THROMBOCYTOPENIA AND COVID-19: DIFFERENTIAL DIAGNOSIS AND THERAPY

Keywords: thrombocytopenia, COVID-19, SARS-CoV-2, HIT, DIC

Abstract


Thrombocytopenia represents a common manifestation of COVID-19 with a prevalence of up to 35% in certain studies. A low platelet count is an unfavorable prognostic marker in SARS-CoV-2 infected patients. Despite a large number of publications dealing with the prognostic significance of thrombocytopenia in COVID-19, data regarding the differential diagnosis and therapy are scarce. The most common causes of thrombocytopenia in COVID-19 are shown in this review, namely: SARS-CoV-2-induced thrombocytopenia; disseminated intravascular coagulopathy (DIC); immune thrombocytopenia; drug-induced thrombocytopenia, with a special insight into heparin-induced thrombocytopenia (HIT). Although a majority of patients suffer from mild thrombocytopenia and do not require any particular treatment, there are some cases of severe thrombocytopenia which may cause life threatening bleeding. On the other hand, some forms of thrombocytopenia, such as DIC or HIT, carry a high risk of the development of thrombotic events, which is why anticoagulant prophylaxis is required in these patients. At the end of each section of this review, treatment recommendations are given for each aforementioned type of thrombocytopenia developing in COVID-19.

 

Author Biography

Mirjana Mitrovic, University Clinical Center of Serbia, Faculty of Medicine

University Clinical Center of Serbia, Clinic of Hematology, Belgrade, Serbia

University of Belgrade, Faculty of Medicine, Belgrade Serbia

References


  1. COVID-19 live update. Available at: https://www.worldometers.info/coronavirus/. [Accessed: 01.11.2021.]

  2. 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):834–847.

  3. Iba T, Levy J, Levi M, Connors JM, Thachil J. Coagulopathy of coronavirus disease 2019. Crit Care Med 2020; 48(9):1358-1364.

  4. Jiang S, Huang Q, Xie W, Lv C, Quan X. The association between severe COVID-19 and low platelet count: evidence from 31 observational studies involving 7613 participants. Br J Haematol 2020;190(1):e29-e33.

  5. Zong X, Gu Y, Yu H, Li Z, Wang Y. Thrombocytopenia Is Associated with COVID-19 Severity and Outcome: An Updated Meta-Analysis of 5637 Patients with Multiple Outcomes. Lab Med 2021;52(1):10-15.

  6. Xu P, Zhou Q, Xu J. Mechanism of thrombocytopenia in COVID-19 patients. Ann Hematol 2020;99(6):1205-1208.

  7. Tang XD, Ji TT, Dong JR, Feng H, Chen FQ, Chen X, et al. Pathogenesis and Treatment of Cytokine Storm Induced by Infectious Diseases. Int J Mol Sci 2021;22(23):13009.

  8. Delshad M, Safaroghli-Azar A, Pourbagheri-Sigaroodi A, Poopak B, Shokouhi S, Bashash D. Platelets in the perspective of COVID-19; pathophysiology of thrombocytopenia and its implication as prognostic and therapeutic opportunity. Int Immunopharmacol 2021;99:107995.

  9. Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest 2020;130(5):2620-2629.

  10. Zhang Y, Zeng X, Jiao Y, Li Z, Liu Q, Ye J, et al. Mechanisms involved in the development of thrombocytopenia in patients with COVID-19. Thromb Res 2020;193:110-115.

  11. Gu SX, Tyagi T, Jain K, Gu VW, Lee SH, Hwa JM, et al. Thrombocytopathy and endotheliopathy: crucial contributors to COVID-19 thromboinflammation. Nat Rev Cardiol 2021;18(3):194-209.

  12. Lefrançais E, Ortiz-Muñoz G, Caudrillier A, Mallavia B, Liu F, Sayah DM, et al. The lung is a site of platelet biogenesis and a reservoir for haematopoietic progenitors. Nature 2017;544(7648):105-109.

  13. Valdivia-Mazeyra MF, Salas C, Nieves-Alonso JM, Martín-Fragueiro L, Bárcena C, Muñoz-Hernández P, et al. Increased number of pulmonary megakaryocytes in COVID-19 patients with diffuse alveolar damage: an autopsy study with clinical correlation and review of the literature. Virchows Arch 2021;478(3):487-496.

  14. Mandal RV, Mark EJ, Kradin RL. Megakaryocytes and platelet homeostasis in diffuse alveolar damage. Exp Mol Pathol 2007;83(3):327-31.

  15. Battina HL, Alentado VJ, Srour EF, Moliterno AR, Kacena MA. Interaction of the inflammatory response and megakaryocytes in COVID-19 infection. Exp Hematol. 2021 Dec;104:32-39.

