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Background: Patients with hematological malignancies (HM) frequently present thrombocytopenia and higher risk of bleeding. Although transfusion is associated with higher risk of adverse events and poor outcomes, prophylactic transfusion of platelets is a common practice to prevent hemorrhagic complications. Thromboelastometry has been considered a better predictor for bleeding than isolated platelet counts in different settings. In early stages of sepsis, hypercoagulability may occur due to higher fibrinogen levels. Objectives: To evaluate the behavior of coagulation in patients with HM who develop sepsis and to verify whether a higher concentration of fibrinogen is associated with a proportional increase in maximum clot firmness (MCF) even in the presence of severe thrombocytopenia. Methods: We performed a unicentric analytical cross-sectional study with 60 adult patients with HM and severe thrombocytopenia, of whom 30 had sepsis (sepsis group) and 30 had no infections (control group). Coagulation conventional tests and specific coagulation tests, including thromboelastometry, were performed. The main outcome evaluated was MCF. Results: Higher levels of fibrinogen and MCF were found in sepsis group. Both fibrinogen and platelets contributed to MCF. The relative contribution of fibrin was significantly higher (60.5 ± 12.8% vs 43.6 ± 9.7%; P < .001) and that of platelets was significantly lower (39.5 ± 12.8% vs 56.4 ± 9.7%; P < .001) in the sepsis group compared with the control group. Conclusion: Patients with sepsis and HM presented higher concentrations of fibrinogen than uninfected patients, resulting in greater MCF amplitudes even in the presence of thrombocytopenia.

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Hypercoagulability and reduced fibrinolysis are well-established complications associated with COVID-19. However, the timelines for the onset and resolution of these complications remain unclear. The aim of this study was to evaluate, in a cohort of COVID-19 patients, changes in coagulation and fibrinolytic activity through ROTEM assay at different time points during the initial 30 days following the onset of symptoms in both mild and severe cases. Blood samples were collected at five intervals after symptoms onset: 6-10 days, 11-15 days, 16-20 days, 21-25 days, and 26-30 days. In addition, fibrinogen, plasminogen, PAI-1, and alpha 2-antiplasmin activities were determined. Out of 85 participants, 71% had mild COVID-19. Twenty uninfected individuals were evaluated as controls. ROTEM parameters showed a hypercoagulable state among mild COVID-19 patients beginning in the second week of symptoms onset, with a trend towards reversal after the third week of symptoms. In severe COVID-19 cases, hypercoagulability was observed since the first few days of symptoms, with a tendency towards reversal after the fourth week of symptoms onset. A hypofibrinolytic state was identified in severe COVID-19 patients from early stages and persisted even after 30 days of symptoms. Elevated activity of PAI-1 and alpha 2-antiplasmin was also detected in severe COVID-19 patients. In conclusion, both mild and severe cases of COVID-19 exhibited transient hypercoagulability, reverted by the end of the first month. However, severe COVID-19 cases sustain hypofibrinolysis throughout the course of the disease, which is associated with elevated activity of fibrinolysis inhibitors. Persistent hypofibrinolysis could contribute to long COVID-19 manifestations.

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Chronic mountain sickness is a maladaptive syndrome that affects individuals living permanently at high altitude and is characterized primarily by excessive erythrocytosis (EE). Recent results concerning the impact of EE in Andean highlanders on clotting and the possible promotion of hypercoagulability, which can lead to thrombosis, were contradictory. We assessed the coagulation profiles of Andeans highlanders with and without excessive erythrocytosis (EE+ and EE-). Blood samples were collected from 30 EE+ and 15 EE- in La Rinconada (Peru, 5100-5300 m a.s.l.), with special attention given to the sampling pre-analytical variables. Rotational thromboelastometry tests were performed at both native and normalized (40%) haematocrit using autologous platelet-poor plasma. Thrombin generation, dosages of clotting factors and inhibitors were measured in plasma samples. Data were compared between groups and with measurements performed at native haematocrit in 10 lowlanders (LL) at sea level. At native haematocrit, in all rotational thromboelastometry assays, EE+ exhibited hypocoagulable profiles (prolonged clotting time and weaker clot strength) compared with EE- and LL (all P < 0.01). At normalized haematocrit, clotting times were normalized in most individuals. Conversely, maximal clot firmness was normalized only in FIBTEM and not in EXTEM/INTEM assays, suggesting abnormal platelet activity. Thrombin generation, levels of plasma clotting factors and inhibitors, and standard coagulation assays were mostly normal in all groups. No highlanders reported a history of venous thromboembolism based on the dedicated survey. Collectively, these results indicate that EE+ do not present a hypercoagulable profile potentially favouring thrombosis.

