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Review

Long-term hypercoagulability, endotheliopathy and inflammation following acute SARS-CoV-2 infection

ORCID Icon, , &
Pages 1035-1048 | Received 06 Jul 2023, Accepted 22 Nov 2023, Published online: 28 Nov 2023

References

  • Welsh FKS, Walsh CM, Chandrakumaran K, et al. Peri-operative thrombophilia in patients undergoing liver resection for colorectal metastases [observational study]. HPB. 2023 Jan;25(1):63–72. doi: 10.1016/j.hpb.2022.09.013
  • Ejaz H, Alsrhani A, Zafar A, et al. COVID-19 and comorbidities: deleterious impact on infected patients. J Infect Public Health. 2020 Dec;13(12):1833–1839. doi: 10.1016/j.jiph.2020.07.014
  • Lala A, Johnson KW, Januzzi JL, et al. Prevalence and Impact of myocardial injury in patients hospitalized with COVID-19 infection. J Am Coll Cardiol. 2020 Aug 4;76(5):533–546. doi: 10.1016/j.jacc.2020.06.007
  • Nakano H, Shiina K, Tomiyama H. Cardiovascular outcomes in the acute phase of COVID-19. Int J Mol Sci. 2021 Apr 15;22(8):4071. doi: 10.3390/ijms22084071
  • Wang W, Wang CY, Wang SI, et al. Long-term cardiovascular outcomes in COVID-19 survivors among non-vaccinated population: a retrospective cohort study from the TriNetX US collaborative networks. EClinicalMedicine. 2022 Nov;53:101619.
  • Xie Y, Xu E, Bowe B, et al. Long-term cardiovascular outcomes of COVID-19. Nat Med. 2022 Mar;28(3):583–590. doi: 10.1038/s41591-022-01689-3
  • Salah HM, Fudim M, O’Neil ST, et al. Post-recovery COVID-19 and incident heart failure in the National COVID cohort Collaborative (N3C) study. Nat Commun. 2022 Jul 15;13(1):4117. doi: 10.1038/s41467-022-31834-y
  • Giannis D, Allen SL, Tsang J, et al. Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry. Blood. 2021 May 20;137(20):2838–2847. doi: 10.1182/blood.2020010529
  • Tereshchenko LG, Bishop A, Fisher-Campbell N, et al. Risk of cardiovascular events after COVID-19. Am J Cardiol. 2022 Sep 15;179:102–109. doi: 10.1016/j.amjcard.2022.06.023
  • Wiemken TL, McGrath LJ, Andersen KM, et al. COVID-19 severity and risk of subsequent cardiovascular events. Clin Infect Dis. 2023 Feb 8;76(3):e42–e50. doi: 10.1093/cid/ciac661
  • Cuomo G, Puzzolante C, Iadisernia V, et al. Development of post-COVID-19 cardiovascular events: an analysis of clinical features and risk factors from a single hospital retrospective study. Infez Med. 2021;29(4):538–549.
  • Marfella R, Paolisso P, Sardu C, et al. SARS-COV-2 colonizes coronary thrombus and impairs heart microcirculation bed in asymptomatic SARS-CoV-2 positive subjects with acute myocardial infarction. Crit Care. 2021 Jun 24;25(1):217. doi: 10.1186/s13054-021-03643-0
  • Evans PC, Rainger GE, Mason JC, et al. Endothelial dysfunction in COVID-19: a position paper of the ESC working group for atherosclerosis and vascular biology, and the ESC council of basic cardiovascular science. Cardiovasc Res. 2020 Dec 1;116(14):2177–2184. doi: 10.1093/cvr/cvaa230
  • Varga Z, Flammer AJ, Steiger P, et al. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020 May 2;395(10234):1417–1418. doi: 10.1016/S0140-6736(20)30937-5
  • Oikonomou E, Souvaliotis N, Lampsas S, et al. Endothelial dysfunction in acute and long standing COVID-19: a prospective cohort study. Vasc Pharmacol. 2022 Jun;144:106975.
