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Review
. 2020;49(4):451-458.
doi: 10.1159/000509581. Epub 2020 Jul 20.

Mechanisms of Stroke in COVID-19

J David Spence  1 , Gabriel R de Freitas  2 , L Creed Pettigrew  3 , Hakan Ay  4 , David S Liebeskind  5 , Carlos S Kase  6 , Oscar H Del Brutto  7 , Graeme J Hankey  8 , Narayanaswamy Venketasubramanian  9
Affiliations
Review

Mechanisms of Stroke in COVID-19

J David Spence et al. Cerebrovasc Dis. 2020.
No abstract available

PubMed Disclaimer

Conflict of interest statement

Dr. Ay is employed by Takeda Pharmaceutical Company Limited; none of the other authors has a disclosure that is relevant to this topic.

Figures

Fig. 1
Fig. 1
Potential mechanisms of ischemic stroke in patients with COVID-19. While COVID-19-related systemic and cardiovascular alterations could potentially promote all types of ischemic stroke, the attributable risk is expected to be greater for Other and CE subtypes (larger arrows). LAA, large artery atherosclerosis; CE, cardiac embolism; SAO, small artery occlusion; Other, other uncommon causes of stroke; Undetermined, undetermined causes of stroke; DVT, deep venous thrombosis. It should be noted that in COVID-19, many large artery occlusions may not be due to atherosclerosis but to embolization (from an intracardiac thrombus, or paradoxical emboli from deep vein thrombosis).
Fig. 2
Fig. 2
The contact system in disease states. FXII is activated into FXIIa either by endogenous activator (nucleic acids RNA/DNA, neutrophil extracellular traps (NETs), polyphosphate, and heparin) or artificial surfaces. FXIIa then activates 4 different pathways: (1) The inflammation kallikrein-kinin pathway by converting plasma prekallikrein (PPK) into active plasma kallikrein (PK), which cleaves both FXII into FXIIa and high molecular weight kininogen (HK) to bradykinin (BK). The latter binds to kinin receptors (B2 and B1 receptors) and triggers inflammation. (2) The complement system by activation of the C1qrs complex subunits C1r and C1s leading formation of the membrane attack complex by the classical complement pathway. (3) The fibrinolytic system by PK activation of prourokinase into urokinase that in turn cleaves plasminogen into plasmin, an enzyme that degrades fibrin clots. (4) The intrinsic coagulation pathway by FXI activation into FXIa leading to thrombin activation and fibrin generation. The contact system is controlled mainly by C1 inhibitor (C1-Inh) that inhibits both FXIIa and PK. Other endogenous inhibitors including antithrombin III (ATIII), α-2-macroglobulin (α2M), and α-2-antiplasmin (α2AP) contribute in controlling contact system proteases and new synthetic “exogenous” inhibitors have been developed to interfere with contact system-mediated diseases. Green arrows indicate activation, and red arrows inhibition. Protein in bold is the result of proteolytic cleavage of their precursors. Boxed text indicates pathways (underlined) and related disease states (reproduced by permission of Elsevier from: Weidmann H, Heikaus L, Long AT, Naudin C, Schluter H, Renne T. The plasma contact system, a protease cascade at the nexus of inflammation, coagulation and immunity. Biochim Biophys Acta Mol Cell Res. 2017;1864(11 Pt B):2118–27).
See this image and copyright information in PMC

References

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