Time Course of Coagulopathy Evaluated with Rotational Thromboelastometry in Patients with Severe Coronavirus Disease 2019.

Objectives Coronavirus disease 2019 (COVID-19) reportedly causes thromboembolic complications due to coagulopathy with hypercoagulability and a hypofibrinolytic state. We evaluated the time-course of coagulopathy in patients with severe COVID-19 from admission to discharge from our intensive-care unit (ICU). Methods We conducted a retrospective study of adults with severe COVID-19 admitted to our ICU between January 20, 2021, and March 31, 2022. We obtained clinical information, laboratory data, and rotational thromboelastometry (ROTEM) parameters at admission and discharge. Results Fifteen patients were included. Fibrinogen and D-dimer values did not change significantly but were above the normal ranges at admission and discharge. Regarding ROTEM parameters, the maximum clot firmness in fibrinogen function (FIBTEM), a marker of hypercoagulability, did not change significantly but was above the normal range at admission and discharge [median (interquartile range), admission vs. discharge: 31 (25-34) mm vs. 31 (27-32) mm, p=0.589]. The maximum lysis at 60 minutes in the extrinsic coagulation pathway (EXTEM) and intrinsic coagulation pathway (INTEM), as markers of the fibrinolytic function, were both significantly lower at discharge than at admission [median (interquartile range), admission vs. discharge: EXTEM, 3 (2-4) vs. 1 (0-2), p=0.011; INTEM, 3 (1-6) vs. 1 (0-2), p=0.008]. Conclusion This study revealed a persistent hypercoagulable state at ICU discharge and a worse hypofibrinolytic state at discharge than at admission. These results may contribute to a better understanding of coagulopathies in the acute to subacute phases of severe COVID-19.

Viscoelastic testing: an illustrated review of technology and clinical applications.

Viscoelastic testing (VET), including thromboelastography and thromboelastometry, provides a rapid and comprehensive picture of whole blood coagulation dynamics and hemostasis that can be reviewed and evaluated at the point-of-care. This technology is over 50 years old; however, over the past few years, there has been a significant increase in research examining the use of VET. Best practice guidelines for the use of VET exist in both the United States and Europe, particularly for elective cardiac surgery, although recommendations for implementation are somewhat limited in some clinical areas by the lack of studies constituting high-grade evidence. Other challenges to implementation surround validation of the technology in some care settings as well as lack of training. Nevertheless, there is a wide range of potential clinical applications, such as treating coagulopathies in liver disease and transplant surgery, critical care, as well as within obstetrical hemorrhage. In this illustrated review, we provide an overview of viscoelastic testing technology (also called viscoelastic hemostatic assays) and describe how the assays can be used to provide a broad overview of hemostasis from clot formation to clot lysis, while highlighting the contribution of coagulation factors and platelets. We then summarize the major clinical applications for viscoelastic testing, including more recent applications, such as in COVID-19. Each section describes the clinical context, and key publications, followed by a representative algorithm and key guidelines.

Are Viscoelastometric Assays of Old Generation Ready for Disposal? Comment on Volod et al. Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices. J. Clin. Med. 2022, 11, 860.

With the advent of new viscoelastometric hemostatic assay (VHA) devices, with ready-to-use cartridge reagents allowing for their use by people without special laboratory skills, the appreciation of the actual clinical value of VHAs in settings such as severe trauma, post-partum hemorrhage, cardiac surgery and liver transplantation still needs to be fully validated. While two of the newest versions remain based on a 'cup and pin' system (ROTEM® sigma, ClotPro®), two other new devices (TEG® 6s, Quantra®) rely on very different technologies: clotting blood is no longer in contact with the probe and challenged by oscillation of one of the components but explored with ultrasound exposure. A systematic literature search (including Sonoclot®) retrieved 20 observational studies (19 prospective). Most studies pointed to imperfect agreements, highlighting the non-interchangeability of devices. Only a few studies, often with a limited number of patients enrolled, used a clinical outcome. No study compared VHA results with conventional laboratory assays obtained through a rapid tests panel. Clinical evidence of the utility of the new VHAs largely remains to be proven through randomized clinical trials, with clinically relevant outcomes, and compared to rapid panel hemostasis testing. The availability of new, improved VHA devices provides an impetus and an opportunity to do so.

