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Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers.

ABSTRACT: The association between severity of fibrinolysis, ascertained by rotational thromboelastometry to diagnose hyperfibrinolysis in patients with out-of-hospital cardiac arrest (OHCA), and conventional fibrinolysis markers (ie, tissue-plasminogen activator [t-PA], plasminogen, ?2-plasmin inhibitor [?2-PI], and plasminogen activator inhibitor [PAI]) with key roles in the fibrinolytic system was investigated. This prospective observational study included 5 healthy volunteers and 35 patients with OHCA from the Hokkaido University Hospital. Blood samples were drawn immediately upon admission to the emergency department. Assessments of the extrinsic pathway using tissue factor activation (EXTEM) and of fibrinolysis by comparison with EXTEM after aprotinin addition (APTEM) were undertaken. Conventional coagulation and fibrinolysis markers were measured in the stored plasma samples. Significant hyperfibrinolysis observed in EXTEM disappeared in APTEM. Patients exhibited significantly higher levels of fibrinogen/fibrin degradation products, plasmin-?2-PI complex, and t-PA but lower levels of fibrinogen, plasminogen, and ?2-PI than healthy controls. The PAI level was unchanged. Fibrinolytic parameters of EXTEM correlated with levels of lactate and conventional fibrinolysis markers, especially t-PA. Increased t-PA activity and decreased plasminogen and ?2-PI significantly correlated with increased severity of fibrinolysis (hyperfibrinolysis).

SUBMITTER: Saito T

PROVIDER: S-EPMC7427038 | biostudies-literature | 2020 Jan-Dec

REPOSITORIES: biostudies-literature

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Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers.

Saito Tomoyo T Hayakawa Mineji M Honma Yoshinori Y Mizugaki Asumi A Yoshida Tomonao T Katabami Kenichi K Wada Takeshi T Maekawa Kunihiko K

Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis 20200101

The association between severity of fibrinolysis, ascertained by rotational thromboelastometry to diagnose hyperfibrinolysis in patients with out-of-hospital cardiac arrest (OHCA), and conventional fibrinolysis markers (ie, tissue-plasminogen activator [t-PA], plasminogen, α<sub>2</sub>-plasmin inhibitor [α<sub>2</sub>-PI], and plasminogen activator inhibitor [PAI]) with key roles in the fibrinolytic system was investigated. This prospective observational study included 5 healthy volunteers and ...[more]

