COVID-19相關凝血功能異常及抗凝血藥物的使用

10.6666/ClinMed.202205_89(5).0053

李宛靜；林庭安

COVID-19 ； 凝血功能異常（coagulopathy） ； 抗凝血用藥（anti-thrombotic agents）

臨床醫學月刊

89卷5期（2022 / 05 / 27）

329 - 336

繁體中文

凝血功能異常及血栓事件是COVID-19常見的併發症。COVID-19感染造成局部及全身發炎反應，引起微血管內皮細胞凋亡，繼而誘發凝血活性及血小板活化，造成血栓病變。肺部微血管栓塞引起的惡性循環，是進展到呼吸衰竭或呼吸窘迫症候群的重要因素。臨床上，抗凝血藥物的使用是討論的焦點，包括哪些病人需要使用、使用的劑量及相關的出血風險等。這篇文章將介紹COVID-19相關凝血功能異常的臨床表現、病生理機轉、臨床試驗結果、及治療建議。

1. Ackermann, M,Verleden, SE,Kuehnel, M(2020).Pulmonary Vascular Endothelialitis, Thrombosis, and Angiogenesis in Covid-19.N Engl J Med,383,120-128.
2. Barrett, CD,Moore, HB,Moore, EE(2022).Study of Alteplase for Respiratory Failure in SARS-CoV-2 COVID-19: A Vanguard Multicenter, Rapidly Adaptive, Pragmatic, Randomized Controlled Trial.Chest,161,710-727.
3. Berger, JS,Kornblith, LZ,Gong, MN(2022).Effect of P2Y12 Inhibitors on Survival Free of Organ Support Among Non-Critically Ill Hospitalized Patients With COVID-19: A Randomized Clinical Trial.JAMA,327,227-236.
4. Boonyawat, K,Chantrathammachart, P,Numthavaj, P(2020).Incidence of thromboembolism in patients with COVID-19: a systematic review and metaanalysis.Thromb J,18,34.
5. Connors, JM,Brooks, MM,Sciurba, FC(2021).Effect of Antithrombotic Therapy on Clinical Outcomes in Outpatients With Clinically Stable Symptomatic COVID-19: The ACTIV-4B Randomized Clinical Trial.JAMA,326,1703-1712.
6. Giannis, D,Allen, SL,Tsang, J(2021).Postdischarge thromboembolic outcomes and mortality of hospitalized patients with COVID-19: the CORE-19 registry.Blood,137,2838-2847.
7. Gonzalez-Ochoa, AJ,Raffetto, JD,Hernández, AG(2021).Sulodexide in the Treatment of Patients with Early Stages of COVID-19: A Randomized Controlled Trial.Thromb Haemost,121,944-954.
8. Helms, J,Tacquard, C,Severac, F(2020).High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.Intensive Care Med,46,1089-1098.
9. INSPIRATION Investigators,Sadeghipour, P,Talasaz, AH(2021).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,325,1620-1630.
10. Jiménez, D,García-Sanchez, A,Rali, P(2021).Incidence of VTE and Bleeding Among Hospitalized Patients With Coronavirus Disease 2019: A Systematic Review and Meta-analysis.Chest,159,1182-1196.
11. Leentjens, J,van Haaps, TF,Wessels, PF(2021).COVID-19-associated coagulopathy and antithrombotic agents—lessons after 1 year.The Lancet Haematology,8,e524-e533.
12. Lopes, RD,de, Barros, E, Silva, PGM,Furtado, RHM(2021).Therapeutic versus prophylactic anticoagulation f or patients admitted to hospital with COVID-19 and elevated D-dimer concentration(ACTION): an open-label, multicentre, randomised, controlled trial.Lancet,397,2253-2263.
13. Nopp, S,Moik, F,Jilma, B(2020).Risk of venous thromboembolism in patients with COVID-19: A systematic review and meta-analysis.Res Pract Thromb Haemost,4,1178-1191.
14. Perepu, US,Chambers, I,Wahab, A(2021).Standard prophylactic versus intermediate dose enoxaparin in adults with severe COVID-19: A multi-center, open-label, randomized controlled trial.J Thromb Haemost,19,2225-2234.
15. Ramacciotti, E,Barile, Agati, L,Calderaro, D(2022).Rivaroxaban versus no anticoagulation for postdischarge thromboprophylaxis after hospitalisation for COVID-19(MICHELLE): an open-label, multicentre, randomised, controlled trial.Lancet,399,50-59.
16. RECOVERY Collaborative Group(2022).Aspirin in patients admitted to hospital with COVID19(RECOVERY): a randomised, controlled, openlabel, platform trial.Lancet,399,143-151.
17. REMAP-CAP Investigators,ACTIV-4a Investigators,ATTACC Investigators(2021).Therapeutic Anticoagulation with Heparin in Critically Ill Patients with Covid-19.N Engl J Med,385,777-789.
18. Roberts, LN,Whyte, MB,Georgiou, L(2020).Postdischarge venous thromboembolism following hospital admission with COVID-19.Blood,136,1347-1350.
19. Salisbury, R,Iotchkova, V,Jaafar, S(2020).Incidence of symptomatic, image-conf irmed venous thromboembolism following hospitalization for COVID-19 with 90-day follow-up.Blood Adv,4,6230-6239.
20. Sholzberg, M,Tang, GH,Rahhal, H(2021).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,375,n2400.
21. Smilowitz, NR,Subashchandran, V,Yuriditsky, E(2021).Thrombosis in hospitalized patients with viral respiratory infections versus COVID-19.Am Heart J,231,93-95.
22. Talasaz, AH,Sadeghipour, P,Kakavand, H(2021).Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19: JACC State-of-the-Art Review.J Am Coll Cardiol,77,1903-1921.
23. Thachil, J,Cushman, M,Srivastava, A.(2020).A proposal for staging COVID-19 coagulopathy.Res Pract Thromb Haemost,4,731-736.
24. Yang, W,Kandula, S,Huynh, M(2021).Estimating the infection-fatality risk of SARS-CoV-2 in New York City during the spring 2020 pandemic wave: a model-based analysis.Lancet Infect Dis,21,203-212.
25. Zhang, L,Yan, X,Fan, Q(2020).D-dimer levels on admission to predict in-hospital mortality in patients with Covid-19.J Thromb Haemost,18,1324-1329.
26. Zuo, Y,Warnock, M,Harbaugh, A(2021).Plasma tissue plasminogen activator and plasminogen activator inhibitor-1 in hospitalized COVID-19 patients.Sci Rep,11,1580.