Hemostasis in Coronavirus Disease 2019—Lesson from Viscoelastic Methods: A Systematic Review

Abstract

Haemostatic unbalance is often observed in patients with coronavirus disease 2019 (COVID-19), and patients with severe disease are at high risk of developing thromboembolic complications. Viscoelastic methods (VEMs), including thrombelastography (TEG) and thromboelastometry (TEM), provide data on the nature of haemostatic disturbance. In this systematic review, we assessed the performance of TEG and TEM in the assessment of blood coagulation and fibrinolysis in patients with COVID-19. PubMed, Scopus, Web of Science Core Collection, medRxiv and bioRxiv were systematically searched for clinical studies evaluating TEG and/or TEM variables in COVID-19 individuals. Ten studies, with a total of 389 COVID-19 patients, were included, and VEMs were performed in 292 of these patients. Most patients (90%) presented severe COVID-19 and required mechanical ventilation. TEG and TEM variables showed that these patients displayed hypercoagulability and fibrinolysis shutdown, despite the use of appropriate thromboprophylaxis. However, the mechanism underlying these phenomena and their clinical significance in COVID-19 patients who developed thrombosis, is still not clear. Further studies are warranted if VEMs might help to identify those at highest risk of thrombotic events and who therefore may derive the greatest benefit from antithrombotic therapy.

Viscoelastometric Testing to Assess Hemostasis of COVID-19: A Systematic Review

“…Conclusions of the previously published reviews are summarized in Table 11. Overall, the four reviews reported the same findings as we do: COVID-19 patients displayed an abnormal VET pattern [69][70][71][72], but further studies are needed for various reasons. Moreover, we challenge the idea that such a pattern represents hypercoagulability; one main reason is that inhibitory systems are not at all taken into account, in sharp contrast with TGAs.…”

“…Since the beginning of the pandemic, they were used to characterize hemostasis abnormalities in critically ill COVID-19 patients. As already reported in previous reviews [69][70][71][72], almost all the studies we analyzed reported increased clot strength, considered to be a hallmark of the 'hypercoagulable state', often associated with impaired fibrinolysis (with the analytical limitations we have emphasized)-globally referred to as 'prothrombotic pattern', but there was no consistent association with clinical outcomes. Indeed, few studies suggested an association with the occurrence of thrombotic events, as well as with the need for hemodialysis [34,44,51,56].…”

“…This raises questions that include (i) the effect of heparin, particularly at low doses, on VET results, (ii) whether heparinase or polybrene added to heparinized blood completely neutralized circulating heparin, and (iii) whether VETs can be used to guide heparin therapy. These questions were not raised by the previously published reviews [69][70][71][72].…”

“…First, prospective ones comparing the results from the different available devices are needed. Second, as it was already highlighted by previously published reviews [69][70][71][72], further prospective studies are needed, ideally randomized, to highlight the added-value of VET in predicting the clinical course of the disease, addressing patients to the appropriate ward according to their risk stratification, and identifying which patients would benefit from intensified anticoagulant treatment and those who would show clot resistance to fibrinolysis. Third, prospective randomized controlled trials are needed to evaluate the usefulness of VET and TGA in monitoring and adapting thromboprophylaxis.…”

“…Reviews have already been published recently, two of them only being systematic [69][70][71][72], but none has so far investigated the four major commercially available VET devices (i.e., ROTEM, TEG, ClotPro, and Quantra) or included such a large number of studies (n = 44). Characteristics of each review are summarized in Table 2.…”