RESUMO
BACKGROUND: Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding. DESIGN: A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process. RESULTS: So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%. DISCUSSION: DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50ângâml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given. CONCLUSION: In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings.
Assuntos
Hemostáticos , Heparina , Humanos , Heparina/uso terapêutico , Estudos Prospectivos , Hemorragia/prevenção & controle , Anticoagulantes , Hemostáticos/uso terapêutico , Administração OralRESUMO
PURPOSE OF REVIEW: Tranexamic acid is routinely used as part of the management of traumatic bleeding. The dose recommendation in trauma was extrapolated from other clinical settings and the results of pragmatic randomized trials rather than pharmaco-kinetic and -dynamic evaluations. The review addresses current evidence on dosing of tranexamic acid in traumatized patients with a focus on efficacy, safety and risk-benefit profile. RECENT FINDINGS: A majority, but not all, of existing randomized clinical trials reports a reduction in mortality and/or blood loss with tranexamic acid administration. Increasing dose above the general recommendation (1âg bolus + 1âg infusion/8 h intravenously) has not been shown to further increase efficacy and could potentially increase side effects. SUMMARY: The benefit of tranexamic acid as adjuvant therapy in the management of bleeding trauma patients on mortality and transfusion requirements is clear and well documented, being most effective if given early and to patients with clinical signs of hemorrhagic shock. Recent reports suggest that in some patients presenting with a shutdown of their fibrinolytic pathway the administration of tranexamic acid could be associated with an increased risk of thromboembolic events and poor outcomes. A more personalized approach based on bedside assessment of fibrinolytic activation and pharmacokinetic-based dose regimen should be developed moving forward.
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Antifibrinolíticos , Ácido Tranexâmico , Humanos , Ácido Tranexâmico/uso terapêutico , Antifibrinolíticos/uso terapêutico , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Transfusão de SangueRESUMO
Antifibrinolytic drugs are used to reduce blood loss and subsequent transfusions during surgery and following trauma, but the optimal dosing regimen in the pediatric population is still unresolved. The aim of this systematic review was to evaluate efficacy and safety of antifibrinolytic drugs in pediatric surgery and trauma to determine the optimal dosing regimen. A literature search was performed in PubMed, Embase, Cochrane, and Web of Science on May 3, 2020. We included randomized controlled studies investigating the effect of tranexamic acid (TXA), aprotinin, and epsilon-aminocaproic acid, in terms of reducing blood loss, blood transfusions, reoperations, and rebleeds in pediatric patients aged 0 to 18 years undergoing cardiac surgery, noncardiac surgery, or trauma. Fifty randomized controlled trials (RCTs) were included; 28 RCTs investigated cardiac surgery and 22 investigated noncardiac surgery. No RCTs regarding trauma met the inclusion criteria. All antifibrinolytic drugs reduced postoperative blood loss and transfusions when used in pediatric surgery. The dosing regimen varied between studies, but similar effect sizes were found in terms of reduced blood loss regardless of the cumulative dose used. Few studies found adverse events, and no difference in incidence or type of adverse events was seen between the antifibrinolytic and the placebo group. In conclusion, use of antifibrinolytics is efficient and safe in children undergoing surgery. We propose TXA as the drug of choice based on its level of evidence and safety profile; we recommend a dosing regimen composed of a loading dose of 10 to 15 mg/kg prior to surgery followed by 1 to 5 mg/kg/h as continuous infusion throughout surgery.
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Antifibrinolíticos , Preparações Farmacêuticas , Ácido Tranexâmico , Ácido Aminocaproico , Antifibrinolíticos/efeitos adversos , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Humanos , Hemorragia Pós-Operatória , Ácido Tranexâmico/efeitos adversosRESUMO
BACKGROUND: Tranexamic acid (TXA) reduces blood loss and transfusion requirements during craniosynostosis surgery in small children. Possible interaction from TXA on the inflammatory system is unknown. OBJECTIVE: To evaluate the effect of TXA on a wide range of inflammatory markers in children receiving TXA in a randomized, blinded, and placebo controlled study design. METHODS: Thirty children undergoing craniosynostosis surgery with significant blood loss received TXA (bolus dose of 10 mg kg-1 followed by 8 hours continuous infusion of 3 mg kg-1 h-1 ) or placebo in a randomized, double-blinded study design. Using a new proximity extension assays employing a panel of inflammatory biomarkers samples was used for analysis of blood samples obtained pre-operatively, 4 and 24 hours after operation. RESULTS: Ninety-two inflammatory parameters were measured. TXA did not affect any of the measured parameters as compared with placebo. Among 34 of the 92 pro- and antiinflammatory parameters investigated changes were observed between pre-operative, 4 or 24 hours, respectively, reflecting immune activation during surgical stress. CONCLUSION: TXA administration in a low-dose regimen including bolus followed by 8 hours infusion during craniosynostosis surgery did not change any of 92 inflammatory markers as compared with placebo.
