Összefoglaló. A szerzők a SARS-CoV-2 vírus okozta járványnak (COVID–19) a haemostasist érintő, klinikailag fontosabb szempontjait tekintik át röviden. Felhívják a figyelmet a thromboemboliás szövődmények súlyossága és gyakorisága mögött levő patomechanizmus jellegzetességére, vagyis a Virchow-triász három alkotója időben egyszerre történő aktiválódására. A továbbiakban a kórállapotot és -lefolyást jelző fontosabb haemostasis laboratóriumi leleteket érintik, majd rátérnek a megelőzés és a kezelés kérdéseire, mely utóbbiakat a betegség súlyossági csoportokra történő bontásában tárgyalják, a jelenlegi nemzetközi irányelvekre támaszkodva. Végezetül egy összefoglaló táblázatban, a nemzetközi ajánlásokon alapuló, de a hazai szempontokat is figyelembe vevő, általánosan elfogadható antikoagulálási útmutatót igyekeznek adni, hangsúlyozva a kezelés személyre szabásának fontosságát.
Summary. In the present paper the most important, clinically relevant haemostatic effects of SARS-Cov-2 virus infection (COVID-19) is reviewed and an awareness is raised of the unique pathomechanism which allows a concurrent activation of each side of the Virchows’ triad responsible for the aggressivity of thrombotic events in the disease. Subsequently characteristic haemostatic prognostic and staging laboratory results are discussed followed by a brief survey of anticoagulant prophylaxis and therapy in the different severity stages of the disease. Finally a brief guidance is given based on various international guidelines with an adoption of current Hungarian situation and emphasizing the importance of personalized decisions.
Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis and angiogenesis in COVID-19. N Engl J Med. 2020; 383: 120–128.
Aggarwal M, Dass J, Mahapatra M. Hemostatic abnormalizies in COVID-19: an update. Indian J Hematol Blood Transfus. 2020; 36: 616–626. https://doi.org/10.1007/s12288-020-01328-2
Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood 2020; 136: 489–500.
Attia E, Fuentes A, Vassallo M, et al. Establishing a multidisciplinary taskforce to improve anticoagulation safety at a large health system. Am J Health-System Pharmacy November 1, 2021. https://doi.org/10.1093/ajhp/zxab411
Bareille M, Hardy M, Douxfils J, et al. Viscoelastometric testing to assess Hemostasis of COVID-19: A Systematic Review. J Clin Med. 2021; 10(8): 1740–1796. https://doi.org/10.3390/jcm10081740
Barnes GD, Burnett A, Allen A, et al. Thromboembolism and anticoagulant therapy during the COVID‐19 pandemic: interim clinical guidance from the anticoagulation forum. J Thrombos Thrombolys. 2020; 50: 72–81. https://doi.org/10.1007/s11239-020-02138-z
ten Berg J. J Thrombos Thrombolys 2021; 52: 1007–1009. https://doi.org/10.1007/s11239-021-02524-1
Bikdelli 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. Am J Coll Cardiol. 2020; 75: 2950–2973. .
Bozóky G, Ruby É, Mohos A, Bozóky I, Göcző K. Thromboembolic complications in COVID-19 patients. Orv Hetil. 2021; 162(43): 1710–1716.
Connors JM, Brooks MM, Sciurba FC, et al. Effect of antithrombotic therapy on clinical outcomes in outpatients with clinically stable symptomatic COVID-19. The ACTIV-4B Randomized Clinical Trial. JAMA 2021; 326(17): 1703–1712. .
Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood 2020; 135: 2033–2040.
Cui S, Chen S, Li X, Liu S, et al. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost, 2020; 18: 1421–1424.
Cuker A, Tseng EK, Nieuwlaat R, et al. American Society of Hematology 2021 guidelines on the use of anticoagulation for thromboprophylaxis in patients with COVID-19. Blood Adv. 2021; 5(3): 872–888. .
Fogarty H, Townsend L, Ni Cheallaigh C, et al. COVID19 coagulopathy in Caucasian patients. Br J Haematol. 2020; 189(6): 1044–1049. .
Gadó K, Domján Gy. A COVID-19 és a véralvadás. Orvostovábbképző Szle. 2020; 27(9): 50–54.
Gerotziafas GT, Catalano M, Colgan MP, et al. Guidance for the management of patients with vascular disease or cardiovascular risk factors and COVID-19: position paper from VAS-European Independent Foundation in Angiology/Vascular Medicine. Thromb Haemost. 2020; 120(12): 1597–1628. .
Gerotziafas GT, Sergentanis TN, Voiriot G, et al. Derivation and validation of a predictive score for disease worsening in patients with COVID-19. Thromb Haemost. 2020; 120(12): 1680–1690. .
Gibson CM, Spyropoulos AC, Cohen AT, et al. The IMPROVEDD VTE risk score: incorporation of D-dimer into the IMPROVE score to improve venous thromboembolism risk stratification. TH Open 2017; 1: e56–e65. .
INSPIRATION Investigators. Effect of Intermediate-Dose vs Standard-Dose Prophylactic Anticoagulation on Thrombotic Events, Extracorporeal Membrane Oxygenation Treatment, or Mortality Among Patients With COVID-19 Admitted to the Intensive Care Unit: The INSPIRATION Randomized Clinical Trial. JAMA 2021; 325: 1620–1630.
