CC BY-NC-ND 4.0 · TH Open 2021; 05(04): e507-e512
DOI: 10.1055/a-1653-5065
Original Article

Heparin-induced Thrombocytopenia Diagnosis: A Retrospective Study Comparing Heparin-induced Platelet Activation Test to 14C-serotonin Release Assay

Marie-Caroline Gonthier*
1   Laboratory of Vascular Translational Science, Université de Paris, INSERM, et Laboratoire d'Hématologie, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
,
Nicolas Gendron*
1   Laboratory of Vascular Translational Science, Université de Paris, INSERM, et Laboratoire d'Hématologie, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
2   Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris.Centre-Université de Paris (APHP-CUP), Paris, France
,
Philippine Eloy
3   Département d'Epidémiologie, Biostatistique et Recherche Clinique, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
,
1   Laboratory of Vascular Translational Science, Université de Paris, INSERM, et Laboratoire d'Hématologie, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
,
Martine Alhenc-Gelas
2   Hematology Department and Biosurgical Research Lab (Carpentier Foundation), Assistance Publique Hôpitaux de Paris.Centre-Université de Paris (APHP-CUP), Paris, France
,
Claire Pouplard
4   CHRU Tours, Service d'hématologie-hémostase, Université de Tours, Tours, France
,
Bernard Tardy
5   Inserm CIC 1408 CHU Saint Etienne, Saint-Etienne, France
,
Jean Szymezak
6   Laboratoire d'hématologie, CHU Robert Debré, Reims, France
,
Charles Burdet
3   Département d'Epidémiologie, Biostatistique et Recherche Clinique, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
7   Université de Paris, IAME, INSERM, Paris, France
,
Vasiliki Gkalea
1   Laboratory of Vascular Translational Science, Université de Paris, INSERM, et Laboratoire d'Hématologie, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
,
Dorothée Faille
1   Laboratory of Vascular Translational Science, Université de Paris, INSERM, et Laboratoire d'Hématologie, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
,
Nadine Ajzenberg
1   Laboratory of Vascular Translational Science, Université de Paris, INSERM, et Laboratoire d'Hématologie, AH-HP, Bichat–Claude Bernard Hospital, Paris, France
› Author Affiliations

Abstract

Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is of crucial importance and remains challenging and relies on platelet functional assays highlighting the presence of heparin-dependent platelet-activating antibodies in patient serum or plasma. Platelet functional assays using washed platelets include the 14C-serotonin release assay (SRA), usually described as the gold standard, and the heparin-induced platelet activation assay (HIPA). Since its first comparison with SRA there has been no additional published study regarding HIPA diagnostic performances compared with SRA. Aim of our retrospective study was to compare the concordance between HIPA and SRA in HIT suspected-patients with positive anti-PF4/heparin antibodies between October 2010 and October 2015. Fifty-five HIT-suspected patients who beneficiated from both HIPA and SRA were included. Positive and negative percent agreements were 83.8% (95% CI 68.0–93.8%) and 66.7% (95% CI 41.0–86.7%), respectively. Overall percent agreement was 78.2% (95% CI 65.0–92.2%). Agreement was higher in patients who underwent cardiopulmonary bypass with extracorporeal circulation circuit for cardiac surgery. We also confirm that the use of a minimum of 2 platelet donors to establish positive HIT diagnosis and 4 platelet donors to exclude HIT diagnosis allows obtaining a good agreement with SRA. Although HIPA and SRA were performed with different platelet donors and in different laboratories, HIPA had a good positive agreement with SRA for HIT diagnosis, showing that HIPA is a useful functional assay that does not require radioactivity and could be developed worldwide to improve HIT diagnosis.

Author Contributions

CΓ, NG, MCB, MAG, CP, BT, JS, DF and NA performed the research


CG, DF and NA designed the research study


NG, PE, CB, VG, DF and NA analyzed the data


NG, VG, DF and NA wrote the paper.


Disclosures

Authors do not have any conflict of interest to declare.