  • Santoro L, Falsetti L, Zaccone V, et al. Impaired endothelial function in convalescent phase of COVID-19: a 3 month follow up observational prospective study. J Clin Med. 2022 Mar 23;11(7):1774. doi: 10.3390/jcm11071774
  • Jud P, Gressenberger P, Muster V, et al. Evaluation of endothelial dysfunction and inflammatory vasculopathy after SARS-CoV-2 infection-A cross-sectional study. Front Cardiovasc Med. 2021;8:750887. doi: 10.3389/fcvm.2021.750887
  • Jud P, Kessler HH, Brodmann M. Case report: changes of vascular reactivity and arterial stiffness in a patient with covid-19 infection. Front Cardiovasc Med. 2021;8:671669. doi: 10.3389/fcvm.2021.671669
  • Szeghy RE, Province VM, Stute NL, et al. Carotid stiffness, intima-media thickness and aortic augmentation index among adults with SARS-CoV-2. Exp Physiol. 2022 Jul;107(7):694–707. doi: 10.1113/EP089481
  • Ratchford SM, Stickford JL, Province VM, et al. Vascular alterations among young adults with SARS-CoV-2. Am J Physiol Heart Circ Physiol. 2021 Jan 1;320(1):H404–h410. doi: 10.1152/ajpheart.00897.2020
  • Kumar N, Kumar S, Kumar A, et al. The COSEVAST study outcome: evidence of COVID-19 severity proportionate to surge in arterial stiffness. Indian J Crit Care Med. 2021 Oct;25(10):1113–1119. doi: 10.5005/jp-journals-10071-24000
  • Pirzada A, Mokhtar AT, Moeller AD. COVID-19 and myocarditis: what do We know so far? CJC Open. 2020 Jul;2(4):278–285. doi: 10.1016/j.cjco.2020.05.005
  • Gavriilaki E, Anyfanti P, Gavriilaki M, et al. Endothelial dysfunction in COVID-19: lessons learned from coronaviruses. Curr Hypertens Rep. 2020 Aug 27;22(9):63. doi: 10.1007/s11906-020-01078-6
  • D’Ardes D, Boccatonda A, Cocco G, et al. Impaired coagulation, liver dysfunction and COVID-19: discovering an intriguing relationship. World J Gastroenterol. 2022 Mar 21;28(11):1102–1112. doi: 10.3748/wjg.v28.i11.1102
  • Boccatonda A, Ianniello E, D’Ardes D, et al. Can lung ultrasound be used to screen for pulmonary embolism in patients with SARS-CoV-2 pneumonia? Eur J Case Rep Intern Med. 2020;7(7):001748.
  • Degauque N, Haziot A, Brouard S, et al. Endothelial cell, myeloid, and adaptive immune responses in SARS-CoV-2 infection. FASEB J. 2021 May;35(5):e21577. doi: 10.1096/fj.202100024R
  • Davignon J, Ganz P. Role of endothelial dysfunction in atherosclerosis. Circulation. 2004 Jun 15;109(23 Suppl 1):Iii27–32. doi: 10.1161/01.CIR.0000131515.03336.f8
  • Postiga IAL, Teixeira PC, Neves CAM, et al. Systemic redox imbalance in severe COVID-19 patients. Cell Biochem Funct. 2022 Aug 18;40(7):694–705. doi: 10.1002/cbf.3735
  • D’Ardes D, Boccatonda A, Rossi I, et al. COVID-19 and RAS: unravelling an unclear relationship. Int J Mol Sci. 2020 Apr 24;21(8):3003. doi: 10.3390/ijms21083003
  • Simeone P, Boccatonda A, Liani R, et al. Significance of urinary 11-dehydro-thromboxane B(2) in age-related diseases: focus on atherothrombosis. Ageing Res Rev. 2018 Dec;48:51–78.
  • Lessiani G, Santilli F, Boccatonda A, et al. Arterial stiffness and sedentary lifestyle: role of oxidative stress. Vasc Pharmacol. 2016 Apr;79:1–5.
  • Boccatonda A, Tripaldi R, Davì G, et al. Oxidative stress modulation through habitual physical activity. Curr Pharm Des. 2016;22(24):3648–3680. doi: 10.2174/1381612822666160413123806
  • Andrianto A-FM, Nugraha RA, Marsudi BA, et al. Biomarkers of endothelial dysfunction and outcomes in coronavirus disease 2019 (COVID-19) patients: a systematic review and meta-analysis. Microvasc Res. 2021 Nov;138:104224.
  • Lampsas S, Tsaplaris P, Pantelidis P, et al. The role of endothelial related circulating biomarkers in COVID-19. A systematic review and meta-analysis. Curr Med Chem. 2022;29(21):3790–3805. doi: 10.2174/0929867328666211026124033
  • Garnier Y, Claude L, Hermand P, et al. Plasma microparticles of intubated COVID-19 patients cause endothelial cell death, neutrophil adhesion and netosis, in a phosphatidylserine-dependent manner. Br J Haematol. 2022 Mar;196(5):1159–1169. doi: 10.1111/bjh.18019
  • Centa A, Fonseca AS, Ferreira S, et al. Deregulated miRNA expression is associated with endothelial dysfunction in post-mortem lung biopsies of COVID-19 patients. Am J Physiol Lung Cell Mol Physiol. 2020 Dec 2;320(3):L405–12. doi: 10.1152/ajplung.00457.2020
  • Willems LH, Nagy M, Ten Cate H, et al. Sustained inflammation, coagulation activation and elevated endothelin-1 levels without macrovascular dysfunction at 3 months after COVID-19. Thromb Res. 2022 Jan;209:106–114.