  16. Iba T, Connors JM, Levy JH. The coagulopathy, endotheliopathy, and vasculitis of COVID-19. Inflamm Res. 2020 Dec;69(12):1181-1189.

  17. Pelemis M, Stevanovic G, Turklov V, et al. National protocol for COVID-19 patients treatment, version 12. Belgrade (Serbia): Ministry of Health Republic of Serbia; 2020. [Internal report]. Unpublished.

  18. Wada H, Thachil J, Di Nisio M, Mathew P, Kurosawa S, Gando S, Kim, et al. Guidance for diagnosis and treatment of DIC from harmonization of the recommendations from three guidelines. J Thromb Haemost 2013;11:761–767.

  19. Iba T, Levy JH, Warkentin TE, Thachil J, van der Poll T, Levi M, et al. Diagnosis and management of sepsis-induced coagulopathy and disseminated intravascular coagulation. J Thromb Haemost 2019;17(11):1989-1994.

  20. 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(5):1023–1026.

  21. Rodeghiero F, Stasi R, Gernsheimer T, Michel M, Provan D, Arnold DM, et al. Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 2009;113(11):2386-93.

  22. Bhattacharjee S, Banerjee M. Immune Thrombocytopenia Secondary to COVID-19: a Systematic Review. SN Compr Clin Med 2020; 19:1-11.

  23. Mingot-Castellano ME, Alcalde-Mellado P, Pascual-Izquierdo C, Perez Rus G, Calo Pérez A, Martinez MP, et al. Incidence, characteristics and clinical profile of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in patients with pre-existing primary immune thrombocytopenia (ITP) in Spain. Br J Haematol 2021;194(3):537-541.

  24. Pantić N, Mitrović M, Virijević M, Sabljić N, Pravdić Z, Suvajdžić N. SARS-COV-2 infection in a patient with Evans syndrome: A silent enemy or an ally?. Vojnosanitetski pregled. 2020;77(12):1348-1350.

  25. de la Cruz-Benito B, Rivas-Pollmar MI, Álvarez Román MT, Trelles-Martínez R, Martín-Salces M, Lázaro-Del Campo P, et al. Paradoxical effect of SARS-CoV-2 infection in patients with immune thrombocytopenia. Br J Haematol2021;192(6):973-977.

  26. Pantic N, Suvajdzic-Vukovic N, Virijevic M, Pravdic Z, Sabljic N, Adzic-Vukicevic T, et al. Coronavirus disease 2019 in patients with chronic immune thrombocytopenia on thrombopoietin receptor agonists: new perspectives and old challenges. Blood Coagul Fibrinolysis. 2021; Epub ahead of print.

  27. Pantić N, Suvajdžić-Vuković N. Treating ITP: What are the options in the era of new guidelines and new drugs?.Medicinski podmladak 2020;71(4):40-6.

  28. Rodeghiero F, Cantoni S, Carli G, Carpenedo M, Carrai V, Chiurazzi F, et al. Practical Recommendations for the Management of Patients with ITP During the COVID-19 Pandemic. Mediterr J Hematol Infect Dis. 2021;13(1):e2021032.

  29. Pavord S, Thachil J, Hunt BJ, Murphy M, Lowe G, Laffan M, et al. Practical guidance for the management of adults with immune thrombocytopenia during the COVID-19 pandemic. Br J Haematol 2020;189(6):1038-1043.

  30. Suvajdžić-Vuković N, Miljić P, Mitrović M. Vodič za dijagnostiku i lečenje odraslih bolesnika sa ITP-om. Aktiv za ITP, SLD. Beograd, Srbija; 2016.

  31. Bakchoul T, Marini I. Drug-associated thrombocytopenia. Hematology Am Soc Hematol Educ Program.2018;2018(1):576-583.

  32. Coutre S, Crowther M. Management of heparin-induced thrombocytopenia. Up to date. [Accessed: Mart 2021.]

  33. Greinacher A. CLINICAL PRACTICE. Heparin-Induced Thrombocytopenia. N Engl J Med. 2015;373(3):252-61.

  34. Uaprasert N, Tangcheewinsirikul N, Rojnuckarin P, Patell R, Zwicker JI, Chiasakul T. Heparin-induced thrombocytopenia in patients with COVID-19: a systematic review and meta-analysis. Blood Adv 2021;5(21):4521-4534.

  35. Cuker A, Arepally GM, Chong BH, Cines DB, Greinacher A, Gruel Y, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv2018;2(22):3360-3392.

  36. Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S, et al. Treatment and prevention of heparin-induced thrombocytopenia: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012;141(2 Suppl):e495S-e530S.

Published
2022/03/24
Section
Reviews