A Pathophysiological Perspective on the SARS‐CoV‐2 Coagulopathy

Kuşadasi, Nuray; Sikma, Maaike A.; Huisman, Albert; Westerink, Jan; Maas, Coen; Schutgens, Roger E.G.

doi:10.1097/hs9.0000000000000457

Cited by 5 publications

(6 citation statements)

References 85 publications

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“…Our report focuses on the clinical and laboratory abnormalities related to thrombosis and haemostasis. Multiple scientific publications pointing to the high thrombotic risk in COVID-19 [ 9 , 10 , 11 , 12 , 13 , 32 ], trying to understand its pathophysiology [ 33 , 34 , 35 ], suggesting the prognostic value of haemostatic laboratory parameters [ 4 , 36 , 37 ] and proposing prophylactic and/or therapeutic measures to improve the outcome have been provided [ 11 , 38 ].…”

Section: Discussionmentioning

confidence: 99%

No Evidence for Classic Thrombotic Microangiopathy in COVID-19

Falter

Rossmann

Menge

et al. 2021

JCM

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Background: Coronavirus disease-2019 (COVID-19) triggers systemic infection with involvement of the respiratory tract. There are some patients developing haemostatic abnormalities during their infection with a considerably increased risk of death. Materials and Methods: Patients (n = 85) with SARS-CoV-2 infection attending the University Medical Center, Mainz, from 3 March to 15 May 2020 were retrospectively included in this study. Data regarding demography, clinical features, treatment and laboratory parameters were analyzed. Twenty patients were excluded for assessment of disseminated intravascular coagulation (DIC) and thrombotic microangiopathy (TMA) due to lack of laboratory data. Results: COVID-19 patients (n = 65) were investigated, 19 with uncomplicated, 29 with complicated, and 17 with critical course; nine (13.8%) died. Seven patients showed overt DIC according to the ISTH criteria. The fibrinogen levels dropped significantly in these patients, although not below 100 mg/dl. Hallmarks of TMA, such as thrombocytopenia and microangiopathic haemolytic anaemia, were not detected in any of our COVID-19 patients. ADAMTS13 activity was mildly to moderately reduced in 4/22 patients, all having strongly elevated procalcitonin levels. Conclusion: DIC occurred in 7/65 COVID-19 patients but fibrinogen and platelet consumption were compensated in almost all. ADAMTS13 assays excluded TTP and hallmarks of classic TMA were absent in all investigated patients. We hypothesize that the lacking erythrocyte fragmentation and only mild platelet consumption in severe COVID-19 are due to a microangiopathy predominantly localized to the alveolar microcirculation with a low blood pressure gradient.

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Section: Discussionmentioning

confidence: 99%

No Evidence for Classic Thrombotic Microangiopathy in COVID-19

Falter

Rossmann

Menge

et al. 2021

JCM

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“…(Kusadasi et al, 2020) also note the inter-relationship of the Renin-Aldosterone-Angiotensin system, complement system, Kinin-Kallekrein system and coagulation system as well as the relationship to ACE-2 while (Urwyler et al, 2020) report their initial findings with the use of Conestat Alfa In COVID-19, which targets the Kallikrein-Kinin system. (Curran et al, 2020) provide a model of pathology in COVID-19 involving a number of systems including the RAAS system and suggest that COVID-19 disrupts regulatory networks.…”

