Thrombosis

A forum investigating the similarities between COVID-19 and fluoride poisoning, thyroid dysfunction and Gq/11 pathways.
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Thrombosis

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Thrombosis
©2020 PFPC

COVID-19

"The initial coagulopathy of COVID-19 presents with prominent elevation of D-dimer and fibrin/fibrinogen degradation products, while abnormalities in prothrombin time, partial thromboplastin time, and platelet counts are relatively uncommon in initial presentations." (Connors & Levy, 2020)


Connors JM, Levy JH - "COVID-19 and its implications for thrombosis and anticoagulation" Blood (2020) blood.2020006000. doi: 10.1182/blood.2020006000. Epub ahead of print. PMID: 32339221.
https://pubmed.ncbi.nlm.nih.gov/32339221/
"Coronavirus disease 2019 (COVID-19)...may predispose patients to thrombotic disease, both in the venous and arterial circulations, due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. In addition, many patients receiving antithrombotic therapy for thrombotic disease may develop COVID-19, which can have implications for choice, dosing, and laboratory monitoring of antithrombotic therapy." (Bikdeli et al, 2020)
Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, Nigoghossian C, Ageno W, Madjid M, Guo Y, Tang LV, Hu Y, Giri J, Cushman M, Quéré I, Dimakakos EP, Gibson CM, Lippi G, Favaloro EJ, Fareed J, Caprini JA, Tafur AJ, Burton JR, Francese DP, Wang EY, Falanga A, McLintock C, Hunt BJ, Spyropoulos AC, Barnes GD, Eikelboom JW, Weinberg I, Schulman S, Carrier M, Piazza G, Beckman JA, Steg PG, Stone GW, Rosenkranz S, Goldhaber SZ, Parikh SA, Monreal M, Krumholz HM, Konstantinides SV, Weitz JI, Lip GYH - "COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-up" J Am Coll Cardiol S0735-1097(20)35008-7 (2020) doi: 10.1016/j.jacc.2020.04.031. Epub ahead of print. PMID: 32311448; PMCID: PMC7164881.
https://pubmed.ncbi.nlm.nih.gov/32311448/

Dujardin RWG, Hilderink BN, Haksteen WE, Middeldorp S, Vlaar APJ, Thachil J, Müller MCA, Juffermans NP - "Biomarkers for the prediction of venous thromboembolism in critically ill COVID-19 patients" Thromb Res 196:308-312 (2020) doi: 10.1016/j.thromres.2020.09.017
https://pubmed.ncbi.nlm.nih.gov/32977128/
Elevated CRP and D-dimer have a high positive predictive value for VTE in critically ill COVID-19 patients.

Fluoride:
"It is suggested that administration of low doses of sodium fluoride, induce new bone formation enhancing fibrinogen levels. But in high doses of sodium fluoride, moderate tissue damage results in high levels of plasma fibrinogen." (Suheela & Sharman, 1981)
Susheela AK, Sharma YD - "Chemical profile of blood in fluoride toxicity. III. Plasma fibrinogen levels in rabbit" Toxicol Eur Res 3(2):105-7 (1981) PMID: 7245186.
https://pubmed.ncbi.nlm.nih.gov/7245186/

"Higher blood clot for groups 5 and 50 ppm of F at 30 days was observed." (Fernandes et al., 2014) NOTE: 5 to 50 ppm F in rats = concentration required to cause dental fluorosis)


Fernandes Mda S, Yanai MM, Martins GM, Iano FG, Leite AL, Cestari TM, Taga R, Buzalaf MA, de Oliveira RC - "Effects of fluoride in bone repair: an evaluation of RANKL, OPG and TRAP expression" Odontology 102(1):22-30 (2014)
https://pubmed.ncbi.nlm.nih.gov/22878484/

G q/11:

"Together, these results indicate that SFK phosphorylation in response to thrombin receptor stimulation is downstream from Gq/Ca2+ signaling". (Xiang et al., 2012)



Xiang B, Zhang G, Stefanini L, Bergmeier W, Gartner TK, Whiteheart SW, Li Z - "The Src family kinases and protein kinase C synergize to mediate Gq-dependent platelet activation" J Biol Chem 287(49):41277-87 (2012) doi: 10.1074/jbc.M112.393124. Epub 2012 Oct 12. PMID: 23066026; PMCID: PMC3510826.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3510826/
"In conclusion, we demonstrate a platelet priming mechanism initiated by suboptimal activation of PAR4 or other platelet G(q)-linked GPCRs through a PLC-dependent signaling cascade that promotes enhanced alpha(2)beta(1) binding to collagens containing GFOGER sites." (Marjoram et al., 2009)


Marjoram RJ, Voss B, Pan Y, Dickeson SK, Zutter MM, Hamm HE, Santoro SA - "Suboptimal activation of protease-activated receptors enhances alpha2beta1 integrin-mediated platelet adhesion to collagen" J Biol Chem 284(50):34640-7 (2009) doi: 10.1074/jbc.M109.020990. Epub 2009 Oct 8. PMID: 19815553; PMCID: PMC2787326.
https://pubmed.ncbi.nlm.nih.gov/19815553/

