The effect of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on the coagulation system is not fully understood. SARS-CoV-2 penetrates cells through angiotensin-converting enzyme 2 (ACE2) receptors, leading to its downregulation. Des-arginine9-bradykinin (DA9B) is degraded by ACE2 and causes vasodilation and increased vascular permeability. Furthermore, DA9B is associated with impaired platelet function. Therefore, the aim of this study was to evaluate the effects of DA9B on platelet function and coagulopathy in critically ill coronavirus disease 2019 (COVID-19) patients. In total, 29 polymerase-positive SARS-CoV-2 patients admitted to the intensive care unit of the University Hospital of Giessen and 29 healthy controls were included. Blood samples were taken, and platelet impedance aggregometry and rotational thromboelastometry were performed. Enzyme-linked immunosorbent assays measured the concentrations of DA9B, bradykinin, and angiotensin 2. Significantly increased concentrations of DA9B and angiotensin 2 were found in the COVID-19 patients. A negative effect of DA9B on platelet function and intrinsic coagulation was also found. A sub-analysis of moderate and severe acute respiratory distress syndrome patients revealed a negative association between DA9B and platelet counts and fibrinogen levels. DA9B provokes inhibitory effects on the intrinsic coagulation system in COVID-19 patients. This negative feedback seems reasonable as bradykinin, which is transformed to DA9B, is released after contact activation. Nevertheless, further studies are needed to confirm our findings.

OBJECTIVE: The occurrence of unpredictable pain crises are the principal determinant of the quality of life for patients with venous malformations (VM). A definite coagulation phenomenon, characterized by an increase in D-dimer levels and the presence of phleboliths within the malformation, has been previously reported. By applying Virchow\'s triad and evaluating intralesional samples, our objective is to delineate the coagulation profile and the extent of endothelial dysfunction within the malformation.
METHODS: With the authorization of the Ethics Committee, a research project was undertaken on intralesional and extralesional blood samples from 30 pediatric patients afflicted with spongiform VM. Thromboelastometry analyses were performed using ROTEM Sigma, and the concentration of syndecan-1 was determined by ELISA.
RESULTS: In the ROTEM analyses, the A5, A10, and maximum clot firmness (MCF) values were below the established reference ranges in the intralesional samples in both the EXTEM and INTEM assays, indicating that intralesional clots had significant instability. Furthermore, during the investigation of the delayed fibrinolysis phase using recombinant tissue plasminogen activator (rtPA) in EXTEM analysis, widespread hyperfibrinolysis was observed intralesional. Additionally, analysis of syndecan-1 showed significant differences between extralesional and intralesional levels (p < .026) and controls (p < .03), suggesting differences in the state of endothelium.
CONCLUSIONS: For the first time, we developed a comprehensive understanding of the coagulopathic profile of VM and the role of endothelial dysfunction in its pathogenesis. These findings will enable the implementation of targeted therapies based on the individual coagulation profiles.

Rotational thromboelastometry (ROTEM) is a blood test used to measure in vitro clot strength as a surrogate for a patient\'s ability to form clots in vivo. This provides information about induction, formation, and clot lysis, allowing goal-directed transfusion therapy for specific hemostatic needs. We sought to evaluate the effect of ROTEM-guided transfusion on blood product usage and in-hospital mortality among patients with a traumatic injury.
This was a single-center observational cohort analysis of emergency department patients in a Level 1 trauma center. We compared blood usage in trauma patients in whom ratio-based massive hemorrhage protocols were activated in the twelve months before the introduction of ROTEM (pre-ROTEM group) to the twelve months following the introduction of ROTEM (ROTEM-period group). ROTEM was implemented in this center in November 2016. The ROTEM device allowed clinicians to make real-time decisions about blood product therapy in resuscitation for trauma.
The pre-ROTEM group contained 21 patients. Forty-three patients were included from the ROTEM-period, of whom 35 patients received ROTEM-guided resuscitation (81% compliance). The use of fibrinogen concentrate was significantly higher in the ROTEM-period group (pre-ROTEM mean 0.2 vs. ROTEM-period mean 0.8; p = 0.006). There was no significant difference in the number of units of red blood cells, platelets, cryoprecipitate, or fresh frozen plasma transfused between these groups. There was no significant difference in the mortality rate between the pre-ROTEM and ROTEM-period groups (33% vs. 19%; p = 0.22).
The introduction of ROTEM-guided transfusion at this institution was associated with increased fibrinogen usage, but this did not impact mortality rates. There was no difference in the administration of red blood cell, fresh frozen plasma, platelet, and cryoprecipitate. Future research should focus on increased ROTEM compliance and optimizing ROTEM-guided transfusion to prevent blood product overuse among trauma patients.