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Antifibrinolíticos , Ácido Tranexâmico , Biomarcadores , Perda Sanguínea Cirúrgica/prevenção & controle , Criança , Método Duplo-Cego , Humanos , Inflamação/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Tranexamic acid (TXA) reduces intraoperative blood loss and transfusion during paediatric craniosynostosis surgery. Additional reduction of postoperative blood loss may further reduce exposure to allogeneic blood products. We studied the effect of combined intra- and postoperative TXA treatment on postoperative blood loss in children. METHODS: Thirty children admitted for craniosynostosis surgery were randomised to combined intra- and postoperative TXA treatment or placebo. The primary endpoint was postoperative blood loss. Secondary endpoints included total blood loss, transfusion requirements, and clot stability evaluated by tissue plasminogen activator-stimulated clot lysis assay. RESULTS: TXA reduced postoperative blood loss by 18 ml kg-1 (95% confidence interval 8.9) and total blood loss from a mean of 52 ml kg-1 (standard deviation [SD]; 20) ml kg-1 to 28 (14) ml kg-1 (P<0.001). Intraoperative red blood cell (RBC) and fresh frozen plasma (FFP) transfusions were reduced in the treatment group from RBC 14.0 (5.2) ml kg-1 to 8.2 (5.1) ml kg-1 (P=0.01) and from FFP 13.0 (6.3) ml kg-1 to 7.8 (5.9) ml kg-1 (P=0.03). Postoperative RBC transfusion median was 5 (inter-quartile range [IQR] 0-6) ml kg-1 in the placebo group and 0 (0-5.7) ml kg-1 in the TXA group. Resistance to lysis was higher in the treatment group (P<0.001). CONCLUSIONS: Combined intra- and postoperative tranexamic acid treatment reduced postoperative and overall blood loss and transfusion requirements. Improved clot stability represents a possible mechanism for blood loss reduction.
Assuntos
Antifibrinolíticos/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Craniossinostoses/cirurgia , Hemorragia Pós-Operatória/prevenção & controle , Ácido Tranexâmico/uso terapêutico , Anestesia Geral/métodos , Antifibrinolíticos/administração & dosagem , Pré-Escolar , Método Duplo-Cego , Transfusão de Eritrócitos , Feminino , Fibrinólise/efeitos dos fármacos , Humanos , Lactente , Infusões Intravenosas , Masculino , Assistência Perioperatória/métodos , Ácido Tranexâmico/administração & dosagemAssuntos
Assistência Perioperatória , Tromboembolia Venosa , Humanos , Tromboembolia Venosa/prevenção & controle , Tromboembolia Venosa/etiologia , Assistência Perioperatória/métodos , Assistência Perioperatória/normas , Europa (Continente) , Anticoagulantes/administração & dosagem , Anticoagulantes/uso terapêutico , Complicações Pós-Operatórias/prevenção & controle , Complicações Pós-Operatórias/etiologia , Dispositivos de Compressão Pneumática IntermitenteRESUMO
Pediatric craniosynostosis (CS) surgery is frequently associated with extensive blood loss and transfusion requirements. The aim of the study was to evaluate the authors' institutional procedure with 2-surgeon approach and early transfusion strategy on blood loss and blood product transfusions in children undergoing craniofacial surgery. A retrospective analysis of medical records was performed of pediatric CS corrections during a 15-year period. Primary endpoint was blood loss and transfusion requirement during and the following 24âhours postoperatively. Linear regression analyses were performed of associations between intra and- postoperative blood loss and blood loss and weight. A total of 276 children (median 9 months) were included. Intraoperative blood loss was 22âmL/kg (14-33âmL/kg) and postoperatively 27âmL/kg (18-37âmL/kg), with no change during the study period. Intraoperative transfusions of red blood cell and plasma were 16âmL/kg (10-24âmL/kg) and postoperative 14âmL/kg (9-21âmL/kg). Postoperative red blood cell and plasma transfusions were 2âmL/kg (0-6âmL/kg) and of 0âmL/kg, respectively. Craniosynostosis type was related to blood loss (Pâ<â0.001). There was an association between intraoperative and postoperative blood loss (Pâ=â0.012) and intra- and postoperative blood loss and weight (Pâ=â0.002, Pâ=â<â0.001). Duration of surgery was 110âminutes (range 60-300âminutes).Pediatric CS surgery is associated with substantial intra- and postoperative blood loss and transfusion requirements, which did not change over a 15-year period. Blood loss was associated with type of CS. Intraoperative blood loss was correlated to postoperative blood loss and body weight.
