Semin Thromb Hemost 2022; 48(07): 858-868
DOI: 10.1055/s-0042-1756306
Review Article

Relative Hypercoagulopathy of the SARS-CoV-2 Beta and Delta Variants when Compared to the Less Severe Omicron Variants Is Related to TEG Parameters, the Extent of Fibrin Amyloid Microclots, and the Severity of Clinical Illness

Lize M. Grobbelaar
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
Arneaux Kruger
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
Chantelle Venter
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
Este M. Burger
2   BioCODE Technologies, Stellenbosch, South Africa
Gert J. Laubscher
3   Mediclinic Stellenbosch, Stellenbosch, South Africa
Tongai G. Maponga
4   Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, Cape Town, South Africa
Maritha J. Kotze
5   Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Tygerberg Hospital, Cape Town, South Africa
Hau C. Kwaan
6   Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois
Joseph B. Miller
7   Departments of Emergency Medicine and Internal Medicine, Henry Ford Hospital, Detroit, Michigan
Daniel Fulkerson
8   Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, Indiana
Wei Huff
8   Department of Neurosurgery, St. Joseph Regional Medical Center, Mishawaka, Indiana
Eric Chang
9   Indiana University School of Medicine - South Bend, Notre Dame, Indiana
Grant Wiarda
10   Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
Connor M. Bunch
7   Departments of Emergency Medicine and Internal Medicine, Henry Ford Hospital, Detroit, Michigan
Mark M. Walsh
9   Indiana University School of Medicine - South Bend, Notre Dame, Indiana
10   Department of Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
11   Department of Emergency Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
Syed Raza
12   Department of Critical Care Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
Mahmud Zamlut
12   Department of Critical Care Medicine, Saint Joseph Regional Medical Center, Mishawaka, Indiana
Hunter B. Moore
13   Division of Transplant Surgery, Department of Surgery, Denver Health and University of Colorado Health Sciences Center, Denver, Colorado
Ernest E. Moore
14   Department of Surgery, Ernest E. Moore Shock Trauma Center at Denver Health and University of Colorado Health Sciences Center, Denver, Colorado
Matthew D. Neal
15   Pittsburgh Trauma Research Center, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
16   Department of Biochemistry and Systems Biology, Institute of Systems, Molecular and Integrative Biology, Faculty of Health and Life Sciences, University of Liverpool, England, United Kingdom
17   The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Lyngby, Denmark
1   Department of Physiological Sciences, Faculty of Science, Stellenbosch University, Stellenbosch, Matieland, South Africa
17   The Novo Nordisk Foundation Centre for Biosustainability, Technical University of Denmark, Lyngby, Denmark
› Author Affiliations
Funding D.B.K.: Novo Nordisk Foundation for support (grant NNF20CC0035580). M.J.K. and T.G.M.: Research reported in this article was supported by the South African Medical Research Council with funds received from the Department of Science and Innovation (Project Code 96825). E.P.: Laboratory research supported by NRF of South Africa (grant number 142142) and SA MRC (self-initiated research (SIR) grant). The content and findings reported and illustrated are the sole deduction, view, and responsibility of the researchers and do not reflect the official position and sentiments of the funders.


Earlier variants of SARS-CoV-2 have been associated with hypercoagulability and an extensive formation of fibrin amyloid microclots, which are considered to contribute to the pathology of the coronavirus 2019 disease (COVID-19). The newer omicron variants appear to be far more transmissible, but less virulent, even when taking immunity acquired from previous infections or vaccination into account. We here show that while the clotting parameters associated with omicron variants are significantly raised over those of healthy, matched controls, they are raised to levels significantly lower than those seen with more severe variants such as beta and delta. We also observed that individuals infected with omicron variants manifested less extensive microclot formation in platelet-poor plasma compared with those harboring the more virulent variants. The measurement of clotting effects between the different variants acts as a kind of “internal control” that demonstrates the relationship between the extent of coagulopathies and the virulence of the variant of interest. This adds to the evidence that microclots may play an important role in reflecting the severity of symptoms observed in COVID-19.

