ReviewInternational journal of hematology2022
COVID-19 microthrombosis: unusually large VWF multimers are a platform for activation of the alternative complement pathway under cytokine storm.
Review in International journal of hematology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Influence of therapeutic plasma exchange treatment on short-term mortality of critically ill adult patients with sepsis-induced organ dysfunction: a systematic review and meta-analysis.Critical care (London, England) · 2024Pooled it
- Prognostic value of von Willebrand factor and ADAMTS13 in patients with COVID-19: A systematic review and meta-analysis.Thrombosis research · 2022Pooled it
- Unique Features and Collateral Immune Effects of mRNA-LNP COVID-19 Vaccines: Plausible Mechanisms of Adverse Events and Complications.Pharmaceutics · 2025Review
- Can COVID-19 Lead to Refractory Thrombotic Thrombocytopenic Purpura (TTP) During Pregnancy and Postpartum? A Case Report and a Review of the Literature.Clinical case reports · 2025Article
- Multisystem Endothelial Inflammation: A Key Driver of Adverse Events Following mRNA-Containing COVID-19 Vaccines.Vaccines · 2025Review
- Irradiation with 265-nm Ultraviolet Light-Emitting Diodes to Plasma: Alterations of Hemostatic Parameters and von Willebrand Factor.Transfusion medicine and hemotherapy : offizielles Organ der Deutschen Gesellschaft fur Transfusionsmedizin und Immunhamatologie · 2025Article
- A Disintegrin and Metalloprotease with Thrombospondin Motif, Member 13, and Von Willebrand Factor in Relation to the Duality of Preeclampsia and HIV Infection.International journal of molecular sciences · 2025Review
- Two causes of COVID-19-related myocardial injury-associated cardiogenic shock: Myocarditis and microvascular thrombosis.ESC heart failure · 2025Article
- Article
- How Electricity Prevents Us from Bleeding to Death.Reviews of physiology, biochemistry and pharmacology · 2025Review
- Cardiovascular toxicity of tisagenlecleucel in children and adolescents: analysis of spontaneous reports submitted to FAERS.Frontiers in immunology · 2025Article
- Complex Pattern of Platelet Activation/Reactivity After SARS-CoV-2 Infection.International journal of molecular sciences · 2024Review
- A predominately pulmonary activation of complement in a mouse model of severe COVID-19.bioRxiv : the preprint server for biology · 2024Article
- Article
- Hereditary TTP/Upshaw-Schulman syndrome: the ductus arteriosus controls newborn survival.International journal of hematology · 2024Review
- mRNA-LNP COVID-19 Vaccine Lipids Induce Complement Activation and Production of Proinflammatory Cytokines: Mechanisms, Effects of Complement Inhibitors, and Relevance to Adverse Reactions.International journal of molecular sciences · 2024Article
- Special Issue "COVID-19 Coagulopathy: Advances on Pathophysiology and Therapies".International journal of molecular sciences · 2024Article
- The dynamics of the endothelial glycocalyx: a rare snapshot by electron microscopy.Angiogenesis · 2023Article
- Complement and COVID-19: Three years on, what we know, what we don't know, and what we ought to know.Immunobiology · 2023Review
- SARS-CoV-2 Spike Protein and Neutralizing Anti-Spike Protein Antibodies Modulate Blood Platelet Function.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
ADAMTS13, a metalloproteinase, specifically cleaves unusually large multimers of von Willebrand factor (VWF), newly released from vascular endothelial cells. The ratio of ADAMTS13 activity to VWF antigen (ADAMTS13/VWF) and indicators of the alternative complement pathway (C3a and sC5b-9) are both related to the severity of COVID-19. The ADAMTS13/VWF ratio is generally moderately decreased (0.18-0.35) in patients with severe COVID-19. When these patients experience cytokine storms, both interleukin-8 and TNFα stimulate VWF release from vascular endothelial cells, while interleukin-6 inhibits both production of ADAMTS13 and its interaction with VWF, resulting in localized severe deficiency of ADAMTS13 activity. Platelet factor 4 and thrombospondin-1, both released upon platelet activation, bind to the VWF-A2 domain and enhance the blockade of ADAMTS13 function. Thus, the released unusually-large VWF multimers remain associated with the vascular endothelial cell surface, via anchoring with syndecan-1 in the glycocalyx. Unfolding of the VWF-A2 domain, which has high sequence homology with complement factor B, allows the domain to bind to activated complement C3b, providing a platform for complement activation of the alternative pathway. The resultant C3a and C5a generate tissue factor-rich neutrophil extracellular traps (NETs), which induce the mixed immunothrombosis, fibrin clots and platelet aggregates typically seen in patients with severe COVID-19.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.