Assuntos
Transfusão de Sangue , Hemorragia Pós-Operatória , Adolescente , Perda Sanguínea Cirúrgica , Criança , Pré-Escolar , Craniossinostoses/cirurgia , Humanos , Lactente , Estudos RetrospectivosRESUMO
: The risk for postoperative venous thromboembolism (VTE) is increased in patients aged more than 70 years and in elderly patients presenting with co-morbidities, for example cardiovascular disorders, malignancy or renal insufficiency. Therefore, risk stratification, correction of modifiable risks and sustained perioperative thromboprophylaxis are essential in this patient population. Timing and dosing of pharmacoprophylaxis may be adopted from the non-aged population. Direct oral anti-coagulants are effective and well tolerated in the elderly; statins may not replace pharmacological thromboprophylaxis. Early mobilisation and use of non-pharmacological means of thromboprophylaxis should be exploited. In elderly patients, we suggest identification of co-morbidities increasing the risk for VTE (e.g. congestive heart failure, pulmonary circulation disorder, renal failure, lymphoma, metastatic cancer, obesity, arthritis, post-menopausal oestrogen therapy) and correction if present (e.g. anaemia, coagulopathy) (Grade 2C). We suggest against bilateral knee replacement in elderly and frail patients (Grade 2C). We suggest timing and dosing of pharmacological VTE prophylaxis as in the non-aged population (Grade 2C). In elderly patients with renal failure, low-dose unfractionated heparin (UFH) may be used or weight-adjusted dosing of low molecular weight heparin (Grade 2C). In the elderly, we recommend careful prescription of postoperative VTE prophylaxis and early postoperative mobilisation (Grade 1C). We recommend multi-faceted interventions for VTE prophylaxis in elderly and frail patients, including pneumatic compression devices, low molecular weight heparin (and/or direct oral anti-coagulants after knee or hip replacement) (Grade 1C). : This article is part of the European guidelines on perioperative venous thromboembolism prophylaxis. For details concerning background, methods, and members of the ESA VTE Guidelines Task Force, please, refer to:Samama CM, Afshari A, for the ESA VTE Guidelines Task Force. European guidelines on perioperative venous thromboembolism prophylaxis. Eur J Anaesthesiol 2018; 35:73-76.A synopsis of all recommendations can be found in the following accompanying article: Afshari A, Ageno W, Ahmed A, et al., for the ESA VTE Guidelines Task Force. European Guidelines on perioperative venous thromboembolism prophylaxis. Executive summary. Eur J Anaesthesiol 2018; 35:77-83.
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Assistência Perioperatória/normas , Complicações Pós-Operatórias/prevenção & controle , Embolia Pulmonar/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Tromboembolia Venosa/prevenção & controle , Administração Oral , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Anestesiologia/instrumentação , Anestesiologia/métodos , Anestesiologia/normas , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Anticoagulantes/normas , Cuidados Críticos/métodos , Cuidados Críticos/normas , Relação Dose-Resposta a Droga , Esquema de Medicação , Deambulação Precoce/efeitos adversos , Deambulação Precoce/normas , Europa (Continente) , Feminino , Idoso Fragilizado , Avaliação Geriátrica/métodos , Heparina de Baixo Peso Molecular/administração & dosagem , Heparina de Baixo Peso Molecular/efeitos adversos , Humanos , Dispositivos de Compressão Pneumática Intermitente , Masculino , Assistência Perioperatória/instrumentação , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/etiologia , Embolia Pulmonar/etiologia , Medição de Risco/métodos , Fatores de Risco , Sociedades Médicas/normas , Meias de Compressão/efeitos adversos , Tromboembolia Venosa/etiologiaRESUMO
: Institutional protocols need to address the indications for pharmacological and mechanical thromboprophylaxis. The use of graduated compression stockings (GCS) and intermittent pneumatic compression (IPC) strongly differs between institutions. As a consequence, no strong recommendations can be made based on the contemporary high-level evidence. Although different clinical practices can be supported, such approaches should be part of an institutional strategy to reduce the burden of venous thromboembolism (VTE). We recommend against the use of GCS alone without pharmacological thromboprophylaxis for prevention of VTE in patients at intermediate and high risk. For patients at high risk of VTE with contraindications for pharmacological thromboprophylaxis, we recommend the use of mechanical prophylaxis and suggest the use of IPC over GCS. However, for those patients receiving pharmacological thromboprophylaxis who are without a very high risk of VTE prophylaxis, we recommend against the routine use of mechanical thromboprophylaxis either with GCS or IPC. We suggest combined mechanical and pharmacological prophylaxis in selected patients at very high risk of VTE prophylaxis and suggest IPC rather than GCS in these selected patients.