  • Flaskamp L, Roubal C, Uddin S, et al. Serum of post-COVID-19 syndrome patients with or without ME/CFS differentially affects endothelial cell function in vitro. Cells. 2022 Aug 2;11(15):2376. doi: 10.3390/cells11152376
  • Desimmie BA, Raru YY, Awadh HM, et al. Insights into SARS-CoV-2 persistence and its relevance. Viruses. 2021 May 29;13(6):1025. doi: 10.3390/v13061025
  • Buonsenso D, Martino L, Morello R, et al. Viral persistence in children infected with SARS-CoV-2: current evidence and future research strategies. Lancet Microbe. 2023 Sep;4(9):e745–e756. doi: 10.1016/S2666-5247(23)00115-5
  • Eymieux S, Uzbekov R, Rouillé Y, et al. Secretory vesicles are the Principal means of SARS-CoV-2 egress. Cells. 2021 Aug 10;10(8):2047. doi: 10.3390/cells10082047
  • Barberis E, Vanella VV, Falasca M, et al. Circulating exosomes are strongly involved in SARS-CoV-2 infection. Front Mol Biosci. 2021;8:632290. doi: 10.3389/fmolb.2021.632290
  • Falconieri F, Raevsky E, Davies S, et al. Pseudoaneurysm of a branch of left internal mammary artery: a late and potentially fatal complication after redo-sternotomy. Interact Cardiovasc Thorac Surg. 2015 Jun;20(6):866–867. doi: 10.1093/icvts/ivv059
  • Borowiec BM, Angelova Volponi A, Mozdziak P, et al. Small extracellular vesicles and COVID19—using the “trojan horse” to tackle the giant. Cells. 2021 Dec 1;10(12):3383. doi: 10.3390/cells10123383
  • Amenta EM, Spallone A, Rodriguez-Barradas MC, et al. Postacute COVID-19: an overview and approach to classification. Open Forum Infect Dis. 2020 Dec;7(12):ofaa509. doi: 10.1093/ofid/ofaa509
  • Peluso MJ, Lu S, Tang AF, et al. Markers of immune activation and inflammation in individuals with postacute sequelae of severe acute respiratory syndrome coronavirus 2 infection. J Infect Dis. 2021 Dec 1;224(11):1839–1848. doi: 10.1093/infdis/jiab490
  • Fernández-Lázaro D, Sánchez-Serrano N, Mielgo-Ayuso J, et al. Long COVID a New derivative in the chaos of SARS-CoV-2 infection: the emergent pandemic? J Clin Med. 2021 Dec 11;10(24):5799. doi: 10.3390/jcm10245799
  • Ceban F, Ling S, Lui LMW, et al. Fatigue and cognitive impairment in post-COVID-19 syndrome: a systematic review and meta-analysis. Brain Behav Immun. 2022 Mar;101:93–135.
  • Laing AG, Lorenc A, Del Molino Del Barrio I, et al. A dynamic COVID-19 immune signature includes associations with poor prognosis. Nat Med. 2020 Oct;26(10):1623–1635. doi: 10.1038/s41591-020-1038-6
  • Yong SJ. Long COVID or post-COVID-19 syndrome: putative pathophysiology, risk factors, and treatments. Infect Dis. 2021 Oct;53(10):737–754. doi: 10.1080/23744235.2021.1924397
  • Townsend L, Fogarty H, Dyer A, et al. Prolonged elevation of D-dimer levels in convalescent COVID-19 patients is independent of the acute phase response. J Thromb Haemost. 2021 Apr;19(4):1064–1070. doi: 10.1111/jth.15267
  • Pasini E, Corsetti G, Romano C, et al. Serum metabolic profile in patients with long-covid (PASC) syndrome: clinical implications. Front Med. 2021;8:714426. doi: 10.3389/fmed.2021.714426
  • Phetsouphanh C, Darley DR, Wilson DB, et al. Immunological dysfunction persists for 8 months following initial mild-to-moderate SARS-CoV-2 infection. Nat Immunol. 2022 Feb;23(2):210–216. doi: 10.1038/s41590-021-01113-x
  • Volpicelli G, Gargani L, Perlini S, et al. Lung ultrasound for the early diagnosis of COVID-19 pneumonia: an international multicenter study. Intensive care Med. 2021 Apr;47(4):444–454. doi: 10.1007/s00134-021-06373-7
  • Fogarty H, Ward SE, Townsend L, et al. Sustained VWF-ADAMTS-13 axis imbalance and endotheliopathy in long COVID syndrome is related to immune dysfunction. J Thromb Haemost. 2022 Oct;20(10):2429–2438. doi: 10.1111/jth.15830
  • Buonsenso D, Valentini P, De Rose C, et al. Recovering or persisting: the immunopathological features of SARS-CoV-2 infection in children. J Clin Med. 2022 Jul 27;11(15):4363. doi: 10.3390/jcm11154363
  • Files JK, Sarkar S, Fram TR, et al. Duration of post-COVID-19 symptoms is associated with sustained SARS-CoV-2-specific immune responses. JCI Insight. 2021 Aug 9;6(15). doi: 10.1172/jci.insight.151544
  • Yao L, Wang GL, Shen Y, et al. Persistence of antibody and cellular immune responses in coronavirus disease 2019 patients over nine months after infection. J Infect Dis. 2021 Aug 16;224(4):586–594. doi: 10.1093/infdis/jiab255
  • Chang SE, Feng A, Meng W, et al. New-onset IgG autoantibodies in hospitalized patients with COVID-19. Nat Commun. 2021 Sep 14;12(1):5417. doi: 10.1038/s41467-021-25509-3
  • Knight JS, Caricchio R, Casanova JL, et al. The intersection of COVID-19 and autoimmunity. J Clin Invest. 2021 Dec 15;131(24). doi: 10.1172/JCI154886
  • Sawadogo SA, Dighero-Kemp B, Ouédraogo DD, et al. How NETosis could drive “post-COVID-19 syndrome” among survivors. Immunol Lett. 2020 Dec;228:35–37.