Ethics Statement

Ethical approval for blood collection and microclot analysis of blood samples from participants with COVID-19 and healthy individuals was given by the Health Research Ethics Committee (HREC) of Stellenbosch University (reference N19/03/043, project ID 9521; renewal 2021 and 2022). This laboratory study was performed in strict adherence to the International Declaration of Helsinki, South African Guidelines for Good Clinical Practice, and the South African Medical Research Council (SAMRC) Ethical Guidelines for research. Consent was obtained from all participants. A positive COVID-19 test was confirmed before blood collection. Genomic sequencing to confirm SARS-CoV-2 is covered under Health Research Ethics Committee (HREC) of Stellenbosch University (reference #N20/04/008_COVID-19) as part of the National Genomics Surveillance Program.

Publication History

Article published online:
29 September 2022

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  • References

  • 1 WHO. WHO Coronavirus (COVID-19) Dashboard. Accessed 23 June, 2022 at:
  • 2 Aleem A, Akbar Samad AB, Slenker AK. Emerging Variants of SARS-CoV-2 And Novel Therapeutics Against Coronavirus (COVID-19). StatPearls. StatPearls Publishing LLC; 2022
  • 3 Meo SA, Meo AS, Al-Jassir FF, Klonoff DC. Omicron SARS-CoV-2 new variant: global prevalence and biological and clinical characteristics. Eur Rev Med Pharmacol Sci 2021; 25 (24) 8012-8018
  • 4 Ong SWX, Chiew CJ, Ang LW. et al. Clinical and virological features of SARS-CoV-2 variants of concern: a retrospective cohort study comparing B.1.1.7 (alpha), B.1.315 (beta), and B.1.617.2 (delta). Clin Infect Dis 2021; ciab721 DOI: 10.1093/cid/ciab721.
  • 5 Viana R, Moyo S, Amoako DG. et al. Rapid epidemic expansion of the SARS-CoV-2 omicron variant in southern Africa. Nature 2022; 603 (7902): 679-686
  • 6 Tegally H, Wilkinson E, Giovanetti M. et al. Detection of a SARS-CoV-2 variant of concern in South Africa. Nature 2021; 592 (7854): 438-443
  • 7 Tegally H, Wilkinson E, Lessells RJ. et al. Sixteen novel lineages of SARS-CoV-2 in South Africa. Nat Med 2021; 27 (03) 440-446
  • 8 Tegally H, Moir M, Everatt J. et al. Continued Emergence and Evolution of Omicron in South Africa: New BA.4 and BA.5 Lineages. Cold Spring Harbor Laboratory; 2022
  • 9 WHO. Tracking SARS-CoV-2 Variants. Accessed June 25, 2022 at
  • 10 Salyer SJ, Maeda J, Sembuche S. et al. The first and second waves of the COVID-19 pandemic in Africa: a cross-sectional study. Lancet 2021; 397 (10281): 1265-1275
  • 11 Jassat W, Mudara C, Ozougwu L. et al; DATCOV Author Group. Difference in mortality among individuals admitted to hospital with COVID-19 during the first and second waves in South Africa: a cohort study. Lancet Glob Health 2021; 9 (09) e1216-e1225
  • 12 Giandhari J, Pillay S, Wilkinson E. et al. Early Transmission of SARS-CoV-2 in South Africa: An Epidemiological and Phylogenetic Report. Cold Spring Harbor Laboratory; 2020
  • 13 Engelbrecht S, Delaney K, Kleinhans B. et al. Multiple early introductions of SARS-CoV-2 to Cape Town, South Africa. Viruses 2021; 13 (03) 526
  • 14 Mahase E. Omicron: South Africa says fourth wave peak has passed as it lifts curfew. BMJ 2022; o7 DOI: 10.1136/bmj.o7.