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Venom-induced consumption coagulopathy and thrombocytopenia are common and potentially severe manifestations of viperid snakebite envenoming since they contribute to local and systemic hemorrhage. Therefore, the assessment of the efficacy of antivenoms to neutralize coagulopathic and thrombocytopenic toxins should be part of the preclinical evaluation of these drugs. To evaluate the efficacy of the polyvalent (Crotalinae) antivenom produced in Costa Rica, in this study we have used a mouse model of coagulopathy and thrombocytopenia induced by the venom of Bothrops asper, based on the bolus intravenous (i.v.) injection of venom. When venom and antivenom were incubated before injection, or when antivenom was administered i.v. immediately after venom injection, venom-induced hemostatic alterations were largely abrogated. We also studied the recovery rate of clotting parameters in conditions where antivenom was administered when mice were coagulopathic. Some parameters recovered more rapidly in antivenom-treated mice than in control envenomed animals, but others showed a spontaneous recovery without antivenom. This is due to a rapid clearance of plasma venom levels in these experimental conditions. This implies that models based on the bolus i.v. injection of venom have limitations for assessing the effect of antivenom in the recovery of clotting alterations once coagulopathy has developed. It is suggested that alternative models should be developed based on a slower systemic absorption of venom. Overall, our findings provide a protocol for the preclinical evaluation of antivenoms and demonstrate that the polyvalent antivenom is effective in neutralizing the toxins of B. asper venom responsible for coagulopathy and thrombocytopenia.

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Background: Sensitivity of classical coagulation assays by using mammalian plasmas to pro‐ and anticoagulant compounds includ ing venom or toxins occurs on a microscale level (micrograms). Al though it improves responses to agonists, recalcification triggers a relatively fast thrombin formation process. The Recalcification Time (RT) of factor XII- deficient Chicken Plasma (CP) is comparatively long (≥1800 seconds) when compared to human plasma or others. Our objective was to compare its sensitivity with that presented by human plasma samples to Unfractionated Heparin (UH), a pro totype anticoagulant compound, under similar conditions through rotational thromboelastometry. Methods: To find doses of UH sufficient enough to prolong the Clotting Time (CT) parameter of these activated plasmas to values within their normal RT ranges. Results: In total, 0.0065±0.0009 IU of UH (n=6) was detected in 260µL of CP samples, but only 0.125±0.012 IU of UH was sufficient to induce a similar effect in activated human plasma samples. Conclusion: The higher sensitivity of CP to anticoagulants could be useful for (a) detection of anticoagulant compounds in substanc es of unknown origin; (b) purification procedures of anticoagulant toxins from crude animal venoms and (c) determination of relative potencies of agonists and their selective antagonists such as phar maceutical agents, antivenoms or natural inhibitors of venom tox ins with a better result in kinetic clothing parameters

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Resumen: La tromboelastometría evalúa los cambios viscoelásticos en el proceso de coagulación. Nos ofrece una representación gráfica de la formación del coágulo, la estabilidad del mismo y la presencia de lisis. La tromboelastometría rotacional es una herramienta diagnóstica que representa de forma gráfica la funcionalidad del coágulo para un manejo dirigido e individualizado de la coagulopatía asociada a hemorragia. En este trabajo se puntualiza cómo la tromboelastometría rotacional es a la coagulación como el electrocardiograma es al corazón.

Abstract: Thromboelastometry evaluates viscoelastic changes in the coagulation process. It offers us a graphic representation of the formation of the clot, its stability and the presence of lysis. Rotational thromboelastometry is a diagnostic tool that graphs the functionality of the clot, for a targeted and individualized management of bleeding-associated coagulopathy. In this work it is specified how rotational thromboelastometry is to coagulation as the electrocardiogram is to the heart.