Assuntos
Anticoagulantes/administração & dosagem , Dispositivos de Compressão Pneumática Intermitente/normas , Assistência Perioperatória/normas , Complicações Pós-Operatórias/prevenção & controle , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Tromboembolia Venosa/prevenção & controle , Anestesiologia/instrumentação , Anestesiologia/métodos , Anestesiologia/normas , Anticoagulantes/efeitos adversos , Anticoagulantes/normas , Terapia Combinada/efeitos adversos , Terapia Combinada/métodos , Terapia Combinada/normas , Cuidados Críticos/métodos , Cuidados Críticos/normas , Europa (Continente) , Humanos , Dispositivos de Compressão Pneumática Intermitente/efeitos adversos , Assistência Perioperatória/instrumentação , Assistência Perioperatória/métodos , Complicações Pós-Operatórias/etiologia , Fatores de Risco , Sociedades Médicas/normas , Meias de Compressão/efeitos adversos , Tromboembolia Venosa/etiologiaRESUMO
BACKGROUND: Total thrombus formation velocity calculated using amplitude parameters obtained at different times could be used to estimate the amplification and the propagation phases observed during coagulation processes, and therefore might be useful to predict postoperative hemostatic products administration in pediatric patients. METHODS: We retrospectively analyzed data from 49 children <3 months of age who underwent cardiac surgery. Children ≤1 month of age routinely received fresh frozen plasma during bypass while children >1 month of age did not. The EXTEM parameters were used to calculate velocity curves using amplitudes obtained at different times, the area under the curve called total thrombus formation and the maximum rate of thrombus formation. These parameters were compared between children who received fresh frozen plasma and those who did not. Receiver operating characteristics curves were used to define variables that could be used to predict postoperative fresh frozen plasma transfusion. RESULTS: Total thrombus formation and maximum rate of thrombus formation significantly increased in children who received fresh frozen plasma compared to those who did not. Both total thrombus formation and maximum rate of thrombus formation have a better specificity to predict postoperative fresh frozen plasma transfusion compared to clotting time or maximal clot firmness. CONCLUSION: Based on this descriptive study, dynamic ROTEM(®) parameters of total thrombus formation could be used to estimate the amplification and the propagation phases of coagulation in children. These parameters might be used in further well-designed study to predict the need for hemostatic products in children undergoing cardiac surgery with cardiopulmonary bypass.
Assuntos
Coagulação Sanguínea/fisiologia , Procedimentos Cirúrgicos Cardíacos , Ponte Cardiopulmonar , Tromboelastografia/métodos , Trombose/diagnóstico , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Plasma , Curva ROC , Estudos RetrospectivosRESUMO
BACKGROUND: A main cause of trauma morbidity and mortality is multiple-organ failure, and endotheliopathy has been implicated. Pilot studies indicate that low-dose prostacyclin improves endothelial functionality in critically ill patients, suggesting that this intervention may improve trauma patient outcome. METHODS: We conducted a multicenter, randomized, blinded, clinical investigator-initiated trial in 229 trauma patients with hemorrhagic shock who were randomized 1:1 to 72 hours infusion of the prostacyclin analog iloprost (1 ng/kg/min) or placebo. The primary outcome was the number of intensive care unit (ICU)-free days alive within 28 days of admission. Secondary outcomes included 28-day all-cause mortality and hospital length of stay. RESULTS: The mean number of ICU-free days alive within 28 days was 15.64 days in the iloprost group versus 13.99 days in the placebo group (adjusted mean difference, -1.63 days [95% confidence interval (CI), -4.64 to 1.38 days]; p = 0.28). The 28-day mortality was 18.8% in the iloprost group versus 19.6% in the placebo group (odds ratio, 1.01 [95% CI, 0.51-2.0]; p = 0.97). The mean hospital length of stay was 19.96 days in the iloprost group versus 27.32 days in the placebo group (adjusted mean difference, 7.84 days [95% CI, 1.66-14.02 days], p = 0.01). CONCLUSION: Iloprost did not result in a statistically significant increase in the number of ICU-free days alive within 28 days of admission, whereas it was safe and a statistically significant reduction in hospital length of stay was observed. Further research on prostacyclin in shocked trauma patients is warranted. LEVEL OF EVIDENCE: Therapeutic/Care Management; Level II.