  • 15 Jassat W, Abdool Karim SS, Mudara C. Clinical Severity of COVID-19 Patients Admitted to Hospitals during the Omicron Wave in South Africa. Cold Spring Harbor Laboratory; 2022
  • 16 Maxmen A. Are new omicron subvariants a threat? Here's how scientists are keeping watch. Nature 2022; 604 (7907): 605-606
  • 17 Sguazzin A. South Africa Had Fifth COVID Wave Despite 97% Antibody Protection. 2022 . Accessed July 28, 2022 at:
  • 18 Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID-19. J Thromb Haemost 2020; 18 (09) 2103-2109
  • 19 Gómez-Mesa JE, Galindo-Coral S, Montes MC, Muñoz Martin AJ. Thrombosis and coagulopathy in COVID-19. Curr Probl Cardiol 2021; 46 (03) 100742
  • 20 Hadid T, Kafri Z, Al-Katib A. Coagulation and anticoagulation in COVID-19. Blood Rev 2021; 47: 100761
  • 21 Nägele MP, Haubner B, Tanner FC, Ruschitzka F, Flammer AJ. Endothelial dysfunction in COVID-19: current findings and therapeutic implications. Atherosclerosis 2020; 314: 58-62
  • 22 Choudhary S, Sharma K, Singh PK. Von Willebrand factor: a key glycoprotein involved in thrombo-inflammatory complications of COVID-19. Chem Biol Interact 2021; 348: 109657
  • 23 Cremer S, Jakob C, Berkowitsch A. et al; LEOSS Study Group. Elevated markers of thrombo-inflammatory activation predict outcome in patients with cardiovascular comorbidities and COVID-19 disease: insights from the LEOSS registry. Clin Res Cardiol 2021; 110 (07) 1029-1040
  • 24 Gerotziafas GT, Catalano M, Colgan MP. et al; Scientific Reviewer Committee. Guidance for the management of patients with vascular disease or cardiovascular risk factors and COVID-19: position paper from VAS-European Independent Foundation in Angiology/Vascular Medicine. Thromb Haemost 2020; 120 (12) 1597-1628
  • 25 Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol 2020; 127: 104362
  • 26 Grobler C, Maphumulo SC, Grobbelaar LM. et al. COVID-19: the rollercoaster of fibrin(ogen), D-Dimer, Von Willebrand factor, P-selectin and their interactions with endothelial cells, platelets and erythrocytes. Int J Mol Sci 2020; 21 (14) E5168
  • 27 Kell DB, Laubscher GJ, Pretorius E. A central role for amyloid fibrin microclots in long COVID/PASC: origins and therapeutic implications. Biochem J 2022; 479 (04) 537-559
  • 28 Kollias A, Kyriakoulis KG, Dimakakos E, Poulakou G, Stergiou GS, Syrigos K. Thromboembolic risk and anticoagulant therapy in COVID-19 patients: emerging evidence and call for action. Br J Haematol 2020; 189 (05) 846-847
  • 29 Laubscher GJ, Lourens PJ, Venter C, Kell DB, Pretorius E. TEG®, Microclot and platelet mapping for guiding early management of severe COVID-19 coagulopathy. J Clin Med 2021; 10 (22) 5381
  • 30 Miesbach W, Makris M. COVID-19: coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost 2020; 26: 1076029620938149
  • 31 Moriarty PM, Gorby LK, Stroes ES, Kastelein JP, Davidson M, Tsimikas S. Lipoprotein(a) and its potential association with thrombosis and inflammation in COVID-19: a testable hypothesis. Curr Atheroscler Rep 2020; 22 (09) 48
  • 32 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; 20 (01) 172
  • 33 Smadja DM, Mentzer SJ, Fontenay M. et al. COVID-19 is a systemic vascular hemopathy: insight for mechanistic and clinical aspects. Angiogenesis 2021; 24 (04) 755-788
  • 34 Smolarz A, McCarthy P, Shmookler A, Badhwar V, Hayanga AJ, Sakhuja A. Utilization of thromboelastogram and inflammatory markers in the management of hypercoagulable state in patients with COVID-19 requiring ECMO support. Case Rep Crit Care 2021; 2021: 8824531
  • 35 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; 19 (04) 1064-1070
