Limited concordance of heparin/platelet factor 4 antibody assays for the diagnosis of heparin-induced thrombocytopenia: an analysis of the TORADI-HIT study

Hammerer-Lercher, Angelika; Nilius, Henning; Studt, Jan‐Dirk; Tsakiris, Dimitrios Α.; Greinacher, Andreas; Méndez, Adriana; Schmidt, Adrian; Wuillemin, Walter A.; Gerber, Bernhard; Hovinga, Johanna A. Kremer; Vishnu, Prakash; Graf, Lukas; Bakchoul, Tamam; Nagler, Michael

doi:10.1016/j.jtha.2023.05.016

Cited by 2 publications

(8 citation statements)

References 27 publications

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“…Abbreviation: HIT, heparin-induced thrombocytopenia. a Patient characteristics have previously been published b New, recurrent, or progressive thromboembolism.…”

Section: Resultsmentioning

confidence: 99%

“…However, since we were interested in the initial performance and the associated clinical decisions, we did not do consider these scorings for the purpose of this study. Of note, a smaller subset of the reported results was required in other manuscripts that answered different research questions …”

Section: Discussionmentioning

confidence: 99%

“…This analysis is part of Towards Precise and Rapid Diagnosis of Heparin-Induced Thrombocytopenia: A Prospective, Multicentre Cohort Study (TORADI-HIT), which includes consecutive patients with suspected HIT from 11 tertiary hospitals localized in Switzerland, Germany, or the United States. A detailed description of study design, setting, participants, study procedures, and collection of data are provided in previous publications that have addressed (1) the development of a decision support tool and (2) the consistency of different heparin/PF4 immunoassays . Inclusion criteria were (1) suspected HIT (PF4/heparin antibodies ordered, 4Ts score applied, or consultancy service requested), (2) aged 18 years or older, and (3) written informed consent provided.…”

Section: Methodsmentioning

confidence: 99%

“…As a reference standard, the presence of HIT was determined by a washed-platelet functional assay, the HIPA . Like the SRA, the washed-platelet HIPA is recognized as the criterion standard of reference by major scientific societies and many authors . The HIPA was conducted as described in detail previously .…”

Section: Methodsmentioning

confidence: 99%

“…Of note, a smaller subset of the reported results was required in other manuscripts that answered different research questions. 18,19 JAMA Network Open | Hematology…”

Section: Strengths and Limitationsmentioning

confidence: 99%

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Accuracy of Diagnosing Heparin-Induced Thrombocytopenia

Larsen,

Nilius,

Studt

et al. 2024

JAMA Netw Open

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ImportanceHeparin-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.ObjectiveTo evaluate the current diagnostic practice for managing the suspicion of HIT.Design, Setting, and ParticipantsThis 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.ExposuresSuspicion of HIT.Main Outcomes and MeasuresThe primary outcome was the diagnostic accuracy of the 4Ts score, the CLIA, and the recommended algorithm serially combining both tests.ResultsOf 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 RelevanceIn 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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“…Abbreviation: HIT, heparin-induced thrombocytopenia. a Patient characteristics have previously been published b New, recurrent, or progressive thromboembolism.…”

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“…Of note, a smaller subset of the reported results was required in other manuscripts that answered different research questions. 18,19 JAMA Network Open | Hematology…”

Section: Strengths and Limitationsmentioning

confidence: 99%

See 3 more Smart Citations

Accuracy of Diagnosing Heparin-Induced Thrombocytopenia

Larsen,

Nilius,

Studt

et al. 2024

JAMA Netw Open

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Proteomic profiling for biomarker discovery in heparin-induced thrombocytopenia

Nilius,

Hamzeh-Cognasse,

Hastings

et al. 2024

Blood Advances

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New analytical techniques can assess hundreds of proteins simultaneously with high sensitivity, facilitating the observation of their complex interplay and role in disease mechanisms. We hypothesized that proteomic profiling targeting proteins involved in thrombus formation, inflammation, and the immune response would identify potentially new biomarkers for heparin-induced thrombocytopenia (HIT). Four existing panels of the Olink proximity extension assay covering 356 proteins involved in thrombus formation, inflammation, and immune response were applied to randomly selected patients with suspected HIT (confirmed HIT, n=32; HIT ruled-out, n=38; positive heparin/PF4 [H/PF4] antibodies, n=28). The relative difference in protein concentration was analyzed using a linear regression model adjusted for sex and age. To confirm the test results, soluble P-selectin was determined using ELISA in above mentioned patients and an additional second dataset (n=49). HIT was defined as a positive heparin-induced platelet aggregation test (HIPA; washed platelet assay). Among 98 patients of the primary dataset, the median 4Ts score was 5 in patients with HIT, 4 in patients with positive heparin/PF4 antibodies, and 3 in patients without HIT. The median OD of a polyspecific heparin/PF4 ELISA was 3.0, 0.9, and 0.3, respectively. Soluble P-selectin remained statistically significant after multiple test adjustments. The area under the receiver-operating-characteristics-curve was 0.81 for Olink and 0.8 for ELISA. Future studies shall assess the diagnostic and prognostic value of soluble P-selectin in the management of HIT.

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Limited concordance of heparin/platelet factor 4 antibody assays for the diagnosis of heparin-induced thrombocytopenia: an analysis of the TORADI-HIT study

Cited by 2 publications

References 27 publications

Accuracy of Diagnosing Heparin-Induced Thrombocytopenia

Accuracy of Diagnosing Heparin-Induced Thrombocytopenia

Proteomic profiling for biomarker discovery in heparin-induced thrombocytopenia

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