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Viperid snakebite envenoming is often characterized by a venom-induced consumption coagulopathy due to the procoagulant effect of venom components, resulting in the alteration of clotting laboratory tests. There is a growing trend to use rotational thromboelastometry in the assessment of clotting disturbances in a variety of pathologies, although its use in experimental models of envenoming has been limited. An in vivo murine model was implemented to assess the coagulopathy induced by three Central American viperid venoms which have different mechanisms of action on clotting factors, i.e., Bothrops asper, Crotalus simus and Bothriechis lateralis. Venom was injected by the intravenous route and blood samples were collected at 1, 3, 5 and 24 h after envenoming. Coagulopathy was assessed by standard clotting tests and by routine rotational thromboelastometric parameters. In addition, the changes in platelet number were followed. B. asper and C. simus venoms induced coagulopathy and thrombocytopenia 1 h after injection, followed by a slow recovery at 3, 5 and 24 h, although the majority of clotting parameters were still significantly affected by 3 and 5 h, and were corrected by 24 h. In general, a similar time-course of alterations was observed for standard clotting tests and most rotational thromboelastomeric assays. However, some thromboelastometric parameters, especially those related to Fibtem, showed more drastic alterations than standard tests and remained altered even at 24 h in some cases. This is likely related to the low fibrinogen concentration observed at most time intervals. B. lateralis venom did not induce a consumption coagulopathy, although it caused a marked thrombocytopenia.

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OBJECTIVES: The surgical treatment for diseases of the descending aorta is related to a high mortality rate because of the activation of a systemic inflammatory process due to ischaemia and reperfusion (I/R) injury. Activation of coagulation can contribute to the inflammatory process, resulting in microcirculatory damage and multiple organ failure. Our goal was to evaluate the role of prophylactic intravenous 17ß-oestradiol (E2) in coagulation, the inflammatory response and hepatic injury after occlusion of the descendent proximal aorta in male rats. METHODS: Wistar male rats were randomized and allocated to 3 groups (n = 8 per group): sham, surgically manipulated; IR, animals subjected to I/R; and E2, animals treated with E2 (280 µg/kg, intravenously) before I/R. I/R was induced by insertion of a 2-Fr Fogarty arterial embolectomy catheter in the descending aorta, which was occluded for 20 min, followed by a reperfusion period of 2 h. Serological markers, platelet aggregation, hepatic vascular flow, systemic and liver inflammatory response and apoptosis were analysed. The coagulation process was evaluated by thromboelastometry. RESULTS: The aortic occlusion led to a reduction in plasma fibrinogen concentration in parallel with increased clotting time, greater clot firmness and reduced lysis. E2 treatment was able to increase fibrinogen, prevent the increase in clotting time and normalize clot firmness, but it exerted only a mild effect on clot lysis. Platelet aggregation was increased by IR, and E2 treatment was able to reduce it. There was a reduction in flow percentage in the IR group that was not prevented by E2. In parallel, higher aggregate formation was observed in the vessels of the IR group of animals. There was increased systemic release of interleukin-1-ß, interleukin-6 and interleukin-10 in the IR group, which was reduced in the treated animals. CONCLUSIONS: The current results suggest that pretreatment with E2 before an ischaemic period induced by occlusion of the proximal descending aorta is effective in preventing alterations in coagulation and systemic inflammation due to I/R injury.

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Resumen Introducción: Un adecuado manejo del sangrado debe incluir la correcta valoración y eventual reposición de fibrinógeno. Las fuentes tradicionales de este elemento hemostático incluyen el plasma fresco congelado y los crioprecipitados. Los concentrados liofilizados de fibrinógeno humano (CFH) son una alternativa terapéutica novedosa en el mercado chileno. Objetivo: Este estudio describe el curso clínico de los primeros pacientes en nuestra institución requirentes de CFH, dentro de un algoritmo de reposición hemostática por metas. Materiales y Método: Serie de pacientes con hipofibrinogenemia secundaria a sangrado perioperatorio severo, en los que se utilizó CFH como método de reposición de fibrinógeno. Se utilizó tromboelastometría para definir dosis. Se registraron variables demográficas, operatorias, complicaciones y seguimiento hasta los 3 meses. Resultados: Se utilizaron CFH en 18 pacientes. La mediana de edad fue 40,7 (56,5-63) años y dos tercios de los pacientes fueron de sexo masculino. Fallecieron 5 pacientes de la serie. Todos los pacientes requirieron manejo posoperatorio en una unidad de cuidados intensivos. Ocho pacientes fueron sometidos a cirugía cardiaca. El uso de hemocomponentes y concentrados liofilizados fue heterogéneo, pero en todos los casos su uso fue determinado por tromboelastometría. Ningún paciente fue reintervenido a causa de sangrado posoperatorio. Conclusión: El uso de concentrados de fibrinógeno humano dentro de un algoritmo de manejo de sangrado guiado por tromboelastometría, es un recurso hemostático factible en la realidad nacional. El impacto clínico de esta intervención requiere una subsiguiente evaluación basada en la evidencia.