Holdfeldt A, Dahlstrand Rudin A, Gabl M, Rajabkhani Z, König GM, Kostenis E, Dahlgren C, Forsman H - "Reactivation of Gαi-coupled formyl peptide receptors is inhibited by Gαq-selective inhibitors when induced by signals generated by the platelet-activating factor receptor" J Leukoc Biol 102(3):871-880 (2017) doi: 10.1189/jlb.2A0317-086RR. Epub 2017 Jul 31. PMID: 28760822
https://pubmed.ncbi.nlm.nih.gov/28760822
  • SEE ALSO:
    The pattern of COVID-19 pneumonitis was predominantly a pauci-inflammatory septal capillary injury with significant septal capillary mural and luminal fibrin deposition and permeation of the interalveolar septa by neutrophils." (Magro et al., 2020)
    Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, Baxter-Stoltzfus A, Laurence J - "Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases" Transl Res 15:S1931-5244(20)30070-0 (2020). doi: 10.1016/j.trsl.2020.04.007. Epub ahead of print. PMID: 32299776; PMCID: PMC7158248.
    https://pubmed.ncbi.nlm.nih.gov/32299776/
    "The lung of group I was characterized by presence of blood and lymph congestion. Thickening of alveolar septa was also observed with rupture of septa and widening of the air spaces. The area % of collagen (1.13 ±0.5), septal wall thickness (13.47 ±6.1), and number of macrophages (5 ±2.5) increased in comparison to the control group (p ≤ 0.05). With discontinuation of sodium fluoride (group II), not much improvement was observed.

    Conclusions: Chronic fluorosis has many pathological effects on the lung which are irreversible."(Abdel-Gawad et al., 2014)
    Abdel-Gawad FA, Ashmawy MH, Zaki SM, Abdel-Fatah GH - "Lung damage after long-term exposure of adult rats to sodium fluoride" Arch Med Sci 10(5):1035‐1040 (2014) doi:10.5114/aoms.2014.46221
    https://pubmed.ncbi.nlm.nih.gov/25395957/

    Henry BM, Vikse J, Benoit S, Favaloro EJ, Lippi G - "Hyperinflammation and derangement of renin-angiotensin-aldosterone system in COVID-19: A novel hypothesis for clinically suspected hypercoagulopathy and microvascular immunothrombosis" Clin Chim Acta 507:167-173 (2020) doi: 10.1016/j.cca.2020.04.027. Epub ahead of print. PMID: 32348783; PMCID: PMC7195008.
    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7195008/

TSH/Thyroid

"Those receptors shown to activate G12and G13 (Offermanns et al 1994a, Laugwitz et al 1996) were characterized as coupling primarily to Gq (thromboxane A2 and thrombin receptors) or to Gs (thyrotropin receptor)." (Gudermann et al., 1997)


Gudermann T, Schöneberg T, Schultz G - "Functional and structural complexity of signal transduction via G-protein-coupled receptors" Annu Rev Neurosci 20:399-427 (1997) doi: 10.1146/annurev.neuro.20.1.399. PMID: 9056720
https://pubmed.ncbi.nlm.nih.gov/9056720/

"Among patients with suspected venous thromboembolism (VTE) TSH concentration was found to be an independent predictor of VTE in addition to gender, D-dimer, C-reactive protein (CRP), and age." (Kovářová et al., 2015)


Kovářová M, Koller T, Štvrtinová V, Payer J - "Thyroid-stimulating hormone concentration as an independent risk factor of venous thromboembolism regardless of thyroid function" Endokrynol Pol 66(6):474-9 (2015)
https://pubmed.ncbi.nlm.nih.gov/26662645/

SEE ALSO:
C-Reactive Protein
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COVID Vaccine and Thrombosis

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German Institute confirms link between blood clot deaths and AstraZeneca vaccine
https://www.pei.de/SharedDocs/Downloads ... onFile&v=2

EU says AstraZeneca vaccine is safe, will add blood clot warning
https://www.syracuse.com/coronavirus/20 ... rning.html

March 19, 2021 AstraZeneca: Greifswalder Forscher haben offenbar Thrombose-Ursache gefunden
https://www.ndr.de/nachrichten/mecklenb ... s4660.html
admin
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Spike protein - minimal levels can initiate

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Theuerkauf SA, Michels A, Riechert V, Maier TJ, Flory E, Cichutek K, Buchholz CJ - "Quantitative assays reveal cell fusion at minimal levels of SARS-CoV-2 spike protein and fusion from without" iScience 24(3):102170 (2021) doi: 10.1016/j.isci.2021.102170. Epub 2021 Feb 9. PMID: 33585805; PMCID: PMC7871100
https://pubmed.ncbi.nlm.nih.gov/33585805/
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