Section: Resultsmentioning

confidence: 99%

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

Marley

2020

Preprint

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BackgroundThe COVID-19 pandemic has claimed over 1 million lives globally and results from the SARS-COV2 virus. COVID-19 is associated with a coagulopathy. In this mixed-methods PRISMA-compliant scoping review, we set out to determine if ARDS, sepsis and DIC could account for the coagulopathy and if there were any other features of the coagulopathy we could determine so as to inform future research. Methods: We used a search strategy to identify papers with clinically relevant thromboembolic events in COVID-19. We then developed a technique referred to as an Abridged Thematic Analysis (ATA) to quickly identify themes in the papers so as to increase the yield of clinically relevant information. We further developed Validated Abridged Thematic Analysis (VATA) to validate the resulting taxonomy of themes. Finally we developed a number of methods that can be used by other researchers to take forwards this work. Results: We identified 56 studies with 10,523 patients, 456 patients with COVID-19 and thromboembolic events (TBE’s) and 586 thrombembolic events. There were an average of 1.3 TBE’s per patient. There were five main arterial territories with corresponding clinical sequelae: Acute limb ischaemia, myocardial infarcts, strokes, mesenteric ischaemia and pulmonary embolism. We also identified DVT’s. There were two further groups: medical-device-related coagulopathy and dermal lesions. In a subgroup of 119 patients we found mortality ranged from 26% in DVT to 79% in acute limb ischaemia although there was evidence of selection bias in the latter group. All patients were hospitalised and the average age of survivors was 63 versus 73 for those who died. 91/150 patients with TE’s had fever. From the ATA, we identified 16 characteristics of the clotting pathology in COVID-19. From the VATA, we identified 34 mechanisms leading to coagulopathy and grouped them according to Virchow’s triad of vascular damage, stasis and hypercoagulability. Coagulopathy occurred with and without each of ARDS, Sepsis and DIC. We conclude that COVID-19 leads to the syndrome of a viral clotting fever in a subgroup of patients and that the presentation of coagulopathy and fever should raise the possibility of COVID-19 as a differential. We make recommendations for future research studies.

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“…In addition, coagulation can directly be triggered by virus-induced tissue damage and subsequent exposure to TF (extrinsic pathway) and activation via a coagulation factor XII (intrinsic pathway) [77]. It has been proposed that TF plays a major role in the histone-induced hypercoagulable state of COVID-19 patients.…”

Section: )mentioning

confidence: 99%

The role of extracellular histones in COVID‐19

et al. 2022

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The severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) had spread from China and, within 2 months, became a global pandemic. The infection from this disease can cause a diversity of symptoms ranging from asymptomatic to severe acute respiratory distress syndrome with an increased risk of vascular hyperpermeability, pulmonary inflammation, extensive lung damage, and thrombosis. One of the host defense systems against coronavirus disease 2019 (COVID‐19) is the formation of neutrophil extracellular traps (NETs). Numerous studies on this disease have revealed the presence of elevated levels of NET components, such as cell‐free DNA, extracellular histones, neutrophil elastase, and myeloperoxidase, in plasma, serum, and tracheal aspirates of severe COVID‐19 patients. Extracellular histones, a major component of NETs, are clinically very relevant as they represent promising biomarkers and drug targets, given that several studies have identified histones as key mediators in the onset and progression of various diseases, including COVID‐19. However, the role of extracellular histones in COVID‐19 per se remains relatively underexplored. Histones are nuclear proteins that can be released into the extracellular space via apoptosis, necrosis, or NET formation and are then regarded as cytotoxic damage‐associated molecular patterns that have the potential to damage tissues and impair organ function. This review will highlight the mechanisms of extracellular histone‐mediated cytotoxicity and focus on the role that histones play in COVID‐19. Thereby, this paper facilitates a bench‐to‐bedside view of extracellular histone‐mediated cytotoxicity, its role in COVID‐19, and histones as potential drug targets and biomarkers for future theranostics in the clinical treatment of COVID‐19 patients.

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A Pathophysiological Perspective on the SARS‐CoV‐2 Coagulopathy

Cited by 5 publications

References 85 publications

No Evidence for Classic Thrombotic Microangiopathy in COVID-19

No Evidence for Classic Thrombotic Microangiopathy in COVID-19

Characterising COVID-19 as a Viral Clotting Fever: A Mixed Methods Scoping Review

The role of extracellular histones in COVID‐19

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