Guidelines interpretation of the ISTH guidelines for antithrombotic treatment in COVID-19_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LI Zhichao , CHEN Zuoguan ,  LI Yongjun

Department of Vascular Surgery, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine Chinese Academy of Medical Sciences, Beijing 100730, P. R. China;

Corresponding author：

LI Yongjun, Email: liyongjun4679@bjhmoh.cn

Keywords：

the International Society on Thrombosis and Hemostasis guidelines for antithrombotic treatment in COVID-19; interpretation; antithrombotic treatment; COVID-19

DOI：

10.7507/1007-9424.202302033

Video：

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The International Society on Thrombosis and Hemostasis (ISTH) recently released the first ISTH guideline for antithrombotic treatment of COVID-19, which provides recommendations on anticoagulant and antiplatelet agents for patients with COVID-19 in different clinical settings. The target audience includes clinicians in internal medicine, intensive care, infectious diseases, hematology, vascular medicine, residents, family physicians, and other health care providers providing inpatient or outpatient care to COVID-19 patients. This article interprets the important parts of ISTH guideline.

Citation： LI Zhichao, CHEN Zuoguan, LI Yongjun. Guidelines interpretation of the ISTH guidelines for antithrombotic treatment in COVID-19. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(5): 534-538. doi: 10.7507/1007-9424.202302033 Copy

