Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests
Abstract
:1. Introduction
2. Material and Methods
2.1. Laboratory Measurements
2.1.1. Cytokines
2.1.2. Endothelium
2.1.3. Coagulation and Platelet Activation
2.1.4. Blood Viscoelastic Analysis
2.1.5. Statistical Analysis
3. Results
4. Discussion
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
- Huang, C.; Wang, Y.; Li, X.; Ren, L.; Zhao, J.; Hu, Y.; Zhang, L.; Fan, G.; Xu, J.; Gu, X.; et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan. China Lancet 2020, 395, 497–506. [Google Scholar] [CrossRef] [Green Version]
- Chen, N.; Zhou, M.; Dong, X.; Dong, X.; Qu, J.; Gong, F.; Han, Y.; Qiu, Y.; Wang, J.; Liu, Y.; et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhun, China: A descriptive study. Lancet 2020, 395, 507–513. [Google Scholar] [CrossRef] [Green Version]
- Tang, N.; Li, D.; Wang, X.; Sun, Z. Abnormal coagulation parameters are asociated with poor prognosis in patients with novel coronavirus pneumonia. J. Thromb. Haemost. 2020, 2020, 844–847. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yin, S.; Huang, M.; Li, D.; Tang, N. Difference of coagulation features between severe pneumonia indiuced by SARS-CoV-2 and non-SARS-CoV2. J. Thromb. Thrombol. 2020, 51, 1107–1110. [Google Scholar] [CrossRef] [Green Version]
- Zhou, F.; Yu, T.; Du, R.; Fan, G.; Liu, Y.; Liu, Z.; Xiang, J.; Wang, Y.; Song, B.; Gu, X.; et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020, 395, 1054–1062. [Google Scholar] [CrossRef]
- Connors, J.M.; Levi, J.H. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020, 135, 2033–2040. [Google Scholar] [CrossRef]
- Iba, T.; Levy, J.H.; Wada, H.; Thachil, J.; Warkentin, T.E.; Levi, M. Subcommittee on Disseminated Intravascular Coagulation. Differential Diagnoses for sepsis-induced disseminated intravascular coagulation: Communication from the SSC of the ISTH. J. Thromb. Haemost. 2019, 17, 415–419. [Google Scholar] [CrossRef] [Green Version]
- Ackermann, M.; Verleden, S.E.; Kuehnel, M.; Haverich, A.; Welte, T.; Laenger, F.; Vanstapel, A.; Werlein, C.; Stark, H.; Tzankov, A.; et al. Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in COVID-19. N. Engl. J. Med. 2020, 38, 120–128. [Google Scholar] [CrossRef]
- Calabretta, E.; Moraleda, J.M.; Iacobelli, M.; Jara, R.; Vlodavsky, I.; O’Gorman, P.; Pagliuca, A.; Mo, C.; Baron, R.M.; Aghemo, A.; et al. COVID-19-induced Endotheliitis: Emerging evidence and possible therapeutic strategies. BJH 2021, 193, 43–51. [Google Scholar] [CrossRef]
- Esmon, C.T. Inflammation and thrombosis. J. Thromb. Haemost. 2003, 1, 1343–1348. [Google Scholar] [CrossRef]
- Taylor, F.B., Jr.; Chang, A.; Esmon, C.T.; D’Angelo, A.; Vigano-D’Angelo, S.; Blick, K.E. Protein C prevents the coagulopathic and lethal effects of E. coli infusion in the baboon. J. Clin. Investig. 1987, 79, 918–925. [Google Scholar] [CrossRef] [PubMed]
- Mucha, S.R.; Dugar, S.; McCrae, K.; Joseph, S.; Bartholomew, J.; Sacha, G.L.; Militello, M. Update to coagulopathy in COVID-19: Manifestations and management. Clevel. Clin. J. Med. 2021, 1–10. [Google Scholar] [CrossRef]
