Ozcan EREL, Fatma Meric YILMAZ, Merve ERGİN TUNCAY, Esra YAKIŞIK, Serpil ERDOĞAN, Deniz ERDEM, Hurrem BODUR, Sumeyye KAZANCIOĞLU, Aliye BASTUG

COVID-19 HASTALIK ŞİDDETİ İLE İLİŞKİLİ TROMBOSİT HİPERREAKTİVİTESİ

Amaç: SARS-CoV-2 enfeksiyonunda bir hiperkoagulasyon durumu rapor edilmiştir. Trombositler geleneksel rollerinin yanı sıra bağışıklık hücreleri olarak da adlandırılır. Çalışmanın amacı, COVID-19'da trombosit aktivasyonunu ve agregasyonunu incelemekti. Materyal ve Metot: Bu vaka-kontrol çalışması SARS-CoV-2 enfeksiyonu olan 61 hasta ve 18 sağlıklı bireyden oluşmuştur. Hastalar yoğun bakım ünitesinde (YBÜ) tedavi ihtiyacına göre gruplara ayrıldı. Tüm gruplarda CD41, CD61, CD42a ve CD42b saptandı ve trombosit agregasyon testleri incelendi. Bulgular: Trombosit CD41, CD61, CD42a ve CD42b ekspresyonları, YBÜ hastalarında sağlıklı donörlere YBÜ olmayan hastalara kıyasla önemli ölçüde yüksekti. YBÜ grubundaki hastalar, YBÜ olmayan hastalar ve kontrollere göre trombosit agregasyonlarında artışa sahipti. Ek olarak, trombosit aktivasyonu ve trombosit fonksiyon testleri, C-reaktif protein, interlökin-6, nötrofil-lenfosit oranı, trombosit-lenfosit oranı, monositlenfosit oranı, D-dimer ve fibrinojeni içeren inflamatuar ve pıhtılaşma belirteçleri ile korelasyon göstermiştir. Sonuç: YBÜ COVID-19 hastalarında artmış trombosit aktivitesi ve daha hızlı trombosit agregasyonu gözlendi. Trombosit hiperreaktivitesinin SARS-CoV-2 enfeksiyonunun ilerlemesine katkıda bulunması olasıdır. Trombosit aktivasyon ve fonksiyon testlerinin inflamatuar ve pıhtılaşma belirteçleri ile arasındaki ilişkiler, sistemik inflamasyonun ve sitokinlerin YBÜ'deki COVID-19 hastalarında hiperkoagulasyonu tetikleyebileceğini veya hiperaktif trombositlerin inflamasyonu artırabileceğini göstermektedir.

PLATELET HYPERREACTIVITY RELATED WITH COVID19 DISEASE SEVERITY

Objectives: A hypercoagulability status has been reported in SARS-CoV-2 infection. Beside their traditional roles, platelets are referred to as immune cells. The purpose of the study was to examine platelet activation and aggregation in COVID-19. Materials and Methods: This case-control study comprised 61 patients with SARS-CoV-2 infection and 18 healthy individuals. The patients were separated into groups with respect to the need for treatment in the intensive care unit (ICU). CD41, CD61, CD42a, and CD42b were determined as platelet activation markers, and platelet aggregation tests were analyzed in all groups. Results: Platelet CD41, CD61, CD42a, and CD42b expressions were significantly elevated in ICU patients compared to non-ICU patients and healthy donors. Patients in the ICU group had increased platelet aggregations than those in non-ICU patients and controls. Additionally, platelet activation and platelet function tests correlated with inflammatory and coagulation markers involving C‐reactive protein, Interleukin-6, neutrophil-to-lymphocyte ratio, platelet‐to‐lymphocyte ratio, monocyte to lymphocyte ratio, D-dimer, and fibrinogen concentrations. Conclusion: Enhanced platelet activity and faster platelet aggregation were observed in ICU COVID-19 patients. It is possible that platelet hyperreactivity may contribute to the progression of SARS-CoV-2 infection. The relationships between platelet activation and functions tests with inflammatory and coagulation markers show that systemic inflammation and cytokines may trigger the hypercoagulability in COVID-19 patients in ICU, or hyperactivated platelets could augment the inflammation.

