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Review
. 2020 Jun 18;24(1):360.
doi: 10.1186/s13054-020-03077-0.

The unique characteristics of COVID-19 coagulopathy

Toshiaki Iba  1 , Jerrold H Levy  2 , Jean Marie Connors  3 , Theodore E Warkentin  4 , Jecko Thachil  5 , Marcel Levi  6
Affiliations
Review

The unique characteristics of COVID-19 coagulopathy

Toshiaki Iba et al. Crit Care. .

Abstract

Thrombotic complications and coagulopathy frequently occur in COVID-19. However, the characteristics of COVID-19-associated coagulopathy (CAC) are distinct from those seen with bacterial sepsis-induced coagulopathy (SIC) and disseminated intravascular coagulation (DIC), with CAC usually showing increased D-dimer and fibrinogen levels but initially minimal abnormalities in prothrombin time and platelet count. Venous thromboembolism and arterial thrombosis are more frequent in CAC compared to SIC/DIC. Clinical and laboratory features of CAC overlap somewhat with a hemophagocytic syndrome, antiphospholipid syndrome, and thrombotic microangiopathy. We summarize the key characteristics of representative coagulopathies, discussing similarities and differences so as to define the unique character of CAC.

Keywords: Antiphospholipid syndrome; COVID-19; Coagulopathy; Disseminated intravascular coagulation; Hemophagocytic syndrome; Thrombotic microangiopathy.

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Conflict of interest statement

TI has received a research grant from the Japan Blood Products Organization and JIMRO. JHL serves on the Steering Committees for Boehringer-Ingelheim, CSL Behring, Instrumentation Laboratories, Octapharma, and Leading Biosciences. JMC receives personal fees from the Bristol-Meyer Squibb, Abbott, Portola, and research funding to the institution from CSL Behring. TEW reports receiving consulting fees from the Aspen Global, Bayer, CSL Behring, Ergomed Instrumentation Laboratory, and Octapharma; research support from the Instrumentation Laboratory; royalties from the Informa (Taylor & Francis); and consulting fees related to medical-legal consulting and testimony. ML has received grants and has participated in advisory boards of the NovoNordisk, Eli Lilly, Asahi Kasei Pharmaceuticals America and Johnson & Johnson. The other authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Thrombus formation in disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, and hemolytic uremic syndrome. In bacterial sepsis, immune cells such as monocyte and macrophages are activated by pathogen-associated molecular patterns (PAMPs) and host-derived damage-associated molecular patterns (DAMPs). The immune cells initiate coagulation cascades through expressing tissue factor (TF) and releasing extracellular vesicles (EVs). The activated neutrophils and neutrophil extracellular traps (NETs) are also involved in coagulation. Degradation of fibrin, the end product of coagulation activation, is suppressed by increased levels of plasminogen activator inhibitor-1 (PAI-1). In thrombotic thrombocytopenic purpura (TTP), increased high multimers of von Willebrand factor (VWF) caused by ant-ADAMTS13 antibodies stimulate platelet aggregation. In hemolytic uremic syndrome (HUS), dysregulated complement system and its terminal product, membrane attack protein (MAC), damage vascular endothelial cells, and initiate clot formation
Fig. 2
Fig. 2
Thrombus formation in COVID-19. In a healthy condition, angiotensin-converting enzyme 2 (ACE2) converts angiotensin II to angiotensin 1–7 which stimulates endothelial cells to produce nitric oxide (NO). NO helps the vessels to vasodilate and suppresses platelet aggregation. In COVID-19, SARS-CoV-2 occupies ACE2 and the angiotensin II level increases, which result in vasoconstriction and decreased blood flow. Von Willebrand factor (VWF) stored in Weibel Palade body is released into the circulation, promoting clot formation. Decreased ADAMTS13 levels (not reported in COVID-19) could contribute to thrombus formation within the vasculature
Fig. 3
Fig. 3
Characteristic features of COVID-19-associated coagulopathy. The clinical and laboratory features of COVID-19-associated coagulopathy (CAC) partially overlap with sepsis-induced coagulopathy (SIC)/disseminated intravascular coagulation (DIC), hemophagocytic syndrome (HPS)/hemophagocytic lymphohistiocytosis (HLH), antiphospholipid syndrome (APS), and thrombotic microangiopathy (TMA); however, it does not perfectly match with any of these other coagulopathies
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