Introduction: An adequate bleeding management should include a proper assessment of fibrinogen values and consequent replacement. Traditional sources for this hemostatic element include fresh frozen plasma and cryoprecipitates. Lyophilized human fibrinogen concentrates are a novel therapeutic alternative for the chilean market. Aim: This study aims to describe the clinical course of the first patients in our institution receiving fibrinogen concentrates, included in a goal directed hemostatic management algorithm. Materials and Method: Case series of patients with hypofibrinogenemia secondary to severe perioperative bleeding, in which fibrinogen concentrate was used for fibrinogen replacement. Thromboelastometry was used to define dose regimens. Demographic and surgical variables, complications and follow-up up to 3 months were registered. Results: Fibrinogen concentrate was used in 18 patients. Median age was 40.7 (56.5-63) years, and two thirds of the patients were male. Five patients died. All of the cases required postoperative intensive care. Eight patients underwent cardiac surgery. There was a heterogenic use of blood derived products and lyophilized concentrates, but in all cases its use was guided by thromboelastometry. No patients needed a secondary exploration due to bleeding. Conclusion: The use of human fibrinogen concentrate included in a bleeding management algorithm is a feasible hemostatic resource in the chilean current situation. The clinical impact of this intervention requires further evidence-based evaluation.

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COVID-19 is a contagious infectious disease, which quickly spreads worldwide, whose clinical presentation includes from mild flu-like symptoms to pneumonia and severe acute respiratory syndrome. The severe presentation of the disease can affect different organs and systems. Coagulopathy has been associated with a worse clinical outcome, with manifestations such as pulmonary embolism and systemic arterial thrombosis. Thromboelastometry has been used to identify hypercoagulability in early stages of disease. We report the case of a 59-year-old woman with COVID-19 infection complicated by pulmonary embolism and acute arterial thrombosis associated with critical lower limb ischemia requiring amputation. This report showed a case of thrombotic complication in patient with infection caused by novel coronavirus 2019 whose thromboelastometry allowed the early identification of hypercoagulability pattern. This is a single case report and the use of thromboelastometry should be further evaluated in large prospective cohort studies.

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INTRODUTION: COVID-19 is associated with an increased risk of thrombotic events. However, the contribution of platelet reactivity (PR) to the aetiology of the increased thrombotic risk associated with COVID-19 remains unclear. Our aim was to evaluate PR in stable patients diagnosed with COVID-19 and hospitalized with respiratory symptoms (mainly dyspnoea and dry cough), in comparison with a control group comprised of non-hospitalized healthy controls. METHODS: Observational, case control study that included patients with confirmed COVID-19 (COVID-19 group, n = 60) and healthy individuals matched by age and sex (control group, n = 60). Multiplate electrode aggregometry (MEA) tests were used to assess PR with adenosine diphosphate (MEA-ADP, low PR defined as < 53 AUC), arachidonic acid (MEA-ASPI, low PR < 86 AUC) and thrombin receptor-activating peptide 6 (MEA-TRAP, low PR < 97 AUC) in both groups. RESULTS: The rates of low PR with MEA-ADP were 27.5% in the COVID-19 group and 21.7% in the control group (OR = 1.60, p = 0.20); with MEA-ASPI, the rates were, respectively, 37.5% and 22.5% (OR = 3.67, p < 0.001); and with MEA-TRAP, the incidences were 48.5% and 18.8%, respectively (OR = 9.58, p < 0.001). Levels of D-dimer, fibrinogen, and plasminogen activator inhibitor 1 (PAI-1) were higher in the COVID-19 group in comparison with the control group (all p < 0.05). Thromboelastometry was utilized in a subgroup of patients and showed a hypercoagulable state in the COVID-19 group. CONCLUSION: Patients hospitalized with non-severe COVID-19 had lower PR compared to healthy controls, despite having higher levels of D-dimer, fibrinogen, and PAI-1, and hypercoagulability by thromboelastometry. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT04447131.

