Assessment of the Level of Protein C in Hospitalized Iraqi Patients with COVID-19 and its Correlation with Hematological and Inflammatory Markers
DOI:
https://doi.org/10.3889/oamjms.2022.8937Keywords:
COVID-19, Protein C, D-Dimer, CoagulopathyAbstract
BACKGROUND: COVID-19 coagulopathy manifests by elevation of certain marker of active coagulation as fibrinogen and this increment associated with increased markers of inflammations.
AIM: To measure protein C (PC) level in hospitalized patients with COVID-19 and to find a possible correlation with hematological and inflammatory markers.
PATIENTS AND METHODS: Seventy-five hospitalized Iraqi adult patients with COVID-19 were included in a descriptive cross-sectional research. PC, D-dimer, and erythrocyte sedimentation rate (ESR) blood samples were collected, and further information was received from patient’s records. Statistical analysis was conducted using SPSS version 23 and Microsoft Office Excel 2019.
RESULTS: Mean age of 75 patients included in the study was 60.13 ± 14.65 years. Sixty-two (62.7%) of patients exhibited neutrophilia, whereas 41 had lymphopenia (54.7%). High ratio of neutrophil/lymphocyte (N/L) was seen in 66 (88.0%), eosinopenia was seen in 46 (61.3%), high lactate dehydrogenase level was seen 68 (90.7%), serum ferritin was high in 66 (88.0%), and high level of C-reactive protein was seen in 68 (90.7%), increased ESR was seen in 69 (92.0%) and high level of D-dimer was seen in 56 (74.7%), while low level of PC was seen in 12 (16.0%) patients. PC had significant negative correlation with prothrombin and partial thromboplastin time but no significant correlation with hematological and inflammatory parameters.
CONCLUSION: COVID-19 coagulopathy is common in majority of patients which include significant changes in WBCs counts, inflammatory markers, PC, and D-dimer levels. Such changes may have a great impact on morbidity and mortality and thus need to be monitored throughout treatment and convalescence.Downloads
Metrics
Plum Analytics Artifact Widget Block
References
Griffin JH, Lyden P. COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation. Res Pract Thromb Haemost. 2020;4(4):506-9. https://doi.org/10.1002/rth2.12362 PMid:32548551 DOI: https://doi.org/10.1002/rth2.12362
Al Otair H, AlSaleh K, AlQahtany FS, Al Ayed K, Al Ammar H, Al Mefgai N, et al. The level of vWF antigen and coagulation markers in hospitalized patients with Covid-19. J Blood Med. 2021;12:809-17. https://doi.org/10.2147/jbm.s318940 PMid:34512061 DOI: https://doi.org/10.2147/JBM.S318940
Zhu N, Zhang D, Wang W, Li X, Yang B, Song J, et al. A novel coronavirus from patients with pneumonia in China, 2019. N Engl J Med. 2020;382(8):727-33. https://doi.org/10.1056/nejmoa2001017 PMid:31978945 DOI: https://doi.org/10.1056/NEJMoa2001017
Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061-9. https://doi.org/10.1001/jama.2020.1585 PMid:32031570 DOI: https://doi.org/10.1001/jama.2020.1585
Liu L, Lei X, Xiao X, Yang J, Li J, Ji M. Epidemiological and clinical characteristics of patients with coronavirus disease-2019 in Shiyan city, China. Front Cell Infect Microbiol. 2020;10:284. https://doi.org/10.3389/fcimb.2020.00284 PMid:32574282 DOI: https://doi.org/10.3389/fcimb.2020.00284