  • Ng H, Havervall S, Rosell A, et al. Circulating markers of neutrophil extracellular traps are of prognostic value in patients with COVID-19. Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):988–994. doi: 10.1161/ATVBAHA.120.315267
  • Levi M, Thachil J, Iba T, et al. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020 Jun;7(6):e438–e440. doi: 10.1016/S2352-3026(20)30145-9
  • Pretorius E, Vlok M, Venter C, et al. Persistent clotting protein pathology in long COVID/Post-acute sequelae of COVID-19 (PASC) is accompanied by increased levels of antiplasmin. Cardiovasc Diabetol. 2021 Aug 23;20(1):172. doi: 10.1186/s12933-021-01359-7
  • Zuin M, Engelen MM, Barco S, et al. Incidence of venous thromboembolic events in COVID-19 patients after hospital discharge: a systematic review and meta-analysis. Thromb Res. 2022 Jan;209:94–98.
  • Lessiani G, Boccatonda A, D’Ardes D, et al. Mondor’s disease in SARS-CoV-2 infection: a Case of superficial vein thrombosis in the era of COVID-19. Eur J Case Rep Intern Med. 2020;7(10):001803. doi: 10.12890/2020_001803
  • Ranucci M, Baryshnikova E, Anguissola M, et al. The long term residual effects of COVID-Associated coagulopathy. Int J Mol Sci. 2023 Mar 14;24(6):5514. doi: 10.3390/ijms24065514
  • von Meijenfeldt FA, Havervall S, Adelmeijer J, et al. Sustained prothrombotic changes in COVID-19 patients 4 months after hospital discharge. Blood Adv. 2021 Feb 9;5(3):756–759. doi: 10.1182/bloodadvances.2020003968
  • Zietz M, Zucker J, Tatonetti NP. Associations between blood type and COVID-19 infection, intubation, and death. Nat Commun. 2020 Nov 13;11(1):5761. doi: 10.1038/s41467-020-19623-x
  • Fan BE, Wong SW, Sum CLL, et al. Hypercoagulability, endotheliopathy, and inflammation approximating 1 year after recovery: assessing the long-term outcomes in COVID-19 patients. Am J Hematol. 2022 Jul;97(7):915–923. doi: 10.1002/ajh.26575
  • Kruger A, Vlok M, Turner S, et al. Proteomics of fibrin amyloid microclots in long COVID/post-acute sequelae of COVID-19 (PASC) shows many entrapped pro-inflammatory molecules that may also contribute to a failed fibrinolytic system. Cardiovasc Diabetol. 2022 Sep 21;21(1):190. doi: 10.1186/s12933-022-01623-4
  • Ryu JK, Sozmen EG, Dixit K, et al. SARS-CoV-2 spike protein induces abnormal inflammatory blood clots neutralized by fibrin immunotherapy. bioRxiv. 2021Oct 13. doi: 10.1101/2021.10.12.464152
  • Grobbelaar LM, Venter C, Vlok M, et al. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: implications for microclot formation in COVID-19. Biosci Rep. 2021 Aug 27;41(8). doi: 10.1042/BSR20210611
  • Kell DB, Pretorius E. The simultaneous occurrence of both hypercoagulability and hypofibrinolysis in blood and serum during systemic inflammation, and the roles of iron and fibrin(ogen). Integr Biol (Camb). 2015 Jan;7(1):24–52. doi: 10.1039/c4ib00173g
  • Kell DB, Pretorius E. Proteins behaving badly. Substoichiometric molecular control and amplification of the initiation and nature of amyloid fibril formation: lessons from and for blood clotting. Prog Biophys Mol Biol. 2017 Jan;123:16–41. doi: 10.1016/j.pbiomolbio.2016.08.006
  • Pretorius E, Venter C, Laubscher GJ, et al. Prevalence of readily detected amyloid blood clots in ‘unclotted’ type 2 diabetes mellitus and COVID-19 plasma: a preliminary report. Cardiovasc Diabetol. 2020 Nov 17;19(1):193. doi: 10.1186/s12933-020-01165-7
  • Pretorius E, Venter C, Laubscher GJ, et al. Prevalence of symptoms, comorbidities, fibrin amyloid microclots and platelet pathology in individuals with long COVID/Post-acute sequelae of COVID-19 (PASC). Cardiovasc Diabetol. 2022 Aug 6;21(1):148. doi: 10.1186/s12933-022-01579-5
  • Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J. 2022 Feb 17;479(4):537–559. doi: 10.1042/BCJ20220016
  • Turner S, Naidoo CA, Usher TJ, et al. Increased levels of inflammatory and endothelial biomarkers in blood of long COVID patients point to thrombotic endothelialitis. Semin Thromb Hemost. 2023 May 19. doi: 10.1055/s-0043-1769014