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BACKGROUND: Since the beginning of the COVID-19 pandemic, the world's attention has been focused on better understanding the relation between the human host and the SARS-CoV-2 virus, as its action has led to hundreds of thousands of deaths. OBJECTIVE: In this context, we decided to study certain consequences of the abundant cytokine release over the innate and adaptive immune systems, inflammation, and hemostasis, comparing mild and severe forms of COVID-19. METHODS: To accomplish these aims, we will analyze demographic characteristics, biochemical tests, immune biomarkers, leukocyte phenotyping, immunoglobulin profile, hormonal release (cortisol and prolactin), gene expression, thromboelastometry, neutralizing antibodies, metabolic profile, and neutrophil function (reactive oxygen species production, neutrophil extracellular trap production, phagocytosis, migration, gene expression, and proteomics). A total of 200 reverse transcription polymerase chain reaction-confirmed patients will be enrolled and divided into two groups: mild/moderate or severe/critical forms of COVID-19. Blood samples will be collected at different times: at inclusion and after 9 and 18 days, with an additional 3-day sample for severe patients. We believe that this information will provide more knowledge for future studies that will provide more robust and useful clinical information that may allow for better decisions at the front lines of health care. RESULTS: The recruitment began in June 2020 and is still in progress. It is expected to continue until February 2021. Data analysis is scheduled to start after all data have been collected. The coagulation study branch is complete and is already in the analysis phase. CONCLUSIONS: This study is original in terms of the different parameters analyzed in the same sample of patients with COVID-19. The project, which is currently in the data collection phase, was approved by the Brazilian Committee of Ethics in Human Research (CAAE 30846920.7.0000.0008). TRIAL REGISTRATION: Brazilian Registry of Clinical Trials RBR-62zdkk; https://ensaiosclinicos.gov.br/rg/RBR-62zdkk. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/24211.

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Coronaviruses can cause a diverse array of clinical manifestations, from fever with symptoms of the common cold to highly lethal severe acute respiratory syndrome (SARS) and middle east respiratory syndrome (MERS). SARS-CoV-2, the coronavirus discovered in Hubei province, China, at the end of 2019, became known worldwide for causing coronavirus disease 2019 (COVID-19). Over one year's time period, the scientific community has produced a large bulk of knowledge about this disease and countless reports about its immune-pathological aspects. This knowledge, including data obtained in postmortem studies, points unequivocally to a hypercoagulability state. However, the name COVID-19 tells us very little about the true meaning of the disease. Our proposal is more comprehensive; it intends to frame COVID-19 in more clinical terminology, making an analogy to viral haemorrhagic fever (VHF). Thus, we found irrefutable evidence in the current literature that COVID-19 is the first viral disease that can be branded as a viral thrombotic fever. This manuscript points out that SARS-CoV-2 goes far beyond pneumonia or SARS. COVID-19 infections promote remarkable interactions among the endothelium, coagulation, and immune response, building up a background capable of promoting a "thrombotic storm," much more than a "cytokine storm." The importance of a viral protease called main protease (Mpro) is highlighted as a critical component for its replication in the host cell. A deeper analysis of this protease and its importance on the coagulation system is also discussed for the first time, mainly because of its similarity with the thrombin and factor Xa molecules, as recently pointed out by structural comparison crystallographic structures.

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OBJECTIVE: To evaluate the clinical effects of early administration of fibrinogen concentrate in patients with severe trauma and hypofibrinogenemia. METHODS: We conducted an open randomized feasibility trial between December 2015 and January 2017 in patients with severe trauma admitted to the emergency department of a large trauma center. Patients presented with hypotension, tachycardia, and FIBTEM findings suggestive of hypofibrinogenemia. The intervention group received fibrinogen concentrate (50 mg/kg), and the control group did not receive early fibrinogen replacement. The primary outcome was feasibility assessed as the proportion of patients receiving the allocated treatment within 60 min after randomization. The secondary outcomes were transfusion requirements and other exploratory outcomes. Randomization was performed using sequentially numbered and sealed opaque envelopes. ClinicalTrials.gov: NCT02864875. RESULTS: Thirty-two patients were randomized (16 in each group). All patients received the allocated treatment within 60 min after randomization (100%, 95% confidence interval, 86.7%-100%). The median length of intensive care unit stay was shorter in the intervention group (8 days, interquartile range [IQR] 5.75-10.0 vs. 11 days, IQR 8.5-16.0; p=0.02). There was no difference between the groups in other clinical outcomes. No adverse effects related to treatment were recorded in either group. CONCLUSION: Early fibrinogen replacement with fibrinogen concentrate was feasible. Larger trials are required to properly evaluate clinical outcomes.

