Top

Published in:

01-10-2020 | Disseminated Intravascular Coagulation | Review Article

Management of Thrombotic Complications in COVID-19: An Update

Authors: Adrija Hajra, Sheetal Vasundara Mathai, Somedeb Ball, Dhrubajyoti Bandyopadhyay, Maedeh Veyseh, Sandipan Chakraborty, Carl J. Lavie, Wilbert S. Aronow

Published in: Drugs | Issue 15/2020

Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV‑2), is now a global pandemic. This virus primarily affects the respiratory tract and causes lung injury characterized by acute respiratory distress syndrome. Although the pathophysiology of COVID-19 is not yet clear, the most widely accepted mechanism is systemic inflammation. A clinically significant effect of the inflammation is coagulopathy. As a result of this effect, patients are found to have a high risk of venous thromboembolism. Studies have reported a high incidence of thrombotic complications in critically ill patients with COVID-19. In this review, we discuss the most updated evidence on the pathophysiology, diagnosis, and treatment of the coagulopathy of COVID-19. Prophylactic anticoagulation is recommended for all in-patients with COVID-19. Those with a higher risk of developing thromboembolic events or who have already developed venous thromboembolism should be treated with therapeutic anticoagulation. We also discuss post-discharge prophylaxis for high-risk patients and some newly proposed treatments for the hypercoagulability that could improve the outcomes of the affected patients.

Center for Disease Control (CDC). Cases in the US. Available from: https://www.cdc.gov/coronavirus/2019-ncov/cases-updates/cases-in-us.html. Accessed 10 June 2020.

Terpos E, Ntanasis-Stathopoulos I, Elalamy I, Kastritis E, Sergentanis TN, Politou M, et al. Hematological findings and complications of COVID-19. Am J Hematol. 2020;95(7):834–47. https://doi.org/10.1002/ajh.25829.CrossRefPubMed

Cattaneo M, Bertinato EM, Birocchi S, Brizio C, Malavolta D, Manzoni M, et al. Pulmonary embolism or pulmonary thrombosis in COVID-19? Is the recommendation to use high-dose heparin for thromboprophylaxis justified? Thromb Haemost. 2020. https://doi.org/10.1055/s-0040-1712097.CrossRefPubMedPubMedCentral

Connors JM, Levy JH. COVID-19 and its implications for thrombosis and anticoagulation. Blood. 2020;135(23):2033–40.CrossRef

Klok FA, Kruip MJ, Van Der Meer NJ, Arbous MS, Gommers D, Kant KM, et al. Confirmation of the high cumulative incidence of thrombotic complications in critically ill ICU patients with COVID-19: an updated analysis. Thromb Res. 2020. https://doi.org/10.1016/j.thromres.2020.04.041.CrossRefPubMedPubMedCentral

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. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14872.CrossRefPubMedPubMedCentral

Ranucci M, Ballotta A, Di Dedda U, Bayshnikova E, Dei Poli M, Resta M, et al. The procoagulant pattern of patients with COVID-19 acute respiratory distress syndrome. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14854.CrossRefPubMedPubMedCentral

Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844–7.CrossRef

Lodigiani C, Iapichino G, Carenzo L, Cecconi M, Ferrazzi P, Sebastian T, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan. Italy Thromb Res. 2020. https://doi.org/10.1016/j.thromres.2020.04.024.CrossRefPubMed

10.

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.CrossRefPubMed

11.

Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MC, et al. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14888.CrossRefPubMedPubMedCentral

12.

Grillet F, Behr J, Calame P, Aubry S, Delabrousse E. Acute pulmonary embolism associated with COVID-19 pneumonia detected by pulmonary CT angiography. Radiology. 2020. https://doi.org/10.1148/radiol.2020201544.CrossRefPubMedPubMedCentral

13.

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. https://doi.org/10.1111/jth.14830.CrossRefPubMedPubMedCentral

14.

Thomas W, Varley J, Johnston A, Symington E, Robinson M, Sheares K, et al. Thrombotic complications of patients admitted to intensive care with COVID-19 at a teaching hospital in the United Kingdom. Thromb Res. 2020;191:76–7.CrossRef

15.

Leonard-Lorant I, Delabranche X, Severac F, Helms J, Pauzet C, Collange O, et al. Acute pulmonary embolism in COVID-19 patients on CT angiography and relationship to d-dimer levels. Radiology. 2020. https://doi.org/10.1148/radiol.2020201561.CrossRefPubMedPubMedCentral

16.

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 Internal Med. 2020. https://doi.org/10.7326/M20-2003.CrossRef

17.