Use of rotational thromboelastometry to predict the outcome of COVID-19 patients: A retrospective observational study.

Background and Aims: The hypercoagulability occurring in COVID-19 patients is detected only by Rotational thromboelastometry (ROTEM). However, the benefit of performing ROTEM in the management of disease and predicting the outcome of COVID-19 patients is yet to be established. Material and Methods: The data of 23 critically ill and 11 stable COVID-19 adult patients were extracted from the hospital information system admitted between July and August 2020 and patient charts and analyzed retrospectively. The critically ill patients were divided as a survivor and non-survivor groups. The Intrinsic pathway part of ROTEM (INTEM) and Fibrinogen part of ROTEM (FIBTEM) were performed on day 0 for both critically ill and stable patients, and on day 10 for critically ill patients. The statistical package for social science (SPSS) version 26 was used for statistical analysis. Results: The median FIBTEM amplitude at 5 min (A5) and maximum clot firmness (MCF) were elevated in both stable and critically ill patients (24 vs 27 mm, P = 0.46 and 27.5 vs 40 mm, P = 0.011) with a significant difference in FIBTEM MCF. But there was no significant difference between number of survivors and non-survivors with FIBTEM MCF >25 at day 0 and day 10. Conclusion: The Hypercoagulability state as detected by ROTEM parameters at day 0 and day 10 had no association with the outcome (mortality) of critically ill COVID-19 patients. Hence it cannot be used as a prognostic test. The increasing age, comorbidities and D-dimer values were associated with a poor prognosis in COVID-19 patients.

Rotational thromboelastometry in critically ill COVID-19 patients does not predict thrombosis.

Background: Critically ill COVID-19 patients are in a hypercoagulable state with increased risk of thrombotic complications. Rotational thromboelastometry (ROTEM) is a viscoelastic test with the potential to reflect COVID-19-associated hypercoagulability and may therefore be useful to predict thrombotic complications. Objective: To investigate the potential of ROTEM profiles to predict thrombotic complications in critically ill COVID-19 patients. Patients/Methods: Retrospective multicenter cohort study in 113 adult patients with confirmed COVID-19 infection admitted to the intensive care unit (ICU) of two large teaching hospitals in the United States and in the Netherlands. ROTEM profiles of the EXTEM, INTEM, and FIBTEM tracings were measured within 72 h of ICU admission. Thrombotic complications encompass both arterial and venous thromboembolic complications, diagnosed with electrocardiogram, ultrasound, or computed tomography. ROTEM profiles were compared between patients with and without thrombosis. Univariable logistic regression followed by receiver operating characteristic (ROC) curves analysis was performed to identify ROTEM parameters associated with thrombosis. Results and Conclusions: Of 113 patients, 27 (23.9%) developed a thrombotic event. In the univariable analysis, EXTEM clot amplitude at 10 min (CA10) and EXTEM maximum clot formation (MCF) were associated with thrombosis with a p < 0.2 (p = 0.07 and p = 0.05, respectively). In ROC curve analysis, EXTEM CA10 had an area under the curve (AUC) of 0.58 (95% CI 0.47-0.70) and EXTEM MCF had an AUC of 0.60 (95% CI 0.49-0.71). Thereby, ROTEM profiles at ICU admission did not have the potential to differentiate between patients with a high and low risk for thrombotic complications.

Viscoelastic Testing in Pediatric Mechanical Circulatory Support.