  • Pretorius E, Page MJ, Engelbrecht L, et al. Substantial fibrin amyloidogenesis in type 2 diabetes assessed using amyloid-selective fluorescent stains. Cardiovasc Diabetol. 2017 Nov 2;16(1):141. doi: 10.1186/s12933-017-0624-5
  • Nunes JM, Kruger A, Proal A, et al. The occurrence of hyperactivated platelets and fibrinaloid microclots in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Pharmaceuticals (Basel). 2022 Jul 27;15(8):931. doi: 10.3390/ph15080931
  • Fox T, Hunt BJ, Ariens RA, et al. Plasmapheresis to remove amyloid fibrin(ogen) particles for treating the post-COVID-19 condition. Cochrane Database Syst Rev. 2023 Jul 26;7(7):Cd015775. doi: 10.1002/14651858.CD015775
  • Rolla R, Puricelli C, Bertoni A, et al. Platelets: “multiple choice” effectors in the immune response and their implication in COVID-19 thromboinflammatory process. Int J Lab Hematol. 2021 Oct;43(5):895–906. doi: 10.1111/ijlh.13516
  • Manne BK, Denorme F, Middleton EA, et al. Platelet gene expression and function in patients with COVID-19. Blood. 2020 Sep 10;136(11):1317–1329. doi: 10.1182/blood.2020007214
  • Hottz ED, Azevedo-Quintanilha IG, Palhinha L, et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood. 2020 Sep 10;136(11):1330–1341. doi: 10.1182/blood.2020007252
  • Martins-Gonçalves R, Campos MM, Palhinha L, et al. Persisting platelet activation and hyperactivity in COVID-19 survivors. Circ Res. 2022 Nov 11;131(11):944–947. doi: 10.1161/CIRCRESAHA.122.321659
  • Hoepel W, Chen HJ, Geyer CE, et al. High titers and low fucosylation of early human anti-SARS-CoV-2 IgG promote inflammation by alveolar macrophages. Sci Transl Med. 2021 Jun 2;13(596). doi: 10.1126/scitranslmed.abf8654
  • Philippe A, Günther S, Rancic J, et al. VEGF-A plasma levels are associated with impaired DLCO and radiological sequelae in long COVID patients. Angiogenesis. 2023 Aug 1. doi: 10.1007/s10456-023-09890-9
  • Constantinescu-Bercu A, Kessler A, de Groot R, et al. Analysis of thrombogenicity under flow reveals new insights into the prothrombotic state of patients with post-COVID syndrome. J Thromb Haemost. 2023 Jan;21(1):94–100. doi: 10.1016/j.jtha.2022.10.013
  • Mobayen G, Dhutia A, Clarke C, et al. Severe COVID-19 is associated with endothelial activation and abnormal glycosylation of von Willebrand factor in patients undergoing hemodialysis. Res Pract Thromb Haemost. 2021 Aug;5(6):e12582. doi: 10.1002/rth2.12582
  • Khan S, Shafiei MS, Longoria C, et al. SARS-CoV-2 spike protein induces inflammation via TLR2-dependent activation of the NF-κB pathway. Elife. 2021 Dec 6;10. doi: 10.7554/eLife.68563
  • Prasannan N, Heightman M, Hillman T, et al. Impaired exercise capacity in post-COVID-19 syndrome: the role of VWF-ADAMTS13 axis. Blood Adv. 2022 Jul 12;6(13):4041–4048. doi: 10.1182/bloodadvances.2021006944
  • Fogarty H, Townsend L, Morrin H, et al. Persistent endotheliopathy in the pathogenesis of long COVID syndrome. J Thromb Haemost. 2021 Oct;19(10):2546–2553. doi: 10.1111/jth.15490
  • Santilli F, Marchisio M, Lanuti P, et al. Microparticles as new markers of cardiovascular risk in diabetes and beyond. Thromb Haemost. 2016 Aug 1;116(2):220–234. doi: 10.1160/TH16-03-0176
  • Campello E, Radu CM, Duner E, et al. Activated platelet-derived and leukocyte-derived circulating microparticles and the risk of thrombosis in heparin-induced Thrombocytopenia: a role for PF4-bearing microparticles? Cytometry B Clin Cytom. 2018 Mar;94(2):334–341. doi: 10.1002/cyto.b.21507
  • Campello E, Spiezia L, Radu CM, et al. Microparticles as biomarkers of venous thromboembolic events. Biomarker Med. 2016 Jul;10(7):743–755. doi: 10.2217/bmm-2015-0063
  • Campello E, Zanetto A, Spiezia L, et al. Hypercoagulability detected by circulating microparticles in patients with hepatocellular carcinoma and cirrhosis. Thromb Res. 2016 Jul;143:118–121.
