Skip to main content
Log in

Platelet factor 4/heparin-particle gel immunoassay (PaGIA) is a weak method for heparin-induced thrombocytopenia (HIT) evaluation of post cardio-pulmonary bypass surgery patients

  • Published:
Journal of Thrombosis and Thrombolysis Aims and scope Submit manuscript

Abstract

Diagnosis of heparin induced thrombocytopenia (HIT) is not always easy, especially when a confirmatory functional test is not available. In most cases the diagnosis relies on the combination of pretest probability and an immunologic test. Among patients post cardiopulmonary bypass (CPB) surgery, anti-platelet factor 4/heparin antibodies tend to be high but with low clinical implication. The current retrospective study examined the behavior of patients with positive PF4/heparin-PaGIA results, divided into two groups according to whether or not they have undergone CPB surgery. The main focus of the study was on the reliability of the PF4/heparin-PaGIA test in these two settings. The files of 104 single center patients, who had a positive PF4/heparin-PaGIA test, were reviewed. 62 % were post CPB and 38 % were not. An association between the intensity of positivity of PF4/heparin-PaGIA test and both the 4Ts pretest probability method (p = 0.003) and the incidence of thrombosis (p = 0.02) was found only in the patients who have not undergone CPB surgery, but not in the CPB patients. This study suggests that PF4/heparin-PaGIA is not a reliable method in patients post CPB surgery who are investigated for a possible diagnosis of HIT.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4(4):759–765. doi:10.1111/j.1538-7836.2006.01787.x

    Article  CAS  PubMed  Google Scholar 

  2. Cuker A, Arepally G, Crowther MA, Rice L, Datko F, Hook K, Propert KJ, Kuter DJ, Ortel TL, Konkle BA, Cines DB (2010) The HIT expert probability (HEP) score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost 8(12):2642–2650. doi:10.1111/j.1538-7836.2010.04059.x

    Article  CAS  PubMed  Google Scholar 

  3. Lillo-Le Louet A, Boutouyrie P, Alhenc-Gelas M, Le Beller C, Gautier I, Aiach M, Lasne D (2004) Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost 2(11):1882–1888. doi:10.1111/j.1538-7836.2004.00949.x

    Article  CAS  PubMed  Google Scholar 

  4. Sheridan D, Carter C, Kelton JG (1986) A diagnostic test for heparin-induced thrombocytopenia. Blood 67(1):27–30

    CAS  PubMed  Google Scholar 

  5. Bakchoul T, Giptner A, Najaoui A, Bein G, Santoso S, Sachs UJ (2009) Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 7(8):1260–1265. doi:10.1111/j.1538-7836.2009.03465.x

    Article  CAS  PubMed  Google Scholar 

  6. Warkentin TE, Sheppard JI, Moore JC, Sigouin CS, Kelton JG (2008) Quantitative interpretation of optical density measurements using PF4-dependent enzyme-immunoassays. J Thromb Haemost 6(8):1304–1312. doi:10.1111/j.1538-7836.2008.03025.x

    Article  CAS  PubMed  Google Scholar 

  7. Whitlatch NL, Perry SL, Ortel TL (2008) Anti-heparin/platelet factor 4 antibody optical density values and the confirmatory procedure in the diagnosis of heparin-induced thrombocytopenia. Thromb Haemost 100(4):678–684

    CAS  PubMed Central  PubMed  Google Scholar 

  8. Zwicker JI, Uhl L, Huang WY, Shaz BH, Bauer KA (2004) Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia. J Thromb Haemost 2(12):2133–2137. doi:10.1111/j.1538-7836.2004.01039.x

    Article  CAS  PubMed  Google Scholar 

  9. Baroletti S, Hurwitz S, Conti NA, Fanikos J, Piazza G, Goldhaber SZ (2012) Thrombosis in suspected heparin-induced thrombocytopenia occurs more often with high antibody levels. Am J Med 125(1):44–49. doi:10.1016/j.amjmed.2011.06.025

    Article  CAS  PubMed  Google Scholar 

  10. Ruf KM, Bensadoun ES, Davis GA, Flynn JD, Lewis DA (2011) A clinical-laboratory algorithm incorporating optical density value to predict heparin-induced thrombocytopenia. Thromb Haemost 105(3):553–559. doi:10.1160/TH10-09-0610

    Article  CAS  PubMed  Google Scholar 

  11. Cuker A, Cines DB (2012) How I treat heparin-induced thrombocytopenia. Blood 119(10):2209–2218. doi:10.1182/blood-2011-11-376293

    Article  CAS  PubMed  Google Scholar 

  12. Meyer O, Salama A, Pittet N, Schwind P (1999) Rapid detection of heparin-induced platelet antibodies with particle gel immunoassay (ID-HPF4). Lancet 354(9189):1525–1526. doi:10.1016/S0140-6736(99)03625-9