* These two authors contributed equally to the work




Publication History

Received: 27 July 2021

Accepted: 08 September 2021

Accepted Manuscript online:
24 September 2021

Article published online:
09 November 2021

© 2021. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Greinacher A. Heparin-Induced Thrombocytopenia. N Engl J Med 2015; 373 (19) 1883-1884
  • 2 Arepally GM. Heparin-induced thrombocytopenia. Blood 2017; 129 (21) 2864-2872
  • 3 Amiral J, Bridey F, Dreyfus M. et al. Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost 1992; 68 (01) 95-96
  • 4 Linkins L-A, Dans AL, Moores LK. et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest; 2012. 141. e495S-e530S
  • 5 Cuker A, Arepally GM, Chong BH. et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv 2018; 2 (22) 3360-3392
  • 6 Nagler M, Bachmann LM, ten Cate H, ten Cate-Hoek A. Diagnostic value of immunoassays for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood 2016; 127 (05) 546-557
  • 7 Tardy B, Lecompte T, Mullier F, Vayne C, Pouplard C. Detection of Platelet-Activating Antibodies Associated with Heparin-Induced Thrombocytopenia. J Clin Med 2020; 9 (04) 1226 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230370/cited2021Jul27 [Internet]
  • 8 Warkentin TE, Greinacher A, Gruel Y, Aster RH, Chong BH. scientific and standardization committee of the international society on thrombosis and haemostasis. Laboratory testing for heparin-induced thrombocytopenia: a conceptual framework and implications for diagnosis. J Thromb Haemost 2011; 9 (12) 2498-2500
  • 9 Greinacher A, Michels I, Kiefel V, Mueller-Eckhardt C. A rapid and sensitive test for diagnosing heparin-associated thrombocytopenia. Thromb Haemost 1991; 66 (06) 734-736
  • 10 Warkentin TE, Arnold DM, Nazi I, Kelton JG. The platelet serotonin-release assay. Am J Hematol 2015; 90 (06) 564-572
  • 11 Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood 1986; 67 (01) 27-30
  • 12 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
  • 13 Arangalage D, Lepage L, Faille D. et al. Presentation, management and outcome of heparin-induced thrombocytopenia after valvular heart surgery. Eur J Cardiothorac Surg 2016; 50 (06) 1132-1138
  • 14 Jandrot-Perrus M, Lagrue AH, Okuma M, Bon C. Adhesion and activation of human platelets induced by convulxin involve glycoprotein VI and integrin alpha2beta1. J Biol Chem 1997; 272 (43) 27035-27041
  • 15 Carré J, Guérineau H, Le Beller C. et al. Direct Oral Anticoagulants as Successful Treatment of Heparin-Induced Thrombocytopenia: A Parisian Retrospective Case Series. Front Med (Lausanne) 2021; 8: 713649
  • 16 Meier K. Guidance for Industry and FDA Staff - Statistical Guidance on Reporting Results from Studies Evaluating Diagnostic Tests. 2007 [cited 1019 Dec 1]; 39. Available from: https://www.fda.gov/media/71147/download
  • 17 R Core Team. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing. Vienna, Austria: 2018. . Available from: https://www.r-project.org/
  • 18 Bakchoul T, Giptner A, Najaoui A, Bein G, Santoso S, Sachs UJ. Prospective evaluation of PF4/heparin immunoassays for the diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 2009; 7 (08) 1260-1265
  • 19 Eichler P, Budde U, Haas S. et al. First workshop for detection of heparin-induced antibodies: validation of the heparin-induced platelet-activation test (HIPA) in comparison with a PF4/heparin ELISA. Thromb Haemost 1999; 81 (04) 625-629
  • 20 Eekels JJM, Althaus K, Bakchoul T. et al. An international external quality assessment for laboratory diagnosis of heparin-induced thrombocytopenia. J Thromb Haemost 2019; 17 (03) 525-531
  • 21 Greinacher A, Thiele T, Warkentin TE, Weisser K, Kyrle PA, Eichinger S. Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination. N Engl J Med 2021; 384 (22) 2092-2101