Magro C, Mulvey JJ, Berlin D, Nuovo G, Salvatore S, Harp J, et al. Complement associated microvascular injury and thrombosis in the pathogenesis of severe COVID-19 infection: a report of five cases. Transl Res. 2020. https://doi.org/10.1016/j.trsl.2020.04.007.CrossRefPubMedPubMedCentral

18.

Zuo Y, Yalavarthi S, Shi H, Gockman K, Zuo M, Madison JA, et al. Neutrophil extracellular traps in COVID-19. JCI Insight. 2020. https://doi.org/10.1172/jci.insight.138999.CrossRefPubMedPubMedCentral

19.

Levi M, van der Poll T. Coagulation and sepsis. Thromb Res. 2017;149:38–44.CrossRef

20.

Ten VS, Pinsky DJ. Endothelial response to hypoxia: physiologic adaptation and pathologic dysfunction. Curr Opin Crit Care. 2002;8(3):242–50.CrossRef

21.

Iba T, Levy JH, Levi M, Connors JM, Thachil J. Coagulopathy of coronavirus disease 2019. Crit Care Med. 2020. https://doi.org/10.1097/CCM.0000000000004458.CrossRefPubMedPubMedCentral

22.

McGonagle D, O’Donnell JS, Sharif K, Emery P, Bridgewood C. Immune mechanisms of pulmonary intravascular coagulopathy in COVID-19 pneumonia. Lancet Rheumatol. 2020. https://doi.org/10.1016/S2665-9913(20)30121-1.CrossRefPubMedPubMedCentral

23.

Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: incidence, pathophysiology, and management. Thromb Res. 2020;194:101–15. https://doi.org/10.1016/j.thromres.2020.06.029.CrossRefPubMedPubMedCentral

24.

Bösmüller H, Traxler S, Bitzer M, Häberle H, Raiser W, Nann D, et al. The evolution of pulmonary pathology in fatal COVID-19 disease: an autopsy study with clinical correlation. Virchows Arch. 2020. https://doi.org/10.1007/s00428-020-02881-x.CrossRefPubMedPubMedCentral

25.

Yu B, Li X, Chen J, Ouyang M, Zhang H, Zhao X, et al. Evaluation of variation in d-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis. J Thromb Thrombolysis. 2020. https://doi.org/10.1007/s11239-020-02171-y.CrossRefPubMedPubMedCentral

26.

Macciò A, Madeddu C, Caocci G, La Nasa G. Multifactorial pathogenesis of COVID-19-related coagulopathy: can defibrotide have a role in the early phases of coagulation disorders? J Thromb Haemost. 2020. https://doi.org/10.1111/jth.15021.CrossRefPubMedPubMedCentral

27.

Wang T, Chen R, Liu C, Liang W, Guan W, Tang R, et al. Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19. Lancet Haematol. 2020;7(5):e362–e363363.CrossRef

28.

Available from: https://emergencymedicinecases.com/wp-content/uploads/2020/04/COVID-19-Anticoagulation-Algorithm-version_final_1.1.pdf. Accessed 10 June 2020.

29.

Available from: https://www.massgeneral.org/assets/MGH/pdf/news/coronavirus/guidance-from-mass-general-hematology.pdf. Accessed 10 June 2020.

30.

Bikdeli B, Madhavan MV, Jimenez D, Chuich T, Dreyfus I, Driggin E, et al. COVID-19 and thrombotic or thromboembolic disease: implications for prevention, antithrombotic therapy, and follow-up. J Am Coll Cardiol. 2020;75(23):2950–73.CrossRef

31.

Zhai Z, Li C, Chen Y, Gerotziafas G, Zhang Z, Wan J, et al. Prevention and treatment of venous thromboembolism associated with coronavirus disease 2019 infection: a consensus statement before guidelines. Thromb Haemost. 2020;120(06):937–48. https://doi.org/10.1055/s-0040-1710019.CrossRefPubMedPubMedCentral

32.

Obi AT, Barnes GD, Wakefield TW, Eliason JL, Arndt E, Henke PK. Practical diagnosis and treatment of suspected venous thromboembolism during COVID-19 pandemic. J Vasc Surg Venous Lymphat Disord. 2020;8(4):526–34. https://doi.org/10.1016/j.jvsv.2020.04.009.CrossRefPubMedPubMedCentral

33.

NIH. Coronavirus disease 2019 (COVID-19) treatment guidelines. Available from: https://files.covid19treatmentguidelines.nih.gov/guidelines/covid19treatmentguidelines.pdf. Accessed 12 June 2020.

34.

Fogarty H, Townsend L, Ni Cheallaigh C, Bergin C, Martin-Loeches I, Browne P, et al. COVID-19 coagulopathy in Caucasian patients. Br J Haematol. 2020. https://doi.org/10.1111/bjh.16749.CrossRefPubMedPubMedCentral

35.