  • Zahran AM, El-Badawy O, Ali WA, et al. Circulating microparticles and activated platelets as novel prognostic biomarkers in COVID-19; relation to cancer. PLoS One. 2021;16(2):e0246806. doi: 10.1371/journal.pone.0246806
  • Guervilly C, Bonifay A, Burtey S, et al. Dissemination of extreme levels of extracellular vesicles: tissue factor activity in patients with severe COVID-19. Blood Adv. 2021 Feb 9;5(3):628–634. doi: 10.1182/bloodadvances.2020003308
  • Rosell A, Havervall S, von Meijenfeldt F, et al. Patients with COVID-19 have elevated levels of circulating extracellular vesicle tissue factor activity that is associated with severity and mortality-brief report. Arterioscler Thromb Vasc Biol. 2021 Feb;41(2):878–882. doi: 10.1161/ATVBAHA.120.315547
  • Argañaraz GA, Palmeira JDF, Argañaraz ER. Phosphatidylserine inside out: a possible underlying mechanism in the inflammation and coagulation abnormalities of COVID-19. Cell Commun Signal. 2020 Dec 27;18(1):190. doi: 10.1186/s12964-020-00687-7
  • Althaus K, Marini I, Zlamal J, et al. Antibody-induced procoagulant platelets in severe COVID-19 infection. Blood. 2021 Feb 25;137(8):1061–1071. doi: 10.1182/blood.2020008762
  • Cappellano G, Raineri D, Rolla R, et al. Circulating Platelet-Derived Extracellular Vesicles Are a Hallmark of Sars-Cov-2 Infection. Cells. 2021 Jan 7;10(1):85. doi: 10.3390/cells10010085
  • Burrello J, Caporali E, Gauthier LG, et al. Risk stratification of patients with SARS-CoV-2 by tissue factor expression in circulating extracellular vesicles. Vasc Pharmacol. 2022 Aug;145:106999.
  • Campello E, Radu CM, Simion C, et al. Longitudinal trend of plasma concentrations of extracellular vesicles in patients hospitalized for COVID-19. Front Cell Dev Biol. 2021;9:770463. doi: 10.3389/fcell.2021.770463
  • Luijten D, de Jong CMM, Ninaber MK, et al. Post-pulmonary embolism syndrome and functional outcomes after acute pulmonary embolism. Semin Thromb Hemost. 2022 Jul 12;49(08):848–860. doi: 10.1055/s-0042-1749659
  • Cueto-Robledo G, Porres-Aguilar M, Puebla-Aldama D, et al. Severe pulmonary hypertension: an important sequel after severe post-acute COVID-19 pneumonia. Curr Probl Cardiol. 2022 Mar;47(3):101004. doi: 10.1016/j.cpcardiol.2021.101004
  • Boccatonda A, Cocco G, Ianniello E, et al. One year of SARS-CoV-2 and lung ultrasound: what has been learned and future perspectives. J Ultrasound. 2021 Jun;24(2):115–123. doi: 10.1007/s40477-021-00575-x
  • Pizzuto DA, Buonsenso D, Morello R, et al. Lung perfusion assessment in children with long-COVID: a pilot study. Pediatr Pulmonol. 2023 Jul;58(7):2059–2067. doi: 10.1002/ppul.26432
  • Buonsenso D, Di Giuda D, Sigfrid L, et al. Evidence of lung perfusion defects and ongoing inflammation in an adolescent with post-acute sequelae of SARS-CoV-2 infection. Lancet Child Adolesc Health. 2021 Sep;5(9):677–680. doi: 10.1016/S2352-4642(21)00196-6
  • Buonsenso D, Morello R, De Rose C, et al. Long-term outcome of a child with postcovid condition: role of cardiopulmonary exercise testing and 24-h holter ECG to monitor treatment response and recovery. Pediatr Pulmonol. 2023 Jun 28;58(10):2944–2946. doi: 10.1002/ppul.26578
  • Moasefi N, Fouladi M, Norooznezhad AH, et al. How could perfluorocarbon affect cytokine storm and angiogenesis in coronavirus disease 2019 (COVID-19): role of hypoxia-inducible factor 1α. Inflamm Res. 2021 Jul;70(7):749–752. doi: 10.1007/s00011-021-01469-8
  • Thachil J. Hypoxia-an overlooked trigger for thrombosis in COVID-19 and other critically ill patients. J Thromb Haemost. 2020 Nov;18(11):3109–3110. doi: 10.1111/jth.15029
