Managing thrombosis and cardiovascular complications of COVID-19: answering the questions in COVID-19-associated coagulopathy

ABSTRACT

Introduction

The first patients with Coronavirus disease 2019 (COVID-19) emerged at the end of 2019. This novel viral infection demonstrated unique features that include prothrombotic clinical presentations. However, one year after the first occurrence, there remain many unanswered questions. We tried to address some of the important queries in this review.

Areas covered

We raised the following critical questions. ‘Why is COVID-19 so hypercoagulable?’, ‘Why are most coagulation test results relatively normal?’, ‘Why is COVID-19-associated coagulopathy more thrombotic than most other infectious diseases?’, ‘Why is arterial thrombus formed frequently?’, ‘Is anticoagulant therapy for COVID-19 effective?’, and ‘Are there racial disparities in thrombosis in COVID-19?’

Expert opinion

There are commonalities and differences in the pathogeneses and clinical features between COVID-19 and other infectious diseases. Correct understanding will help discussing appropriate anticoagulation prophylaxis or treatment for thromboembolism.

KEYWORDS:

• COVID-19
• thrombosis
• coagulopathy
• endothelial cell
• disseminated intravascular coagulation
• anticoagulant therapy

Article highlights

• Excess inflammation and coagulation activation are the two driving factors that maximize host response to SARS-CoV-2 infection.

• COVID-19 is complicated by thrombotic events more often than other infectious diseases, and these events, including pulmonary emboli, affect outcomes.

• Thrombus formation is localized in the pulmonary microcirculation in the early phase of COVID-19, then spreads systemically as the disease progresses.

• Endothelial cell injury induced by direct SARS-CoV-2 invasion is a significant contributor to the prothrombotic state.

• A variety of factors, including inflammatory cytokines, factor VIII, von Willebrand factor, angiopoietin 2, P-selectin, and antiphospholipid antibodies, contribute to thrombus formation in COVID-19.

• Vasculitis induced by the host immune response to endothelial infection may play a role in the development of arterial thrombosis.

• Recent multiplatform randomized controlled trial demonstrated that full-dose heparin could reduce the duration of organ support in moderately ill COVID-19 patients, but the similar findings were not recognized in severe cases.

Acknowledgments

The authors wish to thank the co-chairs of ISTH/DIC scientific standardization subcommittee for their support.

Declaration of interest

T Iba has received a research grant from Japan Blood Products Organization and JIMRO. JH Levy serves on the Steering Committees for Boehringer-Ingelheim, CSL Behring, Instrumentation Laboratories, Octapharma, and Leading Biosciences. JM Connors receives personal fees from Bristol-Meyer Squibb, Abbott, Portola, and research funding to the institution from CSL Behring. TE Warkentin reports receiving consulting fees from Aspen Global, Bayer, CSL Behring, Ergomed Instrumentation Laboratory, and Octapharma; research support from Instrumentation Laboratory; royalties from Informa (Taylor & Francis); and consulting fees related to medical-legal consulting and testimony. M Levi has received grants and has participated in advisory boards of NovoNordisk, Eli Lilly, Asahi Kasei Pharmaceuticals America and Johnson & Johnson. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Author contributions

T Iba, JH Levy, and JM Connors wrote the draft. TE Warkentin, J Thachil, and M Levi reviewed and revised the manuscript. All authors read and approved the final manuscript.

Additional information

Funding

This paper was funded by a Grant-in-Aid from the Ministry of Health, Labor and Welfare of Japan and from the Ministry of Education, Culture, Sports, Science and Technology of Japan.