The challenges of diagnosing heparin‐induced thrombocytopenia in patients with COVID‐19

May, Jori E.; Siniard, Rance C.; Marques, Marisa B.

doi:10.1002/rth2.12416

Cited by 16 publications

(22 citation statements)

References 3 publications

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“…To date, HIT data in SARS-CoV-2-infected patients are scarce, limited to the report of a few HIT cases confirmed using platelet activation assay, and HIT-associated antibody prevalence remains poorly investigated. [3][4][5][6][7][8][9][10][11][12][13] Our prospective cohort study aimed to characterize patients with clinical suspicion of HIT and determine HIT-associated antibody prevalence in hospitalized SARS-CoV-2-infected patients. This study was part of the ICU-COVID and French-COVID cohort registries approved by our institutional ethics committee (IDRCB, 2020-A00256-33; CPP, 11-202020.02.04.68737).…”

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confidence: 99%

Contrast between Prevalence of HIT Antibodies and Confirmed HIT in Hospitalized COVID-19 Patients: A Prospective Study with Clinical Implications

et al. 2020

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confidence: 99%

Contrast between Prevalence of HIT Antibodies and Confirmed HIT in Hospitalized COVID-19 Patients: A Prospective Study with Clinical Implications

et al. 2020

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“…Several other studies also detected increased PF4/H-reactive antibodies in COVID-19 patients in the context of heparin treatment and patients are suspected of developing "classical" HIT, i.e. heparin exposure-induced HIT [38][39][40][41][42] . A recent randomized trial reported that therapeutic dose of UFH and LMWH did not improve organ dysfunction in critically ill patients with COVID-19 43 .…”

Section: Discussionmentioning

confidence: 88%

SARS-CoV-2 receptor binding domain-specific antibodies activate platelets with features resembling the pathogenic antibodies in heparin-induced thrombocytopenia

Zhu¹,

Zheng²,

Yu³

et al. 2021

Preprint

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Severe COVID-19 is associated with unprecedented thromboembolic complications. We found that hospitalized COVID-19 patients develop immunoglobulin Gs (IgGs) that recognize a complex consisting of platelet factor 4 and heparin similar to those developed in heparin-induced thrombocytopenia and thrombosis (HIT), however, independent of heparin exposure. These antibodies activate platelets in the presence of TLR9 stimuli, stimuli that are prominent in COVID-19. Strikingly, 4 out of 42 antibodies cloned from IgG1+ RBD-binding B cells could activate platelets. These antibodies possessed, in the heavy-chain complementarity-determining region 3, an RKH or Y5 motif that we recently described among platelet-activating antibodies cloned from HIT patients. RKH and Y5 motifs were prevalent among published RBD-specific antibodies, and 3 out of 6 such antibodies tested could activate platelets. Features of platelet activation by these antibodies resemble those by pathogenic HIT antibodies. B cells with an RKH or Y5 motif were robustly expanded in COVID-19 patients. Our study demonstrates that SARS-CoV-2 infection drives the development of a subset of RBD-specific antibodies that can activate platelets and have activation properties and structural features similar to those of the pathogenic HIT antibodies.

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“…These ndings were attributed to EIA testing detecting all anti-PF4/Heparin antibodies and the potential for false positive EIAs due to increased in ammation and immunoreactivity in COVID-19, leading to production of anti-PF4/heparin antibodies that are nonpathogenic for HIT. 26 It is unclear how to accurately diagnose HIT in COVID-19 patients due to varying sensitivity and speci city between different EIA and con rmatory tests. 27 Even with our institution's highly sensitive and speci c IgG EIA test, 62.5% patients who were con rmatory testing negative.…”

Section: Discussionmentioning

confidence: 99%

Heparin Induced Thrombocytopenia in Patients with COVID-19

Warrior

Behrens

Gezer

et al. 2021

Preprint

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Background Acute respiratory and renal failure as well as systemic coagulopathy are critical aspects of the morbidity and mortality in patients with COVID-19. Heparin Induced Thrombocytopenia (HIT) occurs when IgG antibodies form against platelet factor 4-Heparin complex, resulting in platelet activation and removal, leading to a prothrombotic state. Studies have shown that only 6% who are investigated serologically for HIT actually have the diagnosis. Methods A retrospective analysis was performed on all COVID-19 positive patients hospitalized between March and June 2020. Patients with suspicion for HIT were tested for HIT antibodies with IgG-specific platelet factor 4(PF4)-dependent enzyme immunoassay (EIA). Confirmatory testing with serotonin release assay (SRA) and heparin-induced platelet aggregation were used in cases with intermediate or low optical density (OD) with EIA positivity (EIA+). Due to rarity of disease, a through literature review on HIT in COVID-19 patients was also analyzed. Results Incidence of EIA + in COVID-19 patients was 0.6%, significantly higher than in the general population 0.2% (p < 0.0001). The incidence of thromboembolic events in EIA + patients was 87.5%, significantly higher than the rate of 10.90% in all COVID-19 patients (p < 0.0001). The mortality rate in EIA + patients was 50%, significantly greater than the mortality rate of 12% in all hospitalized COVID-19 patients (p = 0.0011). Serological confirmation of HIT diagnosis was 37.5% which is significantly higher than confirmation of HIT in nonCOVID-19 patients 6% (p < 0.0001). Of 39 HIT antibody positive patients in the literature, 23.07% had positive confirmatory testing (6 SRA, 3 HIPAA) which is significantly higher than 5.6% in the general population (p = 0.00001). The incidence of thrombosis in EIA + COVID-19 patients in the literature was 56.4% which is significantly higher than reported rates of thrombotic events in in all COVID-19 patients in the literature at 4.8%1 (p = 0.00001). Conclusion Our study indicates incidence of HIT is higher in the COVID-19 population. This can be attributed to the cytokine storm and severe sepsis seen in critically ill COVID-19 patients. Our study also suggests that development of HIT can contribute to increased risk for thromboembolic events as well as mortality of COVID-19 patients, however, our study is limited due to small sample size.

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The challenges of diagnosing heparin‐induced thrombocytopenia in patients with COVID‐19

Abstract: This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 16 publications

References 3 publications

Contrast between Prevalence of HIT Antibodies and Confirmed HIT in Hospitalized COVID-19 Patients: A Prospective Study with Clinical Implications

Contrast between Prevalence of HIT Antibodies and Confirmed HIT in Hospitalized COVID-19 Patients: A Prospective Study with Clinical Implications

SARS-CoV-2 receptor binding domain-specific antibodies activate platelets with features resembling the pathogenic antibodies in heparin-induced thrombocytopenia

Heparin Induced Thrombocytopenia in Patients with COVID-19

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