Han H, Yang L, Liu R, Liu F, Wu KL, Li J, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020. https://doi.org/10.1515/cclm-2020-0188.CrossRefPubMed

36.

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.CrossRefPubMedPubMedCentral

37.

Panigada M, Bottino N, Tagliabue P, Grasselli G, Novembrino C, Chantarangkul V, 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. https://doi.org/10.1111/jth.14850.CrossRefPubMed

38.

Bandyopadhyay D, Akhtar T, Hajra A, Gupta M, Das A, Chakraborty S, et al. COVID-19 pandemic: cardiovascular complications and future implications. Am J Cardiovasc Drugs. 2020. https://doi.org/10.1007/s40256-020-00420-2.CrossRefPubMedPubMedCentral

39.

Moores LK, Tritschler T, Brosnahan S, Carrier M, Collen JF, Doerschug K, et al. Prevention, diagnosis and treatment of venous thromboembolism in patients with COVID-19: CHEST Guideline and Expert Panel Report. Chest. 2020. https://doi.org/10.1016/j.chest.2020.05.559.CrossRefPubMedPubMedCentral

40.

Fischer EA, Kinnear B, Sall D, Kelleher M, Sanchez O, Mathews B, et al. Hospitalist-operated compression ultrasonography: a point-of-care ultrasound study (HOCUS-POCUS). J Gen Intern Med. 2019;34(10):2062–7.CrossRef

41.

Tak T, Karturi S, Sharma U, Eckstein L, Poterucha JT, Sandoval Y. Acute pulmonary embolism: contemporary approach to diagnosis, risk-stratification, and management. Int J Angiol. 2019;28(2):100–11. https://doi.org/10.1055/s-0039-1692636.CrossRefPubMedPubMedCentral

42.

Zhu R, Ma XC. Clinical value of ultrasonography in diagnosis of pulmonary embolism in critically ill patients. J Transl Intern Med. 2017;5(4):200–4.CrossRef

43.

Buonsenso D, Raffaelli F, Tamburrini E, Biasucci DG, Salvi S, Smargiassi A, et al. Clinical role of lung ultrasound for the diagnosis and monitoring of COVID-19 pneumonia in pregnant women. Ultrasound Obstet Gynecol. 2020. https://doi.org/10.1002/uog.22055.CrossRefPubMedPubMedCentral

44.

American Society of Hematology. COVID-19 and VTE/anticoagulation: frequently asked questions. Available from: https://www.hematology.org/covid-19/covid-19-and-vte-anticoagulation. Accessed 13 June 2020.

45.

Rotzinger DC, Beigelman-Aubry C, von Garnier C, Qanadli SD. Pulmonary embolism in patients with COVID-19: time to change the paradigm of computed tomography. Thromb Res. 2020;190:58–9. https://doi.org/10.1016/j.thromres.2020.04.011.CrossRefPubMedPubMedCentral

46.

Thachil J, Tang N, Gando S, Falanga A, Cattaneo M, Levi M, et al. ISTH interim guidance on recognition and management of coagulopathy in COVID-19. J Thromb Haemost. 2020;18:1023–6. https://doi.org/10.1111/jth.14810.CrossRefPubMed

47.

Poterucha TJ, Libby P, Goldhaber SZ. More than an anticoagulant: do heparins have direct anti-inflammatory effects? Thromb Haemost. 2017;117(03):437–44.CrossRef

48.

Thachil J. The versatile heparin in COVID-19. J Thromb Haemost. 2020;18(5):1020–2. https://doi.org/10.1111/jth.14821.CrossRefPubMed

49.

Barrett CD, Moore HB, Yaffe MB, Moore EE. ISTH interim guidance on recognition and management of coagulopathy in COVID-19: a comment. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14860.CrossRefPubMedPubMedCentral

50.

Wang TF, Milligan PE, Wong CA, Deal EN, Thoelke MS, Gage BF. Efficacy and safety of high dose thromboprophylaxis in morbidly obese inpatients. Thromb Haemost. 2014;111(1):88–93. https://doi.org/10.1160/TH13-01-0042.CrossRefPubMed

51.

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.CrossRefPubMed

52.

NIH. Antithrombotic therapy in patients with COVID-19. Last updated: May 12, 2020. Available from: https://www.covid19treatmentguidelines.nih.gov/antithrombotic-therapy/. Accessed 8 June 2020.

53.

