50 family for harmonized testing in a large laboratory network. Int J Lab Hematol 2022; 44 (03) 654-665
  • 45 Favaloro EJ, Mohammed S, Vong R. et al. Harmonizing factor assay-related testing performed in a large laboratory network. Blood Coagul Fibrinolysis 2022; 33 (07) 402-411
  • 46 Favaloro EJ, Mohammed S, Vong R. et al. Harmonizing platelet function analyzer testing and reporting in a large laboratory network. Int J Lab Hematol 2022; 44 (05) 934-944
  • 47 Sydney West Area Health Service. . Accessed December 28, 2022 at: https://researchdata.edu.au/sydney-west-area-health-service/167702
  • 48 NSW Health Pathology Strategic Priorities. . Accessed December 28, 2022 at: https://pathology.health.nsw.gov.au/about-us/our-strategy/strategic-priorities
  • 49 NSW Health Pathology test catalogue. . Accessed December 28, 2022 at: https://catalogue.pathology.health.nsw.gov.au/home
  • 50 Favaloro EJ. von Willebrand factor (VWF) collagen binding (activity) assay (VWF:CBA) in the diagnosis of von Willebrand's disorder (VWD): a 15-year journey. Semin Thromb Hemost 2002; 28 (02) 191-202
  • 51 Favaloro EJ. An update on the von Willebrand factor collagen binding assay: 21 years of age and beyond adolescence but not yet a mature adult. Semin Thromb Hemost 2007; 33 (08) 727-744
  • 52 Favaloro EJ. Evaluation of commercial von Willebrand factor collagen binding assays to assist the discrimination of types 1 and 2 von Willebrand disease. Thromb Haemost 2010; 104 (05) 1009-1021
  • 53 Favaloro EJ, Bonar RA, Meiring M. et al. Evaluating errors in the laboratory identification of von Willebrand disease in the real world. Thromb Res 2014; 134 (02) 393-403
  • 54 Favaloro EJ, Dean E, Arunachalam S, Vong R, Mohammed S. Evaluating errors in the laboratory identification of von Willebrand disease using contemporary von Willebrand factor assays. Pathology 2022; 54 (03) 308-317
  • 55 Favaloro EJ, Mohammed S, Vong R. et al. How we diagnose 2M von Willebrand disease (VWD): use of a strategic algorithmic approach to distinguish 2M VWD from other VWD types. Haemophilia 2021; 27 (01) 137-148
  • 56 Laffan MA, Lester W, O'Donnell JS. et al. The diagnosis and management of von Willebrand disease: a United Kingdom Haemophilia Centre Doctors Organization guideline approved by the British Committee for Standards in Haematology. Br J Haematol 2014; 167 (04) 453-465
  • 57 James PD, Connell NT, Ameer B. et al. ASH ISTH NHF WFH 2021 guidelines on the diagnosis of von Willebrand disease. Blood Adv 2021; 5 (01) 280-300
  • 58 Favaloro EJ, Dean M, Grispo L, Exner T, Koutts J. von Willebrand's disease: use of collagen binding assay provides potential improvement to laboratory monitoring of desmopressin (DDAVP) therapy. Am J Hematol 1994; 45 (03) 205-211
  • 59 Favaloro EJ, Kershaw G, Bukuya M, Hertzberg M, Koutts J. Laboratory diagnosis of von Willebrand disorder (vWD) and monitoring of DDAVP therapy: efficacy of the PFA-100 and vWF:CBA as combined diagnostic strategies. Haemophilia 2001; 7 (02) 180-189
  • 60 Favaloro EJ, Thom J, Patterson D. et al. Potential supplementary utility of combined PFA-100 and functional von Willebrand factor testing for the laboratory assessment of desmopressin and factor concentrate therapy in von Willebrand disease. Blood Coagul Fibrinolysis 2009; 20 (06) 475-483
  • 61 Mammen EF, Comp PC, Gosselin R. et al. PFA-100 system: a new method for assessment of platelet dysfunction. Semin Thromb Hemost 1998; 24 (02) 195-202