Joly BS, Siguret V, Veyradier A. Understanding pathophysiology of hemostasis disorders in critically ill patients with COVID-19. Intensive Care Med. 2020; 46: 1603–1606.
Kluge S, Janssens U, Welte T, et al. S3-Leitlinie – Empfehlungen zur stationaeren Therapie von Patienten mit COVID-19. Stand 05.10.2021. AWMF-Register-Nr. 113/001. Versionsnummer 6.1. https://awmf.org.
Kovács E, Kovács E, Kolozsvári L, et al. Koronavírus elleni oltások antithrombotikus kezelésben részesülő és vérzékeny betegek körében. Orvostovábbképző Szle. 2021; 28: 41–43.
Lawler PR, Goligher EC, Berger JS, et al. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med. 2021; 385: 777–789. .
Levi M, Thachil J, Iba T, et al. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol. 2020; 7: e438–e40.
Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-2019 infection. Clin Chem Lab Med. 2020; 58(7): 1131–1134. .
Lopes RD, Barros e Silva de PGB, Furtado RHM, ACTION Coalition COVID-19 Brazil IV Investigators. Therapeutic versus prophylactic anticoagulation for patients admitted to hospital with COVID-19 and elevated D-dimer concentration (ACTION): an open-label, multicentre, randomised, controlled trial. Lancet 2021; 397: 2253–2263. .
Mackman N, Antoniak S, Wolberg A, et al. Coagulation abnormalities and thrombosis in patients infected with SARS-Cov-2 and other pandemic viruses. Arterioscler Thromb Vasc Biol. 2020; 40: 2033–2044.
Marietta M, Ageno W, Artoni A, et al. COVID-19 and haemostasis: a position paper from Italian Society on Thrombosis and Haemostasis (SOSET). Blood Transfus. 2020; 18: 167–169. .
Mason RJ. Pathogenesis of COVID-19 from a cell biology perspective. Eur Respir J. 2020; 55: 2000607. https://doi.org/10.1183/13993003.00607-2020.
Mehta P, McAuley DF, Brown M, et al. COVID-19: consider cytokine storm syndromes and immunosuppression. Lancet 2020; 395: 1033–1034.
Moores LK, Tritschler T, Brosnahan S, e al. Prevention, Diagnosis, and Treatment of VTE in Patients With Coronavirus Disease 2019: CHEST Guideline and Expert Panel Report. 2020; 158(3): 1143–1163. .
Orosz L, Pfliegler G. Fertőző betegségek és haemostasis. Orv Hetil. 1990, 131: 521–524.
Panigada M, Bottino N, Tagliabue P, et al. 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.
Peyvandi F, Artoni A, Novembrino C, et al. Hemostatic alterations in COVID-19. Haematologica 2021; 106(5). .
Piazza G, Morrow DA. Diagnosis, management, and pathophysiology of arterial and venous thrombosis in COVID-129. JAMA 2020; 324(24): 2548–2549.
Roberts DM, Lévi M, McKee M, et al. COVID-19 a complex multisystem disorder. Br Anaesth, 2020; 25: 238–242.
Roberts LN, Whyte MB, Georgiou L, et al. Postdischarge venous thromboembolism following hospital admission with COVID-19. Blood 2020; 136(11): 1347–1350. .
Singh B, Mechineni A, Kaur P, et al. COVID-19 and bleeding at unusual locations: Report of four cases. Hemato Transfus Cell Ther. 2021; 43(2): 214–218. https://doi.org/10.1016/j.htct.2021.01.007.
Song JC, Wang G, Zhang W, et al. Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID- 19. Mil Med Res. 2020; 7: 19. https://doi.org/10.1186/s40779-020-00247-7.
Spyropoulos AC, Levy JH, Ageno W, et al. Scientific and Standardization Committee communication: Clinical guidance on the diagnosis, prevention, and treatment of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020; 18(8): 1859–1865. .
Talasaz AH, Sadeghipour P, Kakavand H. et al. Recent randomized trials of antithrombotic therapy for patients with COVID- 19. JACC State-of-the-Art Review. J Am Coll Cardiol. 2021; 77: 1903–1921.
Tan BK, Mainbourg S, Friggeri A, et al. Arterial and venous thromboembolism in COVID-19: a study-level meta-analysis. Thorax 2021; 76(10): 970–979. .
Tang N, Li D, Wang X, et al. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020; 18(4): 844–847. .
Thachil J. The protective rather than prothrombotic fibrinogen in COVID-19 and other inflammatory states. J Thromb Haemost. 2020; 18: 1849–1852.
Thachil J, Juffermans NP, Ranucci M, et al. ISTH DIC subcommittee communication on anticoagulation in COVID-19. J Thromb Haemost. 2020; 18: 2138–2144.
Thachil J, Tang N, Gando S, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020; 18: 1023–1026.
World Health Organization (WHO) Living guidance for clinical management of COVID-19: Living guidance, 23 November 2021 WHO/2019-nCoV/clinical/2021.2, https://who.int
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.
Wool GD, Miller JL. The impact of COVID-19 disease on platelets and coagulation. Pathobiology 2021; 88: 15–27. .
Zhang S, Li Y, Liu G, et al. Intermediate-to-therapeutic versus prophylactic anticoagulation for coagulopathy in hospitalized COVID-19 patents: a systemic review and metaanalysis. Thrombosis Journal 2021; 19: 91. https://doi.org/10.1186/s12959-021-00343-1