Download PDF
Semin Thromb Hemost 2013; 39(03): 235-249
DOI: 10.1055/s-0033-1336833
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Regulation in Hemostasis and Thrombosis: Part I—In Vitro Diagnostics

Emmanuel J. Favaloro
1   Department of Haematology, Institute of Clinical Pathology and Medical Research (ICPMR), Pathology West, Westmead Hospital, Westmead, New South Wales, Australia
,
Mario Plebani
2   Department of Laboratory Medicine, University-Hospital, Padova, Italy
,
Giuseppe Lippi
3   Department of Pathology and Laboratory Medicine, Clinical Chemistry and Hematology Laboratory, Academic Hospital of Parma, Italy
› Author Affiliations
Further Information

Publication History

Publication Date:
12 March 2013 (online)

    Permissions and Reprints

Abstract

The diagnostic or test-performance process, as associated to the evaluation or diagnosis of hemostasis and thrombosis and related disorders, is influenced or controlled by the activity of a large number of professional, expert, and government organizations. These may be involved in driving standardization or harmonization, providing professional or expert guidelines, or in regulation of therapeutic products and diagnostic products such as in vitro diagnostic devices or reagents (IVDs). Although all organizations involved in this activity would propose an intention to drive improvements in diagnostics and human health and although there are benefits to the overall process of standardization and regulation for tests of hemostasis and thrombosis, it should also be recognized there are several specific problems and limitations to this process. As highlighted in this report, which specifically relates to the regulation of IVDs, several case studies are used as examples to show that regulation, aimed to reduce risks associated with the implementation of diagnostic testing, may instead encourage the adverse outcome of locking out clinically useful, new, and improved technologies and locking in old and outdated technologies. This has a potential for significant adverse outcomes related to the clinical diagnosis and management of hemostasis and thrombosis-related disorders.

Keywords

standardization - regulation - harmonization - hemostasis testing - diagnostic practice - in vitro diagnostics - IVDs
 

  • References

  • 1 Lippi G, Favaloro EJ, Franchini M, Guidi GC. Milestones and perspectives in coagulation and hemostasis. Semin Thromb Hemost 2009; 35 (1) 9-22
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Favaloro EJ, Lippi G. Coagulation update: what's new in hemostasis testing?. Thromb Res 2011; 127 (Suppl. 02) S13-S16
    PubMedGoogle Scholar
  • 3 Lippi G, Favaloro EJ. Laboratory hemostasis: milestones in Clinical Chemistry and Laboratory Medicine. Clin Chem Lab Med 2013; 51 (1) 91-97
    PubMedGoogle Scholar
  • 4 Lippi G, Mattiuzzi C. Testing volume is not synonymous of cost, value and efficacy in laboratory diagnostics. Clin Chem Lab Med 2013; 51 (2) 243-245
    PubMedGoogle Scholar
  • 5 Lippi G, Simundic AM. Laboratory networking and sample quality: a still relevant issue for patient safety. Clin Chem Lab Med 2012; 50 (10) 1703-1705
    PubMedGoogle Scholar
  • 6 Adams O, Cooper G, Fraser C , et al. Collective opinion paper on findings of the 2011 convocation of experts on laboratory quality. Clin Chem Lab Med 2012; 50 (9) 1547-1558
    PubMedGoogle Scholar
  • 7 Sédille-Mostafaie M, Engler H, Lutz S, Korte W. Advancing haemostasis automation - successful implementation of robotic centrifugation and sample processing in a tertiary service hospital. Clin Chem Lab Med 2013; DOI: 10.1515/cclm-2012-0625.
