Consensus of the Brazilian association of hematology, hemotherapy and cellular therapy on patient blood management: Antifibrinolytics

Abstract The use of strategies to reduce blood loss and transfusions is essential in the treatment of surgical patients, including in complex cardiac surgeries and those that use cardiopulmonary bypass. Antifibrinolytics, such as epsilon-aminocaproic acid (EACA) and tranexamic acid (TXA), are widely used in these procedures, as well as in other types of surgeries. These medicines are included in the World Health Organization (WHO) list of 'essential medicines'. Scientific evidence demonstrates the effectiveness of EACA in reducing bleeding and the need for transfusions in heart surgery. EACA is highly recommended for use in heart surgery by the American Society of Anesthesiology Task Force on Perioperative Blood Management. Regarding the safety of EACA, there is no robust evidence of any significant thrombotic potential. TXA has also been shown to be effective in reducing the use of blood transfusions in cardiac and non-cardiac surgeries and is considered safer than other antifibrinolytic agents. There is no evidence of any increased risk of thromboembolic events with TXA, but doses greater than 2 g per day have been associated with an increased risk of seizures. It is also important to adjust the dose in patients with renal impairment. In conclusion, antifibrinolytics, such as EACA and TXA, are effective in reducing blood loss and transfusion use in cardiac and non-cardiac surgeries, without causing serious adverse effects.

Intraarticular epsilon aminocaproic acid versus tranexamic acid in total knee arthroplasty / Acido épsilon aminocaproico intra-articular versus acido tranexâmico na prótese total do joelho

ABSTRACT Objective: To examine and compare the clinical efficacy of intraarticular epsilon aminocaproic acid (EACA) and tranexamic acid (TXA) in total knee arthroplasty (TKA). Methods: This study was a prospective, single-center, double-blinded randomized controlled trial, including sixty patients with osteoarthritis of the knee divided into two groups of 30 patients. In the TXA group, 1 g of TXA (0.05 g/ml) was applied intraarticularly, and in the EACA group, 4 g of EACA (0.2 g/ml) was applied intraarticularly. Serum hemoglobin (Hgb) and hematocrit (Htb) were measured during the preoperatively and 24 and 48 hours postoperatively. The range of motion and pain were evaluated by clinical examination. To evaluate knee function before and 2 months after surgery, the Western Ontario and McMaster Universities Index (WOMAC) questionnaire was used. Results: In total, 56 (93.3%) patients were evaluated up to the second postoperative month. No significant difference between the groups (p > 0.05) was found in the decrease in Hgb or Htb at 24 or 48 hours. Regarding assessment of the pain, WOMAC score and gain in knee flexion, no significant advantages up to 60 days after surgery (p > 0.05) were found. Conclusions: The decrease in Hgb and Htb during the first 48 hours postoperatively and the risk of transfusion were similar with the intraarticular use of 1 g of TXA and 4 g of EACA in TKA. The possible benefits regarding knee pain, gain in flexion and function were also similar for the two drugs. Level of Evidence II, Randomized, Double-Blinded, Single-Centre, Prospective Clinical Trial.

RESUMO Objetivo: Avaliar e comparar a eficácia clinica do uso intra-articular do ácido épsilon aminocaproico (AEAC) versus o ácido tranexâmico (ATX) na prótese total do joelho. Métodos: Estudo clínico prospectivo, centro-único, duplo-cego e randomizado. Sessenta pacientes com osteoartrose de joelho foram incluídos. Os participantes foram divididos em dois grupos de 30 pacientes. No grupo ATX, foi aplicado 1 g de ATX (0.05 g/ml) intra-articular e, no grupo AEAC, foram aplicados 4 g de AEAC (0.2 g/ml) intra-articular. Valores séricos da hemoglobina (Hb) e hemtatócrito (Ht) foram dosados no pré-operatório e com 24 e 48 horas após a cirurgia. A amplitude de movimento e a dor também foram avaliadas no exame clínico. O índice WOMAC foi utilizado para avaliar a função do joelho antes e após dois meses da cirurgia. Resultados: Foram avaliados 56 (93.3%) pacientes até o segundo mês pós-operatório. Depois da cirurgia, não houve diferenças entre os grupos (p > 0.05) na queda do valor de Hb e Ht com 24 ou 48 horas. Com relação à avaliação da dor, WOMAC e ganho de flexão do joelho, não houve vantagem significativa para nenhum dos grupos até os 60 dias depois da cirurgia(p > 0.05). Conclusão: A queda do valor da Hb e do Ht durante as primeiras 48 horas pós-operatórias e o risco de transfusão foram similares com o uso intra-articular de 1 g de ATX e 4 g de AEAC na artroplastia total do joelho. Os possíveis benefícios com relação ao controle da dor, ganho de flexão e função foram similares entre as duas drogas. Nível de Evidência II, Ensaio-Clínico Prospectivo, Randomizado, Duplo Cego, Centro-Único.