Miesbach W, Makris M. COVID-19: Coagulopathy, risk of thrombosis, and the rationale for anticoagulation. Clin Appl Thromb Hemost. 2020;26:1076029620938149. https://doi.org/10.1177/1076029620938149 PMid:32677459 DOI: https://doi.org/10.1177/1076029620938149
Vajari MK, Shirin M, Pourbagheri-Sigaroodi A, Akbari ME, Abolghasemi H, Bashash D. COVID-19-related coagulopathy: A review of pathophysiology and pharmaceutical management. Cell Biol Int. 2021;45(9):1832-50. https://doi.org/10.1002/cbin.11623 PMid:33945651 DOI: https://doi.org/10.1002/cbin.11623
Liu Q, Wang RS, Qu GQ, Wang YY, Liu P, Zhu YZ, et al. Gross examination report of a COVID-19 death autopsy. Fa Yi Xue Za Zhi. 2020;36(1):21-3. https://doi.org/10.12116/j.issn.1004-5619.2020.01.005 PMid:32198987
Dahlbäck B, Villoutreix BO. Regulation of blood coagulation by the protein C anticoagulant pathway: Novel insights into structure-function relationships and molecular recognition. Arterioscler Thromb Vasc Biol. 2005;25(7):1311-20. https://doi.org/10.1161/01.atv.0000168421.13467.82 PMid:15860736 DOI: https://doi.org/10.1161/01.ATV.0000168421.13467.82
Bashash D, Hosseini-Baharanchi FS, Rezaie-Tavirani M, Safa M, Dilmaghani NA, Faranoush M, et al. The prognostic value of thrombocytopenia in COVID-19 patients; a systematic review and meta-analysis. Arch Acad Emerg Med. 2020;8(1):e75. PMid:33134971
Gupta N, Zhao YY, Evans CE. The stimulation of thrombosis by hypoxia. Thromb Res. 2019;181:77-83. https://doi.org/10.1016/j.thromres.2019.07.013 PMid:31376606 DOI: https://doi.org/10.1016/j.thromres.2019.07.013
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. https://doi.org/10.1016/j.jcv.2020.104362 PMid:32305883 DOI: https://doi.org/10.1016/j.jcv.2020.104362
Wang YD, Zhang SP, Wei QZ, Zhao MM, Mei H, Zhang ZL, et al. COVID-19 complicated with DIC: 2 cases report and literatures review. Zhonghua Xue Ye Xue Za Zhi. 2020;41(3):245-7. https://doi.org/10.3760/cma.j.issn.0253-2727.2020.0001 PMid:32133824
Stanne TM, Pedersen A, Gisslén M, Jern C. Low admission protein C levels are a risk factor for disease worsening and mortality in hospitalized patients with COVID-19. Thromb Res. 2021;204:13-15. https://doi.org/10.1016/j.thromres.2021.05.016 PMid:34102452 DOI: https://doi.org/10.1016/j.thromres.2021.05.016
Francischetti IM, Toomer K, Zhang Y, Jani J, Siddiqui Z, Brotman DJ, et al. Upregulation of pulmonary tissue factor, loss of thrombomodulin and immunothrombosis in SARS-CoV-2 infection. EClinicalMedicine. 2021;39:101069. https://doi.org/10.1016/j.eclinm.2021.101069 PMid:34377969 DOI: https://doi.org/10.1016/j.eclinm.2021.101069
Fan BE, Chong VC, Chan SS, Lim GH, Lim KG, Tan GB, et al. Hematologic parameters in patients with COVID-19 infection. Am J Hematol. 2020;95(6):E131-4. https://doi.org/10.1002/ajh.25774 PMid:32129508 DOI: https://doi.org/10.1002/ajh.25774
Kong M, Zhang H, Cao X, Mao X, Lu Z. Higher level of neutrophil-to-lymphocyte is associated with severe COVID-19. Epidemiol Infect. 2020;148:e139. https://doi.org/10.1017/s0950268820001557 PMid:32641174 DOI: https://doi.org/10.1017/S0950268820001557