    PubMedGoogle Scholar
  • 8 Favaloro EJ, Mohammed S, Pati N, Ho MY, McDonald D. A clinical audit of congenital thrombophilia investigation in tertiary practice. Pathology 2011; 43 (3) 266-272
    CrossrefPubMedGoogle Scholar
  • 9 Favaloro EJ, Reben R, Mohammed S, Koutts J. Clinical audit of antiphospholipid antibody testing in tertiary practice: towards improved relevance in thrombophilia investigations. Intern Med J 2012; 42 (4) 427-434
    CrossrefPubMedGoogle Scholar
  • 10 Favaloro EJ, McDonald D. Futility of testing for factor V Leiden. Blood Transfus 2012; 10 (3) 260-263
    PubMedGoogle Scholar
  • 11 Favaloro EJ, Lippi G. Laboratory testing and/or monitoring of the new oral anticoagulants/antithrombotics: for and against?. Clin Chem Lab Med 2011; 49 (5) 755-757
    CrossrefPubMedGoogle Scholar
  • 12 Favaloro EJ, Lippi G. The new oral anticoagulants and the future of haemostasis laboratory testing. Biochem Med (Zagreb) 2012; 22 (3) 329-341
    PubMedGoogle Scholar
  • 13 Favaloro EJ, Lippi G, Koutts J. Laboratory testing of anticoagulants: the present and the future. Pathology 2011; 43 (7) 682-692
    CrossrefPubMedGoogle Scholar
  • 14 Samama MM, Guinet C. Laboratory assessment of new anticoagulants. Clin Chem Lab Med 2011; 49 (5) 761-772
    CrossrefPubMedGoogle Scholar
  • 15 Tripodi A, Di Iorio G, Lippi G, Testa S, Manotti C. Position paper on laboratory testing for patients taking new oral anticoagulants. Consensus document of FCSA, SIMeL, SIBioC and CISMEL. Clin Chem Lab Med 2012; 50 (12) 2137-2140
    PubMedGoogle Scholar
  • 16 Harenberg J, Giese C, Marx S, Krämer R. Determination of dabigatran in human plasma samples. Semin Thromb Hemost 2012; 38 (1) 16-22
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Harenberg J, Erdle S, Marx S, Krämer R. Determination of rivaroxaban in human plasma samples. Semin Thromb Hemost 2012; 38 (2) 178-184
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Harenberg J, Du S, Krämer S , et al. Novel methods for assessing oral direct factor Xa and thrombin inhibitors: use of point of care testing and urine samples. Semin Thromb Hemost 2013; 39 (1) 66-71
    PubMedGoogle Scholar
  • 19 Favaloro EJ, Plebani M, Lippi G. Quality in hemostasis and thrombosis—part I. Semin Thromb Hemost 2012; 38 (6) 549-552
    Article in Thieme ConnectPubMedGoogle Scholar
  • 20 Hughes S. Lab automation services. J Lab Autom 2012; 17 (6) 405-407
    PubMedGoogle Scholar
  • 21 van Geffen M, van Heerde WL. Global haemostasis assays, from bench to bedside. Thromb Res 2012; 129 (6) 681-687
    CrossrefPubMedGoogle Scholar
  • 22 Lippi G, Plebani M. Continuous-flow automation and hemolysis index: a crucial combination. J Lab Autom 2012; DOI: 10.1177/2211068212450014.
    PubMedGoogle Scholar
  • 23 Barletta G, Zaninotto M, Faggian D, Plebani M. Shop for quality or quantity? Volumes and costs in clinical laboratories. Clin Chem Lab Med 2013; 51 (2) 295-301
    PubMedGoogle Scholar
  • 24 Zaninotto M, Plebani M. The “hospital central laboratory”: automation, integration and clinical usefulness. Clin Chem Lab Med 2010; 48 (7) 911-917
    CrossrefPubMedGoogle Scholar
  • 25 Favaloro EJ. Standardization, regulation, quality assurance and emerging technologies in hemostasis: issues, controversies, benefits, and limitations. Semin Thromb Hemost 2007; 33 (3) 290-297
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 International organization for Standardization. ISO 17511: 2003. In vitro medical devices-measurement of quantities in biological samples-metrological traceability of values assigned to calibrators and controls. Geneva, Switzerland: 2003
    Google Scholar
  • 27 Siekmann L. Metrological traceability - a concept for standardization in laboratory medicine. Clin Chem Lab Med 2013; DOI: 10.1515/cclm-2012-0710.
