Lessons learnt from COVID‐19 coagulopathy

Thachil, Jecko

doi:10.1002/jha2.228

Cited by 14 publications

(13 citation statements)

References 74 publications

(96 reference statements)

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“…Coagulopathies [84][85][86][87][88][89][90][91][92][93][94][95][96][97][98][99][100][101][102], and especially the formation of extensive microclots in vivo, are a hallmark of both COVID [85,[103][104][105][106][107][108][109][110][111][112][113][114][115] and long COVID [116,117], and we have demonstrated that these microclots too are amyloid in character [108,109,116]. Importantly, the addition of purified, recombinant SARS-CoV-2 S1 spike protein to coagulation-competent normal plasma is sufficient to induce the formation of anomalous clots [118] that adopt amyloid states that are also resistant to fibrinolysis [108].…”

Section: Amyloid Fibrin Microclots (Fibrinaloids) In Covid-19 and Lon...mentioning

confidence: 67%

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Kell

Laubscher

Pretorius

2022

Biochemical Journal

189

212

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Post-acute sequelae of COVID (PASC), usually referred to as ‘Long COVID’ (a phenotype of COVID-19), is a relatively frequent consequence of SARS-CoV-2 infection, in which symptoms such as breathlessness, fatigue, ‘brain fog’, tissue damage, inflammation, and coagulopathies (dysfunctions of the blood coagulation system) persist long after the initial infection. It bears similarities to other post-viral syndromes, and to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Many regulatory health bodies still do not recognize this syndrome as a separate disease entity, and refer to it under the broad terminology of ‘COVID’, although its demographics are quite different from those of acute COVID-19. A few years ago, we discovered that fibrinogen in blood can clot into an anomalous ‘amyloid’ form of fibrin that (like other β-rich amyloids and prions) is relatively resistant to proteolysis (fibrinolysis). The result, as is strongly manifested in platelet-poor plasma (PPP) of individuals with Long COVID, is extensive fibrin amyloid microclots that can persist, can entrap other proteins, and that may lead to the production of various autoantibodies. These microclots are more-or-less easily measured in PPP with the stain thioflavin T and a simple fluorescence microscope. Although the symptoms of Long COVID are multifarious, we here argue that the ability of these fibrin amyloid microclots (fibrinaloids) to block up capillaries, and thus to limit the passage of red blood cells and hence O2 exchange, can actually underpin the majority of these symptoms. Consistent with this, in a preliminary report, it has been shown that suitable and closely monitored ‘triple’ anticoagulant therapy that leads to the removal of the microclots also removes the other symptoms. Fibrin amyloid microclots represent a novel and potentially important target for both the understanding and treatment of Long COVID and related disorders.

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Section: Amyloid Fibrin Microclots (Fibrinaloids) In Covid-19 and Lon...mentioning

confidence: 67%

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

Kell

Laubscher

Pretorius

2022

Biochemical Journal

189

212

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“…12-14 All the patients had elevated D-dimer and CRP but these alone cannot be used as an indicator toward a higher propensity for coagulopathy. 15…”

Section: Discussionmentioning

confidence: 99%

The Outcome of Catheter-Directed Thrombolysis in COVID-19-Associated Deep Vein Thrombosis

