Download PDF
Semin Thromb Hemost 2008; 34(7): 585-592
DOI: 10.1055/s-0028-1104537
© Thieme Medical Publishers

The History of Phenotypic Testing in Thrombosis and Hemostasis

Armando Tripodi1
  • 1Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Department of Internal Medicine, University and IRCCS Maggiore Hospital, Mangiagalli and Regina Elena Foundation, Milano, Italy
Further Information

Publication History

Publication Date:
15 December 2008 (online)

    Permissions and Reprints

ABSTRACT

This article takes the reader through a journey of the history of the phenotypic tests for hemostasis and thrombosis starting from the most simple (which were based on the visual inspection and recording of the time needed for native whole blood to clot) to the more complex ones based on the addition to plasma of exogenous substances, use of sophisticated coagulometers or synthetic substrates, and use of computer software to record coagulation times or visualize coagulation tracings and thrombin generation curves. One can see how the simple tests evolved over the years and how such old and time-honored tests as thrombin generation and thromboelastography, devised more than 50 years ago and neglected for many years, are now gaining momentum thanks to the progress made by the technology combined with a better understanding of the coagulation mechanisms. This progress notwithstanding, it should be realized that current tests are still somewhat far from being adequate to investigate hemostasis and thrombosis. The challenge in the future will be to devise newer tests mimicking more closely what occurs in vivo.