Pediatric mechanical circulatory support can be lifesaving. However, managing anticoagulation is one of the most challenging aspects of care in patients requiring mechanical circulatory support. Effective anticoagulation is even more difficult in pediatric patients due to the smaller size of their blood vessels, increased turbulent flow, and developmental hemostasis. Recently, viscoelastic testing (VET) has been used as a qualitative measure of anticoagulation efficacy in patients receiving extracorporeal membrane oxygenation (ECMO) and ventricular assist devices (VAD). Thromboelastography (TEG®) and thromboelastometry (ROTEM®) provide a global qualitative assessment of hemostatic function from initiation of clot formation with the platelet-fibrin interaction, platelet aggregation, clot strength, and clot lysis. This review focuses on the TEG®/ROTEM® and important laboratory and patient considerations for interpretation in the ECMO and VAD population. We summarize the adult and pediatric ECMO/VAD literature regarding VET values, VET-platelet mapping, utility over standard laboratory monitoring, and association with outcome measures such as blood product utilization, bleeding, and thrombosis.

Platelets genetically modified with mRNA-lipid nanoparticles are functionally similar to clinically transfused platelets in vitro

Background: Platelet transfusions are an essential treatment for attenuating bleeding but are often ineffective in cases of intractable haemorrhage. Although anucleate, mature platelets synthesize protein de novo, making them amenable to mRNA gene therapy;however, there remains to be an effective transfection technique. Advancements in lipid nanoparticle technology has enabled leading COVID vaccines and is an efficient method to deliver nucleic acids into target cells. Recently, we developed a LNP approach to successfully express exogenous protein in platelets [unpublished data], a first step towards demonstrating that donor platelet coagulability can be engineered. However, the effects of LNP treatment on platelet function has yet to be investigated. Aims: To determine whether LNP-treated donor platelets are functionally similar, or better, in vitro, than platelets currently transfused clinically as a next step to establish LNP engineered platelets as a new cell therapy. Methods: The hemostatic profiles of LNP-treated and clinical donor platelets were assessed using an adapted rotational thromboelastometry model of dilutional coagulopathy. LNP-treated platelets were also stimulated with conventional platelet agonists to test if responsiveness is similar, or better than clinical platelets using flow cytometry. Results: LNP-treated platelets have a comparable hemostatic profile to clinically transfused platelets and significantly improved clotting dynamics when spiked into hemodiluted whole blood in an in vitro transfusion simulation. LNP-treated platelets also respond comparably, and in some cases more potently to agonist simulation compared to untreated platelets as indicated by similar p-selectin surface presentation. Summary/Conclusions: LNPs are an effective way to deliver exogenous nucleic acids into platelets;they do not significantly change platelet coagulability or responsiveness to agonists. LNP platelet engineering is a promising new approach to load platelets with procoagulant protein to enhance their function.

Fibrinolytic Proteins and Factor XIII as Predictors of Thrombotic and Hemorrhagic Complications in Hospitalized COVID-19 Patients.

Introduction: In a prospective cohort of hospitalized COVID-19 patients, an extensive characterization of hemostatic alterations by both global and specific assays was performed to clarify mechanisms underlying the coagulopathy and identify predictive factors for thrombotic and hemorrhagic events during hospitalization. Materials and Methods: Intensive care unit (ICU; n = 46) and non-ICU (n = 55) patients were enrolled, and the occurrence of thrombotic and hemorrhagic events was prospectively monitored. At study inclusion, thromboelastometry together with the measurement of specific coagulation proteins and hypercoagulation markers was performed. Results: Patients (median age 67 years) showed significantly shorter clot formation time together with greater maximum clot firmness by thromboelastometry, increased levels of F1 + 2 and D-dimer, as biomarkers of hypercoagulability, and of procoagulant factors V, VIII, IX, XI, and fibrinogen, while FXIII was significantly reduced. The concentration of fibrinolytic proteins, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor type 1 (PAI-1) were elevated in the overall cohort of patients. Many of these hemostatic alterations were significantly greater in ICU compared to non-ICU subjects and, furthermore, they were associated with inflammatory biomarker elevation [i.e., interleukin 6 (IL-6), C-reactive protein (CRP), neutrophil to lymphocyte ratio (NLR), and procalcitonin]. After enrollment, 7 thrombosis and 14 major bleedings occurred. Analysis of clinical and biological data identified increased t-PA, PAI-1, and NLR values as independent predictive factors for thrombosis, while lower FXIII levels were associated with bleeding. Conclusion: This study demonstrates alterations in all different hemostatic compartments analyzed, particularly in severe COVID-19 conditions, that strongly correlated with the inflammatory status. A potential role of fibrinolytic proteins together with NLR and of FXIII as predictors of thrombotic and hemorrhagic complications, respectively, is highlighted.

