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The Seroprevalence of Anti-heparin-PF4 (Anti-HPF4) Antibodies Among COVID-19 Patients and Its Relevance to ICU Hospitalization and Mortality

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Abstract

Anti-heparin–platelet factor 4 (anti-HPF4) antibodies play a key role in heparin-induced thrombocytopenia (HIT). These antibodies can participate in thrombosis and mortality through platelet activation. HIT is a life-threatening complication. Recently, HIT has been reported as a risk factor of thrombocytopenia exacerbation in COVID-19 patients. In the present study, we assessed the incidence of anti-HPF4 in patients with COVID-19 and the relationship with ICU hospitalization and mortality. This cross-sectional descriptive study was performed on 97 COVID-19 patients in Yasuj City (Southwest zone of Iran). Demographic factors and platelet count, PT, APTT, and D-dimer were recorded and checked at admission and during hospitalization. Anti-HPF4 antibody assay was performed for all eligible patients by ELISA method. Statistical significance was based on two-sided design-based tests evaluated at the 0.05 level of significance. Most of the patients (n = 57, 58.8%) were male. The mean age of the patients was 55.46 ± 15.2 years, and the mean hospitalization was 17.57 ± 7.2 days. The mean length of stay was 209.9 ± 79.8 × 103/µL. The results of the anti-HPF4 antibody assay showed that 9.3% (n = 9) of the patients were positive for anti-HPF4 antibody. The mortality rate was higher in the HPF4-positive patients. Although the true frequency of HIT in this study was unclear, it can be concluded that anti-HPF4 antibodies are involved in the pathophysiology of HIT which is a life-threatening complication in COVID-19 patients receiving heparin treatment, with a high rate of morbidity and mortality.

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Abbreviations

SARS-CoV-2:

Severe acute respiratory syndrome coronavirus 2

COVID-19:

Coronavirus disease 2019

HIT:

Heparin-induced thrombocytopenia

PF4:

Platelet factor 4

PT:

Prothrombin time

APTT:

Activated partial thromboplastin time

FDP:

Fibrin(ogen) degradation product

ICU:

Intensive care unit

HPF4:

Heparin-platelet factor 4

ISTH:

International Society for Thrombosis and Homeostasis

LMWH:

Low-molecular-weight heparin

UFH:

Unfractionated heparin

ELISA:

Enzyme-linked immunosorbent assay

DIC:

Disseminated intravascular coagulation

ECMO:

Extracorporeal membrane oxygenation

SRA:

Serotonin-release assay

LIA:

Latex immunoturbidimetric assay

EIA:

Enzyme-immunoassay

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Acknowledgements

We would like to thank the staff of Shahid Jalil Hospital in Yasuj for their kind assistance with the collection of our data.

Funding

The study was funded by Vice-chancellor for Research and Technology, Hamadan University of Medical Sciences (Grant No. 9912128930).

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Authors and Affiliations

  1. Cellular and Molecular Research Center, Yasuj University of Medical Sciences, Yasuj, Iran

    Fariba Rad & Sareh Jahanbakhshi

  2. Department of Pathology, Gonabad University of Medical Sciences, Gonabad, Iran

    Mehdi Karimi Shahri

  3. Department of Hematology and Blood Transfusion, School of Allied Medicine, University of Medical Sciences, Tehran, Iran

    Akbar Dorgalaleh

  4. Department of Medical Laboratory Sciences, School of Paramedicine, Hamadan University of Medical Sciences, Hamadan, Iran

    Alireza Goodarzi

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  1. Fariba Rad
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  2. Mehdi Karimi Shahri
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Contributions

Acquisition of data: F.R., M.K.S.

Analysis and interpretation of data: F.R., A.G.

Drafting of manuscript: F.R., M.K.S., A.D., S.J.

Critical revision: F.R., A.G., A.D.

Corresponding author

Correspondence to Alireza Goodarzi.

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Ethics Approval

This research was implemented under ethic codes IR.UMSHA.REC.1399.700 and IR.YUMS.REC.1399.057 which are accepted by Ethical Committee of the Yasuj University of Medical Sciences and Ethics Committee of Hamadan University of Medical Sciences, respectively.

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The authors declare no competing interests.

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Rad, F., Shahri, M.K., Jahanbakhshi, S. et al. The Seroprevalence of Anti-heparin-PF4 (Anti-HPF4) Antibodies Among COVID-19 Patients and Its Relevance to ICU Hospitalization and Mortality. SN Compr. Clin. Med. 6, 38 (2024). https://doi.org/10.1007/s42399-024-01669-3

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