- Kabrhel, C.; Courtney, M.D.; Camargo, C.A.; Plewa, M.C.; Nordenholz, K.E.; Moore, C.L.; Richman, P.V.; Smithline, H.A.; Beam, D.M.; Kline, J.A. Factors associated with positive D-dimer results in patients evaluated for pulmonary embolism. Acad. Emerg. Med. 2010, 17, 589–597. [Google Scholar] [CrossRef] [PubMed]
- Chaudary, R.; Kreutz, R.P.; Bliden, K.P.; Tantry, U.S.; Gurbel, P. Personalizing antithrombotic therapy in COVID-19: Role of Thromboelastography and Thromboelastometry. Thromb. Haemost. 2020, 120, 1594–1596. [Google Scholar] [CrossRef] [PubMed]
- Kaplan, K.L.; Owen, J. Plasma Levels of β-Thromboglobulin and Platelet Factor 4 as Indices of Platelet Activation In Vivo. Blood 1981, 57, 199–202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Busch, C.; Dawes, J.; Pepper, D.S.; Wasteson, A. Binding of platelet factor 4 to cultured human endothelial cells. Thromb. Res. 1980, 19, 129. [Google Scholar] [CrossRef]
- Dawes, J.; Smith, R.C.; Pepper, D.S. The release, distribution and clearance of human β-thromboglobulin and platelet factor 4. Thromb. Res. 1978, 12, 851. [Google Scholar] [CrossRef]
- Liao, D.; Zhou, F.; Luo, L.; Xu, M.; Wang, H.; Xia, J.; Gao, Y.; Cai, L.; Wang, Z.; Yin, P.; et al. Haematological characteristics and risk factors in the classification and prognosis evaluation of COVID-19: A retrospective cohort study. Lancet Haematol. 2020, 7, e671–e678. [Google Scholar] [CrossRef]
- Amgalan, A.; Othman, M. Exploring possible mechanisms for COVID-19 induced thrombocytopenia: Unanswered questions. J. Thromb. Haemost. 2020, 18, 1514–1516. [Google Scholar] [CrossRef] [Green Version]
- O’Donnel, J.; Peyvandi, F.; Loeches, M.I. Pulmonary immune-thrombosis in COVID-19 ARDS pathogenesis. Intensive Care Med. 2021, 47, 899–902. [Google Scholar] [CrossRef]
- Schechter, M.E.; Andrade, B.B.; He, T.; Richter, G.H.; Tosh, K.W.; Policicchio, B.B.; Singh, A.; Raehtz, K.D.; Sheikh, V.; Ma, D.; et al. Inflammatory monocytes expressing tissue factor drive SIV and HIV coagulopathy. Sci. Transl. Med. 2017, 9, eaam5441. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- White, D.; MacDonald, S.; Edwards, T.; Bridgeman, C.; Hayman, M.; Sharp, M.; Cox-Morton, S.; Duff, E.; Mahjan, S.; Moore, C.; et al. Evaluation of COVID-19 coagulopathy; laboratory charactrization using thrombin generation and nonconventional haemostasis assays. Int. J. Lab. Hematol. 2021, 43, 123–130. [Google Scholar] [CrossRef] [PubMed]
- Jin, X.; Duan, Y.; Bao, T.; Gu, J.; Che, Y.; Li, Y.; Mao, S.; Chen, Y.; Xie, W. The values of coagulation function in COVID-19 patients. PLoS ONE 2020, 15, e0241329. [Google Scholar] [CrossRef] [PubMed]
- Panigada, M.; Bottino, N.; Taglabue, P.; Grasselli, G.; Novembrino, C.; Chantarangkul, V.; Pesenti, A.; Peyvandi, F.; Tripodi, A. Hypercoagulability of COVID-19 patients in intensive care unit. A report of thromboelastography findings and other parameters of hemostasis. J. Thromb. Haemost. 2020, 18, 1738–1742. [Google Scholar] [CrossRef] [PubMed]
- Maatman, T.K.; Jalali, F.; Feizpour, C.; Douglas, A.; McGuire, S.P.; Kinnaman, G.; Hartwell, J.; Mamatman, B.T.; Kreutz, R.P.; Kapoor, R.; et al. Routine venous thromboebolism prophylaxis may be inadequate in the hypercoagulable state of severe coronavirus disease 2019. Crit. Care Med. 2020, 27, 1097. [Google Scholar]