Evaluation of coagulation function in critically ill patients with severe Covid-19 pneumonia

Background-aim: In addition to typical respiratory symptoms, COVID-19 is associated with coagulation abnormalities that lead to thromboembolic complications. Methods: Retrospective study of critically ill patients admitted to an intensive care unit (ICU) a cause of severe COVID-19 pneumonia (Group 1) and we evaluated coagulation function using coagulation standard parameters on day of admission (T0) and 10 (T10) days after admission to ICU and rotational thromboelastometry (ClotPro). In addition, we compared coagulation standard parameters to patients with severe non–COVID-19 pneumonia (Group 2). Results: Eighty-four patients participated in our study. Traditional coagulation parameters were similar between group 1 and group 2. Only D-dimer levels (2442.11 ng / ml vs 370 ng / ml, p = 0.03) were significantly higher in COVID-19 pneumonia than in non-COVID-19 pneumonia. In addition, we concluded an increase in D-dimer levels during the hospital stay (T0 = 2442.11 ng / ml vs T10 = 8564.39 ng / ml, p = 0.000). Finally, patients with SARS-CoV-2 pneumonia exhibited hypercoagulant thromboelatometry profiles, characterized by elevated maximum clot firmness (MCF) values. Conclusions: The results observed in our study support hypercoagulability in a severe inflammatory state, rather than a disseminated intravascular coagulation (DIC). More studies are needed to allow a better understanding of the coagulopathy produced in patients with severe COVID-19 pneumonia.

Evaluation of coagulation function by rotation thromboelastometry in critically ill patients with severe Covid-19 Pneumonia

Background-aim: Critically ill patients with COVID-19 pneumonia suffered both high thrombotic and bleeding risk. The effect of SARS-CoV-2 on coagulation and fibrinolysis is not well known. Methods: Retrospective cohort study including 84 patients, during 16 months, divided into two groups: patients with severe SARS-Cov-2 pneumonia (group 1, N=42) and patients with severe non-COVID-19 pneumonia (group 2, N=42). We evaluated coagulation standard parameters (hemoglobin, platelet count and conventional laboratory coagulation tests) in group 1 vs group 2 and coagulation standard parameters on day of admission (T0) and 10 (T10) days after admission to ICU and coagulation function using rotational thromboelastometry (ROTEM) in patients with severe SARS-Cov-2 pneumonia. Results: 84 patients were enrolled into the study. Similar results in conventional laboratory coagulation tests were detected in group 1 and group 2: prothrombin time (15.14s vs 14.76s, p=0.212), international normalized ratio (1.21 vs 1.19, p=0.112), activated partial thromboplastin time (32.17s vs 25.52s, p=0.06), fibrinogen level (6.15 mg/dl vs 3.39 mg/dl, p=0.208), hemoglobin (11.81 g/dl vs 11.20 g/dl, p=0.139) and platelet count (208.98x103/ul vs 288.74 x103/ul, p=0.123). However, a statistically significant difference was observed in the D-dimer count (2442.11 ng/ml vs 370 ng/ml, p=0.03). In addition, statistically significant increase in D-dimer count during Intensive Care Unit (ICU) stay (T0=2442.11 ng/ml vs T10=8564.39 ng/ml, p=0.000) in group 1 were detected. Finally, blood thromboelastometry profiles were consistent with hypercoagulability characterized by higher clot strength (MCF or maximum clot firmness close to upper limit in FIBTEM test, MCF median value= 25.9 mm). Clotting time presented normal results in INTEM (163.41 s) and EXTEM (68.74 s). No sign of secondary hyperfibrinolysis were found during the study period. In six patients a deep vein thrombosis and in six patients a thromboembolic event. Eighteen patients (43%) died during hospitalization due to coagulopathy produced by SARS-Cov-2 pneumonia. Conclusions: The results observed in our study support hypercoagulability in a severe inflammatory state, rather than a Consumption Coagulopathy (DIC) state. More studies are needed to better understanding of coagulopathy produced in patients with severe COVID-19 pneumonia.