KEYWORDS

PT - APTT - coagulation tests - thrombin generation - synthetic substrates

REFERENCES

  • 1 Langdell R D, Wagner R H, Brinkhous K M. Effect of anti-hemophilic factor on one stage clotting tests: a presumptive test for hemophilia and a simple one-stage anti-hemophilic assay procedure.  J Lab Clin Med. 1953;  41 637-647
    PubMedSearch in Google Scholar
  • 2 Bell W N, Alton H G. A brain extract as a substitute for platelet suspension in the thromboplastin generation time.  Nature. 1954;  174 880-881
    PubMedSearch in Google Scholar
  • 3 Proctor R R, Rapaport S I. The partial thromboplastin time with kaolin. A simple screening test for first stage plasma clotting factor deficiencies.  Am J Clin Pathol. 1961;  36 212-219
    CrossrefPubMedSearch in Google Scholar
  • 4 Margolis J. The kaolin clotting time. A rapid one-stage method for diagnosis of coagulation defects.  J Clin Pathol. 1958;  11 406-409
    CrossrefPubMedSearch in Google Scholar
  • 5 Conley C L, Hartmann R C. A hemorrhagic disorder caused by circulating anticoagulant in patients with disseminated lupus erythematosus.  J Clin Invest. 1952;  31 621-622
    PubMedSearch in Google Scholar
  • 6 Bowie E J, Thompson Jr J H, Pascuzzi C A, Owen Jr C A. Thrombosis in systemic lupus erythematosus despite circulating anticoagulants.  J Lab Clin Med. 1963;  62 416-430
    PubMedSearch in Google Scholar
  • 7 Basu D, Gallus A, Hirsh J, Cade J. A prospective study of the value of monitoring heparin treatment with the activated partial thromboplastin time.  N Engl J Med. 1972;  287 324-327
    CrossrefPubMedSearch in Google Scholar
  • 8 Van der Velde E A, Poller L. The APTT monitoring of heparin–the ISTH/ICSH collaborative study.  Thromb Haemost. 1995;  73 73-81
    PubMedSearch in Google Scholar
  • 9 Dahlbäck B, Carlsson M, Svensson P J. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C.  Proc Natl Acad Sci U S A. 1993;  90 1004-1008
    PubMedSearch in Google Scholar
  • 10 Tripodi A, Chantarangkul V, Martinelli I, Bucciarelli P, Mannucci P M. A shortened activated partial thromboplastin time is associated with the risk of venous thromboembolism.  Blood. 2004;  104 3631-3634
    CrossrefPubMedSearch in Google Scholar
  • 11 Hron G, Eichinger S, Weltermann A, Quehenberger P, Halbmayer W M, Kyrle P A. Prediction of recurrent venous thromboembolism by the activated partial thromboplastin time.  J Thromb Haemost. 2006;  4 752-756
    CrossrefPubMedSearch in Google Scholar
  • 12 Lippi G, Favaloro E J. Activated partial thromboplastin time: new tricks for an old dogma.  Semin Thromb Hemost. 2008;  34 604-611
    Thieme ConnectPubMedSearch in Google Scholar
  • 13 Quick A J. The prothrombin in hemophilia and in obstructive jaundice.  J Biol Chem. 1935;  109 73-74
    PubMedSearch in Google Scholar
  • 14 Butt H R, Allen A V, Bollman J R. A preparation from spoiled sweet lover which prolong coagulation time of blood.  Proc Staff Meet Mayo Clin. 1941;  16 388-395
    PubMedSearch in Google Scholar
  • 15 Poller L. The effect of the use of different tissue extracts on one-stage prothrombin times.  Acta Haematol. 1964;  32 292-298
    PubMedSearch in Google Scholar
  • 16 Poller L. Standardization of anticoagulant treatment: the Manchester Regional Thromboplastin Scheme.  Br Med J. 1964;  2 564-566
    PubMedSearch in Google Scholar
  • 17 Owren P A. Thrombotest. A new method for controlling anticoagulant therapy.  Lancet. 1959;  2 754-758
    PubMedSearch in Google Scholar
  • 18 De Vries S I. Introduction to thrombotest at the Netherlands Thrombosis Service. In: Hemker HC, Loeliger EA, Veltkamp JJ Human Blood Coagulation. Leiden, The Netherlands; Leiden University Press 1969: 314-317
    Search in Google Scholar
  • 19 Biggs R, Denson K WE. Standardization of the one-stage prothrombin time for control of anticoagulant therapy.  BMJ. 1967;  1 84-88
    PubMedSearch in Google Scholar
  • 20 Bangham D R, Biggs R, Brozovic M, Denson K WE. Calibration of five different thromboplastins using fresh and freeze-dried plasma.  Thromb Diath Haemorrh. 1973;  29 228-239
    PubMedSearch in Google Scholar
  • 21 International Committee on Thrombosis and Haemostasis (ICTH) and International Committee for Standardization in Haematology (ICSH) . Prothrombin time standardization: report of the export panel on anticoagulant control.  Thromb Haemost. 1979;  42 1073-1114
    PubMedSearch in Google Scholar
  • 22 Expert WHO Committee on Biological Standardization .Twenty-eighth report. Technical Report Series, No. 610. Geneva, Switzerland; WHO 1977
    Search in Google Scholar
  • 23 Hermans J, van den Besselaar A M, Loeliger E A, van der Velde E A. A collaborative study of reference material for thromboplastins.  Thromb Haemost. 1983;  50 712-717
    PubMedSearch in Google Scholar
  • 24 Kirkwood T BL. Calibration of reference thromboplastins and standardization of the prothrombin time ratio.  Thromb Haemost. 1983;  49 238-244
    PubMedSearch in Google Scholar
  • 25 Expert WHO Committee on Biological Standardization .Thirty-third report. Technical Report Series, No. 687. Geneva, Switzerland; WHO 1983
    Search in Google Scholar
  • 26 Van den Besselaar AMHP, Gralnick HR, Lewis SM Thromboplastin Calibration and Oral Anticoagulant Control. Boston, MA; Martinus Nijhoff Publishers 1984
    Search in Google Scholar
  • 27 Thomson J M, Tomenson J A, Poller L. The calibration of second primary international reference preparation for thromboplastin (thromboplastin, human, plain, coded BCT/253).  Thromb Haemost. 1984;  52 336-342
