The Procoagulant Effect of COVID-19 on the Thrombotic Risk of Patients with Hip Fractures Due to Enhanced Clot Strength and Fibrinolysis Shutdown

Introduction: Coronavirus disease 2019 (COVID-19) in patients with hip fractures is associated with increased incidence of venous thromboembolism (VTE). The purpose of this study was to evaluate the hemostatic alterations of COVID-19 that are associated with a higher thrombotic risk using rotational thromboelastometry (ROTEM). Methods: A retrospective observational study was performed including 20 COVID-19 patients with hip fractures. To compare the coagulopathy of patients with mild COVID-19 and hip fractures with the coagulopathy associated with each of these two conditions separately, we used two previously recruited groups of patients; 198 hip fracture patients without COVID-19 and 21 COVID-19 patients without hip fractures. The demographics, clinical parameters, conventional coagulation parameters and ROTEM findings of the three groups were analyzed and compared. Results: COVID-19 hip fracture patients had higher amplitude of clot firmness at 10 min (p < 0.001), higher alpha angle (p < 0.001), higher lysis index at 60 min (p < 0.001), and shorter clot formation time (p < 0.001) than non-COVID-19 hip fracture patients, indicating increased clot strength and impaired fibrinolysis due to COVID-19. The value of lysis index at 60 min (99%) in COVID-19 patients with hip fractures was consistent with fibrinolysis shut down. Multivariable linear regression analysis further confirmed that COVID-19 resulted in increased amplitude of clot firmness at 10 min (p < 0.001), increased maximum clot firmness (p < 0.001), increased lysis index at 60 min (p < 0.001) and increased alpha angle (p < 0.001), but significantly shortened clot formation time (p < 0.001). Discussion: The higher thrombotic risk in COVID-19 patients with hip fractures is characterized by increased clot strength and fibrinolysis shutdown, as shown by ROTEM findings. Further prospective studies are warranted to evaluate the need for modification of thromboprophylaxis to balance the hemostatic derangements of COVID-19 patients with hip fractures.

Prevalence and impact of fibrinolytic dysregulation in patients with acute coronary syndromes

Objective Dual antiplatelet therapy can reduce coronary thrombosis and improve the prognosis in patients with acute coronary syndrome (ACS). However, there was limited prognostic information about fibrinolytic dysregulation in patients with ACS. This study is aimed to evaluated the prevalence and impact of fibrinolytic dysregulation in patients with acute coronary syndrome (ACS). Methods We retrospectively analyzed coagulation and fibrinolysis related indexes of ACS in hospitalized adults with rapid thrombelastography between May 2016 and December 2018. All of the follow-up visits were ended by December 2019. The primary outcome was the occurrence of major adverse cardiovascular events (MACEs), which included unstable angina pectoris, non-fatal myocardial infarction, non-fatal cerebral infarction, heart failure and all-cause death. Results Three hundred thirty-eight patients were finally included with an average age of 62.5 ± 12.8 years old, 273 (80.5%) were males, 137(40.5%) patients were with ST-elevation myocardial infraction. Fibrinolysis shutdown (LY30<0.8%) and hyperfibrinolysis (LY30 >3.0%) were observed among 163 (48.2%) and 76(22.5%) patients, respectively. During a total of 603.2 person·years of follow-up period, 77 MACEs occurred (22.8%). Multivariate Cox regression analysis indicated that LY30 [HR: 1.101, 95% CI: 1.010–1.200, P = 0.028] was independently correlated with the occurrence of MACEs. The hazard ratios pertaining to MACEs in patients with fibrinolysis shutdown and hyperfibrinolysis compared with those in the physiologic range (LY30: 0.8–3.0%) were 1.196 [HR: 1.196, 95% CI: 0.679–2.109,P = 0.535] and 2.275 [HR: 2.275, 95% CI: 1.241–4.172, P = 0.003], respectively. Conclusions Fibrinolytic dysregulation is very common in selected patients with ACS, and hyperfibrinolysis (LY30 > 3%) is associated with poor outcomes in patients with ACS.

