Fragkou Paraskevi C, Palaiodimou Lina, Stefanou Maria Ioanna, Katsanos Aristeidis H, Lambadiari Vaia, Paraskevis Dimitrios, Andreadou Elisabeth, Dimopoulou Dimitra, Zompola Christina, Ferentinos Panagiotis, Vassilakopoulos Theodoros I, Kotanidou Anastasia, Sfikakis Petros P, Tsiodras Sotirios, Tsivgoulis Georgios
First Department of Critical Care Medicine and Pulmonary Services, School of Medicine, National and Kapodistrian University of Athens, Evangelismos Hospital, Athens, Greece.
Second Department of Neurology, School of Medicine, National and Kapodistrian University of Athens, 'Attikon' University Hospital, Athens, Greece.
Ther Adv Neurol Disord. 2022 May 24;15:17562864221099472. doi: 10.1177/17562864221099472. eCollection 2022.
Coronavirus disease 2019 (COVID-19) is associated with increased thrombosis prevalence. However, there are insufficient data supporting the appropriate anticoagulation dose in COVID-19.
We aim to systematically assess the currently available data regarding the effects of different dosing regimens of low molecular weight heparin and/or fondaparinux (LMWH/F) on mortality risk as well as the risk of arterial/venous thrombotic events and hemorrhagic complications in confirmed COVID-19 cases.
We conducted a living systematic review and meta-analysis on the effects of different LMWH/F doses on mortality, thrombotic and hemorrhagic events in COVID-19 patients.
MEDLINE, Scopus, Embase, Cochrane Library, Cochrane COVID-19 study register, European Union Drug Regulating Authorities Clinical Trials Database, and ClinicalTrials.gov were searched to detect observational cohort studies and randomized-controlled clinical trials (RCTs) comparing difference doses of LMWH/F among confirmed COVID-19 cases.
Thirty-one eligible studies (6 RCTs and 25 cohort studies) with 11,430 hospitalized patients were included. No association was found between LMWH/F and mortality during the following comparisons: (1) no LMWH/F versus any LMWH/F; (2) prophylactic versus higher than prophylactic LMWH/F; (3) prophylactic versus therapeutic LMWH/F; (4) intermediate versus therapeutic LMWH/F; and (5) lower than therapeutic versus therapeutic LMWH/F. Mortality was higher in patients receiving prophylactic versus intermediate LMWH/F (OR = 2.01; 95% CI: 1.19-3.39). However, this effect was mostly driven by observational data. No associations were detected between the intensity of LMWH/F and the risk of thrombotic and hemorrhagic events, except the lower risk for hemorrhage in patients on prophylactic compared to higher LMWH/F doses.
The risk for all-cause mortality was higher in patients receiving prophylactic LMWH/F compared to those on an intermediate dose of LMWH/F, based on observational data. These results should be interpreted in light of the moderate quality and heterogeneity of the included studies.
The study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (Registration number: CRD42021229771).
2019冠状病毒病（COVID-19）与血栓形成患病率增加有关。然而，支持COVID-19患者适当抗凝剂量的数据不足。
我们旨在系统评估目前关于低分子量肝素和/或磺达肝癸钠（LMWH/F）不同给药方案对确诊COVID-19病例的死亡风险、动脉/静脉血栓形成事件风险和出血并发症影响的现有数据。
我们对不同LMWH/F剂量对COVID-19患者死亡率、血栓形成和出血事件的影响进行了一项实时系统评价和荟萃分析。
检索了MEDLINE、Scopus、Embase、Cochrane图书馆、Cochrane COVID-19研究注册库、欧盟药品监管机构临床试验数据库和ClinicalTrials.gov，以检测比较确诊COVID-19病例中不同剂量LMWH/F的观察性队列研究和随机对照临床试验（RCT）。
纳入了31项符合条件的研究（6项RCT和25项队列研究），共11430例住院患者。在以下比较中未发现LMWH/F与死亡率之间存在关联：（1）未使用LMWH/F与使用任何LMWH/F；（2）预防性使用LMWH/F与高于预防性剂量的LMWH/F；（3）预防性使用LMWH/F与治疗性使用LMWH/F；（4）中等剂量与治疗性剂量的LMWH/F；（5）低于治疗性剂量与治疗性剂量的LMWH/F。接受预防性LMWH/F的患者与接受中等剂量LMWH/F的患者相比，死亡率更高（OR = 2.01；95% CI：1.19 - 3.39）。然而，这种影响主要由观察性数据驱动。除了与较高LMWH/F剂量相比，接受预防性剂量的患者出血风险较低外，未发现LMWH/F强度与血栓形成和出血事件风险之间存在关联。
根据观察性数据，接受预防性LMWH/F的患者全因死亡率风险高于接受中等剂量LMWH/F的患者。应根据纳入研究的中等质量和异质性来解释这些结果。
该研究方案已在国际前瞻性正在进行的系统评价注册库PROSPERO中注册（注册号：CRD42021229771）。
