The Importance of Hemorheological Parameters in the Etiopathogenesis of COVID-19

Öz

COVID-19 disease, which emerged in Wuhan, China on November 17, 2019, was declared a global epidemic by the World Health Organization (WHO) on March 11, 2020. This virus, which causes severe disease and many deaths worldwide, has been named severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2). Although all age groups are susceptible to the disease, it has been observed that the probability of developing a serious disease is higher in elderly individuals and those with underlying diseases such as cardiovascular disease, diabetes, chronic respiratory disease or cancer. Spike (S) protein, which is one of the proteins on the surface of the SARS-CoV-2 virus, binds to angiotensin converting enzyme2 (ACE2) receptors in the epithelial cells of the lower respiratory tract, leaving its own genome in the cytoplasm of the cell, thus performing the synthesis of new virus particles. In studies, it has been stated that various hematological and hemorheological parameters change in COVID-19 disease. Some hematological parameters frequently observed in this disease are lymphopenia, neutrophilia, and thrombocytopenia. Platelet activation and endothelial dysfunction were detected depending on the increase in inflammation and thrombosis formation due to stasis. Studies on COVID-19 coagulopathy have shown high levels of D-dimer. It has also been found that increased fibrinogen causes erythrocyte hyperaggregation in COVID-19 patients, which is associated with the development of blood coagulation. Decreased deformability of erythrocytes results in an increase in erythrocyte rigidity. It has been suggested that the increase in hemorheological parameters such as D-dimer, blood viscosity, erythrocyte aggregation and deformability as a result of the deterioration in the coagulation/fibrinolytic system in COVID-19 disease is associated with the prognosis of the disease. The purpose of our review was to evaluate the roles of hemorheological parameters in the etiopathogenesis of COVID-19.

Anahtar Kelimeler

• COVID-19
• hemorheology
• coagulopathy
• viscosity
• erythrocyte aggregation

COVID-19’un Etiyopatogenezinde Hemoreolojik Parametrelerin Önemi

Öz

17 Kasım 2019’da Çin’in Wuhan kentinde ortaya çıkan COVID-19 hastalığı, 11 Mart 2020 tarihinde Dünya Sağlık Örgütü (DSÖ) tarafından küresel salgın olarak ilan edilmiştir. Ağır hastalık tablosuna ve dünya genelinde çok sayıda ölüme neden olan bu virüs, Şiddetli Akut Solunum Sendromu-Koronavirus-2 (SARS-CoV-2) olarak adlandırılmıştır. Hastalığa tüm yaş grupları hassas olmakla beraber yaşlı bireyler ile kardiyovasküler hastalık, diyabet, kronik solunum yolu hastalığı veya kanser gibi altta yatan hastalıkları olanlarda ciddi hastalık gelişme olasılığının daha yüksek olduğu gözlenmiştir. SARS-CoV-2 virüsü yüzeyindeki proteinlerden biri olan spike (S) proteini ile alt solunum yolu epitel hücrelerinde bulunan anjiyotensin dönüştürücü enzim- 2 (ACE2) reseptörlerine bağlanarak kendi genomunu hücre sitoplazmasına bırakır ve böylece yeni virüs partiküllerinin sentezini gerçekleştirir. Yapılan çalışmalarda, COVID-19 hastalığında çeşitli hematolojik ve hemoreolojik parametrelerin değiştiği belirtilmiştir. Bu hastalıkta sıklıkla gözlenen bazı hematolojik parametreler lenfopeni, nötrofili ve trombositopenidir. Enflamasyondaki artışa bağlı olarak, trombosit aktivasyonu, endotel disfonksiyonu ve staz nedeniyle hastalarda tromboz oluşumu saptanmıştır. COVID-19 koagülopatisi ile ilgili çalışmalarda, yüksek D-dimer düzeylerinin olduğu görülmüştür. Aynı zamanda artmış fibrinojenin COVID-19 hastalarında eritrosit hiperagregasyonuna neden olduğu ve bunun da kan pıhtılaşmasının gelişmesi ile ilişkili olduğu tespit edilmiştir. Eritrositlerde deformabilite yeteneğinin azalması eritrosit rijiditesinde artış ile sonuçlanmaktadır. COVID-19 hastalığında koagülasyon/fibrinolitik sistemindeki bozulmanın sonucunda, D-dimer, kan viskozitesi, eritrosit agregasyonu ve deformabilitesi gibi hemoreolojik parametrelerin artışı hastalık prognozu ile ilişkili olduğu ileri sürülmüştür. Derlemenin amacı, COVID-19’un etiyopatogenezinde hemoreolojik parametrelerin rollerini değerlendirmektir.

