Introduction/Aim. Although coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily affects the respiratory system, the possibility of multisystem tissue and organ damage is not excluded. In severe forms of the disease, hematological disorders with the accompanying laboratory derangements often occur. The aim of the review was to describe and further improve our understanding of the possible pathophysiological mechanisms involved in hemostatic derangements in COVID-19 patients with accompanying laboratory findings. Material and Methods. A comprehensive investigation was conducted using keywords "COVID-19", "SARS-CoV-2", "hemostatic disturbances in COVID-19", "laboratory findings in COVID-19", in the PubMed, Google Scholar and Science Direct databases to determine the eligible studies. Results. The most recognizable laboratory findings of these disorders include increase in the concentration of D-dimer values, prolonged prothrombin time with or without slight changes in the activated partial thromboplastin time, changes in the number of platelets according to thrombocytopenia or thrombocytosis (rarely), as well as an increase in the concentration of fibrinogen, usually in the initial stages of the disease. Conclusion. The importance of COVID-19 coagulopathy is reflected in an increased mortality rate due to the high frequency of thromboembolic episodes, which can be the reason for multiorgan dysfunction syndrome.
References
1.
Levi M, Iba T. COVID-19 coagulopathy: is it disseminated intravascular coagulation? Internal and Emergency Medicine. 2021;16(2):309–12.
2.
Gorog DA, Storey RF, Gurbel PA, Tantry US, Berger JS, Chan MY, et al. Current and novel biomarkers of thrombotic risk in COVID-19: a Consensus Statement from the International COVID-19 Thrombosis Biomarkers Colloquium. Nature Reviews Cardiology. 2022;19(7):475–95.
3.
Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of Coronavirus Disease 2019. Critical Care Medicine. 2020;48(9):1358–64.
4.
Heinz C, Miesbach W, Herrmann E, Sonntagbauer M, Raimann FJ, Zacharowski K, et al. Greater Fibrinolysis Resistance but No Greater Platelet Aggregation in Critically Ill COVID-19 Patients. Anesthesiology. 2021;134(3):457–67.
5.
Wright FL, Vogler TO, Moore EE, Moore HB, Wohlauer MV, Urban S, et al. Fibrinolysis Shutdown Correlation with Thromboembolic Events in Severe COVID-19 Infection. Journal of the American College of Surgeons. 2020;231(2):193-203e1.
6.
Hayıroğlu Mİ, Çınar T, Tekkeşin Aİ. Fibrinogen and D-dimer variances and anticoagulation recommendations in Covid-19: current literature review. Revista da Associação Médica Brasileira. 66(6):842–8.
7.
Devreese KMJ. COVID‐19–related laboratory coagulation findings. International Journal of Laboratory Hematology. 2021;43(S1):36–42.
8.
Wool GD, Miller JL. The Impact of COVID-19 Disease on Platelets and Coagulation. Pathobiology. 2021;88(1):15–27.
9.
Ranucci M, Ballotta A, Di Dedda U, Baryshnikova E, Dei Poli M, Resta M, et al. The procoagulant pattern of patients with COVID‐19 acute respiratory distress syndrome. Journal of Thrombosis and Haemostasis. 2020;18(7):1747–51.
10.
Luyendyk JP, Schoenecker JG, Flick MJ. The multifaceted role of fibrinogen in tissue injury and inflammation. Blood. 2019;133(6):511–20.
11.
Soni M, Gopalakrishnan R, Vaishya R, Prabu P. D-dimer level is a useful predictor for mortality in patients with COVID-19: Analysis of 483 cases. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(6):2245–9.
12.
Zhan H, Chen H, Liu C, Cheng L, Yan S, Li H, et al. Diagnostic Value of D-Dimer in COVID-19: A Meta-Analysis and Meta-Regression. Clinical and Applied Thrombosis/Hemostasis. 2021;27.
13.
Shah S, Shah K, Patel SB, Patel FS, Osman M, Velagapudi P, et al. Elevated d-Dimer Levels Are Associated With Increased Risk of Mortality in Coronavirus Disease 2019. Cardiology in Review. 2020;28(6):295–302.
14.
Li H, Chen S, Wang S, Yang S, Cao W, Liu S, et al. Elevated D-dimer and Adverse In-hospital Outcomes in COVID-19 Patients and Synergism with Hyperglycemia. Infection and Drug Resistance. Volume 15:3683–91.
15.
Nopp S, Moik F, Jilma B, Pabinger I, Ay C. Risk of venous thromboembolism in patients with COVID‐19: A systematic review and meta‐analysis. Research and Practice in Thrombosis and Haemostasis. 2020;4(7):1178–91.