Viscoelastic hemostatic assays, such as rotational thromboelastometry (ROTEM), are used increasingly in cardiac surgery to guide transfusion decisions. After separation from cardiopulmonary bypass (CPB), achieving hemostasis rapidly is the main goal before chest closure. The authors hypothesized that introducing a ROTEM-guided factor- concentrate transfusion algorithm would reduce the duration from CPB separation to chest closure during cardiac transplantation.
A retrospective cohort study of 21 patients before and 28 patients after implementation of the ROTEM-guided transfusion algorithm who underwent cardiac transplantation.
This single-center study was conducted at Saint Paul\'s Hospital, Vancouver, British Columbia, Canada.
Using a ROTEM-guided factor-concentrate transfusion algorithm for cardiac transplant recipients.
The primary outcome was the duration from CPB separation to chest closure analyzed using Mann-Whitney U tests. The secondary outcomes included the volume of postoperative chest tube drainage, packed red blood cell (pRBC) transfusion requirements within 24 hours of surgery, the incidence of adverse events, and the length of stay before and after introducing a ROTEM-guided factor-concentrate transfusion algorithm. After adjusting for confounders using multivariate linear regression analysis, using a ROTEM-guided factor-concentrate transfusion algorithm resulted in a significant decrease in time from CPB separation to skin closure of 39.4 minutes (-73.1 to 123.5 min, p = 0.016). For the secondary outcomes, the use of ROTEM-guided transfusion showed reductions in pRBC transfusion within 24 hours of surgery (-1.3 units, -2.7 to 0.1 units; p = 0.077) and chest tube bleeding (-0.44 mL, -0.96 to +0.083 mL; p = 0.097); however, neither was statistically significant after adjustment. The median hospital length of stay in the study group was lower by 3 days (13 days v 16) days; p = 0.048).
The introduction of a ROTEM-guided factor-concentrate transfusion algorithm was associated with a significant reduction in time to chest closure after separation from CPB. Although it reduced the total hospital length of stay, there were no differences in mortality, major complications, or intensive care unit length of stay.

BACKGROUND: The use of viscoelastic tests is becoming increasingly popular. There is a paucity of validation of the reproducibility of varying coagulation states. Therefore, we aimed to study the coefficient of variation (CV) for the ROTEM EXTEM parameters clotting time (CT), clot formation time (CFT), alpha-angle and maximum clot firmness (MCF) in blood with varying degrees of coagulation strength. The hypothesis was that CV increases in states of hypocoagulability.
METHODS: Critically ill patients and patients subjected to neurosurgery at a university hospital during three separate periods were included. Each blood sample was tested in eight parallel channels, yielding the CVs for the tested variables. In 25 patients, the blood samples were analysed both at baseline and after dilution with albumin 5%, as well as after being spiked with fibrinogen, simulating weak and strong coagulation.
RESULTS: In total, 225 unique blood samples were collected from 91 patients. All samples were analysed in eight parallel ROTEM channels, resulting in 1,800 measurements. In hypocoagulable samples, defined as those with values outside the normal reference range, the CV of CT was higher (median (interquartile range)) (6.3% (5.1-9.5)) than for normocoagulable samples (5.1% (3.6-7.5)), p < 0.001. CFT showed no difference (p = 0.14), while the CV of alpha-angle was higher in hypocoagulable samples (3.6% (2.5-4.6)) than in normocoagulable samples (1.1% (0.8-1.6), p < 0.001. The CV of MCF was higher in hypocoagulable samples (1.8% (1.3-2.6)) than in normocoagulable samples (1.2% (0.9-1.7)), p < 0.001. The CV ranges for the different variables were as follows: CT: 1.2%-37%, CFT: 1.7%-30%, alpha-angle: 0.0%-17% and MCF: 0.0%-8.1%.
CONCLUSIONS: CVs for the EXTEM ROTEM parameters CT, alpha-angle, and MCF increased in hypocoagulable blood compared to blood with normal coagulation, confirming the hypothesis for CT, alpha-angle, and MCF but not for CFT. Furthermore, the CVs for CT and CFT were much higher than those for alpha-angle and MCF. The results demonstrate that EXTEM ROTEM results from patients with weak coagulation should be interpreted with the notion of limited precision and that procoagulative treatment, based only on ROTEM EXTEM, should be given with some caution.