  • 36 Pretorius E, Venter C, Laubscher GJ, Lourens PJ, Steenkamp J, Kell DB. Prevalence of readily detected amyloid blood clots in ‘unclotted’ type 2 diabetes mellitus and COVID-19 plasma: a preliminary report. Cardiovasc Diabetol 2020; 19 (01) 193
  • 37 Hong Q, Han W, Li J. et al. Molecular basis of receptor binding and antibody neutralization of omicron. Nature 2022; 604 (7906): 546-552
  • 38 McCallum M, Czudnochowski N, Rosen LE. et al. Structural basis of SARS-CoV-2 omicron immune evasion and receptor engagement. Science 2022; 375 (6583): 864-868
  • 39 Wadman M. New omicron begins to take over, despite late start. Science 2022; 375 (6580): 480-481
  • 40 Iacobucci G. COVID-19: runny nose, headache, and fatigue are commonest symptoms of omicron, early data show. BMJ 2021; 375 (3103): n3103
  • 41 Malhotra S, Mani K, Lodha R. et al. COVID-19 infection, and reinfection, and vaccine effectiveness against symptomatic infection among health care workers in the setting of omicron variant transmission in New Delhi, India. Lancet Reg Health Southeast Asia 2022; 100023: 100023
  • 42 Collie S, Champion J, Moultrie H, Bekker LG, Gray G. Effectiveness of BNT162b2 vaccine against omicron variant in South Africa. N Engl J Med 2022; 386 (05) 494-496
  • 43 Tseng HF, Ackerson BK, Luo Y. et al. Effectiveness of mRNA-1273 against SARS-CoV-2 omicron and delta variants. Nat Med 2022; 28 (05) 1063-1071
  • 44 Accorsi EK, Britton A, Fleming-Dutra KE. et al. Association between 3 doses of mRNA COVID-19 vaccine and symptomatic infection caused by the SARS-CoV-2 omicron and delta variants. JAMA 2022; 327 (07) 639-651
  • 45 Hartmann J, Ergang A, Mason D, Dias JD. The role of TEG analysis in patients with COVID-19-associated coagulopathy: a systematic review. Diagnostics (Basel) 2021; 11 (02) 172
  • 46 Pretorius E, Page MJ, Hendricks L, Nkosi NB, Benson SR, Kell DB. Both lipopolysaccharide and lipoteichoic acids potently induce anomalous fibrin amyloid formation: assessment with novel Amytracker™ stains. J R Soc Interface 2018; 15 (139) 20170941
  • 47 Pretorius E, Page MJ, Engelbrecht L, Ellis GC, Kell DB. Substantial fibrin amyloidogenesis in type 2 diabetes assessed using amyloid-selective fluorescent stains. Cardiovasc Diabetol 2017; 16 (01) 141
  • 48 Pretorius E, Mbotwe S, Bester J, Robinson CJ, Kell DB. Acute induction of anomalous and amyloidogenic blood clotting by molecular amplification of highly substoichiometric levels of bacterial lipopolysaccharide. J R Soc Interface 2016; 13 (122) 20160539
  • 49 Pretorius E, Bester J, Vermeulen N. et al. Poorly controlled type 2 diabetes is accompanied by significant morphological and ultrastructural changes in both erythrocytes and in thrombin-generated fibrin: implications for diagnostics. Cardiovasc Diabetol 2015; 14: 30
  • 50 Nunes JM, Fillis T, Page MJ. et al. Gingipain R1 and lipopolysaccharide from Porphyromonas gingivalis have major effects on blood clot morphology and mechanics. Front Immunol 2020; 11: 1551
  • 51 de Villiers S, Swanepoel A, Bester J, Pretorius E. Novel diagnostic and monitoring tools in stroke: an individualized patient-centered precision medicine approach. J Atheroscler Thromb 2016; 23 (05) 493-504
  • 52 Bester J, Soma P, Kell DB, Pretorius E. Viscoelastic and ultrastructural characteristics of whole blood and plasma in Alzheimer-type dementia, and the possible role of bacterial lipopolysaccharides (LPS). Oncotarget 2015; 6 (34) 35284-35303
  • 53 Adams B, Nunes JM, Page MJ. et al. Parkinson's disease: a systemic inflammatory disease accompanied by bacterial inflammagens. Front Aging Neurosci 2019; 11: 210
  • 54 Freed NS. Olin. SARS-CoV2 genome sequencing protocol (1200bp amplicon “midnight” primer set, using nanopore rapid kit) V.6.