16.
Han H, Yang L, Liu R, Liu F, Wu K lang, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clinical Chemistry and Laboratory Medicine (CCLM). 2020;58(7):1116–20.
17.
Jandial A, Gupta A, Malviya A, Agastam S, Kumar D. Coagulation abnormalities & thromboprophylaxis in COVID-19. Indian Journal of Medical Research. 2021;153(5–6):606–18.
18.
Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Medicine. 2020;46(6):1089–98.
19.
Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA, et al. Incidence of venous thromboembolism in hospitalized patients with COVID‐19. Journal of Thrombosis and Haemostasis. 2020;18(8):1995–2002.
20.
Premkumar M, Loganathan S, Kajal K, Hazarika A, Soni S, Puri GD, et al. COVID-19-related dynamic coagulation disturbances and anticoagulation strategies using conventional D-dimer and point-of-care Sonoclot tests: a prospective cohort study. BMJ Open. 2022;12(5):e051971.
21.
Nauen DW, Hooper JE, Stewart CM, Solomon IH. Assessing Brain Capillaries in Coronavirus Disease 2019. JAMA Neurology. 2021;78(6):760.
22.
Wang IE, Cooper G, Mousa SA. Diagnostic Approaches for COVID-19 and Its Associated Complications. Diagnostics. 11(11):2071.
23.
Stefely JA, Christensen BB, Gogakos T, Cone Sullivan JK, Montgomery GG, Barranco JP, et al. Marked factor V activity elevation in severe <scp>COVID</scp>‐19 is associated with venous thromboembolism. American Journal of Hematology. 2020;95(12):1522–30.
24.
Rodríguez Rodríguez M, Castro Quismondo N, Zafra Torres D, Gil Alos D, Ayala R, Martinez‐Lopez J. Increased von Willebrand factor antigen and low ADAMTS13 activity are related to poor prognosis in covid‐19 patients. International Journal of Laboratory Hematology. 2021;43(4).
25.
Marco A, Marco P. Von Willebrand factor and ADAMTS13 activity as clinical severity markers in patients with COVID-19. Journal of Thrombosis and Thrombolysis. 2021;52(2):497–503.
26.
Bazzan M, Montaruli B, Sciascia S, Cosseddu D, Norbiato C, Roccatello D. Low ADAMTS 13 plasma levels are predictors of mortality in COVID-19 patients. Internal and Emergency Medicine. 2020;15(5):861–3.
27.
Srivastava S, Garg I, Bansal A, Kumar B. COVID-19 infection and thrombosis. Clinica Chimica Acta. 2020;510:344–6.
28.
Chen Z, Zhang F, Hu W, Chen Q, Li C, Wu L, et al. Laboratory markers associated with COVID‐19 progression in patients with or without comorbidity: A retrospective study. Journal of Clinical Laboratory Analysis. 2021;35(1).
29.
Pariser DN, Hilt ZT, Ture SK, Blick-Nitko SK, Looney MR, Cleary SJ, et al. Lung megakaryocytes are immune modulatory cells. Journal of Clinical Investigation. 2021;131(1).
30.
Roncati L, Ligabue G, Nasillo V, Lusenti B, Gennari W, Fabbiani L, et al. A proof of evidence supporting abnormal immunothrombosis in severe COVID-19: naked megakaryocyte nuclei increase in the bone marrow and lungs of critically ill patients. Platelets. 2020;31(8):1085–9.
31.
Richardson MA, Gupta A, O’Brien LA, Berg DT, Gerlitz B, Syed S, et al. Treatment of Sepsis-Induced Acquired Protein C Deficiency Reverses Angiotensin-Converting Enzyme-2 Inhibition and Decreases Pulmonary Inflammatory Response. The Journal of Pharmacology and Experimental Therapeutics. 2008;325(1):17–26.
32.
Rapkiewicz AV, Mai X, Carsons SE, Pittaluga S, Kleiner DE, Berger JS, et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: A case series. eClinicalMedicine. 2020;24:100434.
33.
Duarte‐Neto AN, Monteiro RAA, da Silva LFF, Malheiros DMAC, de Oliveira EP, Theodoro‐Filho J, et al. Pulmonary and systemic involvement in COVID‐19 patients assessed with ultrasound‐guided minimally invasive autopsy. Histopathology. 2020;77(2):186–97.
34.
Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Annals of Hematology. 2020;99(6):1205–8.
35.