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Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.(AU)

Os pacientes com doença renal crônica (DRC) apresentam um potencial hemostático paradoxal, pois apresentam episódios de sangramento, mas também são propensos à trombose. Poucos estudos avaliaram as propriedades viscoelásticas sanguíneas em cães com doenças renais, entretanto, a hipercoagulabilidade já foi observada nestes pacientes. Ressalta-se ainda que a função plaquetária e sua participação neste processo ainda não foram totalmente esclarecidas. O objetivo foi avaliar e comparar o teste de geração de trombina (TGT) e as propriedades viscoelásticas sanguíneas medidas pela tromboelastometria (TEM) em cães com DRC proteinúrica. Foram selecionados 20 cães saudáveis (grupo controle) e 19 cães com DRC em estágios III ou IV classificados segundo o IRIS e a relação proteína/creatinina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), geração de trombina, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. Foi observada diferença entre os cães saudáveis e os com DRC proteinúrica observados na TEM. O teste de geração de trombina não foi capaz de diferenciar os grupos doente e saudável. Entretanto, quando os nefropatas foram analisados de forma estratificada, foram observados aumentos do ETP e da concentração máxima de trombina (peak) pelo TGT em fêmeas e em cães com mais de 30 dias de diagnóstico da DRC. Ambos os testes sinalizando para um discreto estado de hipercoagulabiliade. A tromboelastometria é mais sensível para detectar a hipercoagulabilidade em cães com DRC. Entretanto, o teste de geração de trombina tem melhor aplicabilidade por permitir o armazenamento da amostra em longo prazo.(AU)

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Patients with chronic kidney disease (CKD) have paradoxical hemostatic potential because they have bleeding episodes but are also prone to thrombosis. Few studies have evaluated blood viscoelastic properties in dogs with kidney disease; on the other hand, hypercoagulability has been observed in these patients. It is also emphasized that the platelet function and its participation in this process have not yet been fully understood. The objective of this study was to evaluate and compare the Thrombin Generation Test (TGT) and also viscoelastic properties of the blood measured by thromboelastometry (TEM) in dogs with proteinuria in CKD. Twenty healthy dogs (Control Group) and 19 dogs with CKD in stage III or IV, classified according to International Renal Interest Society - IRIS, were selected, and the reference test of urine protein:creatinine ratio (UPCR) should be greater than one (CKD group). Blood samples for TEM, thrombin generation, Prothrombin Time (PT), activated Partial Thromboplastin Time (aPTT), and fibrinogen concentration was collected at a single time for both groups after inclusion criteria being confirmed. Statistical analysis was performed according to the distribution of variables at 5% significance level. Differences were observed between healthy dogs and those with proteinuria in CKD noted in TEM. The TGT was unable to differentiate between sick and healthy groups. However, when the nephropathy was stratified, increases in TTP and peak thrombin concentration by TGT were observed in females and dogs over 30 days of diagnosis of CKD. Both tests signaled a discrete state of hypercoagulability. In fact, TEM is more sensitive to detect hypercoagulability in dogs with CKD. However, the TGT has potential clinical application by allowing long-term sample storage.(AU)