Raval

Rajendran²,

Stephen

2022

Vasc Endovascular Surg

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Introduction Published evidence of venous thrombotic complications of COVID-19 is lacking from India. This case series consists of twenty-nine adult patients who were COVID -19 positive and treated for Deep Vein Thrombosis (DVT) during the second wave of the COVID-19 pandemic, in India. The study was aimed at analyzing patient demographics of patients with DVT and the outcome of Catheter-Directed Thrombolysis (CDT) in COVID positive patients. Material and Methods: Patients who developed DVT while or after being COVID positive were managed between February and April 2021 at the institution of the first two authors and were included in this retrospective study. Demographic, clinical data, laboratory data, and treatment given were analyzed. All patients were followed up for 3 months with a Villalta score. Results: There were a total of 29 patients (12 male and 17 female) included in the study with a mean age of 47 ± 17 years. The average time of presentation from being COVID positive was 17.8 ± 3.6 days and one patient developed DVT after becoming Covid negative. All but one patient had lower limb involvement, with 42.8% having proximal and 57.2% distal DVT. All patients with Iliofemoral and two with Femoropopliteal DVT were treated with catheter-di thrombolysis and the other 15 patients were managed with anticoagulation alone. No re-thrombosis was observed in the thrombolysis group. Overall average Villalta score at 3 months was 10.7 ± 2.1 with a score of 10.58 ± 2.1 in the anticoagulation-only group and 10.85 ± 2.3 in the CDT group. Conclusion: COVID-19 seems to be an additional risk factor in the development of DVT. The outcome of such patients, treated by thrombolysis appears to be similar to non-COVID patients. In this, observational experience of the authors suggests that CDT could be offered to COVID positive patients with symptomatic Iliofemoral DVT with good outcomes and an acceptable post-intervention Villalta score.

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“…The epiphenomenon was likely a secondary event following endothelial cell and platelet protein damage. This epiphenomenon is one of the lessons we have learned from COVID-19 sepsis [53]. In retrospect, some of the vaccinated individuals had ITP-like syndrome and CVST was formed as venous combined micro-macrothrombosis following additional cerebral venous sinus injury [54].…”

Section: Molecular Evidence Of Venous Endotheliopathymentioning

confidence: 97%

Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis

Chang

Hawley

2021

Medicina

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Serious vaccine-associated side effects are very rare. Major complications of vaccines are thrombocytopenia and thrombosis in which pathogenetic mechanism is consistent with endotheliopathy characterized by “attenuated” sepsis-like syndrome, leading to the activation of inflammatory and microthrombotic pathway. In the COVID-19 pandemic, acute respiratory distress syndrome caused by microthrombosis has been the major clinical phenotype from the viral sepsis in association with endotheliopathy-associated vascular microthrombotic disease (EA-VMTD), sometimes presenting with thrombotic thrombocytopenic purpura (TTP)-like syndrome. Often, venous thromboembolism has coexisted due to additional vascular injury. In contrast, clinical phenotypes of vaccine complication have included “silent” immune thrombocytopenic purpura (ITP-like syndrome), multiorgan inflammatory syndrome, and deep venous thrombosis (DVT), cerebral venous sinus thrombosis (CVST) in particular. These findings are consistent with venous (v) EA-VMTD. In vEA-VMTD promoted by activated complement system following vaccination, “consumptive” thrombocytopenia develops as ITP-like syndrome due to activated unusually large von Willebrand factor (ULVWF) path of hemostasis via microthrombogenesis. Thus, the pathologic phenotype of ITP-like syndrome is venous microthrombosis. Myocarditis/pericarditis and other rare cases of inflammatory organ syndrome are promoted by inflammatory cytokines released from activated inflammatory pathway, leading to various organ endotheliitis. Vaccine-associated CVST is a form of venous combined “micro-macrothrombosis” composed of binary components of “microthrombi strings” from vEA-VMTD and “fibrin meshes” from vaccine-unrelated incidental vascular injury perhaps such as unreported head trauma. This mechanism is identified based on “two-path unifying theory” of in vivo hemostasis. Venous combined micro-macrothrombosis due to vaccine is much more serious thrombosis than isolated distal DVT made of macrothrombus. This paradigm changing novel concept of combined micro-macrothrombosis implies the need of combined therapy of a complement inhibitor and anticoagulant for CVST and other complex forms of DVT.

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Lessons learnt from COVID‐19 coagulopathy

Cited by 14 publications

References 74 publications

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications

The Outcome of Catheter-Directed Thrombolysis in COVID-19-Associated Deep Vein Thrombosis

Vaccine-Associated Thrombocytopenia and Thrombosis: Venous Endotheliopathy Leading to Venous Combined Micro-Macrothrombosis

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