Anticoagulant therapy monitoring in COVID-19 patients in the intensive care unit: thromboelastometry and echocardiography

Aim. To determine the effectiveness of thromboelastometry (TEM) and echocar-diography for anticoagulant therapy monitoring in patients with COVID-19. Material and methods. We analyzed treatment regimen of 92 patients with COVID-19. The patients were divided into two groups. In the control group (n=30), anticoagulant therapy with unfractionated heparin (UFH) was carried out under laboratory control of coagulation parameters. In the experimental group (n=62), anticoagulation was maintained by intravenous UFH under control of coagulation, echocardiography (Philips, Epiq 5) and TEM (ROTEM® delta). Echocardiography determined the pulmonary artery acceleration time (AT), mid-systolic notching (SN). The TEM method was used to study external (EXTEM) and internal (INTEM) pathways, differential tests (FIBTEM, HEPTEM) of coagulation. Statistical analysis was performed by calculating non-parametric statistics parameters, comparisons of differences in groups (Mann-Whitney test), area under the curve (AUC), and regression equations. Results. A high correlation level between echocardiographic and TEM parameters was determined. Their levels associated with a positive prognosis were calculated (AT>113,5 ms., AUC 0,979;p<0,0001;no SN, AUC 0,931;p<0,0001;FIBTEM ML (60 min) >1,12%, AUC 0,971, p<0,0001;INTEM ML (60 min) >2,01%, AUC 0,941, p<0,0001, EXTEM ML (60 min) >1,4%, AUC 0,934, p<0,0001;MCFfib not >26 mm, AUC 0,954;p<0,0001;MCFin not >56,6 mm, AUC 0,938;p<0,0001;MCFex not >47,9 mm, AUC 0,838, p<0,0001). In 33,9% of patients in the experimental group, heparin resistance was detected. In this connection, combined therapy with UFH and direct oral anticoagulants (DOACs) was used, followed by the switch to DOACs. In the control group, artificial ventilation was used in 50% of patients, mortality — 36,6%, myocardial infarction — 13,3%, deep vein thrombosis — 6,6%, pulmonary embolism — 6,6%, while in the experimental group, mechanical ventilation — 12,9%, myocardial infarction — 4,8%, mortality — 8,1%. Conclusion. The dynamic assessment of echocardiography and TEM parameters made it possible to monitor pulmonary thrombosis processes, significantly reduce complications, the use of artificial ventilation and mortality in COVID-19 patients.

Hypercoagulation Detected by Rotational Thromboelastometry Predicts Mortality in COVID-19: A Risk Model Based on a Prospective Observational Study.