PMID: 32571089

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Project description:BackgroundData describing the coagulopathy of Crimean-Congo haemorrhagic fever are scarce. We did rotational thromboelastometry (ROTEM) and conventional coagulation testing in patients with Crimean-Congo haemorrhagic fever to increase our understanding of the coagulopathy of this infectious disease.MethodsWe did a prospective observational cohort study of adults aged 18 years and older and admitted to hospitals with PCR-confirmed Crimean-Congo haemorrhagic fever in Samsun and Tokat, Turkey. Demographic, clinical, and laboratory data were collected and blood samples for ROTEM analysis and coagulation testing were drawn at admission and during hospital admission and convalescence (up to 30 days after onset of illness). For the ROTEM analysis we recorded the following extrinsically activated ROTEM (EXTEM S) variables, with normal ranges indicated: clotting time (38-79 s), clot formation time (34-159 s), amplitude at 10 min after clotting time (43-65 mm), maximum clot firmness (50-72 mm), and maximum lysis (>15% at 1 h). The following fibrin-specific ROTEM (FIBTEM S) variables were also recorded: amplitude at 10 min after clotting time (normal range 7-23 mm) and maximum clot firmness (9-25 mm). Disease severity was assessed by Swanepoel criteria, severity grading score (SGS), and the severity scoring index (SSI), with mild disease defined as meeting no Swanepoel criteria, graded mild by SSI, and graded low risk by SGS.FindingsBetween May 27, 2015, and Aug 2, 2015, 65 patients with confirmed Crimean-Congo haemorrhagic fever were recruited and had blood taken at 110 time points. Most were male (40 [62%] of 65) with mild disease (49 [75%] of 65). Haemorrhage occurred in 13 (20%; 95% CI 11·1-31·8) of 65 patients and 23 (35%) of 65 received blood products (15 received fresh frozen plasma and eight received red blood cell concentrates), and 21 patients received platelet transfusions. At admission, the following EXTEM S variables differed significantly between mild cases and moderate to severe cases: median clotting time 56 s (range 42-81; IQR 48-64) versus 69 s (range 48-164; IQR 54-75; p=0·01); mean amplitude at 10 min after clotting time 45·1 mm (SD 7·0) versus 33·9 mm (SD 8·6; p<0·0001); median clot formation time 147 s (range 72-255; IQR 101-171) versus 197 s (range 98-418; IQR 156-296; p=0·006); and maximum clot firmness 54·4 mm (SD 7·2) versus 45·1 mm (SD 12·5; p=0·003). The EXTEM S variables were compared at different time points; maximum clot firmness (p=0·024) and amplitude at 10 min after clotting time (p=0·090) were lowest on days 4-6 of illness. We found no significant differences in FIBTEM variables between mild and moderate to severe cases (median amplitude at 10 min, 13 mm [range 8-20; IQR 11-15] vs 12 mm [range 6-25; IQR 10-15; p=0·68]; and median maximum clot firmness, 15 mm [range 9-60; IQR 13-21] vs 17 mm [range 7-39; IQR 13-23; p=0·21]); and no hyperfibrinolysis (maximum lysis >15%).InterpretationCoagulopathy of Crimean-Congo haemorrhagic fever is related to defects in clot development and stabilisation that are more marked in severe disease than in mild disease. The combination of normal and slightly deranged coagulation screens and FIBTEM results with the absence of hyperfibrinolysis suggests that the coagulopathy of Crimean-Congo haemorrhagic fever relates to platelet dysfunction.FundingWellcome Trust, UK Ministry of Defence, and National Institute for Health Research Health Protection Research Unit.

Project description:BackgroundViscoelastic tests (VETs), specifically thromboelastography (TEG) and rotational thromboelastometry (ROTEM), are gaining popularity in the management of critically ill surgical patients with hemorrhage or thrombosis due to their comprehensive characterization of the coagulation process and point-of-care availability in comparison to conventional coagulation tests (CCTs). We review current evidence for VET use in patients in the surgical intensive care unit (SICU).MethodsWe searched PUBMED, EMBASE and the Cochrane Library through May 30, 2018 for articles that evaluated the use of VETs in patient populations and clinical scenarios germane to the surgical intensivist. Individual articles were critically evaluated for relevance and appropriate methodology using a structured technique. Information on patient characteristics, timing and methods of CCTs/VETs, and outcomes was collected and summarized in narrative form.ResultsOf 2,589 identified articles, 36 were included. Five (14%) were interventional studies and 31 (86%) were observational. Twenty-five (69%) evaluated TEG, 11 (31%) ROTEM and 18 (50%) CCTs. Investigated outcomes included quantitative blood loss (13 (36%)), blood product transfusion (9 (25%)), thromboembolic events (9 (25%)) and mortality (6 (17%)). We identified 12 clinical scenarios with sufficient available evidence, much of which was of limited quantity and poor methodological quality. Nonetheless, research supports the use of VETs for guiding early blood product administration in severe traumatic hemorrhage and for the prediction of abstract excess bleeding following routine cardiac surgery. In contrast, evidence suggests VET-based heparin dosing strategies for venous thromboembolism prophylaxis are not superior to standard dosing in SICU patients.ConclusionWhile VETs have the potential to impact the care of critically ill surgical patients in many ways, current evidence for their use is limited, mainly because of poor methodological quality of most available studies. Further high-quality research, including several ongoing randomized controlled trials, is needed to elucidate the role of TEG/ROTEM in the SICU population.Level of evidenceSystematic review, level IV.

