Thrombotic Conditions in Patients with COVID-19: Dynamics of D-Dimer and Tactics of Anticoagulant Therapy

Keywords: pulmonary embolism, coronavirus disease 2019, D-dimer, venous thrombosis, arterial thrombosis, thromboprophylaxis, antiplatelet agents

Abstract

In patients with COVID-19, histological examination of the pulmonary vessels shows serious disorders (local thrombosis and microangiopathy), significantly different to those in the control group composed of patients with influenza. Some studies have shown that coronavirus enters cells by binding angiotensin-converting enzyme 2 which is found mainly on the alveolar epithelium and endothelium. The increase in D-dimer levels is typical for patients with COVID-19. Although many inflammatory processes can affect D-dimer levels, an increase in D-dimer during COVID-19 is more likely to indicate thrombosis.

The aim. To analyze the patients who have suffered from COVID-19 and to determine possible risk factors for the development of thrombotic complications and define the surgical or medical therapy tactics.

Material and methods. The study was conducted from October 2020 to April 2021 in Ukraine (Zaporizhzhia, Uzhhorod, Kherson and Kyiv). We analyzed 121 patients aged 46.9± 15.3 years, 64 (52.8%) men and 57 (47.1%) women. All the patients had positive PCR test for COVID-19. The changes in D-dimer were analyzed.

Results. Forty-one (33.9%) patients had thrombotic complications. Pulmonary embolism (PE) was diagnosed in 14 patients, deep vein thrombosis (DVT) in 17, acute stroke in 2 and peripheral artery thrombosis in 8 cases.

An increase in D-dimer level was observed in most patients and was not associated with clinical manifestations of thrombosis. At a D-dimer level of 11,000-10,564 ng/ml the patients had clinical symptoms of thrombotic condition which was confirmed by computed tomography or ultrasound examination. At an increase over 725-7000 ng/ml, there were no clinical signs of thrombosis.

We performed standard medical therapy in patients with PE and DVT. In case of arterial thrombosis open surgery was performed in 4 patients and direct catheter thrombolysis in 1 case.

Conclusion. In our opinion, anticoagulants should be prescribed for patients with a D-dimer level of more than 700 ng/ml. Full anticoagulation is prescribed for severe forms of COVID-19 or confirmed thrombosis. We didn’t find any correlation between the development of thrombotic complications in patients with COVID-19 and comorbidities, body mass index and other factors. Medical therapy was successful in all cases of PE and DVT, anticoagulants were prescribed for 1 year. Femoral artery thrombectomy was successfully performed in 4 patients. After direct catheter thrombolysis we got peripheral pulse. In all cases of arterial thrombosis, we prescribed anticoagulants for 2 months after discharge and acetylsalicylic acid for a long time.