Background Severe disease due to the novel coronavirus disease 2019 (COVID-19) has been shown to be associated with hypercoagulation. The aim of this study was to assess the Rotational Thromboelastometry (ROTEM) as a marker of coagulopathy in hospitalized COVID-19 patients. Methods This was a prospective, observational study where patients hospitalized due to a COVID-19 infection were eligible for inclusion. Conventional coagulation tests and ROTEM were taken after hospital admission, and patients were followed for 30 days. A prediction model, including variables ROTEM EXTEM-MCF (Maximum Clot Firmness) which in previous data has been suggested a suitable marker of hypercoagulation, age, and respiratory frequency, was developed using logistic regression to evaluate the probability of death. Results Out of the 141 patients included, 18 (13%) died within 30 days. In the final prediction model, the risk of death within 30 days for a patient hospitalized due to COVID-19 was increased with increased EXTEM-MCF, age, and respiratory frequency. Longitudinal ROTEM data in the severely ill subpopulation showed enhanced hypercoagulation. In an in vitro analysis, no heparin effect on EXTEM-coagulation time (CT) was observed, supporting a severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) effect on prolonged initiation of coagulation. Conclusion Here, we show that hypercoagulation measured with ROTEM predicts 30-day mortality in COVID-19. Longitudinal ROTEM data strengthen the hypothesis of hypercoagulation as a driver of severe disease in COVID-19. Thus, ROTEM may be a useful tool to assess disease severity in COVID-19 and could potentially guide anticoagulation therapy.

Endovascular Thrombectomy for Large Vessel Occlusions in Covid-19 Patients: Technical Challenges and Lessons

INTRODUCTION: Covid 19 infections has been shown to be associated with a range of thromboembolic disease that has implications for the neuro-endovascular management of large vessel occlusions. METHODS: Five consecutive Covid-19 positive patients presented with large vessel occlusions to our institution. Covid-19 testing was performed using nasal swab. All thrombectomy cases was performed under general endotracheal anesthesia using a stent-aspiration combination as primary thrombectomy technique. The technical details of each case and the angiographic outcome are described. Routine labs including D-dimer, platelet count, coagulation panel (aPTT, INR), Interleukin 6 (IL-6), erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) were evaluated in all patients. Rotational thrombelastography (ROTEM) was performed on the patients' blood samples to assess real-time clot formation/dissolution properties. RESULTS: Four patients had anterior circulation large vessel occlusions and one patient had both anterior and posterior circulation occlusions. Mean age was 52.8 years and 80% were males. TICI 3 revascularization was achieved in one patient, TICI 2B achieved in two patients and TICI 2A in two patients. In our cohort, patients were on average 52.8 years old and presented with a median NIHSS of 27. All our patients had very proximal occlusions. Three patients presented with intra-cranial ICA occlusions. Two patients presented with a tandem carotid bulb thrombus in conjunction with an intracranial vessel occlusion. One patient had an ICA terminus occlusion with a concomitant basilar occlusion. Second, the intravascular clots in all our patients were prone to fragment and migrate into both new vascular territories and into distal downstream vasculature. Distal emboli into a different territory (anterior cerebral artery occlusion) was seen in two two of our five patients (40%) and distal emboli into a downstream territory was seen in all five patients (100%). An average of 2.7 pstent-retriever passes was needed to achieve a final TICI revascularization of IIb or better. CONCLUSION: Covid-19 patients are predisposed to a hypercoagulable state. When presenting with large vessel occlusions, these patients present unique challenges that make successful revascularization difficult.

Impaired fibrinolysis is implicated in mortality in COVID-19 infection

Introduction: A significant degree of mortality and morbidity in COVID-19 is due to thromboembolic disease. Changes in coagulation markers have been well described in critically unwell patients on ICU. There is less clear evidence regarding these changes at the time of presentation to the Emergency Department and the progression of disease over time. We sought to investigate how coagulation markers change over the course of COVID-19 infection and whether they might predict disease severity. Methods: Patients were recruited from a single University Teaching Hospital ED at the time of presentation. Those with a positive PCR test were followed up throughout their stay. Rotational thromboelastometry (ROTEM) was performed on arrival, after 24 h, 3-5 days and 7 days, alongside routine haematological and biochemical testing. ROTEM values at each of these time points were analysed, and compared. Length of stay and patient outcome were also recorded for subgroup analysis. The ROTEM parameters selected for analysis were both EXTEM and INTEM Clotting Time (CT), Clot Formation Time (CFT), Maximal Clot Firmness (MCF), Alpha Angle (Alpha) and Maximum Lysis Percentage (ML). This reflects clot formation kinetics, mechanical strength and clot breakdown via both extrinsic and intrinsic pathways. Results: EXTEM (7.64 ± 5.53 vs 11.83 ± 6.30) and INTEM ML (4.69 ± 3.55 vs 9.95 ± 5.22) were significantly reduced in those who died vs patients with a prolonged hospital stay. Over time there were no patterns of change to ROTEM values in any outcome group. Conclusions: Comparisons between groups demonstrated that one distinguishing feature between those who require ICU admission or die of COVID-19 compared with those who survive a prolonged hospital stay to discharge was the extent to which fibrinolysis could occur. Failure to break clots down could be a significant mechanism in the mortality and morbidity of COVID-19.