  • 62 Favaloro EJ. Utility of the platelet function analyser (PFA-100/200) for exclusion or detection of von Willebrand disease: a study 22 years in the making. Thromb Res 2020; 188: 17-24
  • 63 Favaloro EJ, Bonar R. External quality assurance for the PFA-100®. J Thromb Haemost 2011; 9 (04) 878-880
  • 64 Favaloro EJ, Bonar R. Proficiency testing/external quality assurance for the PFA-100(®). Clin Chem Lab Med 2012; 50 (08) 1393-1401
  • 65 Favaloro EJ. Time for a conceptual shift in assessment of internal quality control for whole blood or cell-based testing systems? An evaluation using platelet function and the PFA-100 as a case example. Clin Chem Lab Med 2013; 51 (04) 767-774
  • 66 Favaloro EJ, Bonar R. External quality assessment/proficiency testing and internal quality control for the PFA-100 and PFA-200: an update. Semin Thromb Hemost 2014; 40 (02) 239-253
  • 67 Favaloro EJ, Bonar R. An update on quality control for the PFA-100/PFA-200. Platelets 2018; 29 (06) 622-627
  • 68 Favaloro EJ. Novel approaches to quality control and external quality assessment for platelet function testing with a focus on the platelet function analyser (PFA-100 and PFA-200). Ann Blood 2019; 4: 3
  • 69 Oliver S, Lau KKE, Chapman K, Favaloro EJ. Laboratory testing for Von Willebrand factor multimers. Methods Mol Biol 2017; 1646: 495-511
  • 70 Oliver S, Vanniasinkam T, Mohammed S, Vong R, Favaloro EJ. Semi-automated von Willebrand factor multimer assay for von Willebrand disease: further validation, benefits and limitations. Int J Lab Hematol 2019; 41 (06) 762-771
  • 71 Favaloro EJ, Oliver S, Mohammed S, Vong R. Comparative assessment of von Willebrand factor multimers vs activity for von Willebrand disease using modern contemporary methodologies. Haemophilia 2020; 26 (03) 503-512
  • 72 Mackinlay N, Favaloro E, Arthur C, Smith J, Aboud M. A survey of heparin monitoring in Australasia. Pathology 1996; 28 (04) 343-347
  • 73 Favaloro EJ, Bonar R, Sioufi J. et al; Royal College Pathologists of Australasia Quality Assurance Program in Haematology. An international survey of current practice in the laboratory assessment of anticoagulant therapy with heparin. Pathology 2005; 37 (03) 234-238
  • 74 Favaloro EJ, Bonar R, Aboud M. et al; RCPA QAP in Haematology. How useful is the monitoring of (low molecular weight) heparin therapy by anti-Xa assay? A laboratory perspective. Lab Hematol 2005; 11 (03) 157-162
  • 75 Bonar RA, Favaloro EJ, Marsden K. External quality assurance for heparin monitoring. Semin Thromb Hemost 2012; 38 (06) 632-639
  • 76 Favaloro EJ, Smith J, Petinos P, Collecutt M, Street A, Hertzberg M. RCPA Quality Assurance Program in Haematology Scientific Haemostasis Advisory Panel. Laboratory testing, diagnosis, and management of von Willebrand disease. Current practice in Australasia. Am J Clin Pathol 1999; 112 (05) 712-719
  • 77 Favaloro EJ, Smith J, Petinos P, Hertzberg M, Koutts J. RCPA Quality Assurance Program (QAP) in Haematology Haemostasis Scientific Advisory Panel. Laboratory testing for von Willebrand's disease: an assessment of current diagnostic practice and efficacy by means of a multi-laboratory survey. Thromb Haemost 1999; 82 (04) 1276-1282