  • 55 Marshall JC, Murthy S, Diaz J. et al; WHO Working Group on the Clinical Characterisation and Management of COVID-19 Infection. A minimal common outcome measure set for COVID-19 clinical research. Lancet Infect Dis 2020; 20 (08) e192-e197
  • 56 Pretorius E, Swanepoel AC, DeVilliers S, Bester J. Blood clot parameters: thromboelastography and scanning electron microscopy in research and clinical practice. Thromb Res 2017; 154: 59-63
  • 57 Page MJ, Thomson GJA, Nunes JM. et al. Serum amyloid A binds to fibrin(ogen), promoting fibrin amyloid formation. Sci Rep 2019; 9 (01) 3102
  • 58 Naiki H, Higuchi K, Hosokawa M, Takeda T. Fluorometric determination of amyloid fibrils in vitro using the fluorescent dye, thioflavin T1. Anal Biochem 1989; 177 (02) 244-249
  • 59 Xue C, Lin TY, Chang D, Guo Z. Thioflavin T as an amyloid dye: fibril quantification, optimal concentration and effect on aggregation. R Soc Open Sci 2017; 4 (01) 160696
  • 60 Voropai ES, Samtsov MP, Kaplevskii KN. et al. Spectral properties of thioflavin T and its complexes with amyloid fibrils. J Appl Spectrosc 2003; 70 (06) 868-874
  • 61 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; 41 (08) BSR20210611
  • 62 Cantón R, De Lucas Ramos P, García-Botella A. et al. New variants of SARS-CoV-2. Rev Esp Quimioter 2021; 34 (05) 419-428
  • 63 Lin L, Liu Y, Tang X, He D. The disease severity and clinical outcomes of the SARS-CoV-2 variants of concern. Front Public Health 2021; 9: 775224
  • 64 Nyberg T, Ferguson NM, Nash SG. et al; COVID-19 Genomics UK (COG-UK) Consortium. Comparative analysis of the risks of hospitalisation and death associated with SARS-CoV-2 omicron (B.1.1.529) and delta (B.1.617.2) variants in England: a cohort study. Lancet 2022; 399 (10332): 1303-1312
  • 65 Ulloa AC, Buchan SA, Daneman N, Brown KA. Estimates of SARS-CoV-2 omicron variant severity in Ontario, Canada. JAMA 2022; 327 (13) 1286-1288
  • 66 Meizoso JP, Moore HB, Moore EE. Fibrinolysis shutdown in COVID-19: clinical manifestations, molecular mechanisms, and therapeutic implications. J Am Coll Surg 2021; 232 (06) 995-1003
  • 67 Chu K, Alharahsheh B, Garg N, Guha P. Evaluating risk stratification scoring systems to predict mortality in patients with COVID-19. BMJ Health Care Inform 2021; 28 (01) e100389
  • 68 Yang Z, Hu Q, Huang F, Xiong S, Sun Y. The prognostic value of the SOFA score in patients with COVID-19: a retrospective, observational study. Medicine (Baltimore) 2021; 100 (32) e26900
  • 69 Obermeyer F, Jankowiak M, Barkas N. et al. Analysis of 6.4 Million SARS-CoV-2 Genomes Identifies Mutations Associated with Fitness. Cold Spring Harbor Laboratory; 2021
  • 70 Gowda N, Dominah G, Rogers H. et al. Evaluating APACHE and SOFA scoring systems in patients with COVID-19. Chest 2021; 160 (04) A1077-A1077
  • 71 Sehgal T, Aggarwal M, Baitha U. et al. Thromboelastography determined dynamics of blood coagulation and its correlation with complications and outcomes in patients with coronavirus disease 2019. Res Pract Thromb Haemost 2022; 6 (01) e12645
  • 72 Yuriditsky E, Horowitz JM, Merchan C. et al. Thromboelastography profiles of critically ill patients with coronavirus disease 2019. Crit Care Med 2020; 48 (09) 1319-1326
  • 73 Wolter N, Jassat W, Walaza S. et al. Early assessment of the clinical severity of the SARS-CoV-2 omicron variant in South Africa: a data linkage study. Lancet 2022; 399 (10323): 437-446
  • 74 Whyte CS, Morrow GB, Mitchell JL, Chowdary P, Mutch NJ. Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19. J Thromb Haemost 2020; 18 (07) 1548-1555
