November30, 2022

Abstract Volume: 3 Issue: 1 ISSN:

Post-Acute-COVID-19-Illness Hematological Sequelae
Ruangrong Cheepsattayakorn1, Attapon Cheepsattayakorn 2,3*,Porntep  Siriwanarangsun3


1.Department  of  Pathology, Faculty  of  Medicine, Chiang  Mai  University, Chiang  Mai, Thailand.

2.10th  Zonal  Tuberculosis  and  Chest  Disease  Center, Chiang  Mai, Thailand.

3.Faculty  of  Medicine, Western  University, Pathumtani  Province, Thailand.

Corresponding Author: Attapon Cheepsattayakorn, 10th Zonal Tuberculosis  and  Chest  Disease  Center, 143  Sridornchai  Road  Changklan  Muang  Chiang  Mai  50100  Thailand.

Copy Right: © 2021 Attapon Cheepsattayakorn. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Received Date: June 17, 2021

Published date: July 01, 2021

Post-Acute-COVID-19-Illness Hematological Sequelae

A 2.5 % cumulative incidence of thrombosis, including ischemic stroke, intracardiac thrombus, segmental pulmonary embolism, and thrombosed arteriovenous fistula at 30 days (median duration of 23 days post-discharge) and a 3.7 % cumulative incidence of bleeding, mostly associated with mechanical falls at 30 days after hospital discharge were reported in 163 post-acute-COVID-19-illness patients from the US without post-hospital-discharge thromboprophylaxis [1]. Several previous retrospective studies in the UK revealed similar rates of venous thromboembolism (VTE) [2, 3]. A previous prospective study in Belgium in 102 post-acute-COVID-19-illness patients at 6 weeks post-hospital-discharge follow-up by assessing D-dimer levels and venous ultrasonography revealed that only one asymptomatic VTE event occurred among 8 % of subjects who received post-hospital-discharge [4]. Hypercoagulable state and hyper inflammation were consistent in COVID-19-related coagulopathy [5, 6], contributing to the disproportionately high rates of 20 %-30 % of thromboembolic events rather than bleeding events in the acute COVID-19 phase [7]. The severity and duration of a hyperinflammatory state with unknown persistence are probably associated with the risk of thromboembolic events in the post-acute-COVID-19-illness phase [8]. Release of pro-inflammatory cytokines [9], disruption of normal coagulation pathway [10], complement activation [11-13], neutrophil extracellular traps [12, 14, 15], endothelial injury [16, 17-19], platelet-leukocyte interactions and platelet activation [20-22], and hypoxia [23] are the proposed mechanisms of the thrombo-inflammation. These mechanisms are similar to the pathophysiology that are present in thrombotic microangiopathy syndromes [24]. CORE-19, CISCO-19, and CORONA-VTE are the larger ongoing studies that will assist in establishing thromboembolic complications in the post-acute-COVID-19-illness phase [ 25, 26]. Due to lacking the need to frequently monitor the therapeutic levels and the lower risk of drug-drug interactions, low-molecular-weight heparin and direct oral anticoagulants are preferred anticoagulation drugs over vitamin K antagonists [27, 28]. Similar to provoked VTE, for patients with imaging-confirmed VTE, at least 3 months of therapeutic anticoagulation is recommended [29, 30]. In addition to comorbidities, such as immobility and cancer, the elevation of D-dimer levels (higher than two times the upper limit of the normal value) may be a benefit to risk-stratify cases at the highest risk of post-acute-COVID-19-illness thrombosis [25, 27, 28, 31]. Aspirin, an alternative antiplatelet agent for COVID-19 or post-acute-COVID-19-illness thromboprophylaxis has not yet been defined and is presently studied in cases managed as outpatients [9]. In hospital-discharge-COVID-19 patients with outpatient management, extended post-hospital discharge, up to 6 weeks and prolonged primary thromboprophylaxis, up to 45 days may provide a more favorable risk-benefit ratio in COVID-19 with an increase in thrombotic events during the acute COVID-19 phase, and this is currently being studied [32, 33].

In conclusion, in addition to post-acute-COVID-19-illness primary thromboprophylaxis, when appropriate, ambulation and physical activity should be recommended to all patients.



1.Patell R, et al. “Post-discharge thrombosis and hemorrhage in patients with COVID-19”. Blood 2020; 136 : 1342-1346.  

2.Robert LN, et al. “Post-discharge venous thromboembolism following hospital admission with COVID-19”. Blood 2020; 136 : 1347-1350.

3.Salisbury R, et al. “Incidence of symptomatic, image-confirmed venous thromboembolism following hospitalization for COVID-19 with 90-day follow-up”. Blood Adv 2020; 4 : 6230-6239.  

4.Engelen M, et al. “Incidence of venous thromboembolism in patients discharged after COVID-19 hospitalization”. Res Pract Thromb Haemost 2021. Available at :[atients-discharged-after-covid-19-hospitalisation/ (accessed on May 28, 2021).  

5.Pavoni V, et al. “Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe COVID-19 pneumonia”. J Thromb Thrombolysis 2020; 50 : 281-286.