BACKGROUND: Rotational thromboelastometry (ROTEM) records whole blood coagulation in vitro. Data on dynamic changes of clot patterns during intravenous thrombolysis (IVT) in acute ischemic stroke is scarce. We investigated the feasibility of ROTEM as a potential point-of-care assessment tool for IVT.
METHODS: In this prospective pilot study, patients with acute stroke symptoms received IVT. Whole blood coagulation was tracked on the ROTEM analyzer. Blood samples were analyzed before, and then 2, 15, 30 and 60 min after beginning IVT. In vitro clots (iCLs) were described by their maximum clot firmness (MCF), the time needed to reach MCF (MCF-t), as well as the area under the curve (AR10). National Institutes of Health Stroke Scale (NIHSS) was used as early clinical outcome parameter.
RESULTS: We analyzed 288 iCLs from 12 patients undergoing IVT. In all iCLs, an early fibrinolysis (91% within the first 10 min) was detected during IVT. Three different curve progression patterns were observed: a low-responder pattern with a continuous clot increase, a high-responder pattern with a sustained clot decrease or total clotting suppression and an intermediate-responder pattern with alternating clot characteristics. There was a difference among these groups in early clinical outcome (AR10 and MCF each p = 0.01, MCF-t p = 0.02, Kruskal-Wallis Test).
CONCLUSIONS: The fibrinolysis patterns determined using ROTEM allow for the monitoring of IVT in patients with acute ischemic stroke. This pilot study found a correlation between the in vitro fibrinolysis patterns and early clinical outcomes. These findings support a potential for individualization of IVT in the future.

BACKGROUND: Point-of-care viscoelastic haemostatic assays such as rotational thromboelastometry (including ROTEM and TEG) have been used in the management of postpartum haemorrhage (PPH). This study compared results obtained from the automated ROTEM Sigma with laboratory tests of coagulation and platelet count during PPH.
METHODS: A prospective observational cohort study recruited women with PPH ≥1000 mL (or clinical concern of bleeding). The Fibtem A5, Extem CT and Pltem (Extem A5 - Fibtem A5) results were compared with laboratory tests of fibrinogen, prothrombin time (PT), activated partial thromboplastin time (APTT) and platelet count.
RESULTS: 521 women were recruited, including 274/277 (98.9%) of women with PPH ≥1500 mL. Fibtem A5 results were matched with laboratory fibrinogen in 552/644 (85.7%) samples. The incidence of abnormal laboratory results was low: fibrinogen ≤2 g/L 23/464 (5.0%), PT or APTT >1.5 × midpoint of reference range 4/464 (0.9%), and platelet count <75 × 109/L 11/477 (2.3%). Area-under- the-receiver operator characteristic curve for Fibtem A5 to detect fibrinogen ≤2 g/L was 0.96 (95% Confidence Intervals (CI) 0.94 to 0.98, P<0.001), with sensitivity and specificity of Fibtem A5 ≤11 mm to detect fibrinogen ≤2 g/L of 0.76 and 0.96. Prolonged Extem CT results improved after treatment of hypofibrinogenaemia alone. Intervention points for platelet and fresh frozen plasma (FFP) transfusion based on ROTEM Sigma parameters could not be established.
CONCLUSIONS: During PPH (≥1000 mL or cases of clinical concern about bleeding), ROTEM Sigma Fibtem A5 can detect fibrinogen ≤2 g/L and guide targeted fibrinogen replacement. Laboratory results should continue to be used to guide platelet and FFP transfusion.