Os pacientes com doença renal crônica (DRC) apresentam um potencial hemostático paradoxal, pois apresentam episódios de sangramento, mas também são propensos à trombose. Poucos estudos avaliaram as propriedades viscoelásticas sanguíneas em cães com doenças renais, entretanto, a hipercoagulabilidade já foi observada nestes pacientes. Ressalta-se ainda que a função plaquetária e sua participação neste processo ainda não foram totalmente esclarecidas. O objetivo foi avaliar e comparar o teste de geração de trombina (TGT) e as propriedades viscoelásticas sanguíneas medidas pela tromboelastometria (TEM) em cães com DRC proteinúrica. Foram selecionados 20 cães saudáveis (grupo controle) e 19 cães com DRC em estágios III ou IV classificados segundo o IRIS e a relação proteína/creatinina urinária maior que um (grupo DRC). As amostras de sangue para a realização da tromboelastometria (TEM), geração de trombina, tempo de protrombina (TP), tempo de tromboplastina parcial ativada (TTPA) e concentração de fibrinogênio foram colhidas em momento único para ambos os grupos após os critérios de inclusão confirmados. A análise estatística foi realizada de acordo com a distribuição das variáveis, ao nível de 5% de significância. Foi observada diferença entre os cães saudáveis e os com DRC proteinúrica observados na TEM. O teste de geração de trombina não foi capaz de diferenciar os grupos doente e saudável. Entretanto, quando os nefropatas foram analisados de forma estratificada, foram observados aumentos do ETP e da concentração máxima de trombina (peak) pelo TGT em fêmeas e em cães com mais de 30 dias de diagnóstico da DRC. Ambos os testes sinalizando para um discreto estado de hipercoagulabiliade. A tromboelastometria é mais sensível para detectar a hipercoagulabilidade em cães com DRC. Entretanto, o teste de geração de trombina tem melhor aplicabilidade por permitir o armazenamento da amostra em longo prazo.(AU)

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INTRODUCTION: Thromboelastometry evaluates viscoelastic changes in the coagulation process. It offers a graphic representation of the formation of the coagulum, its stability and the presence of lysis. OBJECTIVE: This first case of transfusion management guided by thromboelastography in Mexico and we conducted a review of the literature. METHOD: A metasearch search was performed (PubMed, Scielo, Medigraphic) with the words thromboelastometry, coagulopathy, transfusion medicine and the most influential works were included. CONCLUSIONS: The rotational thromboelastometry is a diagnostic tool that graphs the functionality of the clot, for a directed and individualized management of the coagulopathy associated with bleeding.

INTRODUCCIÓN: La tromboelastometría evalúa los cambios viscoelásticos en el proceso de coagulación. Ofrece una representación gráfica de la formación del coágulo, su estabilidad y la presencia de lisis. OBJETIVO: Se notifica el primer caso de manejo transfusional guiado por tromboelastografía en México con revisión de la bibliografía. MÉTODO: Se realizó una búsqueda en metabuscadores (PubMed, Scielo, Medigraphic) con las palabras tromboelastometría, coagulopatía y medicina transfusional y se incluyeron los trabajos más influyentes. CONCLUSIONES: La tromboelastometría rotacional es una herramienta diagnóstica que grafica la funcionalidad del coágulo para un manejo dirigido e individualizado de la coagulopatía relacionada con ­hemorragia.

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BACKGROUND AND OBJECTIVES: Modern crystalloid and colloid solutions are balanced solutions which are increasingly used in perioperative period. However, studies investigating their negative effect on whole blood coagulation are missing, and vivid debate is going on about which solution has the minimal coagulopathy effect. The aim of our study was to assess the effect of modern fluid solutions on whole blood coagulation using rotational thromboelastometry. METHODS: Blood samples were obtained from 30 patients during knee arthroscopy before and after administration of 500mL of crystalloid, Hydroxyethyl Starch and gelatin according to the randomization. Rotational thromboelastometry (Extem, Intem and Fibtem tests) was used to assess negative effect of fluid solutions on whole blood coagulation. RESULTS: In Extem test, the initiation phase of fibrin clot formation represented by CT parameter was not influenced by any fluid solution (p>0.05). The speed of clot formation represented by CFT and α angle was impaired by Hydroxyethyl Starch and gelatin but not by crystalloids (p<0.05). The strength of formatted coagulum represented by MCF parameter was impaired both in Extem and Fibtem test by HES and in Fibtem also by crystalloids (p<0.05). Intem test was not negatively influenced by any crystalloid or colloid solution in any parameter (p>0.05). CONCLUSION: Extem test appears to be sensitive to coagulopathy effect of modern colloids and crystalloids. Hydroxyethyl starch has the most obvious negative effect on clot formation followed by gelatin and finally by crystalloids. Intem test seems to be insensitive to adverse effect of modern colloids and crystalloids.