1.	Schulman S, Sholzberg M, Spyropoulos AC, et al. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost, 2022, 20(10): 2214-2225.
2.	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.
3.	Flam B, Wintzell V, Ludvigsson JF, et al. Direct oral anticoagulant use and risk of severe COVID-19. J Intern Med, 2021, 289(3): 411-419.
4.	Rivera-Caravaca JM, Buckley BJR, Harrison SL, et al. Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes. Thromb Res, 2021, 205: 1-7.
5.	Gonzalez-Ochoa AJ, Raffetto JD, Hernández AG, et al. Sulodexide in the treatment of patients with early stages of covid-19: a randomized controlled trial. Thromb Haemost, 2021, 121(7): 944-954.
6.	Hozayen SM, Zychowski D, Benson S, et al. Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients. EClinicalMedicine, 2021, 41: 101139. doi: 10.1016/j.eclinm.2021.101139.
7.	Battistoni I, Francioni M, Morici N, et al. Pre- and in-hospital anticoagulation therapy in coronavirus disease 2019 patients: a propensity-matched analysis of in-hospital outcomes. J Cardiovasc Med (Hagerstown), 2022, 23(4): 264-271.
8.	Di Castelnuovo A, Costanzo S, Antinori A, et al. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicenter Italian CORIST study. Thromb Haemost, 2021, 121(8): 1054-1065.
9.	Ionescu F, Jaiyesimi I, Petrescu I, et al. Association of anticoagulation dose and survival in hospitalized COVID-19 patients: a retrospective propensity score-weighted analysis. Eur J Haematol, 2021, 106(2): 165-174.
10.	Pereyra D, Heber S, Schrottmaier WC, et al. Low-molecular-weight heparin use in coronavirus disease 2019 is associated with curtailed viral persistence: a retrospective multicentre observational study. Cardiovasc Res, 2021, 117(14): 2807-2820.
11.	Poli D, Antonucci E, Ageno W, et al. Low in-hospital mortality rate in patients with COVID-19 receiving thromboprophylaxis: data from the multicentre observational START-COVID Register. Intern Emerg Med, 2022, 17(4): 1013-1021.
12.	Rentsch CT, Beckman JA, Tomlinson L, et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ, 2021, 372: n311. doi: 10.1136/bmj.n311.
13.	Shen L, Qiu L, Liu D, et al. The association of low molecular weight heparin use and in-hospital mortality among patients hospitalized with COVID-19. Cardiovasc Drugs Ther, 2022, 36(1): 113-120.
14.	Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost, 2010, 8(11): 2450-2457.
15.	Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost, 2006, 4(4): 915-916.
16.	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(1): e56-e65.
17.	RECOVERY Collaborative Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet, 2022, 399(10320): 143-151.
18.	Berger JS, Kornblith LZ, Gong MN, et al. Effect of P2Y12 inhibitors on survival free of organ support among non-critically ill hospitalized patients with COVID-19: a randomized clinical trial. JAMA, 2022, 327(3): 227-236.
19.	Lopes RD, de Barros E Silva PGM, Furtado RHM, et al. 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(10291): 2253-2263.
20.	Cohen SL, Gianos E, Barish MA, et al. Prevalence and predictors of venous thromboembolism or mortality in hospitalized COVID-19 patients. Thromb Haemost, 2021, 121(8): 1043-1053.
21.	ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, et al. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med, 2021, 385(9): 790-802.
22.	Sholzberg M, da Costa BR, Tang GH, et al. Randomized trials of therapeutic heparin for COVID-19: a meta-analysis. Res Pract Thromb Haemost, 2021, 5(8): e12638.
23.	Sholzberg M, Tang GH, Rahhal H, et al. Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ, 2021, 375: n2400. doi: 10.1136/bmj.n2400.
24.	Spyropoulos AC, Goldin M, Giannis D, et al. Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19: the HEP-COVID randomized clinical trial. JAMA Intern Med, 2021, 181(12): 1612-1620.
25.	Gonzalez-Porras JR, Belhassen-Garcia M, Lopez-Bernus A, et al. Low molecular weight heparin is useful in adult COVID-19 inpatients. Experience during the first Spanish wave: observational study. Sao Paulo Med J, 2022, 140(1): 123-133.
26.	Meizlish ML, Goshua G, Liu Y, et al. Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis. Am J Hematol, 2021, 96(4): 471-479.
27.	Morici N, Podda G, Birocchi S, et al. Enoxaparin for thromboprophylaxis in hospitalized COVID-19 patients: the X-COVID-19 randomized trial. Eur J Clin Invest, 2022, 52(5): e13735. doi: 10.1111/eci.13735.
28.	Smadja DM, Bonnet G, Gendron N, et al. Intermediate- vs. standard-dose prophylactic anticoagulation in patients with COVID-19 admitted in medical ward: a propensity score-matched cohort study. Front Med (Lausanne), 2021, 8: 747527.
29.	Spyropoulos AC, Connors JM, Douketis JD, et al. Good practice statements for antithrombotic therapy in the management of COVID-19: guidance from the SSC of the ISTH. J Thromb Haemost, 2022, 20(10): 2226-2236.
30.	Bikdeli B, Talasaz AH, Rashidi F, et al. Intermediate-dose versus standard-dose prophylactic anticoagulation in patients with COVID-19 admitted to the intensive care unit: 90-day results from the INSPIRATION randomized trial. Thromb Haemost, 2022, 122(1): 131-141.
31.	Perepu US, Chambers I, Wahab A, et al. Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: a multi-center, open-label, randomized controlled trial. J Thromb Haemost, 2021, 19(9): 2225-2234.
32.	Sadeghipour P, Talasaz AH, Rashidi F, 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): 1620-1630.
33.	PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group; Cook D, Meade M, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med, 2011, 364(14): 1305-1314.
34.	Schünemann HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv, 2018, 2(22): 3198-3225.
35.	REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, et al. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med, 2021, 385(9): 777-789.
36.	Oliynyk O, Barg W, Slifirczyk A, et al. Comparison of the effect of unfractionated heparin and enoxaparin sodium at different doses on the course of COVID-19-associated coagulopathy. Life (Basel), 2021, 11(10): 1032. doi: 10.3390/life11101032.
37.	REMAP-CAP Writing Committee for the REMAP-CAP Investigators; Bradbury CA, Lawler PR, et al. Effect of antiplatelet therapy on survival and organ support-free days in critically ill patients with COVID-19: a randomized clinical trial. JAMA, 2022, 327(13): 1247-1259.
38.	Giannis D, Allen SL, Tsang J, et al. Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry. Blood, 2021, 137(20): 2838-2847.
39.	Lui DTW, Li YK, Lee CH, et al. A prospective study of the impact of glycaemic status on clinical outcomes and anti-SARS-CoV-2 antibody responses among patients with predominantly non-severe COVID-19. Diabetes Res Clin Pract, 2022, 185: 109232. doi: 10.1016/j.diabres.2022.109232.
40.	Ramacciotti E, Barile Agati L, Calderaro D, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet, 2022, 399(10319): 50-59.

