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Journal of Thrombosis and Thrombolysis

, Volume 49, Issue 1, pp 27–33 | Cite as

Comparison of polyspecific versus IgG specific ELISA in predominately cardiac patients with suspected heparin induced thrombocytopenia

  • Sophie SamuelEmail author
  • Mary F. McGuire
  • Jennifer Cortes
  • Miguel Escobar
  • Phillip Weeks
  • Andy Nguyen
Article
  • 46 Downloads

Abstract

A diagnosis of heparin induced thrombocytopenia (HIT) must often be made based on clinical and laboratory evidence. This was a quasi-experimental study of patients admitted from June 2016 to October 2017. The primary endpoint was the incidence of false positive results in polyspecific and IgG specific enzyme-linked immunosorbent assay (ELISA); then we compared the sensitivity and specificity of each assays in predominately cardiac patients with suspected HIT. A sensitivity/specificity analysis was conducted using serotonin release assay (SRA) as the ‘gold standard’. The secondary outcome measures included length of hospital stay. We identified a total of 155 patients who met the inclusion criteria. Confirmatory tests with SRA on both groups were completed; false positive result was higher in the polyspecific group when compared to the IgG group [60% vs. 5%]. The IgG specific ELISA test yielded a sensitivity of 100% and a specificity of 95% however, the polyspecific ELISA had a low yield for specificity of 24% but maintained 100% sensitivity. In the IgG specific group with HIT-, their median length of stay was halved compared to those who were HIT + ; hospital LOS in days, IQR [30 (27–81) vs. 15 (7–33) p = 0.023] and a shorter median LOS in the ICU, IQR [24 (5–47) vs. 6 (2–14); p = 0.079]. Hospital or ICU LOS was the same in both (HIT+ and HIT−) groups managed with polyspecific ELISA. The IgG specific test had few false positive results and a high sensitivity score. Ensuring appropriate testing can bring a substantial decrease in drug expenditure, reduced length of stay and prevent unnecessary anticoagulation.

Keywords

Heparin Enzyme-linked immunosorbent assay Heparin induced thrombocytopenia Direct thrombin inhibitor 

Notes

Author contributions

SS: study concept and design, acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. MM: analysis and interpretation, critical revision of the manuscript for important intellectual content. JC: acquisition of data, analysis and interpretation, critical revision of the manuscript for important intellectual content. ME: analysis and interpretation, critical revision of the manuscript for important intellectual content. PW: analysis and interpretation, critical revision of the manuscript for important intellectual content. AN: analysis and interpretation, critical revision of the manuscript for important intellectual content.

Supplementary material

11239_2019_1957_MOESM1_ESM.doc (26 kb)
Supplementary material 1 (DOC 26 kb)
11239_2019_1957_MOESM2_ESM.doc (26 kb)
Supplementary material 2 (DOC 26 kb)
11239_2019_1957_MOESM3_ESM.doc (137 kb)
Supplementary material 3 (DOC 137 kb)