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Abstract Background and objectives Modern crystalloid and colloid solutions are balanced solutions which are increasingly used in perioperative period. However, studies investigating their negative effect on whole blood coagulation are missing, and vivid debate is going on about which solution has the minimal coagulopathy effect. The aim of our study was to assess the effect of modern fluid solutions on whole blood coagulation using rotational thromboelastometry. Methods Blood samples were obtained from 30 patients during knee arthroscopy before and after administration of 500 mL of crystalloid, Hydroxyethyl Starch and gelatin according to the randomization. Rotational thromboelastometry (Extem, Intem and Fibtem tests) was used to assess negative effect of fluid solutions on whole blood coagulation. Results In Extem test, the initiation phase of fibrin clot formation represented by CT parameter was not influenced by any fluid solution (p > 0.05). The speed of clot formation represented by CFT and α angle was impaired by Hydroxyethyl Starch and gelatin but not by crystalloids (p < 0.05). The strength of formatted coagulum represented by MCF parameter was impaired both in Extem and Fibtem test by HES and in Fibtem also by crystalloids (p < 0.05). Intem test was not negatively influenced by any crystalloid or colloid solution in any parameter (p > 0.05). Conclusion Extem test appears to be sensitive to coagulopathy effect of modern colloids and crystalloids. Hydroxyethyl starch has the most obvious negative effect on clot formation followed by gelatin and finally by crystalloids. Intem test seems to be insensitive to adverse effect of modern colloids and crystalloids.

Resumo Justificativa e objetivos Os cristaloides e coloides modernos são soluções balanceadas e cada vez mais utilizadas no período perioperatório. No entanto, não há estudos que avaliem seu efeito negativo na coagulação do sangue total e o intenso debate sobre a solução que cause um efeito mínimo na coagulopatia permanece. O objetivo de nosso estudo foi avaliar o efeito das soluções líquidas modernas na coagulação do sangue total com o uso da tromboelastometria rotacional. Métodos De acordo com a randomização, amostras de sangue foram colhidas de 30 pacientes durante a artroscopia de joelho, antes e após a administração de 500 mL de cristaloides, hidroxietilamido e gelatina. A tromboelastometria rotacional (testes Extem, Intem e Fibtem) foi utilizada para avaliar o efeito negativo das soluções líquidas na coagulação do sangue total. Resultados No teste Extem, a fase de iniciação da formação de coágulos de fibrina representada pelo parâmetro CT não foi influenciada por qualquer solução líquida (p > 0,05). A velocidade da formação de coágulos representada pelo CFT e pelo ângulo α foi prejudicada pelo hidroxietilamido e pela gelatina, mas não pelos cristaloides (p < 0,05). A força do coágulo formatado representado pelo parâmetro MCF foi prejudicada tanto no teste Extem quanto no teste Fibtem pelo HES e no teste Fibtem também pelos cristaloides (p < 0,05). O teste Intem não foi influenciado negativamente por nenhuma solução cristaloide ou coloide em nenhum parâmetro (p > 0,05). Conclusão O teste Extem parece ser sensível ao efeito de coagulopatia dos coloides e cristaloides modernos. O hidroxietilamido apresentou o efeito negativo mais óbvio na formação do coágulo, seguido pela gelatina e finalmente pelos cristaloides. O teste Intem parece ser insensível ao efeito adverso dos coloides e cristaloides modernos.

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The aim of the study was to evaluate the diagnostic accuracy of thromboelastometry for assessing rivaroxaban concentrations. The accuracy of thromboelastometry was compared with the high-performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method, which is the gold standard for drug plasma monitoring (the reference standard). Forty-six clinically stable patients were treated with 10, 15, or 20 mg of rivaroxaban once daily (OD group) or 15 mg twice a day (BID group) (no particular indication for treatment). Patient samples were collected 2 h after the use of the medication (peak) and 2 h before the next dose (trough). The rivaroxaban plasma concentrations were determined via HPLC-MS/MS, and thromboelastometry was performed using a ROTEM® delta analyzer. There were significant prolongations in clotting time (CT) for the 10, 15, and 20 mg of rivaroxaban treatments in the OD groups. In the 15 mg BID group, the responses at the peak and trough times were similar. At the peak times, there was a positive correlation between the plasma concentration of rivaroxaban and CT (Spearman correlation rho=0.788, P<0.001) and clot formation time (rho=0.784, P<0.001), and a negative correlation for alpha angle (rho=−0.771, P<0.001), amplitude after 5 min (rho=−0.763, P<0.001), and amplitude after 10 min (rho=−0.680, P<0.001). The CT presented higher specificity and sensitivity using the cut-off determined by the receiver characteristics curve. ROTEM has potential as screening tool to measure possible bleeding risk associated with rivaroxaban plasma levels.

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