    PubMedGoogle Scholar
  • 28 Olson JD, Preston FE, Nichols WL. External quality assurance in thrombosis and hemostasis: an international perspective. Semin Thromb Hemost 2007; 33 (3) 220-225
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Favaloro EJ, Plebani M, Lippi G. Regulation of in vitro diagnostics (IVDs) for use in clinical diagnostic laboratories: towards the light or dark in clinical laboratory testing?. Clin Chem Lab Med 2011; 49 (12) 1965-1973
    CrossrefPubMedGoogle Scholar
  • 30 Favaloro EJ. Regulation of in vitro diagnostics (IVDs) for use in Australian pathology laboratories: a gloomy outlook for future pathology testing in this country?. Pathology 2011; 43 (4) 397-402
    CrossrefPubMedGoogle Scholar
  • 31 Favaloro EJ. Harmonising quality to the lowest clinical diagnostic standard? The case against regulation of in vitro diagnostics (IVDs) for use in clinical diagnostic laboratories. Australian Journal of Medical Science 2010; 31: 56-64
    PubMedGoogle Scholar
  • 32 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
    CrossrefPubMedGoogle Scholar
  • 33 Nichols WL, Hultin MB, James AH , et al. von Willebrand disease (VWD): evidence-based diagnosis and management guidelines, the National Heart, Lung, and Blood Institute (NHLBI) Expert Panel report (USA). Haemophilia 2008; 14 (2) 171-232
    CrossrefPubMedGoogle Scholar
  • 34 Favaloro EJ. Von Willebrand disease: local diagnosis and management of a globally distributed bleeding disorder. Semin Thromb Hemost 2011; 37 (5) 440-455
    Article in Thieme ConnectPubMedGoogle Scholar
  • 35 Favaloro EJ. New developments in the diagnosis and treatment of von Willebrand disease. Clin Investig 2012; 2 (8) 781-795
    PubMedGoogle Scholar
  • 36 Favaloro EJ. Rethinking the diagnosis of von Willebrand disease. Thromb Res 2011; 127 (Suppl. 02) S17-S21
    PubMedGoogle Scholar
  • 37 Favaloro EJ, Franchini M, Lippi G. Biological therapies for von Willebrand disease. Expert Opin Biol Ther 2012; 12 (5) 551-564
    CrossrefPubMedGoogle Scholar
  • 38 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 (8) 727-744
    Article in Thieme ConnectPubMedGoogle Scholar
  • 39 Favaloro EJ. Toward a new paradigm for the identification and functional characterization of von Willebrand disease. Semin Thromb Hemost 2009; 35 (1) 60-75
    Article in Thieme ConnectPubMedGoogle Scholar
  • 40 Favaloro EJ. Diagnosis and classification of von Willebrand disease: a review of the differential utility of various functional von Willebrand factor assays. Blood Coagul Fibrinolysis 2011; 22 (7) 553-564
    CrossrefPubMedGoogle Scholar
  • 41 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 (6) 1043-1054
    CrossrefPubMedGoogle Scholar
  • 42 Favaloro EJ, Bonar R, Kershaw G , et al. Reducing errors in identification of von Willebrand disease: the experience of the royal college of pathologists of australasia quality assurance program. Semin Thromb Hemost 2006; 32 (5) 505-513
    Article in Thieme ConnectPubMedGoogle Scholar
  • 43 Favaloro EJ, Bonar R, Kershaw G , et al; Royal College Of Pathologists Of Australasia Quality Assurance Program In Haematology. Laboratory diagnosis of von Willebrand disorder: use of multiple functional assays reduces diagnostic error rates. Lab Hematol 2005; 11 (2) 91-97
    CrossrefPubMedGoogle Scholar
  • 44 Hayes TE, Brandt JT, Chandler WL , et al. External peer review quality assurance testing in von Willebrand disease: the recent experience of the United States College of American Pathologists proficiency testing program. Semin Thromb Hemost 2006; 32 (5) 499-504