References

  1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. https://doi.org/10.1016/S0140-6736(20)30183-5
  2. Chen N, Zhou M, Dong X, Qu J, Gong F, Han Y, Qiu Y, Wang J, Liu Y, Wei Y, Xia J, Yu T, Zhang X, Zhang L. Epidemiological and clinical characteristics of 99 cases of 2019 novel coronavirus pneumonia in Wuhan, China: a descriptive study. Lancet. 2020;395(10223):507-13. https://doi.org/10.1016/S0140-6736(20)30211-7
  3. Boulay F, Berthier F, Schoukroun G, Raybaut C, Gendreike Y, Blaive B. Seasonal variations in hospital admission for deep vein thrombosis and pulmonary embolism: analysis of discharge data. BMJ. 2001;323(7313):601-2. https://doi.org/10.1136/bmj.323.7313.601
  4. Woodhouse PR, Khaw KT, Plummer M, Foley A, Meade TW. Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease. Lancet. 1994;343(8895):435-9. https://doi.org/10.1016/s0140-6736(94)92689-1
  5. Varga Z, Flammer AJ, Steiger P, Haberecker M, Ruschitzka F, Moch H. Endothelial cell infection and endotheliitis in COVID-19. Lancet. 2020;395(10234):1417-8. https://doi.org/10.1016/S0140-6736(20)30937-5
  6. Léonard-Lorant I, Delabranche X, Séverac F, Helms J, Pauzet C, Collange O, Schneider F, Labani A, Bilbault P, Molière S, Leyendecker P, Roy C, Ohana M. Acute pulmonary embolism in patients with COVID-19 at CT angiography and relationship to D-dimer levels. Radiology. 2020;296(3):E189-E191. https://doi.org/10.1148/radiol.2020201561
  7. Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020;18(6):1421-4. https://doi.org/10.1111/jth.14830
  8. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, Xiang J, Wang Y, Song B, Gu X, Guan L, Wei Y, Li H, Wu X, Xu J, Tu S, Zhang Y, Chen H, Cao B. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet. 2020;395(10229):1054-62. https://doi.org/10.1016/S0140-6736(20)30566-3
  9. Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, Vanstapel A, Werlein C, Stark H, Tzankov A, Li WW, Li VW, Mentzer SJ, Jonigk D. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in Covid-19. N Engl J Med. 2020;383(2):120-8. https://doi.org/10.1056/NEJMoa2015432
  10. Marik P. EVMS critical care COVID-19 management protocol [Internet]. 2020; [cited 2022 Jan 9]. Available from: https://www.sbk-vs.de/images/pdf/downloads/Corona/EVMS_Critical_Care_COVID-19_Protocol.pdf
  11. Ejaz H, Alsrhani A, Zafar A, Javed H, Junaid K, Abdalla AE, Abosalif KOA, Ahmed Z, Younas S. COVID-19 and comorbidities: Deleterious impact on infected patients. J Infect Public Health. 2020;13(12):1833-9. https://doi.org/10.1016/j.jiph.2020.07.014
  12. Sanyaolu A, Okorie C, Marinkovic A, Patidar R, Younis K, Desai P, Hosein Z, Padda I, Mangat J, Altaf M. Comorbidity and its Impact on Patients with COVID-19. SN Compr Clin Med. 2020;2(8):1069-76. https://doi.org/10.1007/s42399-020-00363-4
  13. Chen G, Li X, Gong Z, Xia H, Wang Y, Wang X, Huang Y, Barajas-Martinez H, Hu D. Hypertension as a sequela in patients of SARS-CoV-2 infection. PLoS One. 2021;16(4):e0250815. https://doi.org/10.1371/journal.pone.0250815
  14. Shibata S, Arima H, Asayama K, Hoshide S, Ichihara A, Ishimitsu T, Kario K, Kishi T, Mogi M, Nishiyama A, Ohishi M, Ohkubo T, Tamura K, Tanaka M, Yamamoto E, Yamamoto K, Itoh H. Hypertension and related diseases in the era of COVID-19: a report from the Japanese Society of Hypertension Task Force on COVID-19. Hypertens Res. 2020;43(10):1028-46. https://doi.org/10.1038/s41440-020-0515-0
  15. Lim S, Bae JH, Kwon HS, Nauck MA. COVID-19 and diabetes mellitus: from pathophysiology to clinical mana gement. Nat Rev Endocrinol. 2021;17(1):11-30. https://doi.org/10.1038/s41574-020-00435-4
  16. Green I, Merzon E, Vinker S, Golan-Cohen A, Magen E. COVID-19 Susceptibility in Bronchial Asthma. J Allergy Clin Immunol Pract. 2021;9(2):684-92.e1. https://doi.org/10.1016/j.jaip.2020.11.020
  17. Wrapp D, Wang N, Corbett KS, Goldsmith JA, Hsieh CL, Abiona O, Graham BS, McLellan JS. Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation. Science. 2020;367(6483):1260-3. https://doi.org/10.1126/science.abb2507