Fibrin Strands Will Grow from Soluble Fibrin and Hang Up in an In Vitro Microcirculatory Viscoelastic Model: Is This a Major Cause of COVID-19 Associated Coagulopathy?

Viscoelastic testing (VET) by both TEG and ROTEM has demonstrated hypercoagulability early in corona virus disease 2019 (COVID-19) associated coagulopathy (CAC). Additional VET studies demonstrated fibrinolytic shutdown late in a majority of severely ill COVID-19 patients with an associated elevation of d-dimer. Elevated d-dimer confirms that coagulation, followed by fibrinolysis, has occurred. These findings imply that, during CAC, three enzymes-thrombin, Factor XIIIa and plasmin-must have acted in sequence. However, limitations in standard VET analyses preclude exploration of the earliest phases of clot induction, as well as clot formation and clot dissolution in flowing blood. Herein, we describe a novel method illuminating aspects of this unexplored area. In addition, we created an in vitro blood flow model in which the interactions of thrombin, Factor XIII and plasmin with fibrinogen can be studied, allowing the determination of soluble fibrin (SF), the highly unstable form of fibrin that precedes the appearance of a visible clot. This model allows the determination of the SF level at which fibrin microclots begin to form.

Unexplained pulmonary embolism post SARS-CoV2 pneumonia in a patient with MYH9-related disease: a case report

This report describes the case of a man affected by Myosin Heavy Chain 9 (MYH9)-related platelet disorder, with a recent history of SARS-CoV-2 pneumonia, who developed pulmonary embolism (PE). At the admittance the patient presented a marked thrombocytopenia. The rotational thromboelastometry (ROTEM) showed a reduction in maximum clot firmness. The CT scan showed a lobar PE while and no sign of superficial or deep venous thrombosis was found. Given the contraindication of anticoagulant therapy due to severe thrombocytopenia, after collegial evaluation of the case, an inferior vena cava filter was applied. The patient was discharged after 5 days of hospitalization, and fondaparinux 2.5 mg subcutaneously was prescribed for two months. Could MYH9 mutation contribute to thrombotic predisposition? Or rather the endothelial dysfunction induced by SARS-CoV-2 infection? The report presents a dissertation on the possible causes for the PE and describes the therapeutic strategy adopted. (www.actabiomedica.it).

Vaccine-induced thrombotic thrombocytopenia: Novelty testing in the diagnostic workup?

