Coagulopathy and traumatic brain injury (TBI) are complexly intertwined. In isolated TBI, coagulopathy may contribute to hemorrhagic lesion development, progression, or recurrence, as it may lead to a particular pattern of coagulopathy called TBI-induced coagulopathy (TBI-IC). We performed a retrospective and descriptive evaluation of 63 patients admitted to the Emergency Clinical Hospital Bucharest with the diagnosis of moderate/severe brain injury. In addition to demographic data, all included patients had a complete paraclinical evaluation that included rotational thromboelastometric (ROTEM) blood-clot analysis. The platelet component (PLTEM) and the endotheliopathy activation and stress index score (EASIX) were calculated. These parameters were presented comparatively according to survival at 30 days and helped define the two study groups: survivors and non-survivors at 30 days. The contribution of platelets to clot strength is derived from maximum clot elasticity (MCE) and maximum clot firmness (MCF). MCE is defined as (MCF × 100)/(100 - MCF), and PLTEM is defined as EXTEM MCE-FIBTEM MCE. EASIX is a novel biomarker recently studied in TBI patients, calculated according to the following formula: lactate dehydrogenase (U/L) × creatinine (mg/dL)/platelets (109 cells/L). Regarding the demographic data, there were no significant differences between the survivors and non-survivors. All ROTEM parameters related to clot amplitude (A5, A10, A20, MCF in EXTEM and FIBTEM channels) were higher in the group of patients who survived. Also, PLTEM was decreased in the group of deceased patients (89.71 ± 22.86 vs. 132.3 ± 16.56 p < 0.0001). The cut-off point determined with the ROC curve is 114.10, with a sensitivity of 94.74% and a specificity of 93.18%, for the detection of the negative prognosis (death at 30 days). The EASIX score was significantly higher in the patients who survived the traumatic event, with a median difference value of 1.15 (p < 0.0001). The ROC analysis of this biomarker highlights a cut-off point of 2.12, with a sensitivity of 88.64% and a specificity of 94.74% (AUC = 0.95, p < 0.0001), for the prediction of mortality. The comparative analysis of the two studied markers was performed using the Cox proportional hazard ratio and highlighted the greater influence that PLTEM has on survival time (b value = -0.05, p < 0.0001) compared to EASIX (b value = 0.49, p = 0.0026). The present retrospective study indicates the potential of the TBI-IC reflecting parameters PLTEM and EASIX as markers of mortality prognosis. Larger prospective studies are needed to confirm their combined prognostic value and use in decision-making and reduction in the burden of disease by adequate allocation of resources in a personalized and timely manner.

BACKGROUND: Hemophilia A (HA) is an X-linked inherited bleeding disorder caused by reduced factor VIII (FVIII) levels. Approximately 10-15% of patients with severe HA (SHA) do not present with the anticipated bleeding pattern. Here, we assessed the phenotypic severity of hemophilia A using rotational thromboelastometry (ROTEM) and activated partial thromboplastin time-clot waveform analysis (APTT-CWA).
METHODS: Patients diagnosed with hemophilia A were enrolled. Clinical phenotype assignment was performed according to the published literature, and patients were classified into four phenotypic subgroups. The whole blood sample was first run on ROTEM in INTEM mode using platelet-poor plasma, APTT was run, and the APTT-CWA graph was simultaneously recorded.
RESULTS: A total of 66 patients were recruited for this study. Statistically significant differences were observed between the four phenotypically categorized groups using ROTEM and APTT-CWA. On comparing patients with mild/moderate-to-severe phenotypes (Group II) with SHA without inhibitors (Group IV), no significant difference was found for all parameters of ROTEM or APTT-CWA. The MCF, MA30, MAXV, and Alpha angle values using ROTEM were found to be the lowest in patients with SHA with inhibitors, which helped differentiate them from those with SHA without inhibitors. However, these two groups could not be differentiated using the APTT-CWA parameters.
CONCLUSIONS: ROTEM can be used to distinguish patients with SHA with inhibitors from those with SHA without inhibitors using a combination of parameters with high sensitivity and specificity. However, APTT-CWA cannot be used to differentiate these patient groups.

UNASSIGNED: Factor Xa inhibitors are direct oral anticoagulants that are extremely useful in clinical applications, safe, and do not require dose adjustment. It is desirable to be able to monitor their effects in the event of hemorrhagic complications requiring neutralization. However, it is difficult to monitor their activity and neutralization using conventional coagulation tests.
UNASSIGNED: We report three patients taking factor Xa inhibitors who underwent rotational thromboelastography (ROTEM) monitoring before and after neutralization with andexanet alfa. All three patients had hemorrhagic complications that required neutralization of their factor Xa inhibitors using andexanet alfa. One ROTEM parameter, the EXTEM clotting time (EXTEM-CT), was immediately shortened after andexanet alfa bolus administration, without subsequent extension of the EXTEM-CT assessed 4 h after the bolus dose.
UNASSIGNED: ROTEM parameters, particularly EXTEM-CT, might be useful for monitoring neutralization of factor Xa inhibitors.