A randomized, double-blinded trial comparing the effectiveness of tranexamic acid and epsilon-aminocaproic acid in reducing bleeding and transfusion in cardiac surgery

Objectives: To compare the effectiveness of epsilon aminocaproic acid (EACA) to tranexamic acid (TA) in reducing blood loss and transfusion requirements in patients undergone cardiac surgery under cardiopulmonary bypass. Design: Randomized, double blinded study. Outcome variables collected included; baseline demographic characteristics, type of surgery, amount of 24 hour chest tube drainage, amount of 24 hour blood products administered, 30 day mortality and morbidity and length of stay. We analyzed the data using parametric and non-parametric tests as appropriate. Setting: Single center tertiary-care university hospital setting. Participants: 114 patients who had undergone cardiac surgery under cardiopulmonary bypass. Interventions: Standard dose of intra-operative EACA or TA was compared in patients undergone cardiac surgery under cardiopulmonary bypass. Results: There was no statistically significant difference between groups when analyzing chest tube drainage. However, there was a significant difference in the administration of any transfusion (PRBC's, FFP, platelets) intra-operatively to 24 hours postoperatively, with less transfusion in patients receiving EACA compared to TA (25% vs. 44.8%, respectively P = 0.027). Additionally, there was no significant difference in terms of adverse events during the one month follow up period. Conclusion: The findings of this study suggest that EACA and TA have similar effects on chest tube drainage but EACA is associated with fewer transfusions in CABG alone surgeries. Our results suggest that EACA can be used in a similar fashion to TA which may result in a cost and morbidity advantage.

Synthesis and Evaluation of Biotinylated Small Molecular Drugs with Long Chain / 中国药学杂志

OBJECTIVE: To set up an easy and effective method for biotinylation of small molecule drugs with long chain. METHODS: Biotinylated 6-aminocaproic acid was synthesized as intermediate by one step method, doxorubicin(DOX) with auto-fluorescence was used as the first drug, and by DCC and DMAP catalysis, biotinylated DOX was synthesized. Using the double fluorescence system of DOX, the binding ability of biotinylated DOX to avidin and its biological activity were determined. When verified to be reasonable and effective, the method was applied to catalyze biotinylated paclitexal (PTX) which didn′t have auto-fluorescence itself, and the physical and chemical characteristics, and biological activities as well as the visualization were tested. RESULTS: The binding rate of synthesized DOX to avidin was 93.7%; the cells inhibition rate and localization were the same as DOX; the purity of biotinylated PTX was 84.42%, and the structure shown by NMR was correct; the cell inhibition rate was the same as PTX; the combination of PTX with microtubules was observed by visual modification. CONCLUSION: The method supplies a temperate way for biotinylation, and can be used for the synthesis and visualization of small molecules as probes and research of drug mechanism.

Simultaneous Determination of Taurine and Aminocaproic Acid in Compound Taurine Eye Drops by High Performance Liquid Chromatography-Refractive Index Detector / 中国药师

Objective:To establish an HPLC-RID method for the simultaneous determination of taurine and aminocaproic acid in compound taurine eye drops. Methods:A Waters NH2column(250 mm ×4.6 mm,5 μm) was used, the mobile phase was water-acetonitrile (40:60) at a flow rate of 0.8 ml·min-1, the column temperature was 35.0℃, and the temperatures of the detector reference cell and the sample cell were both set at 35.0℃,The injection volume was 20 μl. Results:The linear ranges of taurine and aminocaproic acid were 0.05-2.00 mg·ml-1(r = 0.999 9). The average recovery was 98.57% (RSD = 1.07%,n= 9) and 100.69% (RSD =0.75%,n =9),respectively. Conclusion:The established method is accurate,simple and rapid, and suitable for the quality control of compound taurine eye drops.