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1. Lotfi M, Hamblin MR and Rezaei N. COVID-19: Transmission, prevention, and potential therapeutic opportunities. Clin Chim Acta. 2020; 508:254-66 (doi.org/10.1016/j.cca.2020.05.044).
2. Bastug A, Bodur H, Erdogan S, Gokcinar D, Kazancioglu S, Kosovali BD et al. Clinical and laboratory features of COVID-19: Predictors of severe prognosis. Int Immunopharmacol. 2020; 88:106950 (doi:10.1016/j.intimp.2020.106950)
3. Zarbock A, Polanowska-Grabowska RK and Ley K. Platelet-neutrophil-interactions: linking hemostasis and inflammation. Blood Rev. 2007; 21:99-111. (doi: 10.1016/j.blre.2006.06.001).
4. Hottz ED, Bozza FA and Bozza PT. Platelets in Immune Response to Virus and Immunopathology of Viral Infections. Front Med (Lausanne). 2018; 5:121. (doi:10.3389/fmed.2018.00121).
5. Assinger A. Platelets and infection–an emerging role of platelets in viral infection. Frontiers in immunology. 2014; 5:649. (doi:10.3389/fimmu.2014.00649).
6. Pryzdial EL, Lin BH and Sutherland MR. Virus–platelet associations Platelets in Thrombotic and NonThrombotic Disorders: Springer; 2017: 1085-102. (doi:10.1007/978-3-319-47462-5_72).
7. Rondina MT, Brewster B, Grissom CK, Zimmerman GA, Kastendieck DH, Harris ES et al. In vivo platelet activation in critically ill patients with primary 2009 influenza A(H1N1). Chest. 2012; 141:1490-5. (doi: 10.1378/chest.11-2860).
8. Middleton EA, Weyrich AS and Zimmerman GA. Platelets in Pulmonary Immune Responses and Inflammatory Lung Diseases. Physiol Rev. 2016; 96:1211-59. (doi:10.1152/physrev.00038.2015).
9. Kipshidze N, Dangas G, White CJ, Kipshidze N, Siddiqui F, Lattimer CR et al. Viral Coagulopathy in Patients With COVID-19: Treatment and Care. Clin Appl Thromb Hemost. 2020; 26:1076029620936776. (doi.org/10.1177/1076029620936776).
10. McFadyen JD, Stevens H and Peter K. The Emerging Threat of (Micro)Thrombosis in COVID-19 and Its Therapeutic Implications. Circ Res. 2020; 127:571-87. (doi: 10.1161/CIRCRESAHA.120.317447).
11. Hanff TC, Mohareb AM, Giri J, Cohen JB and Chirinos JA. Thrombosis in COVID-19. Am J Hematol. 2020;1–12 (DOİ: 10.1002/ajh.25982).
12. Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dereyfus I, Driggin E et al. COVID-19 and Thrombotic or Thromboembolic Disease: Implications for Prevention, Antithrombotic Therapy, and Follow-Up: JACC State-of-the-Art Review. J Am Coll Cardiol. 2020; 75:2950-73. (doi: 10.1016/j.jacc.2020.04.031).
13. Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli F et al. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis. 2020;20: e238-44. (doi.org/10.1016/S1473- 3099(20)30484-9).
14. Kaur S, Bansal R, Kollimuttathuillam S, Gowda AM, Singh B, Mehta D et al. The looming storm: Blood and cytokines in COVID-19. Blood Rev. 2020:100743. (doi.org/10.1016/j.blre.2020.100743).
15. Koupenova M, Clancy L, Corkrey HA and Freedman JE. Circulating platelets as mediators of immunity, inflammation, and thrombosis. Circulation research. 2018; 122:337-51. (DOİ: 10.1161/CIRCRESAHA.117.310795).
16. Berndt MC, Metharom P and Andrews RK. Primary haemostasis: newer insights. Haemophilia. 2014; 20:15-22. (doi: 10.1111/hae.12427).
17. Hottz ED, Azevedo-Quintanilha IG, Palhinha L, Teixeira L, Barreto EA, Pão CRR et al. Platelet activation and platelet-monocyte aggregate formation trigger tissue factor expression in patients with severe COVID-19. Blood. 2020; 136:1330-41. (doi: 10.1182/blood.2020007252).
18. Manne BK, Denorme F, Middleton EA, Portier I, Rowley JW, Stubben C et al. Platelet gene expression and function in patients with COVID-19. Blood. 2020; 136:1317-29. (doi:10.1182/blood.2020007214).
19. Kalinskaya A, Dukhin O, Molodtsov I, Maltseva A, Sokorev D, Elizarova A et al. Dynamics of coagulopathy in patients with different COVID-19 severity. medRxiv. 2020 Jul 4;2020.07.02.20145284. (doi: 10.1101/2020.07.02.20145284).