    Article in Thieme ConnectPubMedGoogle Scholar
  • 45 Meijer P, Haverkate F. An external quality assessment program for von Willebrand factor laboratory analysis: an overview from the European concerted action on thrombosis and disabilities foundation. Semin Thromb Hemost 2006; 32 (5) 485-491
    Article in Thieme ConnectPubMedGoogle Scholar
  • 46 Kitchen S, Jennings I, Woods TA, Kitchen DP, Walker ID, Preston FE. Laboratory tests for measurement of von Willebrand factor show poor agreement among different centers: results from the United Kingdom National External Quality Assessment Scheme for Blood Coagulation. Semin Thromb Hemost 2006; 32 (5) 492-498
    Article in Thieme ConnectPubMedGoogle Scholar
  • 47 Chandler WL, Peerschke EIB, Castellone DD, Meijer P. NASCOLA Proficiency Testing Committee. Von Willebrand factor assay proficiency testing. The North American Specialized Coagulation Laboratory Association experience. Am J Clin Pathol 2011; 135 (6) 862-869
    CrossrefPubMedGoogle Scholar
  • 48 Favaloro EJ, Bonar R, Marsden K. Lower limit of assay sensitivity: an under-recognised and significant problem in von Willebrand disease identification and classification. Clin Lab Sci 2008; 21 (3) 178-183
    PubMedGoogle Scholar
  • 49 Flood VH, Friedman KD, Gill JC , et al. Limitations of the ristocetin cofactor assay in measurement of von Willebrand factor function. J Thromb Haemost 2009; 7 (11) 1832-1839
    CrossrefPubMedGoogle Scholar
  • 50 Flood VH, Gill JC, Morateck PA , et al. Common VWF exon 28 polymorphisms in African Americans affecting the VWF activity assay by ristocetin cofactor. Blood 2010; 116 (2) 280-286
    CrossrefPubMedGoogle Scholar
  • 51 Miller CH, Haff E, Platt SJ , et al. Measurement of von Willebrand factor activity: relative effects of ABO blood type and race. J Thromb Haemost 2003; 1 (10) 2191-2197
    CrossrefPubMedGoogle Scholar
  • 52 Flood VH, Lederman CA, Wren JS , et al. Absent collagen binding in a VWF A3 domain mutant: utility of the VWF:CB in diagnosis of VWD. J Thromb Haemost 2010; 8 (6) 1431-1433
    CrossrefPubMedGoogle Scholar
  • 53 Hampshire DJ, Goodeve AC. The international society on thrombosis and haematosis von Willebrand disease database: an update. Semin Thromb Hemost 2011; 37 (5) 470-479
    Article in Thieme ConnectPubMedGoogle Scholar
  • 54 Adcock DM, Bethel M, Valcour A. Diagnosing von Willebrand disease: a large reference laboratory's perspective. Semin Thromb Hemost 2006; 32 (5) 472-479
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Favaloro EJ, Thom J, Patterson D , et al. Desmopressin therapy to assist the functional identification and characterisation of von Willebrand disease: differential utility from combining two (VWF:CB and VWF:RCo) von Willebrand factor activity assays?. Thromb Res 2009; 123 (6) 862-868
    CrossrefPubMedGoogle Scholar
  • 56 EUROPEAN COMMISSION. Proposal for a REGULATION OF THE EUROPEAN PARLIAMENT AND OF THE COUNCIL on in vitro diagnostic medical devices. COM(2012) 541 final 2012/0267 (COD); available at: http://ec.europa.eu/health/medical-devices/documents/revision/index_en.htm ; accessed 21 st November 2012
    PubMedGoogle Scholar
  • 57 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 (5) 1009-1021
    Article in Thieme ConnectPubMedGoogle Scholar
  • 58 Ni Y, Nesrallah J, Agnew M, Geske FJ, Favaloro EJ. Establishment and characterization of a new and stable collagen-binding assay for the assessment of von Willebrand factor activity. Int J Lab Hematol 2013; 35 (2) 170-176
    CrossrefPubMedGoogle Scholar