References

  1. 1.
    Nanwa N, Mittmann N, Knowles S et al (2011) The direct medical costs associated with suspected heparin-induced thrombocytopenia. Pharmacoeconomics 29(6):511–520.  https://doi.org/10.2165/11584330 CrossRefPubMedGoogle Scholar
  2. 2.
    Dang CH, Durkalski VL, Nappi JM (2006) Evaluation of treatment with direct thrombin inhibitors in patients with heparin-induced thrombocytopenia. Pharmacotherapy 26(4):461–468.  https://doi.org/10.1592/phco.26.4.461 CrossRefPubMedGoogle Scholar
  3. 3.
    Cuker A, Arepally G, Crowther MA et al (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.  https://doi.org/10.1111/j.1538-7836.2010.04059.x CrossRefPubMedGoogle Scholar
  4. 4.
    Cuker A, Gimotty PA, Crowther MA, Warkentin TE (2012) Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood 120(20):4160–4167.  https://doi.org/10.1182/blood-2012-07-443051 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Lillo-Le Louët A, Boutouyrie P, Alhenc-Gelas M et al (2004) Diagnostic score for heparin-induced thrombocytopenia after cardiopulmonary bypass. J Thromb Haemost 2(11):1882–1888.  https://doi.org/10.1111/j.1538-7836.2004.00949.x CrossRefPubMedGoogle Scholar
  6. 6.
    Warkentin TE (2006) Think of HIT. Hematology 2006(1):408–414.  https://doi.org/10.1182/asheducation-2006.1.408 CrossRefGoogle Scholar
  7. 7.
    Ahmed I, Majeed A, Powell R (2007) Heparin induced thrombocytopenia: diagnosis and management update. Postgrad Med J 83(983):575–582.  https://doi.org/10.1136/pgmj.2007.059188 CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Walenga JM, Jeske WP, Fasanella AR, Wood JJ, Ahmad S, Bakhos M (1999) Laboratory diagnosis of heparin-induced thrombocytopenia. Clin Appl Thromb Hemost 5(Suppl 1):S21–S27CrossRefGoogle Scholar
  9. 9.
    Warkentin TE, Heddle NM (2003) Laboratory diagnosis of immune heparin-induced thrombocytopenia. Curr Hematol Rep 2(2):148–157PubMedGoogle Scholar
  10. 10.
    Warkentin TE, Sheppard J-AI (2006) Testing for heparin-induced thrombocytopenia antibodies. Transfus Med Rev 20(4):259–272.  https://doi.org/10.1016/j.tmrv.2006.05.001 CrossRefPubMedGoogle Scholar
  11. 11.
    Schallmoser K, Drexler C, Rohde E et al (2009) The particle gel immunoassay as a rapid test to rule out heparin-induced thrombocytopenia? J Thorac Cardiovasc Surg 137(3):781–783.  https://doi.org/10.1016/j.jtcvs.2008.03.044 CrossRefPubMedGoogle Scholar
  12. 12.
    Greinacher A, Ittermann T, Bagemühl J et al (2010) Heparin-induced thrombocytopenia: towards standardization of platelet factor 4/heparin antigen tests. J Thromb Haemost 8(9):2025–2031.  https://doi.org/10.1111/j.1538-7836.2010.03974.x CrossRefPubMedGoogle Scholar
  13. 13.
    Zwicker JI, Uhl L, Huang W-Y, 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.  https://doi.org/10.1111/j.1538-7836.2004.01039.x CrossRefPubMedGoogle Scholar
  14. 14.
    Arepally G, Reynolds C, Tomaski A et al (1995) Comparison of PF4/heparin ELISA assay with the 14C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol 104(6):648–654CrossRefGoogle Scholar
  15. 15.
    Raschke RA, Curry SC, Warkentin TE, Gerkin RD (2013) Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and Bayes theorem. Chest 144(4):1269–1275.  https://doi.org/10.1378/chest.12-2712 CrossRefPubMedGoogle Scholar
  16. 16.
    Morel-Koppm M-C, Aboud M, Tan CW, Kulathilake C, Ward C (2011) Heparin-induced thrombocytopenia: evaluation of IgG and IgGAM ELISA assays. Int J Lab Hematol 33(3):245–250.  https://doi.org/10.1111/j.1751-553X.2010.01276.x CrossRefGoogle Scholar
  17. 17.
    Ruf K, Bensadoun E, Davis G, Flynn J, Lewis D (2011) A clinical-laboratory algorithm incorporating optical density value to predict heparin-induced thrombocytopenia. Thromb Haemost 105(03):553–559.  https://doi.org/10.1160/TH10-09-0610 CrossRefPubMedGoogle Scholar
  18. 18.
    Suvarna S, Espinasse B, Qi R et al (2007) Determinants of PF4/heparin immunogenicity. Blood 110(13):4253–4260.  https://doi.org/10.1182/blood-2007-08-105098 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Pouplard C, May MA, Regina S, Marchand M, Fusciardi J, Gruel Y (2005) Changes in platelet count after cardiac surgery can effectively predict the development of pathogenic heparin-dependent antibodies. Br J Haematol 128(6):837–841.  https://doi.org/10.1111/j.1365-2141.2005.05381.x CrossRefPubMedGoogle Scholar
  20. 20.
    Aljabri A, Huckleberry Y, Karnes J et al (2016) Cost-effectiveness of anticoagulants for the management of suspected heparin-induced thrombocytopenia in the US. Blood.  https://doi.org/10.1182/blood-2016-07-728030 CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Kiser TH, Burch JC, Klem PM, Hassell KL (2008) Safety, efficacy, and dosing requirements of bivalirudin in patients with heparin-induced thrombocytopenia. Pharmacotherapy 28(9):1115–1124.  https://doi.org/10.1592/phco.28.9.1115 CrossRefPubMedGoogle Scholar
  22. 22.
    Boshkov LK, Warkentin TE, Hayward CP, Andrew M, Kelton JG (1993) Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies. Br J Haematol 84(2):322–328CrossRefGoogle Scholar
  23. 23.
    Sheridan D, Carter C, Kelton JG (1986) A diagnostic test for heparin-induced thrombocytopenia. Blood 67(1):27–30CrossRefGoogle Scholar
  24. 24.
    Husseinzadeh HD, Gimotty PA, Pishko AM et al (2017) Diagnostic accuracy of IgG-specific versus polyspecific enzyme-linked immunoassays in heparin-induced thrombocytopenia: a systematic review and meta-analysis. J Thromb Haemost 15(6):1203–1212.  https://doi.org/10.1111/jth.13692 CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chong BH, Burgess J, Ismail F (1993) The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia. Thromb Haemost 69(4):344–350CrossRefGoogle Scholar
  26. 26.
    Gobbi Giuliana et al (2004) New laboratory test in flow cytometry for the combined analysis of serologic and cellular parameters in the diagnosis of heparin-induced thrombocytopenia. Cytometry B (Clin Cytom) 58B:32–38CrossRefGoogle Scholar
  27. 27.
    Ganzel C, Rowe J, Raveh D (2014) 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(3):314–320CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Sophie Samuel
    • 1
    Email author
  • Mary F. McGuire
    • 2
  • Jennifer Cortes
    • 3
  • Miguel Escobar
    • 4
  • Phillip Weeks
    • 5
  • Andy Nguyen
    • 6
  1. 1.Department of Pharmacy, Neuroscience Intensive Care UnitMemorial Hermann - Texas Medical CenterHoustonUSA
  2. 2.Department of Neurosurgery and NeurologyThe University of Texas McGovern Medical SchoolHoustonUSA
  3. 3.Department of Pharmacy, Medical Intensive Care UnitMemorial Hermann - Texas Medical CenterHoustonUSA
  4. 4.Department of HematologyThe University of Texas McGovern Medical SchoolHoustonUSA
  5. 5.Department of Pharmacy, Heart and Vascular InstituteMemorial Hermann - Texas Medical CenterHoustonUSA
  6. 6.Department of Pathology and Laboratory MedicineThe University of Texas McGovern Medical SchoolHoustonUSA

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