1. Schulman S, Sholzberg M, Spyropoulos AC, et al. ISTH guidelines for antithrombotic treatment in COVID-19. J Thromb Haemost, 2022, 20(10): 2214-2225.
2. 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.
3. Flam B, Wintzell V, Ludvigsson JF, et al. Direct oral anticoagulant use and risk of severe COVID-19. J Intern Med, 2021, 289(3): 411-419.
4. Rivera-Caravaca JM, Buckley BJR, Harrison SL, et al. Direct-acting oral anticoagulants use prior to COVID-19 diagnosis and associations with 30-day clinical outcomes. Thromb Res, 2021, 205: 1-7.
5. Gonzalez-Ochoa AJ, Raffetto JD, Hernández AG, et al. Sulodexide in the treatment of patients with early stages of covid-19: a randomized controlled trial. Thromb Haemost, 2021, 121(7): 944-954.
6. Hozayen SM, Zychowski D, Benson S, et al. Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients. EClinicalMedicine, 2021, 41: 101139. doi: 10.1016/j.eclinm.2021.101139.
7. Battistoni I, Francioni M, Morici N, et al. Pre- and in-hospital anticoagulation therapy in coronavirus disease 2019 patients: a propensity-matched analysis of in-hospital outcomes. J Cardiovasc Med (Hagerstown), 2022, 23(4): 264-271.
8. Di Castelnuovo A, Costanzo S, Antinori A, et al. Heparin in COVID-19 patients is associated with reduced in-hospital mortality: the multicenter Italian CORIST study. Thromb Haemost, 2021, 121(8): 1054-1065.
9. Ionescu F, Jaiyesimi I, Petrescu I, et al. Association of anticoagulation dose and survival in hospitalized COVID-19 patients: a retrospective propensity score-weighted analysis. Eur J Haematol, 2021, 106(2): 165-174.
10. Pereyra D, Heber S, Schrottmaier WC, et al. Low-molecular-weight heparin use in coronavirus disease 2019 is associated with curtailed viral persistence: a retrospective multicentre observational study. Cardiovasc Res, 2021, 117(14): 2807-2820.
11. Poli D, Antonucci E, Ageno W, et al. Low in-hospital mortality rate in patients with COVID-19 receiving thromboprophylaxis: data from the multicentre observational START-COVID Register. Intern Emerg Med, 2022, 17(4): 1013-1021.
12. Rentsch CT, Beckman JA, Tomlinson L, et al. Early initiation of prophylactic anticoagulation for prevention of coronavirus disease 2019 mortality in patients admitted to hospital in the United States: cohort study. BMJ, 2021, 372: n311. doi: 10.1136/bmj.n311.
13. Shen L, Qiu L, Liu D, et al. The association of low molecular weight heparin use and in-hospital mortality among patients hospitalized with COVID-19. Cardiovasc Drugs Ther, 2022, 36(1): 113-120.
14. Barbar S, Noventa F, Rossetto V, et al. A risk assessment model for the identification of hospitalized medical patients at risk for venous thromboembolism: the Padua Prediction Score. J Thromb Haemost, 2010, 8(11): 2450-2457.
15. Chopard P, Spirk D, Bounameaux H. Identifying acutely ill medical patients requiring thromboprophylaxis. J Thromb Haemost, 2006, 4(4): 915-916.
16. 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(1): e56-e65.
17. RECOVERY Collaborative Group. Aspirin in patients admitted to hospital with COVID-19 (RECOVERY): a randomised, controlled, open-label, platform trial. Lancet, 2022, 399(10320): 143-151.
18. Berger JS, Kornblith LZ, Gong MN, et al. Effect of P2Y12 inhibitors on survival free of organ support among non-critically ill hospitalized patients with COVID-19: a randomized clinical trial. JAMA, 2022, 327(3): 227-236.
19. Lopes RD, de Barros E Silva PGM, Furtado RHM, et al. 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(10291): 2253-2263.
20. Cohen SL, Gianos E, Barish MA, et al. Prevalence and predictors of venous thromboembolism or mortality in hospitalized COVID-19 patients. Thromb Haemost, 2021, 121(8): 1043-1053.
21. ATTACC Investigators, ACTIV-4a Investigators, REMAP-CAP Investigators, et al. Therapeutic anticoagulation with heparin in noncritically ill patients with Covid-19. N Engl J Med, 2021, 385(9): 790-802.
22. Sholzberg M, da Costa BR, Tang GH, et al. Randomized trials of therapeutic heparin for COVID-19: a meta-analysis. Res Pract Thromb Haemost, 2021, 5(8): e12638.