Bao C, Tao X, Cui W, Yi B, Pan T, Young KH, et al. SARS-CoV-2 induced thrombocytopenia as an important biomarker significantly correlated with abnormal coagulation function, increased intravascular blood clot risk and mortality in COVID-19 patients. Experimental Hematology & Oncology. 2020;9(1).
36.
Althaus K, Marini I, Zlamal J, Pelzl L, Singh A, Häberle H, et al. Antibody-induced procoagulant platelets in severe COVID-19 infection. Blood. 2021;137(8):1061–71.
37.
van der Meijden PEJ, Heemskerk JWM. Platelet biology and functions: new concepts and clinical perspectives. Nature Reviews Cardiology. 2019;16(3):166–79.
38.
Violi F, Pastori D, Cangemi R, Pignatelli P, Loffredo L. Hypercoagulation and Antithrombotic Treatment in Coronavirus 2019: A New Challenge. Thrombosis and Haemostasis. 2020;120(06):949–56.
39.
Lu G, Wang J. Dynamic changes in routine blood parameters of a severe COVID-19 case. Clinica Chimica Acta. 2020;508:98–102.
40.
Xiong M, Liang X, Wei Y. Changes in blood coagulation in patients with severe coronavirus disease 2019 (COVID‐19): a meta‐analysis. British Journal of Haematology. 2020;189(6):1050–2.
41.
Salamanna F, Maglio M, Landini MP, Fini M. Platelet functions and activities as potential hematologic parameters related to Coronavirus Disease 2019 (Covid-19). Platelets. 2020;31(5):627–32.
42.
Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019;133(9):906–18.
43.
Jackson SP, Darbousset R, Schoenwaelder SM. Thromboinflammation: challenges of therapeutically targeting coagulation and other host defense mechanisms. Blood. 2019;133(9):906–18.
44.
Lax SF, Skok K, Zechner P, Kessler HH, Kaufmann N, Koelblinger C, et al. Pulmonary Arterial Thrombosis in COVID-19 With Fatal Outcome. Annals of Internal Medicine. 2020;173(5):350–61.
45.
Ahmed S, Zimba O, Gasparyan AY. Thrombosis in Coronavirus disease 2019 (COVID-19) through the prism of Virchow’s triad. Clinical Rheumatology. 2020;39(9):2529–43.
46.
Miesbach W, Makris M. COVID-19: Coagulopathy, Risk of Thrombosis, and the Rationale for Anticoagulation. Clinical and Applied Thrombosis/Hemostasis. 2020;26.
47.
Arachchillage DRJ, Laffan M. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 2020;18(5):1233–4.
48.
Thachil J, Tang N, Gando S, Falanga A, Levi M, Clark C, et al. Laboratory haemostasis monitoring in COVID‐19. Journal of Thrombosis and Haemostasis. 2020;18(8):2058–60.
49.
Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. Journal of Thrombosis and Haemostasis. 2020;18(4):844–7.
50.
Long H, Nie L, Xiang X, Li H, Zhang X, Fu X, et al. D‐Dimer and Prothrombin Time Are the Significant Indicators of Severe COVID‐19 and Poor Prognosis. BioMed Research International. 2020;2020(1).
51.
Iba T, Levy JH, Levi M, Thachil J. Coagulopathy in COVID‐19. Journal of Thrombosis and Haemostasis. 2020;18(9):2103–9.
52.
Zhang J jin, Dong X, Cao Y yuan, Yuan Y dong, Yang Y bin, Yan Y qin, et al. Clinical characteristics of 140 patients infected with SARS‐CoV‐2 in Wuhan, China. Allergy. 2020;75(7):1730–41.
53.
da Rosa Mesquita R, Francelino Silva Junior LC, Santos Santana FM, Farias de Oliveira T, Campos Alcântara R, Monteiro Arnozo G, et al. Clinical manifestations of COVID-19 in the general population: systematic review. Wiener klinische Wochenschrift. 2021;133(7–8):377–82.
54.
Peiris J, Chu C, Cheng V, Chan K, Hung I, Poon L, et al. Clinical progression and viral load in a community outbreak of coronavirus-associated SARS pneumonia: a prospective study. The Lancet. 2003;361(9371):1767–72.
55.
Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. International Journal of Hematology. 2021;113(1):45–57.
56.
Beyerstedt S, Casaro EB, Rangel ÉB. COVID-19: angiotensin-converting enzyme 2 (ACE2) expression and tissue susceptibility to SARS-CoV-2 infection. European Journal of Clinical Microbiology & Infectious Diseases. 2021;40(5):905–19.
57.
Ni W, Yang X, Yang D, Bao J, Li R, Xiao Y, et al. Role of angiotensin-converting enzyme 2 (ACE2) in COVID-19. Critical Care. 2020;24(1).