Hemostasis Effect of Compound Hemostasis Patches / 中国药师

Objective:To study the hemostasis effect of the ingredients in compound hemostasis patches .Methods:The effect of the ingredients in compound hemostasis patches on the clotting time was studied by the coagulation of rabbit whole blood in vitro.The models of femoral arterial injury in rats and perforation of femoral artery in pigs were established , and the effect of the ingredients in compound hemostasis patches on the bleeding time and the bleeding loss was studied .Results:The results of the whole blood coagula-tion in vitro showed that the clotting time of the three compound hemostasis patches at different concentrations and thrombin group was significantly shorter than that of the blank control group and the saline control group (P<0.01).Compared with to the blank control group, the results of rat femoral artery trauma model test showed that the three patch groups and thrombin group could significantly re -duce the bleeding loss and bleeding time (P<0.05 or P<0.01).The results of pig femoral artery perforation hemorrhage model test showed that the compound hemostasis patches could significantly reduce the bleeding time (P<0.05).Conclusion:Compound hemo-stasis patches can significantly shorten clotting time and decrease bleeding loss .

Implantação de protocolo institucional para o uso racional de hemoderivados e seu impacto no pós-operatório de cirurgias de revascularização miocárdica / Implementation of an institutional protocol for rational use of blood products and its impact on postoperative of coronary artery bypass graft surgery

OBJETIVO: Cirurgias cardíacas são, por vezes, acompanhadas de perdas sanguíneas significativas, e transfusões de sangue podem ser necessárias. No entanto, o uso indiscriminado de hemoderivados pode resultar em efeitos danosos para o paciente. Neste estudo, avaliamos os efeitos imediatos da implantação de um protocolo para o uso racional de hemoderivados no perioperatório de cirurgias de revascularização miocárdica. MÉTODOS: Entre os meses de abril e junho de 2011, foi implementado um protocolo institucional em um hospital privado especializado em cardiologia com a anuência e a colaboração de sete equipes de cirurgia cardíaca, visando ao uso racional de hemoderivados. Foram verificados dados clínicos e demográficos dos pacientes, e avaliados o uso de hemoderivados e os desfechos clínicos no período intra-hospitalar, antes e após a implantação do protocolo. O protocolo consistiu em uma campanha institucional junto às equipes cirúrgicas, de anestesiologia e intensivistas, para difundir a prática do uso de hemoderivados com base em critérios clínicos objetivos (anemia com repercussões hemodinâmicas e disfunção ventricular significativa), bem como tornar rotineira a prescrição de ácido epsilon-aminocaproico no intraoperatório, que é prática recomendada por diretrizes internacionais baseadas em evidência científica. RESULTADOS: Após os 3 meses de implantação do protocolo, houve aumento do uso de ácido epsilon-aminocaproico de 31% para 100%. Antes da implantação do protocolo, 67% das cirurgias utilizaram alguma transfusão sanguínea; após a implantação, 40% das cirurgias necessitaram de alguma transfusão sanguínea nos meses subsequentes do mesmo ano (p<0,001). Não houve diferença significativa nos desfechos clínicos avaliados antes e após implantação do protocolo. CONCLUSÃO: O uso racional de hemoderivados, associado à infusão do ácido epsilon-aminocaproico, tem o potencial de reduzir o número de hemotransfusões no perioperatório de cirurgias cardíacas...

OBJECTIVE: Cardiac surgeries are sometimes followed by significant blood loss, and blood transfusions may be necessary. However, indiscriminant use of blood components can result in detrimental effects for the patient. We evaluated the short-term effects of implementation of a protocol for the rational use of blood products in the perioperative period of cardiac surgery. METHODS: Between April and June 2011, an institutional protocol was implemented in a private hospital specializing in cardiology to encourage rational use of blood products, with the consent and collaboration of seven cardiac surgery teams. We collected clinical and demographic data on the patients. The use of blood products and clinical outcomes were analyzed during hospital stay before and after protocol implementation. The protocol consisted of an institutional campaign with an educational intervention to surgical and anesthesiology teams; the goal was to tailor blood transfusion practice according to clinical goals (anemia with hemodynamic changes and significant ventricular dysfunction) and to make routine the prescription of å-aminocaproic acid intraoperatively, which is recommended by international guidelines based on scientific evidence. RESULTS: After three months of protocol implementation, the use of å-aminocaproic acid increased from 31% to 100%. A total of 67% of surgeries before protocol implementation required any blood transfusion, compared with 40% that required any blood transfusion after protocol implementation in subsequent months of the same year (p<0.001). There was no significant difference in clinical outcomes assessed before and after implementation of the protocol. CONCLUSION: The rational use of blood products associated with infusion of å-aminocaproic acid has the potential to reduce the number of blood transfusions in perioperative of cardiac surgeries, but it can affect the risk of complications.

Antifibrinolítico em cirurgia cardíaca: como e quando usar? / Anfibrinolytic in cardiac surgery: how and when to use?