    Thieme ConnectPubMedSearch in Google Scholar
  • 28 Tripodi A, Arbini A, Chantarangkul V, Mannucci P M. Recombinant tissue factor as substitute for conventional thromboplastin in the prothrombin time test.  Thromb Haemost. 1992;  67 42-45
    PubMedSearch in Google Scholar
  • 29 Tripodi A, Chantarangkul V, Braga M et al.. Results of a multicenter study assessing the status of standardization of a recombinant thromboplastin for the control of oral anticoagulant therapy.  Thromb Haemost. 1994;  72 261-267
    PubMedSearch in Google Scholar
  • 30 Tripodi A, Chantarangkul V, Negri B, Clerici M, Mannucci P M. International collaborative study for the calibration of a proposed reference preparation for thromboplastin, human recombinant, plain. On behalf of the Subcommittee on Control of Anticoagulation.  Thromb Haemost. 1998;  79 439-443
    PubMedSearch in Google Scholar
  • 31 van den Besselaar A MHP, Poller L, Tripodi A. World Health Organization (WHO) Guidelines for Thromboplastins and Plasma Used to Control Oral Anticoagulant Therapy. WHO Technical Report Series, No. 889. Geneva, Switzerland; WHO 1999
    Search in Google Scholar
  • 32 Trotter J F, Brimhall B, Arjal R. Specific laboratory methodologies achieve higher model for endstage liver disease (MELD) scores for patients listed for liver transplantation.  Liver Transpl. 2004;  10 995-1000
    CrossrefPubMedSearch in Google Scholar
  • 33 Wiesner R, Edwards E, Freeman R et al.. United Network for Organ Sharing Liver Disease Severity Score Committee. Model for end-stage liver disease (MELD) and allocation of donor liver.  Gastroenterology. 2003;  124 91-96
    CrossrefPubMedSearch in Google Scholar
  • 34 Tripodi A, Chantarangkul V, Mannucci P M. The International normalized ratio to prioritize patients for liver transplantation. Problems and possible solutions.  J Thromb Haemost. 2008;  6 243-248
    CrossrefPubMedSearch in Google Scholar
  • 35 Favaloro E J, Adcock D. Standardization of the INR: How good is your laboratory's INR and can it be improved?.  Semin Thromb Hemost. 2008;  34 593-603
    Thieme ConnectPubMedSearch in Google Scholar
  • 36 Ciavarella N, Eder G, Mannucci P M, Mariani G Italian CISMEL Study Group et al.. Multicenter comparison of nine coagulometers and manual tilt-tube methods for prothrombin time performance.  Clin Lab Haematol. 1983;  5 177-184
    PubMedSearch in Google Scholar
  • 37 Triplett D A. New methods in coagulation.  Crit Rev Clin Lab Sci. 1981;  15 25-84
    PubMedSearch in Google Scholar
  • 38 Tripodi A, Mannucci P M. Clinical evaluation of a fully automated chromogenic method for prothrombin time compared with a conventional coagulation method.  Clin Chem. 1984;  30 1392-1395
    PubMedSearch in Google Scholar
  • 39 Tripodi A, Poggio M, Scapellato L, Mannucci P M. Automated amidolytic method for activated partial thromboplastin time compared with a conventional coagulation method.  Haemostasis. 1989;  19 205-212
    PubMedSearch in Google Scholar
  • 40 Frantzen Handeland G, Abildgaard U, Aasen A O. Simplified assay for antithrombin III activity using chromogenic peptide substrate. Manual and automated method.  Scand J Haematol. 1983;  31 427-436
    PubMedSearch in Google Scholar
  • 41 Tang J C, Li S, McGray P, Vecchio A. Current status of activity assays for tissue plasminogen activator.  Ann N Y Acad Sci. 1984;  434 536-540
    CrossrefPubMedSearch in Google Scholar
  • 42 Tripodi A, Mannucci P M. Factor VIII activity as measured by an amidolytic assay compared with a one-stage clotting assay.  Am J Clin Pathol. 1986;  86 341-344
    PubMedSearch in Google Scholar
  • 43 Franchi F, Tripodi A, Valsecchi C, Mannucci P M. Functional assay of protein C: comparison of two snake-venom assays with two thrombin assays.  Thromb Haemost. 1988;  60 145-148
    PubMedSearch in Google Scholar
  • 44 Macfarlane R G, Biggs R. A thrombin generation test.  J Clin Pathol. 1953;  6 3-7
    CrossrefPubMedSearch in Google Scholar
  • 45 Hemker H C, Willems G M, Béguin S. A computer assisted method to obtain the prothrombin activation velocity in whole plasma independent of thrombin decay processes.  Thromb Haemost. 1986;  56 9-17
    PubMedSearch in Google Scholar
  • 46 Hemker H C, Wielders S, Kessels H, Béguin S. Continuous registration of thrombin generation in plasma, its use for the determination of the thrombin potential.  Thromb Haemost. 1993;  70 617-624
    PubMedSearch in Google Scholar
  • 47 Hemker H C, Giesen P L, Ramjee M, Wagenvoord R, Béguin S. The thrombogram: monitoring thrombin generation in platelet-rich plasma.  Thromb Haemost. 2000;  83 589-591
    PubMedSearch in Google Scholar
  • 48 Hartert H. Blutgerninnungstudien mit der thromboelastographic.  Einen neven Untersuchingsver Farhen Klinische Wocheschrift. 1948;  16 257-260
    PubMedSearch in Google Scholar
  • 49 Caprini J A, Traverso C I, Arcelus J I. Perspectives on thromboelastography.  Semin Thromb Hemost. 1995;  21(Suppl 4) 91-93
    PubMedSearch in Google Scholar
  • 50 Gillies B S. Thromboelastography and liver transplantation.  Semin Thromb Hemost. 1995;  (21 Suppl 4) 45-49
    PubMedSearch in Google Scholar
  • 51 Mancuso A, Fung K, Cox D et al.. Assessment of blood coagulation in severe liver disease using thromboelastography: use of citrate storage versus native blood.  Blood Coagul Fibrinolysis. 2003;  14 211-216
    CrossrefPubMedSearch in Google Scholar

Armando TripodiPh.D. 

Via Pace 9

20122-Milano, Italy

Email: armando.tripodi@unimi.it