Related Experiment Video
Updated: Aug 26, 2025
Ferric Chloride-induced Murine Thrombosis Models
Published on: September 5, 2016
Thrombosis after SARS-CoV2 infection or COVID-19 vaccination: will a nonpathologic anti-PF4 antibody be a solution?-A
Elizabeth Rao1, Payal Grover1, Hongtao Zhang1
1Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Abstract:
The coronavirus disease 2019 (COVID-19) pandemic was triggered by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a previously unknown strain of coronavirus. To fully understand the consequences and complications of SARS-CoV-2 infections, we have reviewed current literature on coagulation dysfunctions that are related to the disease and vaccination. While COVID-19 is more commonly considered as a respiratory illness, studies indicate that, in addition to respiratory illness, a coagulation dysfunction may develop in individuals after the initial infection, placing them at the risk of developing thrombotic events. Patients who died of COVID-19 had higher levels of D-dimer, a biomarker for blood clot formation and breakdown. Effective treatments for coagulation dysfunctions are critically needed to improve patient survival. On the other hand, antibodies against platelet factor 4 (PF4)/heparin may be found in patients with rare instances of vaccine-induced immunological thrombotic thrombocytopenia (VITT) following vaccination with adenovirus-based vaccines. VITT is characterized by atypical thrombosis and thrombocytopenia, similar to immune-mediated heparin-induced thrombocytopenia (HIT), but with no need for heparin to trigger the immune response. Although both adenovirus-based and mRNA-based vaccines express the Spike protein of SARS-CoV-2, VITT is exclusively related to adenovirus-based vaccines. Due to the resemblance with HIT, the use of heparin is highly discouraged against treating patients with thrombotic thrombocytopenia after SARS-CoV-2 infection or with VITT after vaccination. Intravenous immunoglobulin therapy coupled with anticoagulation is recommended instead. The well-studied anti-PF4 monoclonal antibody RTO, which does not induce pathologic immune complexes in the presence of heparin and has been humanized for a potential treatment modality for HIT, may provide a nonanticoagulant HIT-specific solution to the problem of increased blood coagulation after SARS-CoV-2 infection or the VITT after immunization.
Insights
COVID-19 can cause blood clot issues, while rare vaccine-induced immune thrombotic thrombocytopenia (VITT) is linked to adenovirus vaccines. Heparin is discouraged for VITT; IV immunoglobulin and anticoagulation are recommended treatments.
Area of Science:
- Hematology
- Immunology
- Infectious Diseases
Background:
- COVID-19, caused by SARS-CoV-2, is primarily a respiratory illness but can lead to coagulation dysfunction and thrombotic events.
- Elevated D-dimer levels are observed in fatal COVID-19 cases, indicating increased blood clot formation and breakdown.
- Vaccine-induced immunological thrombotic thrombocytopenia (VITT) is a rare complication associated with adenovirus-based vaccines, presenting with thrombosis and thrombocytopenia.
Purpose of the Study:
- To review the literature on coagulation dysfunctions associated with COVID-19 and vaccination.
- To differentiate VITT from heparin-induced thrombocytopenia (HIT) and discuss treatment implications.
- To explore potential therapeutic strategies for managing COVID-19-related and vaccine-related thrombotic complications.
Main Methods:
- Literature review of studies on COVID-19, SARS-CoV-2, coagulation disorders, and vaccine-related adverse events.
- Analysis of clinical presentations, biomarkers (e.g., D-dimer), and immunological mechanisms.
- Comparison of VITT with immune-mediated heparin-induced thrombocytopenia (HIT).
Main Results:
- COVID-19 patients exhibit coagulation dysfunction, increasing the risk of thrombotic events.
- VITT, characterized by anti-PF4/heparin antibodies, occurs rarely after adenovirus-based vaccines but not mRNA vaccines.
- Heparin is contraindicated for VITT and COVID-19-related thrombosis due to potential exacerbation.
Conclusions:
- Effective treatments for COVID-19-associated coagulation dysfunction are crucial for improving patient outcomes.
- Intravenous immunoglobulin therapy and anticoagulation are recommended for VITT and HIT-like syndromes.
- Anti-PF4 monoclonal antibodies, like RTO, show promise as non-anticoagulant treatments for HIT and potentially VITT.