  • 59 Favaloro EJ, Adcock DM. Standardization of the INR: how good is your laboratory's INR and can it be improved?. Semin Thromb Hemost 2008; 34 (7) 593-603
    Article in Thieme ConnectPubMedGoogle Scholar
  • 60 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 (8) 1079-1090
    PubMedGoogle Scholar
  • 61 Clinical and Laboratory Standards Institute. Procedures for Validation of INR and Local Calibration of PT/INR Systems; Approved Guideline. CLSI document H54-A [ISBN 1-56238-580-1]. Wayne, PA: Clinical and Laboratory Standards Institute; 2005
    Google Scholar
  • 62 van den Besselaar AMHP, Barrowcliffe TW, Houbouyan-Réveillard LL , et al; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the ISTH. Guidelines on preparation, certification, and use of certified plasmas for ISI calibration and INR determination. J Thromb Haemost 2004; 2 (11) 1946-1953
    CrossrefPubMedGoogle Scholar
  • 63 Poller L. Taberner, D A. Dosage and control of oral anticoagulants: an international collaborative survey. Br J Haematol 1982; 51 (3) 479-485
    CrossrefPubMedGoogle Scholar
  • 64 Olson JD, Brandt JT, Chandler WL , et al. Laboratory reporting of the international normalized ratio: progress and problems. Arch Pathol Lab Med 2007; 131 (11) 1641-1647
    PubMedGoogle Scholar
  • 65 Favaloro EJ, Wong RC. Laboratory testing for the antiphospholipid syndrome: making sense of antiphospholipid antibody assays. Clin Chem Lab Med 2011; 49 (3) 447-461
    CrossrefPubMedGoogle Scholar
  • 66 Favaloro EJ, Wong RCW. The antiphospholipid syndrome: a large elephant with many parts or an elusive chameleon disguised by many colours?. Autoimmunity Highlights 2010; 1: 5-14
    CrossrefPubMedGoogle Scholar
  • 67 Miyakis S, Lockshin MD, Atsumi T , et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost 2006; 4 (2) 295-306
    CrossrefPubMedGoogle Scholar
  • 68 Kershaw G, Suresh S, Orellana D, Nguy YM. Laboratory identification of lupus anticoagulants. Semin Thromb Hemost 2012; 38 (4) 375-384
    Article in Thieme ConnectPubMedGoogle Scholar
  • 69 Adams M. Measurement of lupus anticoagulants: an update on quality in laboratory testing. Semin Thromb Hemost 2013; 39 (3) 267-271
    Article in Thieme ConnectPubMedGoogle Scholar
  • 70 Froom P, Barak M. Testing for lupus anticoagulants—fresh or frozen?. Clin Chem Lab Med 2012; 50 (9) 1607-1609
    PubMedGoogle Scholar
  • 71 Harris EN, Gharavi AEM, Boey ML , et al. Anticardiolipin antibodies: detection by radioimmunoassay and association with thrombosis in systemic lupus erythematosus. Lancet 1983; 2 (8361) 1211-1214
    PubMedGoogle Scholar
  • 72 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 (4) 390-403
    Article in Thieme ConnectPubMedGoogle Scholar
  • 73 Favaloro EJ. Trials and tribulations in lupus anticoagulant testing. Clin Chem Lab Med 2013; 51 (2) 253-256
    PubMedGoogle Scholar
  • 74 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 (4) 404-411
    Article in Thieme ConnectPubMedGoogle Scholar
  • 75 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 (2) 142-147
    CrossrefPubMedGoogle Scholar
  • 76 Reber G, Arvieux J, Comby E , et al. Multicenter evaluation of nine commercial kits for the quantitation of anticardiolipin antibodies. The Working Group on Methodologies in Haemostasis from the GEHT (Groupe d'Etudes sur l'Hémostase et la Thrombose). Thromb Haemost 1995; 73 (3) 444-452
    PubMedGoogle Scholar
  • 77 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 (1) 73-84
    Article in Thieme ConnectPubMedGoogle Scholar
  • 78 Wong RC, Adelstein S, Gillis D, Favaloro EJ. Development of consensus guidelines for anticardiolipin and lupus anticoagulant testing. Semin Thromb Hemost 2005; 31 (1) 39-48