  • 78 Favaloro EJ, Bonar R, Chapman K, Meiring M, Adcock DF. Differential sensitivity of von Willebrand factor ‘activity’ assays to large and small VWF molecular weight forms: a cross-laboratory study comparing ristocetin cofactor, collagen binding and monoclonal antibody based assays. J Thromb Haemost 2012; 10 (06) 1043-1054
  • 79 Favaloro EJ, Bonar R, Hollestelle MJ. et al. Differential sensitivity of von Willebrand factor activity assays to reduced VWF molecular weight forms: a large international cross-laboratory study. Thromb Res 2018; 166: 96-105
  • 80 Favaloro EJ. Rethinking internal quality control and external quality assessment for laboratory diagnostics of von Willebrand disease. Ann Blood 2019; 4: 4
  • 81 Salazar E, Long TA, Smock KJ. et al. Analysis of College of American Pathologists von Willebrand Factor Proficiency Testing Program. Semin Thromb Hemost 2022; 48 (06) 690-699
  • 82 Ziemba YC, Abdulrehman J, Hollestelle MJ. et al. Diagnostic testing for von Willebrand disease: trends and insights from North American Laboratories over the last decade. Semin Thromb Hemost 2022; 48 (06) 700-710
  • 83 Favaloro EJ, Dean E, Arunachalam S. Evaluating performance of contemporary and historical von Willebrand Factor (VWF) assays in the laboratory identification of von Willebrand Disease (VWD): the Australasian Experience. Semin Thromb Hemost 2022; 48 (06) 711-731
  • 84 Favaloro EJ, Pasalic L. Laboratory diagnosis of von Willebrand Disease (VWD): geographical perspectives. Semin Thromb Hemost 2022; 48 (06) 750-766
  • 85 Favaloro EJ. Commentary on the ASH ISTH NHF WFH 2021 guidelines on the diagnosis of VWD: reflections based on recent contemporary test data. Blood Adv 2022; 6 (02) 416-419
  • 86 Favaloro EJ, Silvestrini R, Mohammed A. Clinical utility of anticardiolipin antibody assays: high inter-laboratory variation and limited consensus by participants of external quality assurance programs signals a cautious approach. Pathology 1999; 31 (02) 142-147
  • 87 Favaloro EJ, Silvestrini R. Assessing the usefulness of anticardiolipin antibody assays: a cautious approach is suggested by high variation and limited consensus in multilaboratory testing. Am J Clin Pathol 2002; 118 (04) 548-557
  • 88 Favaloro EJ, Wong RC, Silvestrini R, McEvoy R, Jovanovich S, Roberts-Thomson P. A multilaboratory peer assessment quality assurance program-based evaluation of anticardiolipin antibody, and beta2-glycoprotein I antibody testing. Semin Thromb Hemost 2005; 31 (01) 73-84
  • 89 Favaloro EJ, Wong RCW, Jovanovich S, Roberts-Thomson P. A Review of beta2-glycoprotein-l antibody testing results from a peer-driven multilaboratory quality assurance program. Am J Clin Pathol 2007; 127 (03) 441-448
  • 90 Favaloro EJ, Wheatland L, Jovanovich S, Roberts-Thomson P, Wong RCW. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: part I–anticardiolipin and anti-β2-glycoprotein I antibodies. Semin Thromb Hemost 2012; 38 (04) 390-403
  • 91 Hertzberg M, Neville S, Favaloro E, McDonald D. External quality assurance of DNA testing for thrombophilia mutations. Am J Clin Pathol 2005; 123 (02) 189-193
  • 92 Favaloro EJ, Bonar R, Sioufi J. et al. (on behalf of the RCPA QAP in Haematology). Multi-laboratory testing of thrombophilia: current and past practice in Australasia as assessed through the Royal College of Pathologists of Australasia Quality Assurance Program in Haematology. Semin Thromb Hemost 2005; 31 (01) 49-58
  • 93 Dean E, Favaloro EJ. The changing face of activated protein C resistance testing—a 10-year retrospective. Ann Blood 2020; 5: 6