Effect of acute alcohol intoxication on mortality, coagulation, and fibrinolysis in trauma patients

Background The effect of alcohol on the outcome and fibrinolysis phenotype in trauma patients remains unclear. Hence, we performed this study to determine whether alcohol is a risk factor for mortality and fibrinolysis shutdown in trauma patients. Materials and methods A total of 686 patients who presented to our trauma center and underwent rotational thromboelastometry were included in the study. The primary outcome was in-hospital mortality. Logistic regression analysis was performed to determine whether alcohol was an independent risk factor for in-hospital mortality and fibrinolysis shutdown. Results The rate of in-hospital mortality was 13.8% and blood alcohol was detected in 27.7% of the patients among our study population. The patients in the alcohol-positive group had higher mortality rate, higher clotting time, and lower maximum lysis, more fibrinolysis shutdown, and hyperfibrinolysis than those in the alcohol-negative group. In logistic regression analysis, blood alcohol was independently associated with in-hospital mortality (odds ratio [OR] 2.578; 95% confidence interval [CI], 1.550–4.288) and fibrinolysis shutdown (OR 1.883 [95% CI, 1.286–2.758]). Within the fibrinolysis shutdown group, blood alcohol was an independent predictor of mortality (OR 2.168 [95% CI, 1.030–4.562]). Conclusions Alcohol is an independent risk factor for mortality and fibrinolysis shutdown in trauma patients. Further, alcohol is an independent risk factor for mortality among patients who experienced fibrinolysis shutdown.

Pathological findings in rotation thromboelastometry associated with thromboembolic events in COVID-19 patients

Background Severe thromboembolic events are one of the major complications associated with COVID-19 infection, especially among critically ill patients. We analysed ROTEM measurements in COVID-19 patients with a severe disease course and in patients with severe sepsis. Methods In this study, data obtained by extended analysis of haemostasis with standard laboratory tests and thromboelastometry of 20 patients with severe course of COVID-19 were retrospectively analysed and compared with similar data from 20 patients with severe sepsis but no COVID-19. Results The thromboelastometry values obtained from 20 sepsis patients contained a maximum clot firmness above the normal range but among COVID-19 patients, hypercoagulability was much more pronounced, with significantly higher maximum clot firmness (FIBTEM: 38.4 ± 10.1 mm vs. 29.6 ± 10.8 mm; P = 0.012; EXTEM: 70.4 ± 10.4 mm vs. 60.6 ± 14.8 mm; P = 0.022). Additionally, fibrinogen levels were significantly higher among COVID-19 patients (757 ± 135 mg/dl vs. 498 ± 132 mg/dl, P < 0.0001). Furthermore, thromboelastometry showed fibrinolysis shutdown among COVID-19 patients with significantly lower maximum of lysis than among sepsis patients (EXTEM: 0.6 ± 1.2 % vs. 3.3 ± 3.7 %; P = 0.013). Seven of 20 COVID-19 patients experienced thromboembolic events, whereas no patient in the sepsis group experienced such events. Conclusions ROTEM analysis showed significantly different pathological findings characterized by hypercoagulability and fibrinolysis shutdown among COVID-19 patients with a severe disease course compared to patients with severe sepsis. These abnormalities seem to be associated with thromboembolic events.

Haemostasis in coronavirus disease 2019 - lesson from viscoelastic methods: a systematic review

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.

COVID-19 Infection-Related Coagulopathy and Viscoelastic Methods: A Paradigm for Their Clinical Utility in Critical Illness

Hypercoagulability and thrombosis remain a challenge to diagnose and treat in severe COVID-19 infection. The ability of conventional global coagulation tests to accurately reflect in vivo hypo- or hypercoagulability is questioned. The currently available evidence suggests that markedly increased D-dimers can be used in identifying COVID-19 patients who may need intensive care unit (ICU) admission and close monitoring or not. Viscoelastic methods (VMs), like thromboelastography (TEG) and rotational thromboelastometry (ROTEM), estimate the dynamics of blood coagulation. The evaluation of coagulopathy by VMs in severe COVID-19 infection seems an increasingly attractive option. Available evidence supports that COVID-19 patients with acute respiratory failure suffer from severe hypercoagulability rather than consumptive coagulopathy often associated with fibrinolysis shutdown. However, the variability in definitions of both the procoagulant profile and the clinical outcome assessment, in parallel with the small sample sizes in most of these studies, do not allow the establishment of a clear association between the hypercoagulable state and thrombotic events. VMs can effectively provide insight into the pathophysiology of coagulopathy, detecting the presence of hypercoagulability in critically ill COVID-19 patients. However, it remains unknown whether the degree of coagulopathy can be used in order to predict the outcome, establish a diagnosis or guide anticoagulant therapy.