Martín-Rojas RM, Pérez-Rus G, Delgado-Pinos VE, Domingo- González A, Regalado-Artamendi I, Alba-Urdiales N, et al. COVID-19 coagulopathy: An in-depth analysis of the coagulation system. Eur J Haematol. 2020;105(6):741-50. https://doi.org/10.1111/ejh.13501 PMid:32749010 DOI: https://doi.org/10.1111/ejh.13501
Ruscitti P, Bruno F, Berardicurti O, Acanfora C, Pavlych V, Palumbo P, et al. Lung involvement in macrophage activation syndrome and severe COVID-19: Results from a cross-sectional study to assess clinical, laboratory and artificial intelligence-radiological differences. Ann Rheum Dis. 2020;79(9):1152-5. https://doi.org/10.1136/annrheumdis-2020-218048 DOI: https://doi.org/10.1136/annrheumdis-2020-218048
PMid:32719039
Spiezia L, Boscolo A, Poletto F, Cerruti L, Tiberio I, Campello E, et al. COVID-19-related severe hypercoagulability in patients admitted to intensive care unit for acute respiratory failure. Thromb Haemost. 2020;120(6):998-1000. https://doi.org/10.1055/s-0040-1710018 PMid:32316063 DOI: https://doi.org/10.1055/s-0040-1710018
Lin S, Mao W, Zou Q, Lu S, Zheng S. Associations between hematological parameters and disease severity in patients with SARS-CoV-2 infection. J Clin Lab Anal. 2021;35(1):e23604. https://doi.org/10.1002/jcla.23604 PMid:33184946 DOI: https://doi.org/10.1002/jcla.23604
Sayad B, Afshar ZM, Mansouri F, Rahimi Z. Leukocytosis and alteration of hemoglobin level in patients with severe COVID-19: Association of leukocytosis with mortality. Health Sci Rep. 2020;3(4):e194. https://doi.org/10.1002/hsr2.194 PMid:33083572 DOI: https://doi.org/10.1002/hsr2.194
Urrechaga E, Zalba S, Otamendi I, Zabalegui MA, Galbete A, Ongay E, et al. Hemoglobin and anemia in COVID19 patients. Hematol Med Oncol 2020;5:1-4. https://doi.org/10.15761/hmo.1000217 DOI: https://doi.org/10.15761/HMO.1000217
Du Y, Tu L, Zhu P, Mu M, Wang R, Yang P, et al. Clinical features of 85 fatal cases of COVID-19 from Wuhan.Aretrospective observational study. Am J Respir Crit Care Med. 2020;201(11):1372-9. https://doi.org/10.1164/rccm.202003-0543oc PMid:32242738 DOI: https://doi.org/10.1164/rccm.202003-0543OC
Ish P, Malhotra N, Agrawal S, Gupta N. Relative lymphocytosis in COVID-19-a ray of hope. Adv Respir Med. 2020;88(3):287-8. https://doi.org/10.5603/arm.a2020.0098 PMid:32706115 DOI: https://doi.org/10.5603/ARM.a2020.0098
Kasinathan G, Sathar J. Haematological manifestations, mechanisms of thrombosis and anti-coagulation in COVID-19 disease: A review. Ann Med Surg (Lond). 2020;56:173-7. https://doi.org/10.1016/j.amsu.2020.06.035 PMid:32637095 DOI: https://doi.org/10.1016/j.amsu.2020.06.035
Słomka A, Kowalewski M, Żekanowska E. Coronavirus disease 2019 (COVID-19): A short review on hematological manifestations. Pathogens. 2020;9(6):493. https://doi.org/10.3390/pathogens9060493 PMid:32575786 DOI: https://doi.org/10.3390/pathogens9060493
Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: A meta-analysis. Clin Chim Acta. 2020;506:145-8. https://doi.org/10.1016/j.cca.2020.03.022 PMid:32178975 DOI: https://doi.org/10.1016/j.cca.2020.03.022
Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol. 2020;99(6):1205-8. https://doi.org/10.1007/s00277-020-04019-0 PMid:32296910 DOI: https://doi.org/10.1007/s00277-020-04019-0