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Iloprosta , Choque Hemorrágico , Humanos , Iloprosta/uso terapêutico , Epoprostenol/uso terapêutico , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/etiologia , Unidades de Terapia Intensiva , Prostaglandinas IRESUMO
CONTEXT: The effectiveness of postoperative analgesia through a wound catheter is subject to considerable debate. OBJECTIVE: To test the hypothesis that local wound infusion with bupivacaine followed by continuous infusion could reduce postoperative need for opioids in patients undergoing retropubic prostatectomy. DESIGN: Single-centre prospective, double-blinded, placebo-controlled trial. SETTING: A major university hospital in Denmark. PATIENTS: Following written informed consent, 60 patients scheduled for prostatectomy were recruited to the study and 50 completed the protocol to reach data analysis. INTERVENTIONS: Thirty millilitre bolus of bupivacaine (2.5 mg ml) or isotonic saline was injected through a subfascially placed wound catheter followed by continuous infusion at 5 ml h during the following 48 h. All patients were prescribed paracetamol, non-steroidal anti-inflammatory drugs, morphine and oxycodone if needed. OUTCOME MEASURES: Primary outcome was the opioid requirement. Secondary outcomes included pain scores at rest and with activity, and nausea and vomiting scores. RESULTS: The total amount of morphine required during the postoperative period was not significantly higher (P=0.49) in the placebo group (12 mg, 25 to 75% percentile 5 to 18) than the bupivacaine group (10 mg, 25 to 75% percentile 0 to 16). Similarly, the total amount of oxycodone required was not significantly different (P=0.99) and was equal among the groups (5 mg, 25 to 75% percentile 5 to 10). At 2 h postoperatively, a significantly (P=0.0488) higher number of patients required additional morphine in the placebo group. No differences between the groups were detected at any time point regarding pain scores or the presence of nausea and vomiting. CONCLUSION: Additional use of a wound catheter in patients undergoing prostatectomy in the present perioperative setting appears superfluous.
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Analgesia/métodos , Anestésicos Locais/administração & dosagem , Bupivacaína/administração & dosagem , Prostatectomia/métodos , Neoplasias da Próstata/tratamento farmacológico , Idoso , Analgesia Controlada pelo Paciente , Catéteres , Método Duplo-Cego , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Dor , Medição da Dor , Período Pós-Operatório , Resultado do TratamentoRESUMO
Thrombosis and bleeding are significant contributors to morbidity and mortality in patients with hematological cancer, and the impact of altered fibrinolysis on bleeding and thrombosis risk is poorly understood. In this prospective cohort study, we investigated the dynamics of fibrinolysis in patients with hematological cancer. Fibrinolysis was investigated before treatment and 3 months after treatment initiation. A dynamic clot formation and lysis assay was performed beyond the measurement of plasminogen activator inhibitor 1, tissue- and urokinase-type plasminogen activators (tPA and uPA), plasmin-antiplasmin complexes (PAP), α-2-antiplasmin activity, and plasminogen activity. Clot initiation, clot propagation, and clot strength were assessed using rotational thromboelastometry. A total of 79 patients were enrolled. Patients with lymphoma displayed impaired fibrinolysis with prolonged 50% clot lysis time compared with healthy controls (P = .048). They also displayed decreased clot strength at follow-up compared with at diagnosis (P = .001). A patient with amyloid light-chain amyloidosis having overt bleeding at diagnosis displayed hyperfibrinolysis, indicated by a reduced 50% clot lysis time, α-2-antiplasmin activity, and plasminogen activity, and elevated tPA and uPA. A patient with acute promyelocytic leukemia also displayed marked hyperfibrinolysis with very high PAP, indicating extreme plasmin generation, and clot formation was not measurable, probably because of the extremely fast fibrinolysis. Fibrinolysis returned to normal after treatment in both patients. In conclusion, patients with lymphoma showed signs of impaired fibrinolysis and increased clot strength, whereas hyperfibrinolysis was seen in patients with acute promyelocytic leukemia and light-chain amyloidosis. Thus, investigating fibrinolysis in patients with hematological cancer could have diagnostic value.