58.
Wang S, Guo F, Liu K, Wang H, Rao S, Yang P, et al. Endocytosis of the receptor-binding domain of SARS-CoV spike protein together with virus receptor ACE2. Virus Research. 2008;136(1–2):8–15.
59.
van Doremalen N, Bushmaker T, Morris DH, Holbrook MG, Gamble A, Williamson BN, et al. Aerosol and Surface Stability of SARS-CoV-2 as Compared with SARS-CoV-1. New England Journal of Medicine. 2020;382(16):1564–7.
60.
Kumar A, Singh R, Kaur J, Pandey S, Sharma V, Thakur L, et al. Wuhan to World: The COVID-19 Pandemic. Frontiers in Cellular and Infection Microbiology. 11.
61.
Demaria O, Carvelli J, Benmansour NC, Fares J, Batista L, Thibult ML, et al. 483 Association of COVID-19 inflammation with activation of the C5a-C5aR1 axis. Regular and young investigator award abstracts. 2020. p. A299.1-A299.
62.
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. Clinica Chimica Acta. 2020;507:167–73.
63.
Sayyadi M, Hassani S, Shams M, Dorgalaleh A. Status of major hemostatic components in the setting of COVID-19: the effect on endothelium, platelets, coagulation factors, fibrinolytic system, and complement. Annals of Hematology. 2023;102(6):1307–22.
64.
Mikhail N, Wali S. Prognostic value of hypocalcemia in COVID-19. Integrative Food, Nutrition and Metabolism. 7(3).
65.
Straus MR, Tang T, Lai AL, Flegel A, Bidon M, Freed JH, et al. Ca 2+ Ions Promote Fusion of Middle East Respiratory Syndrome Coronavirus with Host Cells and Increase Infectivity. Journal of Virology. 2020;94(13).
66.
Merad M, Martin JC. Pathological inflammation in patients with COVID-19: a key role for monocytes and macrophages. Nature Reviews Immunology. 2020;20(6):355–62.
67.
Qi X, Kong H, Ding W, Wu C, Ji N, Huang M, et al. Abnormal Coagulation Function of Patients With COVID-19 Is Significantly Related to Hypocalcemia and Severe Inflammation. Frontiers in Medicine. 8.
68.
Yan SF, Mackman N, Kisiel W, Stern DM, Pinsky DJ. Hypoxia/Hypoxemia-Induced Activation of the Procoagulant Pathways and the Pathogenesis of Ischemia-Associated Thrombosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 1999;19(9):2029–35.
69.
Joly BS, Siguret V, Veyradier A. Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19. Intensive Care Medicine. 2020;46(8):1603–6.
70.
Amara U, Rittirsch D, Flierl M, Bruckner U, Klos A, Gebhard F, et al. Interaction Between the Coagulation and Complement System. Advances in Experimental Medicine and Biology. 2008. p. 68–76.
71.
Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China. JAMA. 2020;323(13):1239.
72.
Gianni P, Goldin M, Ngu S, Zafeiropoulos S, Geropoulos G, Giannis D. Complement-mediated microvascular injury and thrombosis in the pathogenesis of severe COVID-19: A review. World Journal of Experimental Medicine. 2022;12(4):53–67.
73.
van der Poll T, de Jonge E, Levi M. Regulatory Role of Cytokines in Disseminated Intravascular Coagulation. Seminars in Thrombosis and Hemostasis. 2001;27(06):639–52.
74.
Zhang W, Zhao Y, Zhang F, Wang Q, Li T, Liu Z, et al. The use of anti-inflammatory drugs in the treatment of people with severe coronavirus disease 2019 (COVID-19): The Perspectives of clinical immunologists from China. Clinical Immunology. 2020;214:108393.
75.
Yang AP, Li HM, Tao WQ, Yang XJ, Wang M, Yang WJ, et al. Infection with SARS-CoV-2 causes abnormal laboratory results of multiple organs in patients. Aging. 2020;12(11):10059–69.
76.
Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers D, Kant KM, et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: An updated analysis. Thrombosis Research. 2020;191:148–50.
Yau JW, Teoh H, Verma S. Endothelial cell control of thrombosis. BMC Cardiovascular Disorders. 2015;15(1).
79.
Robba C, Battaglini D, Ball L, Valbusa A, Porto I, Della Bona R, et al. Coagulative Disorders in Critically Ill COVID-19 Patients with Acute Distress Respiratory Syndrome: A Critical Review. Journal of Clinical Medicine. 10(1):140.
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