White D, MacDonald S, Bull T, Hayman M, de Monteverde-Robb R, Sapsford D, et al. Heparin resistance in COVID-19 patients in the intensive care unit. J Thromb Thrombolysis. 2020. https://doi.org/10.1007/s11239-020-02145-0.CrossRefPubMedPubMedCentral

54.

Hardaway RM, Williams CH, Marvasti M, et al. Prevention of adult respiratory distress syndrome with plasminogen activator in pigs. Crit Care Med. 1990;18:1413–8.CrossRef

55.

Wang J, Hajizadeh N, Moore EE, et al. Tissue plasminogen activator (tPA) treatment for COVID-19 associated acute respiratory distress syndrome (ARDS): a case series. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14828.CrossRefPubMedPubMedCentral

56.

Thachil J, Tang N, Gando S, et al. DOACs and “newer” haemophilia therapies in COVID-19. J Thromb Haemost. 2020. https://doi.org/10.1111/jth.14841.CrossRefPubMedPubMedCentral

57.

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. https://doi.org/10.1007/s11739-020-02331-1.CrossRefPubMedPubMedCentral

58.

Testa S, Prandoni P, Paoletti O, Morandini R, Tala M, Dellanoce C, et al. Direct oral anticoagulant plasma levels’ striking increase in severe COVID-19 respiratory syndrome patients treated with antiviral agents: the Cremona experience. J Thromb Haemost. 2020;18:1320–3. https://doi.org/10.1111/jth.14871.CrossRefPubMed

59.

Asakura H, Ogawa H. Potential of heparin and nafamostat combination therapy for COVID-19. J Thromb Haemost. 2020;18(6):1521–2. https://doi.org/10.1111/jth.14858.CrossRefPubMed

60.

Jang S, Rhee JY. Three cases of treatment with nafamostat in elderly patients with COVID-19 pneumonia who need oxygen therapy. Int J Infect Dis. 2020. https://doi.org/10.1016/j.ijid.2020.05.072.CrossRefPubMedPubMedCentral

61.

Magro G. COVID-19: review on latest available drugs and therapies against SARS-CoV-2. Coagulation and inflammation cross-talking. Virus Res. 2020;286:198070. https://doi.org/10.1016/j.virusres.2020.198070.CrossRefPubMedPubMedCentral

62.

Ucciferri C, Auricchio A, Di Nicola M, Potere N, Abbate A, Cipollone F, et al. Canakinumab in a subgroup of patients with COVID-19. Lancet Rheumatol. 2020. https://doi.org/10.1016/S2665-9913(20)30167-3.CrossRefPubMedPubMedCentral

63.

Dominguez-Erquicia P, Dobarro D, Raposeiras-Roubín S, Bastos-Fernandez G, Iñiguez-Romo A. Multivessel coronary thrombosis in a patient with COVID-19 pneumonia. Eur Heart J. 2020;41(22):2132. https://doi.org/10.1093/eurheartj/ehaa393.CrossRefPubMed

64.

Lacour T, Semaan C, Genet T, Ivanes F. Insights for increased risk of failed fibrinolytic therapy and stent thrombosis associated with COVID-19 in ST-segment elevation myocardial infarction patients. Catheter Cardiovasc Interv. 2020. https://doi.org/10.1002/ccd.28948.CrossRefPubMedPubMedCentral

65.

Omarjee L, Meilhac O, Perrot F, Janin A, Mahe G. Can ticagrelor be used to prevent sepsis-induced coagulopathy in COVID-19? Clin Immunol. 2020;216:108468. https://doi.org/10.1016/j.clim.2020.108468.CrossRefPubMedPubMedCentral

Title: Management of Thrombotic Complications in COVID-19: An Update
Authors: Adrija Hajra
Sheetal Vasundara Mathai
Somedeb Ball
Dhrubajyoti Bandyopadhyay
Maedeh Veyseh
Sandipan Chakraborty
Carl J. Lavie
Wilbert S. Aronow
Publication date: 01-10-2020
Publisher: Springer International Publishing
Keywords: Disseminated Intravascular Coagulation
Phlebothrombosis
Acute Respiratory Distress-Syndrome
COVID-19
Heparin
Published in: Drugs / Issue 15/2020
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI: https://doi.org/10.1007/s40265-020-01377-x

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Management of Thrombotic Complications in COVID-19: An Update

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 15/2020

Atezolizumab: A Review in Extensive-Stage SCLC

Bulevirtide: First Approval

Movement of Poly-ADP Ribose (PARP) Inhibition into Frontline Treatment of Ovarian Cancer

Non-Opioid Treatments for Opioid Use Disorder: Rationales and Data to Date

Belantamab Mafodotin: First Approval

Assessment of Cardiovascular Safety of Anti-Osteoporosis Drugs