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Amiloidose , Antifibrinolíticos , Neoplasias Hematológicas , Leucemia Promielocítica Aguda , Linfoma , Trombose , Humanos , Fibrinólise , Tempo de Lise do Coágulo de Fibrina , alfa 2-Antiplasmina , Fibrinolisina , Estudos Prospectivos , Linfoma/complicações , Linfoma/diagnóstico , Trombose/etiologia , Ativador de Plasminogênio Tipo Uroquinase , PlasminogênioRESUMO
Coagulation factor I (fibrinogen) plays an essential role in the hemostatic system by bridging activated platelets and being the key substrate for thrombin in establishing a consolidating fibrin network. Fibrinogen is synthesized in the liver and the plasma concentration is 1 to 5-4.0 g/L. During recent 10 years, fibrinogen has been recognized to play an important role in controlling hemorrhage. Dilutional coagulopathy induced by colloid plasma expanders is characterized by fibrinogen deficiency and dysfunctional fibrin polymerization. Trauma and use of extracorporeal circulation is also known to reduce levels of fibrinogen. A series of laboratory experiments and experimental animal studies have suggested fibrinogen as a potent hemostatic agent. These data are supported by retrospective surveys as well as a series of prospective proof of principal clinical trials. This article provides a description of the biochemistry and mechanisms of fibrinogen as well as the etiology for developing fibrinogen deficiency. Furthermore, it summarizes laboratory and experimental data on the role of fibrinogen in dilutional coagulopathy and addresses laboratory monitoring issues. Finally, it lists retrospective and prospective studies, which have been designed to assess the clinical efficacy and safety of hemostatic intervention with fibrinogen concentrate.
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Fibrinogênio/uso terapêutico , Hemostáticos/uso terapêutico , Humanos , Estudos Prospectivos , Estudos RetrospectivosRESUMO
INTRODUCTION: Supplemental oxygen is commonly used in trauma patients, although it may lead to hyperoxaemia that has been associated with pulmonary complications and increased mortality. The primary objective of this trial, TRAUMOX2, is to compare a restrictive versus liberal oxygen strategy the first 8 hours following trauma. METHODS AND ANALYSIS: TRAUMOX2 is an investigator-initiated, international, parallel-grouped, superiority, outcome assessor-blinded and analyst-blinded, randomised, controlled, clinical trial.Adult patients with suspected major trauma are randomised to eight hours of a restrictive or liberal oxygen strategy. The restrictive group receives the lowest dosage of oxygen (>21%) that ensures an SpO2 of 94%. The liberal group receives 12-15 L O2/min or FiO2=0.6-1.0.The primary outcome is a composite of 30-day mortality and/or development of major respiratory complications (pneumonia and/or acute respiratory distress syndrome).With 710 participants in each arm, we will be able to detect a 33% risk reduction with a restrictive oxygen strategy if the incidence of our primary outcome is 15% in the liberal group. ETHICS AND DISSEMINATION: TRAUMOX2 is carried out in accordance with the Helsinki II Declaration. It has been approved by the Danish Committee on Health Research Ethics for the Capital Region (H-21018062) and The Danish Medicines Agency, as well as the Dutch Medical Research Ethics Committee Erasmus MS (NL79921.078.21 and MEC-2021-0932). A website (www.traumox2.org) is available for updates and study results will be published in an international peer-reviewed scientific journal. TRIAL REGISTRATION NUMBERS: EudraCT 2021-000556-19; NCT05146700.