  • 75 Bois MC, Boire NA, Layman AJ. et al. COVID-19-associated nonocclusive fibrin microthrombi in the heart. Circulation 2021; 143 (03) 230-243
  • 76 Wygrecka M, Birnhuber A, Seeliger B. et al. Altered fibrin clot structure and dysregulated fibrinolysis contribute to thrombosis risk in severe COVID-19. Blood Adv 2022; 6 (03) 1074-1087
  • 77 Zhang X, Yang X, Jiao H, Liu X. Coagulopathy in patients with COVID-19: a systematic review and meta-analysis. Aging (Albany NY) 2020; 12 (24) 24535-24551
  • 78 Zou Y, Guo H, Zhang Y. et al. Analysis of coagulation parameters in patients with COVID-19 in Shanghai, China. Biosci Trends 2020; 14 (04) 285-289
  • 79 Mitra S, Ling RR, Yang IX. et al. Severe COVID-19 and coagulopathy: a systematic review and meta-analysis. Ann Acad Med Singap 2021; 50 (04) 325-335
  • 80 Sui J, Noubouossie DF, Gandotra S, Cao L. Elevated plasma fibrinogen is associated with excessive inflammation and disease severity in COVID-19 patients. Front Cell Infect Microbiol 2021; 11: 734005
  • 81 Boscolo A, Spiezia L, Correale C. et al. Different hypercoagulable profiles in patients with COVID-19 admitted to the internal medicine ward and the intensive care unit. Thromb Haemost 2020; 120 (10) 1474-1477
  • 82 Bunch CM, Moore EE, Moore HB. et al. Immuno-thrombotic complications of COVID-19: implications for timing of surgery and anticoagulation. Front Surg 2022; 9: 889999
  • 83 Volod O, Bunch CM, Zackariya N. et al. Viscoelastic hemostatic assays: a primer on legacy and new generation devices. J Clin Med 2022; 11 (03) 860
  • 84 Moore EE, Moore HB, Kornblith LZ. et al. Trauma-induced coagulopathy. Nat Rev Dis Primers 2021; 7 (01) 30
  • 85 Barrett TJ, Bilaloglu S, Cornwell M. et al. Platelets contribute to disease severity in COVID-19. J Thromb Haemost 2021; 19 (12) 3139-3153
  • 86 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; 136 (11) 1330-1341
  • 87 Althaus K, Marini I, Zlamal J. et al. Antibody-induced procoagulant platelets in severe COVID-19 infection. Blood 2021; 137 (08) 1061-1071
  • 88 Manne BK, Denorme F, Middleton EA. et al. Platelet gene expression and function in patients with COVID-19. Blood 2020; 136 (11) 1317-1329
  • 89 Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: incidence, pathophysiology, and management. Thromb Res 2020; 194: 101-115
  • 90 Zhang S, Liu Y, Wang X. et al. SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19. J Hematol Oncol 2020; 13 (01) 120
  • 91 Len P, Iskakova G, Sautbayeva Z. et al. Meta-analysis and systematic review of coagulation disbalances in COVID-19: 41 studies and 17,601 patients. Front Cardiovasc Med 2022; 9: 794092
  • 92 Bashash D, Hosseini-Baharanchi FS, Rezaie-Tavirani M. et al. The prognostic value of thrombocytopenia in COVID-19 patients; a systematic review and meta-analysis. Arch Acad Emerg Med 2020; 8 (01) e75
  • 93 Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clin Chim Acta 2020; 506: 145-148
  • 94 Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol 2020; 99 (06) 1205-1208
  • 95 Delshad M, Safaroghli-Azar A, Pourbagheri-Sigaroodi A, Poopak B, Shokouhi S, Bashash D. Platelets in the perspective of COVID-19; pathophysiology of thrombocytopenia and its implication as prognostic and therapeutic opportunity. Int Immunopharmacol 2021; 99: 107995
  • 96 Tyagi T, Jain K, Gu SX. et al. A guide to molecular and functional investigations of platelets to bridge basic and clinical sciences. Nature Cardiovascular Research 2022; 1 (03) 223-237