    Article in Thieme ConnectPubMedGoogle Scholar
  • 79 Reber G, Boehlen F, de Moerloose P. Technical aspects in laboratory testing for antiphospholipid antibodies: is standardization an impossible dream?. Semin Thromb Hemost 2008; 34 (4) 340-346
    Article in Thieme ConnectPubMedGoogle Scholar
  • 80 Pierangeli SS, Harris EN. A quarter of a century in anticardiolipin antibody testing and attempted standardization has led us to here, which is?. Semin Thromb Hemost 2008; 34 (4) 313-328
    Article in Thieme ConnectPubMedGoogle Scholar
  • 81 Lakos G, Favaloro EJ, Harris EN , et al. International consensus guidelines on anticardiolipin and anti-β2-glycoprotein I testing: report from the 13th International Congress on Antiphospholipid Antibodies. Arthritis Rheum 2012; 64 (1) 1-10
    CrossrefPubMedGoogle Scholar
  • 82 Pierangeli SS, Favaloro EJ, Lakos G , et al. Standards and reference materials for the anticardiolipin and anti-β2glycoprotein I assays: a report of recommendations from the APL Task Force at the 13th International Congress on Antiphospholipid Antibodies. Clin Chim Acta 2012; 413 (1–2) 358-360
    CrossrefPubMedGoogle Scholar
  • 83 Galli M, Luciani D, Bertolini G, Barbui T. Lupus anticoagulants are stronger risk factors for thrombosis than anticardiolipin antibodies in the antiphospholipid syndrome: a systematic review of the literature. Blood 2003; 101 (5) 1827-1832
    CrossrefPubMedGoogle Scholar
  • 84 Galli M, Luciani D, Bertolini G, Barbui T. Anti-beta 2-glycoprotein I, antiprothrombin antibodies, and the risk of thrombosis in the antiphospholipid syndrome. Blood 2003; 102 (8) 2717-2723
    CrossrefPubMedGoogle Scholar
  • 85 Galli M, Reber G, de Moerloose P, de Groot PG. Invitation to a debate on the serological criteria that define the antiphospholipid syndrome. J Thromb Haemost 2008; 6 (2) 399-401
    CrossrefPubMedGoogle Scholar
  • 86 de Groot PG, Derksen RH, de Laat B. Twenty-two years of failure to set up undisputed assays to detect patients with the antiphospholipid syndrome. Semin Thromb Hemost 2008; 34 (4) 347-355
    Article in Thieme ConnectPubMedGoogle Scholar
  • 87 de Groot PG, Urbanus RT. The future of antiphospholipid antibody testing. Semin Thromb Hemost 2012; 38 (4) 412-420
    Article in Thieme ConnectPubMedGoogle Scholar
  • 88 Urbanus RT, de Groot PG. Antiphospholipid antibodies—we are not quite there yet. Blood Rev 2011; 25 (2) 97-106
    CrossrefPubMedGoogle Scholar
  • 89 Whicher JT, Ritchie RF, Johnson AM , et al. New international reference preparation for proteins in human serum (RPPHS). Clin Chem 1994; 40 (6) 934-938
    PubMedGoogle Scholar
  • 90 Lippi G, Favaloro EJ, Plebani M. Direct-to-consumer testing: more risks than opportunities. Int J Clin Pract 2011; 65 (12) 1221-1229
    CrossrefPubMedGoogle Scholar
  • 91 Plebani M, Lippi G. Direct-to-consumer genomewide profiling. N Engl J Med 2011; 364 (21) 2074-2075 , author reply 2075
    CrossrefPubMedGoogle Scholar
  • 92 Plebani M. The CCLM contribution to improvements in quality and patient safety. Clin Chem Lab Med 2013; 51 (1) 39-46
    PubMedGoogle Scholar
  • 93 Lippi G, Salvagno GL, Montagnana M, Lima-Oliveira G, Guidi GC, Favaloro EJ. Quality standards for sample collection in coagulation testing. Semin Thromb Hemost 2012; 38 (6) 565-575
    Article in Thieme ConnectPubMedGoogle Scholar
  • 94 Adcock Funk DM, Lippi G, Favaloro EJ. Quality standards for sample processing, transportation, and storage in hemostasis testing. Semin Thromb Hemost 2012; 38 (6) 576-585
    Article in Thieme ConnectPubMedGoogle Scholar