  18. Hamming I, Timens W, Bulthuis ML, Lely AT, Navis G, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631-7. https://doi.org/10.1002/path.1570
  19. Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med. 2020;173(4):268-77. https://doi.org/10.7326/M20-2003
  20. Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA, Bouman CCS, Beenen LFM, Kootte RS, Heijmans J, Smits LP, Bonta PI, van Es N. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020;18(8):1995-2002. https://doi.org/10.1111/jth.14888
  21. Poissy J, Goutay J, Caplan M, Parmentier E, Duburcq T, Lassalle F, Jeanpierre E, Rauch A, Labreuche J, Susen S; Lille ICU Haemostasis COVID-19 Group. Pulmonary embolism in patients with COVID-19: awareness of an increased prevalence. Circulation. 2020;142(2):184-6. https://doi.org/10.1161/CIRCULATIONAHA.120.047430
  22. Grillet F, Behr J, Calame P, Aubry S, Delabrousse E. Acute pulmonary embolism associated with COVID-19 pneumonia detected with pulmonary CT angiography. Radiology. 2020;296(3):E186-8. https://doi.org/10.1148/radiol.2020201544
  23. Starko KM. Salicylates and Pandemic Influenza Mortality, 1918-1919 Pharmacology, Pathology, and Historic Evidence. Clin Infect Dis. 2009;49(9):1405-10. https://doi.org/10.1086/606060
  24. Jefferies S, Weatherall M, Young P, Eyers S, Perrin KG, Beasley CR. The Effect of Antipyretic Medications on Mortality in Critically Ill Patients with Infection: A Systematic Review and Meta-analysis. Crit Care Resusc. 2011;13(2):125-31.
  25. McGonagle D, O’Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol. 2020;2(7):e437-45. https://doi.org/10.1016/S2665-9913(20)30121-1
  26. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-98. https://doi.org/10.1007/s00134-020-06062-x
  27. Harzallah I, Debliquis A, Drénou B. Lupus anticoagulant is frequent in patients with Covid-19. J Thromb Haemost. 2020;18(8):2064-5. https://doi.org/10.1111/jth.14867
  28. Grimmer B, Kuebler WM. The endothelium in hypoxic pulmonary vasoconstriction. J Appl Physiol. 2017;123(6):1635-46. https://doi.org/10.1152/japplphysiol.00120.2017
  29. Medcalf RL, Keragala CB, Myles PS. Fibrinolysis and COVID-19: A plasmin paradox. J Thromb Haemost. 2020;18(9):2118-22. https://doi.org/10.1111/jth.14960
  30. Panigada M, Bottino N, Tagliabue 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(7):1738-42. https://doi.org/10.1111/jth.14850
  31. Tang N, Bai H, Chen X, Gong J, Li D, Sun Z. Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy. J Thromb Haemost. 2020;18(5):1094-9. https://doi.org/10.1111/jth.14817
  32. Sadeghipour P, Talasaz AH, Rashidi F, Sharif-Kashani B, Beigmohammadi MT, Farrokhpour M, et al. 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(16):1620-30. https://doi.org/10.1001/jama.2021.4152
  33. Berger JS, Connors JM. Anticoagulation in COVID-19: reaction to the ACTION trial. Lancet. 2021;397(10291):2226-8. https://doi.org/10.1016/S0140-6736(21)01291-5
  34. Fournier M, Faille D, Dossier A, Mageau A, Nicaise Roland P, Ajzenberg N, et al. Arterial Thrombotic Events in Adult In-patients With COVID-19. Mayo Clin Proc. 2021;96(2):295-303. https://doi.org/10.1016/j.mayocp.2020.11.018
  35. Etkin Y, Conway AM, Silpe J, Qato K, Carroccio A, Manvar-Singh P, Giangola G, Deitch JS, Davila-Santini L, Schor JA, Singh K, Mussa FF, Landis GS. Acute Arterial Thromboembolism in Patients with COVID-19 in the New York City Area. Ann Vasc Surg. 2021;70:290-4. https://doi.org/10.1016/j.avsg.2020.08.085
Published
2022-03-23
How to Cite
Nykonenko, A. O., Podluzhniy, H. S., Koliada, N. A., Levchak, Y. A., Hardubey, Y. Y., Zubryk, I. V., Naumova, O. O., Nykonenko, O. S., Horlenko, F. V., Matvieiev, S. O., & Riabokon, O. V. (2022). Thrombotic Conditions in Patients with COVID-19: Dynamics of D-Dimer and Tactics of Anticoagulant Therapy. Ukrainian Journal of Cardiovascular Surgery, 30(1), 64-70. https://doi.org/10.30702/ujcvs/22.30(01)/NP010-6470
Section
GENERAL ISSUES OF TREATMENT OF PATIENTS WITH CARDIOVASCULAR PATHOLOGY