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COVID-19 , SARS-CoV-2 , Adulto , Humanos , Oxigênio/uso terapêutico , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: Thromboelastography/metry (TEG®; Haemoscope, Niles, IL/ROTEM®; Tem International GmbH, Munich, Germany) is increasingly used to guide transfusion therapy. This study investigated the diagnostic performance and therapeutic consequence of using kaolin-activated whole blood compared with a panel of specific TEM®-reagents to distinguish: dilutional coagulopathy, thrombocytopenia, hyperfibrinolysis, and heparinization. METHODS: Blood was drawn from 11 healthy volunteers. Dilutional coagulopathy was generated by 50% dilution with hydroxyethyl starch 130/0.4 whereas thrombocytopenia (mean platelet count 20 ×109/l) was induced using a validated model. Hyperfibrinolysis and heparin contamination were generated by tissue plasminogen activator 2 nM and unfractionated heparin 0.1U/ml, respectively. Coagulation tests were run on ROTEM® delta. RESULTS: Kaolin-activated whole blood showed no differences between dilutional coagulopathy and thrombocytopenia (mean clotting time 450 s vs. 516 s, α-angle 47.1° vs. 41.5°, maximum clot firmness 35.0 mm vs. 34.2 mm, all P values ≥0.14). Hyperfibrinolysis specifically disclosed an increased maximum lysis (median: 100%, all P values less than 0.001), and heparin induced a distinctly prolonged clotting time (2283 s, all P values less than 0.02). The coagulopathies were readily distinguishable using a panel of TEM-reagents. In particular, dilutional coagulopathy was separated from thrombocytopenia using FIBTEM (maximum clot firmness 1.9 mm vs. 11.2 mm, P < 0.001). The run time of analysis to achieve diagnostic data was shorter applying a panel of TEM-reagents. A transfusion algorithm based on kaolin suggested platelets in case of dilutional coagulopathy, whereas an algorithm applying TEM-reagents suggested fibrinogen. CONCLUSION: Monoanalysis with kaolin was unable to distinguish coagulopathies caused by dilution from that of thrombocytopenia. Algorithms based on the use of kaolin may lead to unnecessary transfusion with platelets, whereas the application of TEM-reagents may result in goal-directed fibrinogen substitution.
Assuntos
Transtornos da Coagulação Sanguínea/diagnóstico , Caulim/farmacologia , Tromboelastografia/métodos , Adulto , Algoritmos , Feminino , Fibrinólise , Hemostasia , Humanos , Indicadores e Reagentes , Masculino , Pessoa de Meia-Idade , Trombocitopenia/diagnóstico , Fatores de TempoRESUMO
OBJECTIVES: Acquired type 2A von Willebrand disease may develop as a consequence of aortic valve stenosis and is associated with varying degrees of bleeding tendency. It remains unknown, whether it portends excess blood loss during aortic valve replacement. DESIGN: We consecutively enrolled 45 patients with severe aortic valve stenosis undergoing aortic valve replacement. Patients with acquired type 2A von Willebrand disease were identified measuring the von Willebrand factor high molecular weight multimer. Data on the intraoperative, early postoperative, and the total blood loss within 24 hours of surgery was obtained and compared between groups. RESULTS: Acquired type 2A von Willebrand disease was found in 33% (n = 15/45) of the patients. Baseline characteristics were similar between groups. Patients with acquired type 2A von Willebrand disease neither had excess median intraoperative blood loss (375 ml (interquartile range 100-450 ml) vs. 350 ml (interquartile range 250-500 ml), p = 0.59) nor increased median total blood loss (695 ml (interquartile range 450-850 ml) vs. 752 ml (interquartile range 575-1035 ml), p = 0.41) as compared to patients without acquired type 2A von Willebrand disease. CONCLUSION: Acquired type 2A von Willebrand disease was not associated with increased blood loss during aortic valve replacement in patients with severe aortic valve stenosis.
Assuntos
Estenose da Valva Aórtica/cirurgia , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Implante de Prótese de Valva Cardíaca , Doença de von Willebrand Tipo 2/etiologia , Idoso , Idoso de 80 Anos ou mais , Estenose da Valva Aórtica/complicações , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Fator de von Willebrand/análiseRESUMO
The main goal of perioperative coagulation monitoring is to improve safety of patients undergoing surgical procedures. Various conditions can affect the coagulation system during surgery and bleeding. The value of traditional standard coagulation tests is limited in detecting hemostatic dysfunctions and they are particularly ineffective in diagnosing hyperfibrinolysis. This article reports on key issues and pathophysiologic changes that affect the hemostatic system in the perioperative setting. Values of preoperative coagulation tests are discussed and the basic principles for point-of-care coagulation devices, including platelet analyzers and their clinical use, are evaluated.