Project description:Argatroban or lepirudin anticoagulation therapy in patients with heparin induced thrombocytopenia (HIT) or HIT suspect is typically monitored using the activated partial thromboplastin time (aPTT). Although aPTT correlates well with plasma levels of argatroban and lepirudin in healthy volunteers, it might not be the method of choice in critically ill patients. However, in-vivo data is lacking for this patient population. Therefore, we studied in vivo whether ROTEM or global clotting times would provide an alternative for monitoring the anticoagulant intensity effects in critically ill patients.This study was part of the double-blind randomized trial "Argatroban versus Lepirudin in critically ill patients (ALicia)", which compared critically ill patients treated with argatroban or lepirudin. Following institutional review board approval and written informed consent, for this sub-study blood of 35 critically ill patients was analysed. Before as well as 12, 24, 48 and 72 h after initiation of argatroban or lepirudin infusion, blood was analysed for aPTT, aPTT ratios, thrombin time (TT), INTEM CT,INTEM CT ratios, EXTEM CT, EXTEM CT ratios and maximum clot firmness (MCF) and correlated with the corresponding plasma concentrations of the direct thrombin inhibitor.To reach a target aPTT of 1.5 to 2 times baseline, median [IQR] plasma concentrations of 0.35 [0.01-1.2] ?g/ml argatroban and 0.17 [0.1-0.32] ?g/ml lepirudin were required. For both drugs, there was no significant correlation between aPTT and aPTT ratios and plasma concentrations. INTEM CT, INTEM CT ratios, EXTEM CT, EXTEM CT ratios, TT and TT ratios correlated significantly with plasma concentrations of both drugs. Additionally, agreement between argatroban plasma levels and EXTEM CT and EXTEM CT ratios were superior to agreement between argatroban plasma levels and aPTT in the Bland Altman analysis. MCF remained unchanged during therapy with both drugs.In critically ill patients, TT and ROTEM parameters may provide better correlation to argatroban and lepirudin plasma concentrations than aPTT.ClinicalTrials.gov , NCT00798525 , registered on 25 Nov 2008.

Project description:BACKGROUND:Up to 40% of combat casualties with a truncal injury die of massive hemorrhage before reaching a surgeon. This hemorrhage can be prevented with damage control resuscitation (DCR) methods, which are focused on replacing shed whole blood by empirically transfusing blood components in a 1:1:1:1 ratio of platelets:fresh frozen plasma:erythrocytes:cryoprecipitate (PLT:FFP:RBC:CRYO). Measurement of hemostatic function with rotational thromboelastometry (ROTEM) may allow optimization of the type and quantity of blood products transfused. Our hypothesis was that incorporating ROTEM measurements into DCR methods at the US Role 3 hospital at Bagram Airfield, Afghanistan would change the standard transfusion ratios of 1:1:1:1 to a product mix tailored specifically for the combat causality. METHODS:This retrospective study collected data from the Department of Defense Trauma Registry to compare transfusion practices and outcomes before and after ROTEM deployment to Bagram Airfield. Over the course of six months, 134 trauma patients received a transfusion (pre-ROTEM) and 85 received a transfusion and underwent ROTEM testing (post-ROTEM). Trauma teams received instruction on ROTEM use and interpretation, with no provision of a specific transfusion protocol, to supplement their clinical judgment and practice. RESULTS:The pre and post groups were not significantly different in terms of mortality, massive transfusion protocol activation, mean injury severity score, or coagulation measurements. Despite the difference in size, each group received an equal total number of transfusions. However, the post-ROTEM group received a significant increase in PLT and CRYO transfusions ratios, 4× and 2×, respectively. CONCLUSION:The introduction of ROTEM significantly improved adherence to DCR practices. The transfusion differences suggest that aggressive DCR without thromboelastometry data may result in reduced hemostatic support and underestimate the need for PLT and CRYO. Thus, future controlled trials should include ROTEM-guided coagulation management in trauma resuscitation. LEVEL OF EVIDENCE:Therapeutic, level IV.

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Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers.

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Relationship Between Severity of Fibrinolysis Based on Rotational Thromboelastometry and Conventional Fibrinolysis Markers.

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