  • 94 Favaloro EJ, Bonar R, Duncan E. et al; RCPA QAP in Haematology Haemostasis Committee. Identification of factor inhibitors by diagnostic haemostasis laboratories: a large multi-centre evaluation. Thromb Haemost 2006; 96 (01) 73-78
  • 95 Favaloro EJ, Bonar R, Duncan E. et al. Mis-identification of factor inhibitors by diagnostic haemostasis laboratories: recognition of pitfalls and elucidation of strategies. A follow up to a large multicentre evaluation. Pathology 2007; 39 (05) 504-511
  • 96 Favaloro EJ, Bonar R, Kershaw G, Duncan E, Sioufi J, Marsden K. Investigations from external quality assurance programs reveal a high degree of variation in the laboratory identification of coagulation factor inhibitors. Semin Thromb Hemost 2009; 35 (08) 794-805
  • 97 Favaloro EJ, Bonar R, Kershaw G, Mohammed S, Duncan E, Marsden K. RCPA Haematology QAP Haemostasis Committee. Laboratory identification of factor VIII inhibitors in the real world: the experience from Australasia. Haemophilia 2010; 16 (04) 662-670
  • 98 Bonar RA, Favaloro EJ, Marsden K. External quality assessment of factor VIII inhibitor assays. Semin Thromb Hemost 2013; 39 (03) 320-326
  • 99 Arunachalam S, Favaloro EJ. Ongoing improvements in laboratory performance of coagulation factors VIII and IX: recent experience from the RCPAQAP. Ann Blood 2020; 5: 7
  • 100 Favaloro EJ, Bonar R, Zebeljan D, Kershaw G, Marsden K. Laboratory investigation of lupus anticoagulants: mixing studies are sometimes required. J Thromb Haemost 2010; 8 (12) 2828-2831
  • 101 Bonar R, Favaloro E, Zebeljan D. et al. Evaluating laboratory approaches to the identification of lupus anticoagulants: a diagnostic challenge from the RCPA Haematology QAP. Pathology 2012; 44 (03) 240-247
  • 102 Favaloro EJ, Bonar R, Marsden K. Internal quality control and external quality assurance in testing for antiphospholipid antibodies: part II–Lupus anticoagulant. Semin Thromb Hemost 2012; 38 (04) 404-411
  • 103 Favaloro EJ, Bonar R, Marsden K. Lupus anticoagulant testing—sometimes mixing is required: potential for false negatives without mixing studies. Blood Coagul Fibrinolysis 2013; 24 (06) 673-676
  • 104 Favaloro EJ, Gilmore G, Arunachalam S, Mohammed S, Baker R. Neutralising rivaroxaban induced interference in laboratory testing for lupus anticoagulant (LA): a comparative study using DOAC Stop and andexanet alfa. Thromb Res 2019; 180: 10-19
  • 105 Favaloro EJ, Bonar R, Butler J, Marsden K. Laboratory testing for the new oral anticoagulants: a review of current practice. Pathology 2013; 45 (04) 435-437
  • 106 Bonar R, Favaloro EJ, Mohammed S, Pasalic L, Sioufi J, Marsden K. The effect of dabigatran on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples. Pathology 2015; 47 (04) 355-364
  • 107 Bonar R, Favaloro EJ, Mohammed S. et al. The effect of the direct factor Xa inhibitors apixaban and rivaroxaban on haemostasis tests: a comprehensive assessment using in vitro and ex vivo samples. Pathology 2016; 48 (01) 60-71
  • 108 Favaloro EJ, Gilmore G, Bonar R. et al. Reducing the effect of DOAC interference in laboratory testing for factor VIII and factor IX: a comparative study using DOAC Stop and andexanet alfa to neutralize rivaroxaban effects. Haemophilia 2020; 26 (02) 354-362