COVID-19 vaccination campagnies with several vaccines types are currently undeway. Recently, the ASTRA ZENECA vaccine has raised public alarm with concerns regarding the development of thrombotic events known as vaccine-induced thrombotic thrombocytopenia (VITT). Early and limited studies have implicated an antibody-mediated platelet activation as the mechanism of the clotting events. Aim of this study was to investigate the platelet and coagulation activation using specialized tests. In this study we enrolled 60 patients (40 men, 20 women;mean age 55±10 years) without cardiovascular risk factors or a history of thrombosis who reported having poplitea deep vein thrombosis (35/60) and pulmonary embolism (25/60) revealed with lower-limb ultrasonography and computed tomography (CT) angiography, respectively, 7 days after vaccination with ASTRA ZENECA. All patients were evaluated for initial testing such as platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fib) and D-dimer (DD). Platelets were measured by automated analyzer, PT and APTT by coagulometric test, Fib using Clauss method, and DD using ELISA. Complete blood hemostasis was studied by platelet function assay (PFA-100) on Collagen/ADP (CT-ADP) and Collagen/Epinephrine (CT-EPI) cartridges and Thromboelastometry method on Clotting Time (CT), Clotting Formation Time (CFT), Maximum Clot Firmness (MCF), and clot lysis at 30 minutes (LY-30). All patients had thrombocytopenia (60±5x109/L), longer PT (28±10 s) and PTT (50±10 s), lower Fib (80±20 mg/dl), higher DD ((550±100 mg/l). All patients had shorter C/ADP and C/EPI (C/ADP, n.v. 68-121 s (42±10 s) and C/EPI n.v. 84-160 s (38±5 s) and shorter CT (CT, unit: s. n.v. 100-240 s) (INTEM 30±20 s, EXTEM 18±10 s), shorter CFT (CFT, unit: s, n.v. 30-160 s (INTEM 11±10 s, EXTEM 19±10 s), longer MCF (MCF, unit: mm, n.v. 50-72 mm (INTEM 128±10 mm, EXTEM 110±10 mm), and lower LY-30 (LY-30, %: v.n. 15% (INTEM 0.8%, EXTEM 0.7%). These interesting findings may be the novelty in the diagnostic work-up of the VITT. If these tests may aid in the diagnosis of VITT deserve to be confirmed and need reproducing in other studies.

The Non-Activated Thromboelastometry (NATEM) Assay's Application among Adults and Neonatal/Pediatric Population: A Systematic Review.

The non-activated thromboelastometry (NATEM) assay is a point-of-care assay that can provide a comprehensive insight into the actual hemostatic mechanism. However, there are very limited data about its use in clinical practice. The aim of this study was to systematically review the literature for any data regarding the use of NATEM in several clinical settings. A systematic review of PubMed and Scopus databases was conducted through 20 January 2022 for studies evaluating the use of the NATEM assay in different clinical settings. The literature search yielded a total of 47 publications, 30 of which met the eligibility criteria for this review. Evaluation of NATEM's detecting ability for hemostasis disorders is limited in the literature. The results of the included studies indicate that NATEM seems to be a sensitive method for the detection of hyperfibrinolysis and may have an advantage in the diagnosis of hemostatic disorders. It could be more informative than the other ROTEM assays for detecting changes in coagulation parameters in patients who receive anticoagulants. However, the reported outcomes are highly varying among the included studies. NATEM has a high sensitivity to detect hypo- or hypercoagulability and provides a detailed insight into the whole hemostatic process from clot formation to clot breakdown. It could be a useful technique in variable fields of medicine, not only in adults, but also in pediatric and neonatal populations, to guide different hemostatic treatments and predict coagulation disorders or mortality/morbidity; this issue remains to be further investigated.

Viscoelastic Hemostatic Assays: A Primer on Legacy and New Generation Devices.

Viscoelastic hemostatic assay (VHAs) are whole blood point-of-care tests that have become an essential method for assaying hemostatic competence in liver transplantation, cardiac surgery, and most recently, trauma surgery involving hemorrhagic shock. It has taken more than three-quarters of a century of research and clinical application for this technology to become mainstream in these three clinical areas. Within the last decade, the cup and pin legacy devices, such as thromboelastography (TEG® 5000) and rotational thromboelastometry (ROTEM® delta), have been supplanted not only by cartridge systems (TEG® 6S and ROTEM® sigma), but also by more portable point-of-care bedside testing iterations of these legacy devices (e.g., Sonoclot®, Quantra®, and ClotPro®). Here, the legacy and new generation VHAs are compared on the basis of their unique hemostatic parameters that define contributions of coagulation factors, fibrinogen/fibrin, platelets, and clot lysis as related to the lifespan of a clot. In conclusion, we offer a brief discussion on the meteoric adoption of VHAs across the medical and surgical specialties to address COVID-19-associated coagulopathy.