  • Evans CE. Hypoxia and HIF activation as a possible link between sepsis and thrombosis. Thromb J. 2019;17(1):16. doi: 10.1186/s12959-019-0205-9
  • Santoro F, Nuñez-Gil IJ, Vitale E, et al. Antiplatelet therapy and outcome in COVID-19: the Health outcome predictive evaluation registry. Heart. 2022 Jan;108(2):130–136. doi: 10.1136/heartjnl-2021-319552
  • Meizlish ML, Goshua G, Liu Y, et al. Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis. Am J Hematol. 2021 Apr 1;96(4):471–479. doi: 10.1002/ajh.26102
  • Viecca M, Radovanovic D, Forleo GB, et al. Enhanced platelet inhibition treatment improves hypoxemia in patients with severe covid-19 and hypercoagulability. A case control, proof of concept study. Pharmacol Res. 2020 Aug;158:104950.
  • Chow JH, Rahnavard A, Gomberg-Maitland M, et al. Association of early aspirin use with in-hospital mortality in patients with moderate COVID-19. JAMA Netw Open. 2022 Mar 1;5(3):e223890. doi: 10.1001/jamanetworkopen.2022.3890
  • Higgins AM, Berry LR, Lorenzi E, et al. Long-term (180-day) outcomes in critically ill patients with COVID-19 in the REMAP-CAP randomized clinical trial. JAMA. 2023 Jan 3;329(1):39–51. doi: 10.1001/jama.2022.23257
  • Mohamed-Hussein AAR, Aly KME, Ibrahim MAA. Should aspirin be used for prophylaxis of COVID-19-induced coagulopathy? Med Hypotheses. 2020 Nov;144:109975. doi: 10.1016/j.mehy.2020.109975
  • Homoncik M, Jilma B, Eichelberger B, et al. Inhibitory activity of aspirin on von Willebrand factor-induced platelet aggregation. Thromb Res. 2000 Sep 1;99(5):461–466. doi: 10.1016/S0049-3848(00)00297-8
  • Zhao L, Gray L, Leonardi-Bee J, et al. Effect of aspirin, clopidogrel and dipyridamole on soluble markers of vascular function in normal volunteers and patients with prior ischaemic stroke. Platelets. 2006 Mar;17(2):100–104. doi: 10.1080/09537100500235966
  • Fan M, Xu H, Wang L, et al. Tissue plasminogen activator neurotoxicity is neutralized by recombinant ADAMTS 13. Sci Rep. 2016 May 16;6(1):25971. doi: 10.1038/srep25971
  • Bradbury CA, Lawler PR, Stanworth SJ, et al. Effect of antiplatelet therapy on survival and organ support-free days in critically ill patients with COVID-19: a randomized clinical trial. JAMA. 2022 Apr 5;327(13):1247–1259. doi: 10.1001/jama.2022.2910
  • Abani O, Abbas A, Abbas F. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet. 2022 Jan 8;399(10320):143–151. doi: 10.1016/S0140-6736(21)01825-0
  • Eikelboom JW, Jolly SS, Belley-Cote EP, et al. Colchicine and aspirin in community patients with COVID-19 (ACT): an open-label, factorial, randomised, controlled trial. Lancet Respir Med. 2022 Dec;10(12):1160–1168. doi: 10.1016/S2213-2600(22)00299-5
  • Matli K, Farah R, Maalouf M, et al. Role of combining anticoagulant and antiplatelet agents in COVID-19 treatment: a rapid review. Open Heart. 2021 Jun;8(1):e001628. doi: 10.1136/openhrt-2021-001628
  • Rizk JG, Lavie CJ, Gupta A. Low-dose aspirin for early COVID-19: does the early bird catch the worm? Expert Opin Investig Drugs. 2021 Aug;30(8):785–788. doi: 10.1080/13543784.2021.1950687
  • van der Togt V, McFarland S, Esperti M, et al. Promotion of non-evidence-based therapeutics within patient-led long COVID support groups. Nat Med. 2021 Dec;27(12):2068–2069. doi: 10.1038/s41591-021-01589-y
  • Sahebkar A, Serban C, Ursoniu S, et al. The impact of statin therapy on plasma levels of von Willebrand factor antigen. Systematic review and meta-analysis of randomised placebo-controlled trials. Thromb Haemost. 2016 Mar;115(3):520–532. doi: 10.1160/th15-08-0620
  • de Kruif MD, Lemaire LC, Giebelen IA, et al. Prednisolone dose-dependently influences inflammation and coagulation during human endotoxemia. J Immunol. 2007 Feb 1;178(3):1845–1851. doi: 10.4049/jimmunol.178.3.1845