  • 109 Favaloro EJ, Gilmore G, Bonar R. et al. Laboratory testing for activated protein C resistance: rivaroxaban induced interference and a comparative evaluation of andexanet alfa and DOAC Stop to neutralise interference. Clin Chem Lab Med 2020; 58 (08) 1322-1331
  • 110 Favaloro EJ, Bonar R, Duncan E, Rodgers S, Marsden K. Royal College of Pathologists of Australasia Quality Assurance Program in Haematology. Utility of the PFA-100 as a screening test of platelet function: an audit of haemostasis laboratories in Australia and New Zealand. Blood Coagul Fibrinolysis 2007; 18 (05) 441-448
  • 111 Adcock DM, Brien WF, Duff SL. et al. Procedures for validation of INR and local calibration of PT/INR systems; approved guideline. Nt H54-A, Vol. 25 No. 23 (replaces H54-P Vol. 24 No. 30),. Wayne, PA: Clinical and Laboratory Standards Institute (CLSI); 2005
  • 112 Bonar R, Favaloro EJ. Explaining and reducing the variation in inter-laboratory reported values for international normalised ratio. Thromb Res 2017; 150: 22-29
  • 113 Favaloro EJ, Hamdam S, McDonald J, McVicker W, Ule V. Time to think outside the box? Prothrombin time, international normalised ratio, international sensitivity index, mean normal prothrombin time and measurement of uncertainty: a novel approach to standardisation. Pathology 2008; 40 (03) 277-287
  • 114 Favaloro EJ, McVicker W, Hamdam S, Hocker N. Improving the harmonisation of the international normalized ratio (INR): time to think outside the box?. Clin Chem Lab Med 2010; 48 (08) 1079-1090
  • 115 Favaloro EJ, McVicker W, Zhang Y. et al. Improving the inter-laboratory harmonization of the international normalized ratio (INR): utilizing the concept of transference to estimate and/or validate international sensitivity index (ISI) and mean normal prothrombin time (MNPT) values and/or to eliminate measurement bias. Clin Lab Sci 2012; 25 (01) 13-25
  • 116 Favaloro EJ, McVicker W, Lay M. et al. Harmonizing the international normalized ratio (INR) : standardization of methods and use of novel strategies to reduce interlaboratory variation and bias. Am J Clin Pathol 2016; 145 (02) 191-202
  • 117 Favaloro EJ, Bernal-Hoyos E, Exner T, Koutts J. Heparin-induced thrombocytopenia: laboratory investigation and confirmation of diagnosis. Pathology 1992; 24 (03) 177-183
  • 118 Favaloro EJ, McCaughan G, Mohammed S. et al. HIT or miss? A comprehensive contemporary investigation of laboratory tests for heparin induced thrombocytopenia. Pathology 2018; 50 (04) 426-436
  • 119 Favaloro EJ, Mohammed S, Donikian D. et al. A multicentre assessment of contemporary laboratory assays for heparin induced thrombocytopenia. Pathology 2021; 53 (02) 247-256
  • 120 Favaloro EJ, Pasalic L, Lippi G. Antibodies against platelet factor 4 and their associated pathologies: from HIT/HITT to spontaneous HIT-like syndrome, to COVID-19, to VITT/TTS. Antibodies (Basel) 2022; 11 (01) 7
  • 121 Favaloro EJ, Pasalic L. COVID-19 vaccine induced (immune) thrombotic thrombocytopenia (VITT)/thrombosis with thrombocytopenia syndrome (TTS): an update. Aust J Med Sci 2021; 42 (03) 86-93
  • 122 Zidan A, Noureldin A, Kumar SA, Elsebaie A, Othman M. COVID-19 vaccine-associated immune thrombosis and thrombocytopenia (VITT): diagnostic discrepancies and global implications. Semin Thromb Hemost 2023; 49 (01) 9-14
  • 123 Selvadurai MV, Favaloro EJ, Chen VM. Mechanisms of thrombosis in heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia. Semin Thromb Hemost 2023; 5 DOI: 10.1055/s-0043-1761269.