6.Chaudhary R, Kreutz RP, Bliden KP, Tantry US, Gurbel PA. “Personalizing antithrombotic therapy in COVID-19 : role of thromboelastography and thromboelastometry”. Thromb Haemost 2020; 120 : 1594-1596.

7.Connors JM, Levy JH. “COVID-19 and its implications for thrombosis and anticoagulation”. Blood 2020; 135 : 2033-2040.

8.Nalbandian A, Sehgal K, Gupta K, Madhavan MV, McGroder C, Stevens JS, et al. “Post-acute COVID-19 syndrome”. Nature Medicine 2021; 27 (April) : 601-615.  

9.Bikdeli B, et al. “Pharmacological agents targeting thromboinflammation in COVID-19 : review and implications for future research”. Thromb Haemost 2020; 120 : 1004-1024.

10.Nougier C, et al. “Hypofibrinolytic state and high thrombin generation may play a major role in SARS-CoV-2 associated thrombosis”. J Thromb Haemost 2020; 18 : 2215-2219.

11.Ramlall V, et al. “Immune complement and coagulation dysfunction in adverse outcomes of SARS-CoV-2 infection”. Nat Med 2020; 26 : 1609-1615.

12.Skendros P, et al. “Complement and tissue factor-enriched neutrophil extracellular traps are key drivers in COVID-19 imunothrombosis”. J Clin Invest 2020; 130 : 6151-6157.

13.Cugno M, et al. “Complement activation in patients with COVID-19 : a novel therapeutic target”. J Allergy Clin Immunol 2020; 146 : 215-217.

14.Middleton EA, et al. “Neutrophil extracellular traps (NETS) contribute to immunothrombosis in COVID-19 acute respiratory distress syndrome”. Blood 2020; 136 : 1169-1179.

15.Zuo Y, et al. “Neutrophil extracellular traps in COVID-19”. JCI Insight 2020; 5 : e138999.

16.Ackermann M, Verleden SE, Kuehnel M, Haverich A, Welte T, Laenger F, et al. “Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19”. N Engl J Med 2020; 383 : 120-128.

17.Varga Z, et al. “Endothelial cell infection and endotheliitis in COVID-19”. Lancet 2020; 395 : 1417-1418.

18.Goshuo G, et al. “Endotheliopathy in COVID-19-associated coagulopathy evidence from a single-center, cross-sectional study”. Lancet Haematol 2020; 7 : e575-e582.

19.Libby P, Lu?scher T. “COVID-19 is in the end, an endothelial disease”. Eur Heart J 2020; 41 : 3038-3044.

20.Hottz ED, et al. “Platelet activation and platelet-monocyte aggregates formation trigger tissue factor expression in severe COVID-19 patients”. Blood 2020; 136 : 1330-1341.

21.Manne BK, et al. “Platelet gene expression and function in COVID-19 patients”. Blood 2020; 136 : 1317-1329.

22.Barret TJ, et al. “Platelet and vascular biomarkers associate with thrombosis and death in coronavirus disease”. Circ Res 2020. DOI :

23.Thachil J. “Hypoxia-an overlooked trigger for thrombosis in COVID-19 and other critically ill patients”. J Thromb Haemost 2020; 18 : 3109-3110.

24.Merrill JT, Erkan D, Winakur J, James JA. “Emerging evidence of a COVID-19 thrombotic syndrome has treatment implications”. Nat Rev Rheumatol 2020; 16 : 581-589.

25.Spyropoulos AC, 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 : 1859-1865.

26.Mangion K, et al. “The Chief Scientist Office Cardiovascular and Pulmonary Imaging in SARS Coronavirus Disease-19 (CISCO-19) study”. Cardiovasc Res 2020; 2185-2196.

27.Bikdeli B, 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 : 2950-2973.

28.Barnes GD, et al. “Thromboembolism and anticoagulant therapy during the COVID-19 pandemic : interim clinical guidance from the anticoagulation forum”. J Thromb Thrombolysis 2020; 50 : 72-81.   

29.Bai C, et al. “Updated guidance on the management of COVID-19 : from an American Thoracic Society”/European Respiratory Society coordinated International Force (July 29, 2020). Eur Respir Rev 2020; 200287.

30.Moores LK, et al. “Prevention, diagnosis, and treatment of VTE in patients with coronavirus disease 2019 : CHEST Guidelines and Expert Panel report”. Chest 2020; 158 : 1143-1163.  

31.COVID-19 and VTE/Anticoagulation : Frequent Asked Questions (American Society of Hematology, 2020). Available at : (accessed on May 28, 2021).

32.Bajaj NS, et al. “Extended prophylaxis for venous thromboembolism after hospitalization for medical illness : a trial sequential and cumulative meta-analysis”. PLoS 2019; 16 : e1002797.

33.Chiasakul T, et al. “Extended vs standard-duration thromboprophylaxis in acutely ill medical patients : a systematic review and meta-analysis”. Thromb Res 2019; 184 : 58-61.