    Article  CAS  PubMed  Google Scholar 

  13. Eichler P, Raschke R, Lubenow N, Meyer O, Schwind P, Greinacher A (2002) The new ID-heparin/PF4 antibody test for rapid detection of heparin-induced antibodies in comparison with functional and antigenic assays. Br J Haematol 116(4):887–891

    Article  CAS  PubMed  Google Scholar 

  14. Pouplard C, Gueret P, Fouassier M, Ternisien C, Trossaert M, Regina S, Gruel Y (2007) Prospective evaluation of the ‘4Ts’ score and particle gel immunoassay specific to heparin/PF4 for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 5(7):1373–1379. doi:10.1111/j.1538-7836.2007.02524.x

    Article  CAS  PubMed  Google Scholar 

  15. Nellen V, Sulzer I, Barizzi G, Lammle B, Alberio L (2012) Rapid exclusion or confirmation of heparin-induced thrombocytopenia: a single-center experience with 1,291 patients. Haematologica 97(1):89–97

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Selleng S, Malowsky B, Strobel U, Wessel A, Ittermann T, Wollert HG, Warkentin TE, Greinacher A (2010) Early-onset and persisting thrombocytopenia in post-cardiac surgery patients is rarely due to heparin-induced thrombocytopenia, even when antibody tests are positive. J Thromb Haemost 8(1):30–36. doi:10.1111/j.1538-7836.2009.03626.x

    Article  CAS  PubMed  Google Scholar 

  17. Gruel Y, Pouplard C (2010) Post-operative platelet count profile: the most reliable tool for identifying patients with true heparin-induced thrombocypenia after cardiac surgery. J Thromb Haemost 8(1):27–29. doi:10.1111/j.1538-7836.2009.03646.x

    Article  CAS  PubMed  Google Scholar 

  18. Pouplard C, May MA, Iochmann S, Amiral J, Vissac AM, Marchand M, Gruel Y (1999) Antibodies to platelet factor 4-heparin after cardiopulmonary bypass in patients anticoagulated with unfractionated heparin or a low-molecular-weight heparin: clinical implications for heparin-induced thrombocytopenia. Circulation 99(19):2530–2536

    Article  CAS  PubMed  Google Scholar 

  19. Abramson JH (2011) WINPEPI updated: computer programs for epidemiologists, and their teaching potential. Epidemiol Perspect Innov 8(1):1. doi:10.1186/1742-5573-8-1

    Article  PubMed Central  PubMed  Google Scholar 

  20. Visentin GP, Malik M, Cyganiak KA, Aster RH (1996) Patients treated with unfractionated heparin during open heart surgery are at high risk to form antibodies reactive with heparin: platelet factor 4 complexes. J Lab Clin Med 128(4):376–383

    Article  CAS  PubMed  Google Scholar 

  21. Bauer TL, Arepally G, Konkle BA, Mestichelli B, Shapiro SS, Cines DB, Poncz M, McNulty S, Amiral J, Hauck WW, Edie RN, Mannion JD (1997) Prevalence of heparin-associated antibodies without thrombosis in patients undergoing cardiopulmonary bypass surgery. Circulation 95(5):1242–1246

    Article  CAS  PubMed  Google Scholar 

  22. Warkentin TE, Sheppard JA, Horsewood P, Simpson PJ, Moore JC, Kelton JG (2000) Impact of the patient population on the risk for heparin-induced thrombocytopenia. Blood 96(5):1703–1708

    CAS  PubMed  Google Scholar 

  23. Cella G, Vittadello O, Gallucci V, Girolami A (1981) The release of beta-thromboglobulin and platelet factor 4 during extracorporeal circulation for open heart surgery. Eur J Clin Invest 11(3):165–169

    Article  CAS  PubMed  Google Scholar 

  24. Sachais BS, Litvinov RI, Yarovoi SV, Rauova L, Hinds JL, Rux AH, Arepally GM, Poncz M, Cuker A, Weisel JW, Cines DB (2012) Dynamic antibody-binding properties in the pathogenesis of HIT. Blood 120(5):1137–1142. doi:10.1182/blood-2012-01-407262

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Warkentin TE, Greinacher A (2003) Heparin-induced thrombocytopenia and cardiac surgery. Ann Thorac Surg 76(6):2121–2131

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Chezi Ganzel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ganzel, C., Rowe, J. & Raveh, D. Platelet factor 4/heparin-particle gel immunoassay (PaGIA) is a weak method for heparin-induced thrombocytopenia (HIT) evaluation of post cardio-pulmonary bypass surgery patients. J Thromb Thrombolysis 38, 314–320 (2014). https://doi.org/10.1007/s11239-014-1066-5

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11239-014-1066-5

Keywords

Navigation