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. 2024 Mar 4;7(3):e243786.
doi: 10.1001/jamanetworkopen.2024.3786.

Accuracy of Diagnosing Heparin-Induced Thrombocytopenia

Emil List Larsen  1 , Henning Nilius  2   3 , Jan-Dirk Studt  4 , Dimitrios A Tsakiris  5 , Andreas Greinacher  6 , Adriana Mendez  7 , Adrian Schmidt  8 , Walter A Wuillemin  9 , Bernhard Gerber  10 , Prakash Vishnu  11 , Lukas Graf  12 , Johanna A Kremer Hovinga  13 , Jens P Goetze  1   14 , Tamam Bakchoul  15 , Michael Nagler  2   16
Affiliations

Accuracy of Diagnosing Heparin-Induced Thrombocytopenia

Emil List Larsen et al. JAMA Netw Open. .

Abstract

Importance: Heparin-induced thrombocytopenia (HIT) is a life-threatening condition that requires urgent diagnostic clarification. However, knowledge of the diagnostic utility of the recommended diagnostic tests is limited in clinical practice.

Objective: To evaluate the current diagnostic practice for managing the suspicion of HIT.

Design, setting, and participants: This prospective diagnostic study was conducted from January 2018 to May 2021 among consecutive patients with suspected HIT from 11 study centers in Switzerland, Germany, and the United States. Detailed clinical data and laboratory information were recorded. Platelet factor 4/heparin antibodies were quantified using an automated chemiluminescent immunoassay (CLIA). A washed-platelet heparin-induced platelet activation (HIPA) test was used as a reference standard to define HIT.

Exposures: Suspicion of HIT.

Main outcomes and measures: The primary outcome was the diagnostic accuracy of the 4Ts score, the CLIA, and the recommended algorithm serially combining both tests.

Results: Of 1448 patients included between 2018 and 2021, 1318 were available for the current analysis (median [IQR] age, 67 [57-75] years; 849 [64.6%] male). HIPA was positive in 111 patients (prevalence, 8.4%). The most frequent setting was intensive care unit (487 [37.0%]) or cardiovascular surgery (434 [33.0%]). The 4Ts score was low risk in 625 patients (46.8%). By 2 × 2 table, the numbers of patients with false-negative results were 10 (9.0%; 4Ts score), 5 (4.5%; CLIA), and 15 (13.5%; recommended diagnostic algorithm). The numbers of patients with false-positive results were 592 (49.0%; 4Ts score), 73 (6.0%; CLIA), and 50 (4.1%; recommended diagnostic algorithm), respectively.

Conclusions and relevance: In this diagnostic study of patients suspected of having HIT, when the recommended diagnostic algorithm was used in clinical practice, antibody testing was required in half the patients. A substantial number of patients were, however, still misclassified, which could lead to delayed diagnosis or overtreatment. Development of improved diagnostic algorithms for HIT diagnosis should be pursued.

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Conflict of interest statement

Conflict of Interest Disclosures: Dr Greinacher reported receiving personal fees from Aspen, Bayer Vital, Instrumentation Laboratory, Sanofi-Aventis, Roche, GTH, Dilaflor, Takeda, Falk Foundation, Mylan Germany, Werfen, and Chromatee; grants from Boehringer Ingelheim, Rovi, Sagent, Portola, Biokit, Blau Faraceutics, Prosensa/Biomarin, DRK-BSD Baden-Würtemberg/Hessen, Deutsche Forschungsgemeinschaft, Robert-Koch-Institut, GIZ Else-Körner-Stiftung, and European Medicines Agency; grants and personal fees from Macoharma; grants and other from DRK-BSD NSTOB; and nonfinancial support from Veralox, Vakzine Projekt Management, AstraZeneca, and Janssen Vaccines & Prevention outside the submitted work; in addition, Dr Greinacher has a patent for screening methods for transfusion-related acute lung injury and a patent for universal plasm as well as a patent for PF4 antibodies pending. Dr Mendez reported receiving personal fees from Silamed and Sysmex outside the submitted work. Dr Gerber reported receiving grants to the institution and continued medical education support from Pfizer, Thermo Fisher Scientific, and Axonlab and receiving continued medical education support from Sanofi, Alnylam, Bayer, BMS, Daiichi-Sankyo, Octapharma, Takeda, SOBI, Janssen, Novo Nordisk, and Mitsubishi Taneba outside of the current work. Dr Kremer Hovinga reported receiving grants and personal fees paid to the employer from Takeda; grants to the employer from SNSF, Bayer, Octapharma, FOPH, the Swiss Hemophilia Society, Roche, SOBI, NovoNordisk, and CSL-Behring; personal fees paid to the employer from Sanofi/Ablynx; and travel support from SOBI outside the submitted work. Dr Bakchoul reported receiving grants from Deutsche Forschungsgesellschaft, Stiftung Transfusionsmedizin und Immunhämatologie, DRK Blutspendedienst, Deutsche Herzstiftung, Ministerium für Wissenschaft, Forschung und Kunst Baden Würtemberg, and Gesellschaft für Thrombose- und Hämostaseforschung; receiving lecture fees from Berufsverband Deutscher Internisten, CoaChrom Diagnostica, Robert Bosch, Ergomed, Bayer, Bristol-Myers Squibb, Doctrina Med, Leo Pharma, Schöchl Medical Education, Meet the Expert, Biotest, Mitsubishi Tanabe, Novo Nordisk, and Swedish Orphan Biovitrium; having a patent for screening methods pending from atent; and grant support, consultancy fees, honoraria, or support for attending meetings from Deutsche Forschungsgesellschaft, Stiftung Transfusionsmedizin und Immunhämatologie, DRK Blutspendedienst, Deutsche Herzstiftung, Ministerium für Wissenschaft, Forschung und Kunst Baden Würtemberg, Gesellschaft für Thrombose- und Hämostaseforschung outside the submitted work. Dr Nagler reported receiving grants from Roche Diagnostics, Siemens Healthineers, Stago, and Bühlmann Laboratories as well as lecture fees from Sysmex, Siemens Healthineers, Abbott, COR2ED, Werfen, Viatris, Silamed, Novartis, and Euroimmun outside of the current work. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Receiver Operating Characteristic Curves
Receiver operating characteristic curve of 4Ts score (A) and chemiluminescent immunoassay (CLIA; B) as with 95% CIs (shaded area). Diagnostic thresholds with 95% CIs are marked. AUC indicates area under the curve.
Figure 2.
Figure 2.. Diagnostic Performance of Diagnostic Tests for Heparin-Induced Thrombocytopenia in Clinical Practice
Proportion of true-negative (dark orange), false-negative (light orange), true-positive (blue), and false-positive (gray) results are given using the 4Ts score (A), chemiluminescent immunoassay (CLIA; B), and the recommended diagnostic algorithm (C). Created with Biorender.com.
See this image and copyright information in PMC

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