COVID-19, thrombosis and anticoagulation (WP4927)

Homo sapiens

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Several hospitals and researchers have reported links between thrombosis and anticoagulation quite regularly for COVID-19 patients. This pathways combines this information, including biological mechanisms involved, in one graphical overview. The D-dimer is one of the protein fragments produced when a blood clot dissolves within the (human) body; when not properly degraded could lead to thrombosis. The graphical visualisation of (crosslinked) fibrin mesh leading to D-dimers is inspired by [https://en.wikipedia.org/wiki/D-dimer Wikipedia].

Authors

Denise Slenter , Egon Willighagen , Friederike Ehrhart , and Eric Weitz

Activity

last edited

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Cited In

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Organisms

Homo sapiens

Communities

COVID-19

Annotations

Disease Ontology

severe acute respiratory syndrome COVID-19 thrombosis blood coagulation disease

Pathway Ontology

disease pathway

Cell Type Ontology

hepatocyte

Participants
Query Drugst.One

Label Type Compact URI Comment
Leupeptin Metabolite chebi:6426
Chloroquine Metabolite chebi:3638
Lactacystin Metabolite chebi:52722
NH4Cl Metabolite chebi:31206
MG132 Metabolite pubchem.compound:462382
Fibrinogen Metabolite wikidata:Q381899 Fibrinogen is a so-called Acute Phase Reactant, a class of proteins whose plasma concentrations increase or decrease at least 25 percent during inflammation.
Fibrinogen Metabolite wikidata:Q381899
Fibrin Metabolite wikidata:Q27205
Fibrin degradation products (FDPs) Metabolite wikidata:Q2162109
D-Dimer Metabolite wikidata:Q198526
FGA GeneProduct ncbigene:2243
FGB GeneProduct ncbigene:2244
FGG GeneProduct ncbigene:2266
FGB (Bβ) Protein uniprot:P02675 'FGB is not alternatively spliced'
Plasmin Protein uniprot:P00747
FGG (γ) Protein uniprot:P02679 'fibrinogen gamma chain (also termed the γ chain) encoded by the FGG gene'
FGB (Bβ) Protein uniprot:P02675 'the fibrinogen beta chain (also termed the Bβ or β chain) encoded by the FGB gene'
FGA (Aα) Protein uniprot:P02671 'fibrinogen alpha chain (also termed the Aα or α chain) encoded by the FGA gene'
FGA (AαE) Protein ncbiprotein:NP_000499.1 'Alternate splicing of the FGA gene produces a minor expanded isoform of Aα termed AαE which replaces Aα in 1–3% of circulating fibrinogen'
Factor XIII A chain Protein uniprot:P00488 Catalytically active
Thrombin Protein uniprot:P00734
Factor XIII B chain Protein uniprot:P05160 Not catalytically active, believed to stabilise A chain
FGG (γ') Protein ncbiprotein:NP_068656.2 'alternate splicing of FGG produces a minor isoform of γ termed γ' which replaces γ in 8–10% of circulating fibrinogen'

References

  1. A unique proteolytic fragment of human fibrinogen containing the A alpha COOH-terminal domain of the native molecule. Kirschbaum NE, Budzynski AZ. J Biol Chem. 1990 Aug 15;265(23):13669–76. PubMed Europe PMC Scholia
  2. Synthetic peptides bind to high-affinity thrombin receptors and modulate thrombin mitogenesis. Glenn KC, Frost GH, Bergmann JS, Carney DH. Pept Res. 1988;1(2):65–73. PubMed Europe PMC Scholia
  3. Amino acid sequence of the b subunit of human factor XIII, a protein composed of ten repetitive segments. Ichinose A, McMullen BA, Fujikawa K, Davie EW. Biochemistry. 1986 Aug 12;25(16):4633–8. PubMed Europe PMC Scholia
  4. Fibrinogen biosynthesis. Assembly, intracellular degradation, and association with lipid synthesis and secretion. Redman CM, Xia H. Ann N Y Acad Sci. 2001;936:480–95. PubMed Europe PMC Scholia
  5. D-dimer antigen: current concepts and future prospects. Adam SS, Key NS, Greenberg CS. Blood. 2009 Mar 26;113(13):2878–87. PubMed Europe PMC Scholia
  6. Factor XIII: a coagulation factor with multiple plasmatic and cellular functions. Muszbek L, Bereczky Z, Bagoly Z, Komáromi I, Katona É. Physiol Rev. 2011 Jul;91(3):931–72. PubMed Europe PMC Scholia
  7. Coagulation Factor XIIIA Subunit Missense Mutations Affect Structure and Function at the Various Steps of Factor XIII Action. Thomas A, Biswas A, Dodt J, Philippou H, Hethershaw E, Ensikat HJ, et al. Hum Mutat. 2016 Oct;37(10):1030–41. PubMed Europe PMC Scholia
  8. COVID-19 and its implications for thrombosis and anticoagulation. Connors JM, Levy JH. Blood. 2020 Jun 4;135(23):2033–40. PubMed Europe PMC Scholia
  9. Mild versus severe COVID-19: Laboratory markers. Velavan TP, Meyer CG. Int J Infect Dis. 2020 Jun;95:304–7. PubMed Europe PMC Scholia