Postpartum hemorrhage (PPH) can be associated with coagulopathy, which may be difficult to rapidly assess and may exacerbate blood loss. Rotational thromboelastometry (ROTEM) at the point of care can guide clinician choice of blood products and has been shown in some settings to reduce transfusions and improve outcomes. This hospital-based observational study aims to measure effects of a ROTEM-guided transfusion protocol on transfusion practice and clinical outcomes in patients with PPH managed in the operating theater.
We compared a retrospective cohort of 450 consecutive patients with PPH treated in the operating theater before the introduction of a ROTEM-guided transfusion algorithm in June 2016, with 450 patients treated after its introduction. Multivariate regression was used to evaluate the effect of ROTEM introduction on the primary outcome, patients requiring a packed red blood cell (PRBC) transfusion and adjusting for demographic and obstetric confounders. Secondary outcomes included other blood product transfusions, hysterectomy, and intensive care unit admission.
A total of 90 (20%) of patients treated prior to ROTEM introduction received a PRBC transfusion, compared with 102 (22.7%) of those treated after ROTEM introduction (95% confidence interval [CI] 1.0-2.0, p = .04). There was no difference in PRBC transfusion in patients undergoing caesarean section (95% CI 0.5-1.8, p = .99). There was a trend toward increased use of cryoprecipitate and reduced use of platelets and fresh frozen plasma after ROTEM introduction.
In our institution, the introduction of ROTEM-guided transfusion did not reduce PRBC transfusion in patients with PPH treated in the operating theater.

Coagulopathic bleeding is frequently present after major trauma. However, trauma-induced coagulopathy (TIC) remains incompletely understood. This laboratory analysis of blood samples derived from our completed trial on fibrinogen in the initial resuscitation of severe trauma (FiiRST) was conducted to evaluate TIC and associated responses to fibrinogen replacement.
We conducted a retrospective evaluation of TIC in 45 FiiRST trial patients based on rotational thromboelastometry (ROTEM), international normalized ratio (INR), and biomarkers for hemostasis and endotheliopathy. Whole blood was analyzed by ROTEM. Plasma was analyzed for INR and biomarkers.
Overall, 19.0% and 30.0% of the FiiRST trial patients were coagulopathic on admission defined by EXTEM maximum clot firmness out of the range of 40-71 mm and INR >1.2, respectively. The FiiRST patients showed lower fibrinogen, factor II and V levels, protein C and antiplasmin activities, higher activated protein C, tissue plasminogen activator, d-dimer, and thrombomodulin concentrations at admission than healthy controls. Most of the biomarkers changed their activities during 48-h hospitalization, but were at abnormal levels even 48-h after admission. The fibrinogen treatment reduced hypofibrinogenemia and increased factor XIII level, but had no significant effects on other biomarkers levels. Limited development of endotheliopathy was indicated by syndean-1, thrombomodulin, and sE-selectin.
About 19%-30% of the trauma patients in the FiiRST trial were coagulopathic on hospital admission depending on the definition of TIC. Analyses of the TIC biomarkers demonstrated that hemostasis would not return to normal after 48-h hospitalization, and fibrinogen replacement improved hypofibrinogenemia.

OBJECTIVE: Rotational thromboelastometry (ROTEM®) allows guided blood product resuscitation to correct trauma-induced coagulopathy in bleeding trauma patients. FIBTEM amplitude at 10 min (A10) has been widely used to identify hypofibrinogenaemia; locally a threshold of < 11 mm has guided fibrinogen replacement. Amplitude at 5 min (A5) carries an inherent time advantage. The primary aim was to explore the relationship between FIBTEM A5 and A10 in a trauma. Secondary aim was to investigate the use of A5 as a surrogate for A10 within a fibrinogen-replacement algorithm.
METHODS: Retrospective observational cohort study of arrival ROTEM results from 1539 consecutive trauma patients at a Level 1 trauma centre in Australia. Consistency of agreement between FIBTEM A5 and A10 was assessed. A new fibrinogen replacement threshold was developed for A5 using the A5-A10 bias; this was clinically compared to the existing A10 threshold.
RESULTS: FIBTEM A5 displayed excellent consistency of agreement with A10. Intraclass correlation coefficient = 0.972 (95% confidence interval [CI] 0.969-0.974). Bias of A5 to A10 was - 1.49 (95% CI 1.43-1.56) mm. 19.34% patients met the original local threshold of A10 < 11 mm; 19.28% patients met the new, bias-adjusted threshold of A5 < 10 mm.
CONCLUSIONS: ROTEM FIBTEM A5 reliably predicts A10 in trauma. This further validates use of the A5 result over A10 allowing faster decision-making in time-critical resuscitation of trauma patients. A modification of -1 to the A10 threshold might be appropriate for use with the A5 value in trauma patients.