23. Sholzberg M, Tang GH, Rahhal H, et al. Effectiveness of therapeutic heparin versus prophylactic heparin on death, mechanical ventilation, or intensive care unit admission in moderately ill patients with covid-19 admitted to hospital: RAPID randomised clinical trial. BMJ, 2021, 375: n2400. doi: 10.1136/bmj.n2400.
24. Spyropoulos AC, Goldin M, Giannis D, et al. Efficacy and safety of therapeutic-dose heparin vs standard prophylactic or intermediate-dose heparins for thromboprophylaxis in high-risk hospitalized patients with COVID-19: the HEP-COVID randomized clinical trial. JAMA Intern Med, 2021, 181(12): 1612-1620.
25. Gonzalez-Porras JR, Belhassen-Garcia M, Lopez-Bernus A, et al. Low molecular weight heparin is useful in adult COVID-19 inpatients. Experience during the first Spanish wave: observational study. Sao Paulo Med J, 2022, 140(1): 123-133.
26. Meizlish ML, Goshua G, Liu Y, et al. Intermediate-dose anticoagulation, aspirin, and in-hospital mortality in COVID-19: a propensity score-matched analysis. Am J Hematol, 2021, 96(4): 471-479.
27. Morici N, Podda G, Birocchi S, et al. Enoxaparin for thromboprophylaxis in hospitalized COVID-19 patients: the X-COVID-19 randomized trial. Eur J Clin Invest, 2022, 52(5): e13735. doi: 10.1111/eci.13735.
28. Smadja DM, Bonnet G, Gendron N, et al. Intermediate- vs. standard-dose prophylactic anticoagulation in patients with COVID-19 admitted in medical ward: a propensity score-matched cohort study. Front Med (Lausanne), 2021, 8: 747527.
29. Spyropoulos AC, Connors JM, Douketis JD, et al. Good practice statements for antithrombotic therapy in the management of COVID-19: guidance from the SSC of the ISTH. J Thromb Haemost, 2022, 20(10): 2226-2236.
30. Bikdeli B, Talasaz AH, Rashidi F, et al. Intermediate-dose versus standard-dose prophylactic anticoagulation in patients with COVID-19 admitted to the intensive care unit: 90-day results from the INSPIRATION randomized trial. Thromb Haemost, 2022, 122(1): 131-141.
31. Perepu US, Chambers I, Wahab A, et al. Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: a multi-center, open-label, randomized controlled trial. J Thromb Haemost, 2021, 19(9): 2225-2234.
32. Sadeghipour P, Talasaz AH, Rashidi F, 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): 1620-1630.
33. PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian and New Zealand Intensive Care Society Clinical Trials Group; Cook D, Meade M, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med, 2011, 364(14): 1305-1314.
34. Schünemann HJ, Cushman M, Burnett AE, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: prophylaxis for hospitalized and nonhospitalized medical patients. Blood Adv, 2018, 2(22): 3198-3225.
35. REMAP-CAP Investigators, ACTIV-4a Investigators, ATTACC Investigators, et al. Therapeutic anticoagulation with heparin in critically ill patients with Covid-19. N Engl J Med, 2021, 385(9): 777-789.
36. Oliynyk O, Barg W, Slifirczyk A, et al. Comparison of the effect of unfractionated heparin and enoxaparin sodium at different doses on the course of COVID-19-associated coagulopathy. Life (Basel), 2021, 11(10): 1032. doi: 10.3390/life11101032.
37. REMAP-CAP Writing Committee for the REMAP-CAP Investigators; Bradbury CA, Lawler PR, et al. Effect of antiplatelet therapy on survival and organ support-free days in critically ill patients with COVID-19: a randomized clinical trial. JAMA, 2022, 327(13): 1247-1259.
38. Giannis D, Allen SL, Tsang J, et al. Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry. Blood, 2021, 137(20): 2838-2847.
39. Lui DTW, Li YK, Lee CH, et al. A prospective study of the impact of glycaemic status on clinical outcomes and anti-SARS-CoV-2 antibody responses among patients with predominantly non-severe COVID-19. Diabetes Res Clin Pract, 2022, 185: 109232. doi: 10.1016/j.diabres.2022.109232.
40. Ramacciotti E, Barile Agati L, Calderaro D, et al. Rivaroxaban versus no anticoagulation for post-discharge thromboprophylaxis after hospitalisation for COVID-19 (MICHELLE): an open-label, multicentre, randomised, controlled trial. Lancet, 2022, 399(10319): 50-59.

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Guidelines interpretation of the ISTH guidelines for antithrombotic treatment in COVID-19

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