- Wright, F.L.; Vogler, T.O.; Moore, E.E.; Moore, H.B.; Wohlauer, M.V.; Urban, S.; Nydam, T.L.; Moore, P.K.; Mcintyre, R.C. Fibrinolysis shutdown correlation with thromboembolic events in severe COVID-19 infections. J. Am. Coll. Surg. 2020, 231, 193–203. [Google Scholar] [CrossRef]
- Mortus, J.R.; Manek, S.E.; Brubaker, L.S.; Loor, M.; Cruz, M.A.; Trautner, B.W.; Rosengart, T.K. Thromboelastographic results and hypercoagulability syndrome in patients with Coronavirus Disease 2019 who are critically ill. JAMA Netw. 2020, 3, e2011192. [Google Scholar] [CrossRef]
- Pavoni, V.; Giansello, L.; Pazzi, M.; Stera, C.; Meconi, T.; CovaniFrigieri, F. Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia. J. Thromb. Thrombolysis 2020, 11, 1–6. [Google Scholar] [CrossRef]
- Hottz, E.D.; Azevedo-Quintanilha, I.G.; Palhinha, L.; Teixeira, L.; Barreto, E.A.; Pao, C.R.R.; Righy, C.; Franco, S.; Souza, T.M.L.; Kurtz, P.; et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood 2020, 136, 1330–1341. [Google Scholar] [CrossRef] [PubMed]
- Middleton, E.A.; He, X.Y.; Denorme, F.; Campbell, R.A.; Ng, D.; Salvatore, S.P.; Mostyka, M.; Baxter-Stoltzfus, A.; Borczuk, A.C.; Loda, M.; et al. Neutrophil extracellular traps contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome. Blood 2020, 136, 1169–1179. [Google Scholar] [CrossRef]
Anagraphic and Clinical Data | Patients, n = 100 | Controls, n = 80 |
---|---|---|
Age (yrs) | 45 ± 5 | 40 ± 5 |
Male n | 45 | 40 |
Female, n | 55 | 40 |
Respiratory support | ||
Oxygen supplementation | 0 | 0 |
Mechanical ventilation | 0 | 0 |
Comorbidities | ||
Obesity | 0 | 0 |
Hypertension | 0 | 0 |
Diabetes | 0 | 0 |
Cancer | 0 | 0 |
Heart disease * | 0 | 0 |
Presenting symptoms | ||
Cough | 0 | 0 |
Fever | 100 | 0 |
Dyspnea | 100 | 0 |
Headache | 0 | 0 |
Anosmia | 0 | 0 |
Pulmonary Embolism | 100 | 0 |
Biomarkers | Patients, n = 100 | Controls, n = 80 |
---|---|---|
IL-1α, pg/mL | 2.9 ± 1 | 0.20 ± 0.5 |
IL-8 pg/mL | 60 ± 10 | 21 ± 3 |
TFPI, ng/mL | 166 ± 69 | 81 ± 12 |
TAT, μg/L | 70 ± 10 | 3 ± 1 |
βTG, IU/mL | 245 ± 15 | 10 ± 5 |
Thromboelastometry | Patients, n = 100 | Controls, n = 80 |
---|---|---|
INTEM | ||
CT, s | 45 ± 20 | 100 ± 10 |
CFT, s | 15 ± 10 | 40 ± 5 |
MCF, mm | 120 ± 10 | 60 ± 10 |
LY, % | 0.8 | 15 |
EXTEM | ||
CT, s | 20 ± 10 | 40 ± 10 |
CFT, s | 21 ± 10 | 60 ± 10 |
MCF, mm | 115 ± 10 | 55 ± 5 |
LY, % | 0.7 | 15 |
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Cacciola, R.; Gentilini Cacciola, E.; Vecchio, V.; Cacciola, E. Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests. Reports 2021, 4, 35. https://doi.org/10.3390/reports4040035
Cacciola R, Gentilini Cacciola E, Vecchio V, Cacciola E. Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests. Reports. 2021; 4(4):35. https://doi.org/10.3390/reports4040035
Chicago/Turabian StyleCacciola, Rossella, Elio Gentilini Cacciola, Veronica Vecchio, and Emma Cacciola. 2021. "Adverse Outcome in Non-Severe COVID-19: Potential Diagnostic Coagulation Tests" Reports 4, no. 4: 35. https://doi.org/10.3390/reports4040035