Agbuduwe C, Basu S. Haematological manifestations of COVID-19: From cytopenia to coagulopathy. Eur J Haematol. 2020;105(5):540-6. https://doi.org/10.1111/ejh.13491 PMid:32663356 DOI: https://doi.org/10.1111/ejh.13491
Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan, China. Clin Infect Dis. 2020;71(15):762-8. https://doi.org/10.1093/cid/ciaa248 PMid:32161940 DOI: https://doi.org/10.1093/cid/ciaa248
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. 2020;507:167-73. https://doi.org/10.1016/j.cca.2020.04.027 PMid:32348783 DOI: https://doi.org/10.1016/j.cca.2020.04.027
Testa S, Paoletti O, Giorgi-Pierfranceschi M, Pan A. Switch from oral anticoagulants to parenteral heparin in SARS-CoV-2 hospitalized patients. Intern Emerg Med. 2020;15(5):751-3. https://doi.org/10.1007/s11739-020-02331-1 PMid:32297089 DOI: https://doi.org/10.1007/s11739-020-02331-1
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 Res Int. 2020;2020:6159720. https://doi.org/10.1155/2020/6159720 PMid:32596339 DOI: https://doi.org/10.1155/2020/6159720
Görlinger K, Levy JH. COVID-19-associated coagulopathy. Anesthesiology. 2021;134(3):366-9. https://doi.org/10.1097/aln.0000000000003688 PMid:33417671 DOI: https://doi.org/10.1097/ALN.0000000000003688
Tabatabai A, Rabin J, Menaker J, Madathil R, Galvagno S, Menne A, et al. Factor VIII and functional protein C activity in critically Ill patients with coronavirus disease 2019: A case series. A A Pract. 2020;14(7):e01236. https://doi.org/10.1213/xaa.0000000000001236 PMid:32539272 DOI: https://doi.org/10.1213/XAA.0000000000001236
Calderon-Lopez MT, Garcia-Leon N, Gomez-Arevalillo S, Martin- Serrano P, Matilla-Garcia A. Coronavirus disease 2019 and coagulopathy: Other prothrombotic coagulation factors. Blood Coagul Fibrinolysis. 2021;32(1):44-9. https://doi.org/10.1097/mbc.0000000000000996 PMid:33417336 DOI: https://doi.org/10.1097/MBC.0000000000000996
Mazzeffi M, Chow JH, Amoroso A, Tanaka K. Revisiting the protein C pathway: An opportunity for adjunctive intervention in COVID-19? Anesth Analg. 2020;131(3):690-693. https://doi.org/10.1213/ane.0000000000005059 PMid:32541255 DOI: https://doi.org/10.1213/ANE.0000000000005059
Faust SN, Levin M, Harrison OB, Goldin RD, Lockhart MS, Kondaveeti S, et al. Dysfunction of endothelial protein C activation in severe meningococcal sepsis. N Engl J Med. 2001;345(6):408-16. https://doi.org/10.1056/nejm200108093450603 PMid:11496851 DOI: https://doi.org/10.1056/NEJM200108093450603
Chornenki NL, Dwivedi DJ, Kwong AC, Zamir N, Fox-Robichaud AE, Liaw PC, et al. Identification of hemostatic markers that define the pre-DIC state: A multi-center observational study. J Thromb Haemost. 2020;18(10):2524-31. https://doi.org/10.1111/jth.14973 PMid:32573898 DOI: https://doi.org/10.1111/jth.14973
Al-Attar Z, Jasim S, Hashim I, Badai S. Prevalence of anemia types among overweight and obese patients attending the obesity research and therapy unit at Al-Kindy college of medicine. Int Med J. 2020;24(3)435. https://doi.org/10.47723/kcmj.v13i2.98 DOI: https://doi.org/10.47723/kcmj.v13i2.98
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2022 Hind Shaker Al-Mamoori, Majid Hameed Ahmed, Taha Yaseen Shammar Al-Nafie, Zaid Al-Attar (Author)
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
http://creativecommons.org/licenses/by-nc/4.0