  • Fröhlich GM, Jeschke E, Eichler U, et al. Impact of oral anticoagulation on clinical outcomes of COVID-19: a nationwide cohort study of hospitalized patients in Germany. Clin Res Cardiol. 2021 Jul;110(7):1041–1050. doi: 10.1007/s00392-020-01783-x
  • Kyriakoulis KG, Dimakakos E, Kyriakoulis IG, et al. Practical recommendations for optimal thromboprophylaxis in patients with COVID-19: a consensus Statement based on available clinical trials. J Clin Med. 2022 Oct 11;11(20):5997. doi: 10.3390/jcm11205997
  • Zhai Z, Li C, Chen Y, et al. Prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus Statement before guidelines. Thromb Haemost. 2020 Jun;120(6):937–948. doi: 10.1055/s-0040-1710019
  • Schulman S, Sholzberg M, Spyropoulos AC, et al. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost. 2022 Oct;20(10):2214–2225. doi: 10.1111/jth.15808
  • Spyropoulos AC, Connors JM, Douketis JD, et al. Good practice statements for antithrombotic therapy in the management of COVID-19: guidance from the SSC of the ISTH. J Thromb Haemost. 2022 Oct;20(10):2226–2236. doi: 10.1111/jth.15809
  • Simion C, Campello E, Boccatonda A, et al. POST-discharge thromboprophylaxis in patients with COVID-19: a single-center experience. Intern Emerg Med. 2022 Dec;30:1–6.
  • Engelen MM, Vandenbriele C, Balthazar T, et al. Venous thromboembolism in patients discharged after COVID-19 hospitalization. Semin Thromb Hemost. 2021 Jun;47(4):362–371. doi: 10.1055/s-0041-1727284
  • Ramacciotti E, Barile Agati L, Calderaro D, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet. 2022 Jan 1;399(10319):50–59. doi: 10.1016/S0140-6736(21)02392-8
  • Carvalho de Oliveira CC, Agati LB, Ribeiro CM, et al. Cost-effectiveness analysis of extended thromboprophylaxis with rivaroxaban versus no prophylaxis in high-risk patients after hospitalisation for COVID-19: an economic modelling study. Lancet Reg Health Am. 2023 Aug;24:100543.
  • Dai MF, Xin WX, Kong S, et al. Effectiveness and safety of extended thromboprophylaxis in post-discharge patients with COVID-19: a systematic review and meta-analysis. Thromb Res. 2023 Jan;221:105–112. doi: 10.1016/j.thromres.2022.11.019
  • Rauch-Kröhnert U, Puccini M, Placzek M, et al. Initial therapeutic anticoagulation with rivaroxaban compared to prophylactic therapy with heparins in moderate to severe COVID-19: results of the COVID-PREVENT randomized controlled trial. Clin Res Cardiol. 2023 Jul 5;112(11):1620–1638. doi: 10.1007/s00392-023-02240-1
  • Ismaiel A, Spinu M, Socaciu C, et al. Metabolic biomarkers related to cardiac dysfunction in metabolic-dysfunction-associated fatty liver disease: a cross-sectional analysis. Nutr Diabetes. 2022 Jan 18;12(1):4. doi: 10.1038/s41387-022-00182-7
  • Arachchillage DJ, Rajakaruna I, Odho Z, et al. Impact of thromboprophylaxis on hospital acquired thrombosis following discharge in patients admitted with COVID-19: multicentre observational study in the UK. Br J Haematol. 2023 Aug;202(3):485–497. doi: 10.1111/bjh.18874
  • Cuker A, Tseng EK, Nieuwlaat R, et al. American Society of Hematology living guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19: July 2021 update on postdischarge thromboprophylaxis. Blood Adv. 2022 Jan 25;6(2):664–671. doi: 10.1182/bloodadvances.2021005945
  • Moores LK, Tritschler T, Brosnahan S, et al. Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019: CHEST guideline and Expert panel report. Chest. 2020 Sep;158(3):1143–1163. doi: 10.1016/j.chest.2020.05.559

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