UNASSIGNED: Critically ill COVID-19 patients are at risk for venous thromboembolism (VTE). Therefore, they receive thromboprophylaxis and, when appropriate, therapeutic unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH). To monitor heparins in COVID-19 disease, whole-blood rotational thromboelastometry (ROTEM) may be a promising alternative to the aPTT and anti-Xa assays.
UNASSIGNED: To evaluate the ROTEM INTEM/HEPTEM ratios in mechanically ventilated COVID-19 patients treated with UFH and therapeutic LMWH.
UNASSIGNED: A subcohort of mechanically ventilated COVID-19 patients of the prospective Maastricht Intensive Care Covid (MaastrICCht) cohort was studied. Anti-Xa, aPTT, and ROTEM measurements following treatment with UFH or therapeutic dose of LMWH (nadroparin) were evaluated using uni- and multivariable linear regression analysis and receiver operating characteristics.
UNASSIGNED: A total of 98 patients were included, of which 82 were treated with UFH and 16 with therapeutic LMWH. ROTEM-measured INTEM/HEPTEM CT ratio was higher in patients using UFH (1.4 [1.3-1.4]) compared to patients treated with LMWH (1.0 [1.0-1.1], p < 0.001). Both the aPTT and anti-Xa were associated with the CT ratio. However, the β-regression coefficient (95%CI) was significantly higher in patients on UFH (0.31 (0.001-0.62)) compared to therapeutic LMWH (0.09 (0.05-0.13)) for comparison with the anti-Xa assay. Furthermore, ROC analysis demonstrated an area under the curve for detecting UFH of 0.936(0.849-1.00), 0.851(0.702-1.000), and 0.645(0.465-0.826) for the CT ratio, aPTT, and anti-Xa, respectively.
UNASSIGNED: The ROTEM INTEM/HEPTEM CT ratio appears a promising tool to guide anticoagulant therapy in ICU patients with COVID-19 disease, but associations with clinical endpoints are currently lacking.

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.

BACKGROUND: Intrauterine growth restriction (IUGR) is associated with hemorrhagic and thrombotic complications during the perinatal period. Thrombocytopenia, platelet dysfunction, and prolonged standard coagulation tests are observed in this population. The aim of this study is to examine the hemostatic profile of IUGR neonates with the use of a non-activated assay (NATEM) in cord blood samples.
METHODS: During an 18 month period, a NATEM ROTEM assay was performed on cord blood samples of 101 IUGR neonates. A total of 189 appropriate for gestational age (AGA) neonates were used as a control group. The NATEM variables recorded include the following: clotting time (CT); clot formation time (CFT); clot amplitude at 5, 10, and 20 min (A5, A10, A20); α-angle (a°); maximum clot firmness (MCF); lysis index at 30 and 60 min (LI30, LI60); and maximum clot elasticity (MCE).
RESULTS: IUGR neonates demonstrate a hypocoagulable state, with lower A5, A10, A2, MCF, and MCE values when compared to AGA. Using multiple linear regression, we determined IUGR as an independent factor influencing all NATEM parameters (except CT and LI30) exhibiting a hypocoagulable and hypofibrinolytic profile. Platelet count was positively correlated with A5, A10, A20, MCF, alpha angle, and MCE, and negatively correlated with CFT.
CONCLUSIONS: IUGR neonates appear with lower clot strength and elasticity and prolonged clot kinetics, as illustrated by ROTEM variables.

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav™, Inoserp™ South America, Antivipmyn™ TRI, and PoliVal-ICP™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites.

UNASSIGNED: The type of fluid that should be used in uncontrollable hemorrhages remains an area of research. This study was designed to compare the effects of resuscitation with Ringer\'s lactate (RL) solution versus a normal saline (NS) solution on hemodynamics, renal tissue histopathology, coagulation, and apoptosis in a rat model of hemorrhagic shock.
UNASSIGNED: The study employed groups designated as the control, hemorrhage, NS, and RL groups. Heart rate, mean arterial pressure, and respiratory rate were monitored. Annexin A5 values were assayed, rotational thromboelastometry analysis was performed, and excised kidney tissue samples were histopathologically analyzed.
UNASSIGNED: Blood pressure levels were found to be significantly higher in the control group than those measured in the other groups. While the clotting time (CT) and clot formation time (CFT) in the hemorrhage group were significantly longer than those in the control and RL groups, the CT and CFT measured in the control group were significantly shorter compared to the RL group. The mean Annexin A5 level was in the hemorrhage group, which was significantly higher compared to the other groups. In the renal histopathological evaluation, the scores of proximal tubular injury, distal renal tubular injury, and interstitial renal tubular injury were found to be significantly lower in the control group compared to the other groups.
UNASSIGNED: This study demonstrated that NS or RL can be used safely to improve the hemodynamic symptoms resulting from hemorrhagic shock as a means to reduce apoptosis, and to decrease findings in favor of coagulopathy in bedside coagulation tests during the early stages of hemorrhagic shock until the time of starting a blood transfusion.

Diffuse large B-cell lymphoma (DLCBL) is a heterogenous disease, with many phenotypic subtypes and occasional paraneoplastic syndromes being present. Herein, we describe a case of a 63-year-old woman, with relapsed/refractory DLBCL (RR-DLBCL) with artifactual hypoglycemia on laboratory testing, likely related to the mechanical effects of a new factor VIII inhibitor. We demonstrate our workup, consideration, treatment, and her clinical course. This patient did not present with a bleeding phenotype despite her aberrant laboratory results, and therefore determining her risk of bleeding to weigh against further diagnostic procedures presented a difficult decision. We utilized rotational thromboelastometry (ROTEM) to assist with clinical decision making regarding her paraneoplastic factor VIII inhibitor and the patient\'s bleeding risk. This led to a short course of dexamethasone. Her ROTEM improved, and an excisional biopsy was performed without any bleeding. To our knowledge, this is the only reported instance where this technology was utilized in this setting. We believe utilizing ROTEM to determine bleeding risk may be a beneficial tool for clinical practice in such additional rare cases.

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.