  • 124 Chen VM, Curnow JL, Tran HA, Choi PY. Australian and New Zealand approach to diagnosis and management of vaccine-induced immune thrombosis and thrombocytopenia. Med J Aust 2021; 215 (06) 245-249
  • 125 Favaloro EJ, Clifford J, Leitinger E. et al. Assessment of immunological anti-platelet factor 4 antibodies for vaccine-induced thrombotic thrombocytopenia (VITT) in a large Australian cohort: a multicenter study comprising 1284 patients. J Thromb Haemost 2022; 20 (12) 2896-2908
  • 126 Platton S, Bartlett A, MacCallum P. et al. Evaluation of laboratory assays for anti-platelet factor 4 antibodies after ChAdOx1 nCOV-19 vaccination. J Thromb Haemost 2021; 19 (08) 2007-2013
  • 127 Favaloro EJ. Laboratory testing for suspected COVID-19 vaccine-induced (immune) thrombotic thrombocytopenia. Int J Lab Hematol 2021; 43 (04) 559-570
  • 128 Favaloro EJ, Pasalic L, Henry B, Lippi G. Laboratory testing for platelet factor 4 antibodies: differential utility for diagnosis/exclusion of heparin induced thrombocytopenia versus suspected vaccine induced thrombotic thrombocytopenia. Pathology 2022; 54 (03) 254-261
  • 129 Lippi G, Favaloro EJ. Cerebral venous thrombosis developing after COVID-19 vaccination: VITT, VATT, TTS, and more. Semin Thromb Hemost 2022; 48 (01) 8-14
  • 130 Favaloro EJ, Henry BM, Lippi G. The complicated relationships of heparin-induced thrombocytopenia and platelet factor 4 antibodies with COVID-19. Int J Lab Hematol 2021; 43 (04) 547-558
  • 131 Warkentin TE, Greinacher A. Spontaneous HIT syndrome: knee replacement, infection, and parallels with vaccine-induced immune thrombotic thrombocytopenia. Thromb Res 2021; 204: 40-51
  • 132 Warkentin TE, Greinacher A. Laboratory testing for heparin-induced thrombocytopenia and vaccine-induced immune thrombotic thrombocytopenia antibodies: a narrative review. Semin Thromb Hemost 2022; 49 (06) 621-633
  • 133 Favaloro EJ. Diagnostic issues in thrombophilia: a laboratory scientist's view. Semin Thromb Hemost 2005; 31 (01) 11-16
  • 134 Favaloro EJ, Mohammed S, Curnow J, Pasalic L. Laboratory testing for lupus anticoagulant (LA) in patients taking direct oral anticoagulants (DOACs): potential for false positives and false negatives. Pathology 2019; 51 (03) 292-300
  • 135 Favaloro EJ, Pasalic L, Lippi G. Oral anticoagulation therapy: an update on usage, costs and associated risks. Pathology 2020; 52 (06) 736-741
  • 136 Mammen EF. Laboratory issues in the identification and diagnosis of von Willebrand disease on the 80th anniversary of Erik von Willebrand's original publication. Semin Thromb Hemost 2006; 32 (05) 443-444
  • 137 Mammen EF. Hereditary von Willebrand Disease and acquired von Willebrand syndrome: clinical manifestations, diagnosis, and management. Semin Thromb Hemost 2006; 32 (06) 553-554
  • 138 Favaloro EJ. Standardisation, quality assurance and emerging diagnostic technologies in hemostasis. Semin Thromb Hemost 2007; 33: 217-219
  • 139 Favaloro EJ. Hot topics I: a potpourri of current issues and controversies in thrombosis and hemostasis. Semin Thromb Hemost 2007; 33: 723-726
  • 140 Schiff D. Eulogy. Eberhard Mammen, M.D. 1930–2008. Semin Thromb Hemost 2008; 34: 305
  • 141 Favaloro EJ, Kessler C, Levi M. Editorial. Eberhard Mammen 1930–2008. Semin Thromb Hemost 2008; 34: 703-708
  • 142 Favaloro EJ. A tribute to Eberhard F. Mammen, M.D. (1930-2008). Semin Thromb Hemost 2008; 34 (08) 703-707
  • 143 Gosselin RC. From ink pens to computers: a personal look back at landmark changes during 5 decades as a clinical laboratory scientist in U.S. Hemostasis Laboratories. Semin Thromb Hemost 2022; 49 (03) 225-233