Anahtar Kelimeler

• COVID-19
• hemoreoloji
• koagülopati
• viskozite
• eritrosit agregasyonu

Kaynakça

1. Chen N, Zhou M, Dong X, et al. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. The Lancet. 2020;395(10223):507-513.
2. Kwong KCNK, Mehta PR, Shukla G, Mehta AR. COVID-19, SARS and MERS: A neurological perspective. Journal of Clinical Neuroscience. 2020;77:13-16.
3. Acter T, Uddin N, Das J, Akhter A, Choudhury TR, Kim S. Evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) as coronavirus disease 2019 (COVID-19) pandemic: A global health emergency. Science of the Total Environment. 2020;730:138996.
4. Fan BE. Hematologic parameters in patients with COVID‐19 infection: a reply. American Journal of Hematology. 2020;95(8):E215.
5. Tan L, Wang Q, Zhang D, et al. Lymphopenia predicts disease severity of COVID-19: a descriptive and predictive study. Signal Transduction and Targeted Therapy. 2020;5(1):33.
6. Qian GQ, Yang NB, Ding F, et al. Epidemiologic and clinical characteristics of 91 hospitalized patients with COVID-19 in Zhejiang, China: a retrospective, multi-centre case series. QJM: An International Journal of Medicine. 2020;113(7):474-481.
7. Helms J, Tacquard C, Severac F, 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):1089-1098.
8. Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: An autopsy series from New Orleans. The Lancet Respiratory Medicine. 2020;8(7):681-686.

9. Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. International Journal of Hematology. 2021;113:45-57.
10. Nader E, Nougier C, Boisson C, et al. Increased blood viscosity and red blood cell aggregation in patients with COVID‐19. American Journal of Hematology. 2022;97(3):283-292.
11. Rasyid A, Timan IS, Riyanto DL, et al. Coagulation and hemorheology profile of patient with stroke and COVID-19: A case series during second wave pandemic. Clinical Hemorheology and Microcirculation. 2022(Preprint):1-6.
12. Singhal T. A review of coronavirus disease-2019 (COVID-19). The Indian Journal of Pediatrics. 2020;87(4):281-286.
13. Andersen KG, Rambaut A, Lipkin WI, Holmes EC, Garry RF. The proximal origin of SARS-CoV-2. Nature Medicine. 2020;26(4):450-452.
14. Rothe C, Schunk M, Sothmann P, et al. Transmission of 2019-nCoV infection from an asymptomatic contact in Germany. New England Journal of Medicine. 2020;382(10):970-971.
15. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet. 2020;395(10223):497-506.
16. Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet. 2020;395(10229):1054-1062.
17. Guan WJ, Ni ZY, Hu Y, et al. Clinical characteristics of coronavirus disease 2019 in China. New England Journal of Medicine. 2020;382(18):1708-1720.
18. Astuti I. Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2): An overview of viral structure and host response. Diabetes & Metabolic Syndrome: Clinical Research & Reviews. 2020;14(4):407-412.
19. Jiang S, Hillyer C, Du L. Neutralizing antibodies against SARS-CoV-2 and other human coronaviruses. Trends in Immunology. 2020;41(5):355-359.
20. 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. Journal of Thrombosis and Haemostasis. 2020;18(7):1548-1555.
21. Wu C, Chen X, Cai Y, et al. Risk factors associated with acute respiratory distress syndrome and death in patients with coronavirus disease 2019 pneumonia in Wuhan, China. JAMA Internal Medicine. 2020;180(7):934-943.
22. Lippi G, Plebani M, Henry BM. Thrombocytopenia is associated with severe coronavirus disease 2019 (COVID-19) infections: a meta-analysis. Clinica Chimica Acta. 2020;506:145-148.
23. Bikdeli B, Madhavan MV, Jimenez D, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up: JACC state-of-the-art review. Journal of the American College of Cardiology. 2020;75(23):2950-2973.
24. 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):844-847.
25. Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. Journal of Thrombosis and Haemostasis. 2020;18(5):1023-1026.
26. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance, 28 January 2020: World Health Organization; 2020.
27. Llitjos JF, Leclerc M, Chochois C, et al. High incidence of venous thromboembolic events in anticoagulated severe COVID‐19 patients. Journal of Thrombosis and Haemostasis. 2020;18(7):1743-1746.
28. Leisman DE, Deutschman CS, Legrand M. Facing COVID-19 in the ICU: vascular dysfunction, thrombosis, and dysregulated inflammation. Intensive Care Medicine. 2020;46:1105-1108.
29. Joob B, Wiwanitkit V. Blood viscosity of COVID-19 patient: a preliminary report. American journal of blood research. 2021;11(1):93.
30. Nwose EU, Richards RS. Whole blood viscosity issue VIII: comparison of extrapolation method with diagnostic digital viscometer. North American Journal of Medical Sciences. 2011;3(7):333.
31. Mungmunpuntipantip R, Wiwanitkit V. Blood viscosity at the first clinical presentation in fatal and non-fatal COVID-19: an observation. Clinical and Applied Thrombosis/Hemostasis. 2021;27:10760296211006779.
32. Baskurt O, Boynard M, Cokelet G, et al. International expert panel for standardization of hemorheological methods. New guidelines for hemorheological laboratory techniques. Clin Hemorheol Microcirc. 2009;42(2):75-97.
33. Baskurt O, Meiselman H. Blood Rheology And Hemodynamics in Seminars in Thrombosis and Hemostasis. New York, NY, USA: Thieme Medical Publishers, Inc; 2003.
34. Rampling M, Meiselman H, Neu B, Baskurt O. Influence of cell‐specific factors on red blood cell aggregation. Biorheology. 2004;41(2):91-112.
35. Raj JU, Anderson J. Erythrocyte deformability and lung segmental vascular resistance: effect of hematocrit. Journal of Applied Physiology. 1991;70(3):1386-1392.
36. Simchon S, Jan KM, Chien S. Influence of reduced red cell deformability on regional blood flow. American Journal of Physiology-Heart and Circulatory Physiology. 1987;253(4):H898-H903.
37. Renoux C, Fort R, Nader E, et al. Impact of COVID-19 on red blood cell rheology. British Journal of Haematology. 2021;192(4):e108-e111.
38. Xing Y, Yang W, Jin Y, Wang C, Guan X. D-dimer daily continuous tendency predicts the short-term prognosis for COVID-19 independently: A retrospective study from Northeast China. Clinical Hemorheology and Microcirculation. 2021;79(2):269-277.
39. Jung F, Mrowietz C, Hiebl B, Franke R, Pindur G, Sternitzky R. Influence of rheological parameters on the velocity of erythrocytes passing nailfold capillaries in humans. Clinical Hemorheology and Microcirculation. 2011;48(1-3):129-139.
40. Srihirun S, Sriwantana T, Srichatrapimuk S, et al. Increased platelet activation and lower platelet-monocyte aggregates in COVID-19 patients with severe pneumonia. Plos one. 2023;18(3):e0282785.