O sangramento pós-operatório continua sendo uma das principais complicações em cirurgia cardíaca. A etiologia desse sangramento é multifatorial, com hiperfibrinólise e disfunção plaquetária desempenhando papel fundamental Tendo em vista essas causas, as drogas antifibrinolíticas têm sido preconizadas. Desde a retirada da aprotinina do mercado, o ácido epsilon-aminocaproico e o ácido tranexâmico passaram a ser os únicos representantes disponíveis dessa classe de drogas. Essas medicações diminuem a perda de sangue e agem na resposta inflamatória associada ao procedimento cirúrgico. A eficácia variável dessas drogas ocorre devido aos vários esquemas terapêuticos e níveis séricos existentes. Recentemente têm surgido alguns questionamentos na literatura a respeito das complicações, doses, vias de administração e melhor momento para administração desses agentes...

The postoperative bleeding remains a major complication in cardiac surgery. The etiology of this bleeding is multifactorial, with hyperfibrinolysis and platelet dysfunction playing a key role. Given these causes antifibrinolytic drugs have been recommended Since the with drawal of aprotinin in the market, epsilon-aminocaproic acid and tranexamic acid became the sole representatives of this class of drugs available. These medications reduce blood loss and act on the inflammatory response associated with surgery. The variable efficacy of these drugs is due to multiple drug regimens and serum available. Recently some questions have arisen in the literature regarding the comptications, doses, routes of administration and timing for administration of these agents...

Manejo de la enfermedad de von Willebrand en ginecología y obstetricia: revisión cualitativa de la literatura / A qualitative review of the literature regarding managing Von willebrand disease in obstetrics and gynaecology

Introducción: la enfermedad de Von Willebrand es el trastorno de la coagulación con mayor prevalencia de mujeres en edad fértil y, por lo tanto, es el trastorno genético de la hemostasia más frecuente en la práctica ginecológica y obstétrica. Objetivo: hacer una revisión de la enfermedad de Von Willebrand en pacientes de ginecología y obstetricia con especial énfasis en la fisiopatología, el diagnóstico y el tratamiento. Metodología: se realizó una búsqueda bibliográfica en las bases de datos electrónicas MEDLINE/Pubmed, Elsevier, Interscience, EBSCO, Scopus, SciELO de 1980 al 2009, Cochrane Pregnancy and Childbirth Group (septiembre 30 del 2009) y libros de texto impresos. Resultados: el diagnóstico se basa en una cuidadosa anamnesis y pruebas de laboratorio de detección y confirmatorias. La correcta identificación de los diferentes tipos y subtipos es importante desde el punto de vista terapéutico. El tratamiento requiere medicaciones específicas como la desmopresina, concentrados de factor VIII y terapias coadyuvantes. No existe evidencia para contraindicar la vía vaginal del parto, sin embargo, se debe individualizar cada caso en particular. Conclusión: las mujeres con trastornos de la coagulación presentan durante la menarquia, la gestación, el parto y el puerperio un riesgo mayor de sangrado lo que hace obligatoria una adecuada evaluación y un manejo multidisciplinario durante el embarazo.

Introduction: Von Willebrand disease (vWD) is a disorder of the coagulation, being more prevalent in fertile females and is thus the most frequently occurring genetic haemostasis disorder in obstetric and gynaecological practice. Objective: reviewing the literature concerning vWD in obstetric and gynaecology patients, placing special emphasis on the disease’s physiopathology, diagnosis and treatment. Methodology: a bibliographic search was made of MEDLINE electronic databases via pubmed, Elsevier, Interscience, EBSCO, Scopus and SciELO from 1980 to 2009. The Cochrane Pregnancy and Childbirth Group (September 30th 2009) and printed texts and books were also consulted. Results: diagnosis was based on careful anamnesis and detection and confirmatory laboratory tests. Correct identification of different types and subtypes is important from a therapeutic point of view. Treatment requires specific medication such as desmopressin, factor VIII concentrates and coadjuvant therapies. No evidence was found to contraindicate vaginal birth route; however, each particular case must be taken individually. Conclusion: females suffering from coagulation disorders present a greater risk of bleeding during menarche, pregnancy, giving birth and the puerperium. This means that suitable evaluation and multidisciplinary management must be mandatory during pregnancy.

Uso del ácido épsilon aminocaproico en cirugía torácica electiva / I use of the sour épsilon aminocaproico in elective thoracic surgery

Se realizó un estudio no observacional, de tipo ensayo clínico terapéutico, comparativo, prospectivo y aleatorizado a 60 pacientes a quienes se les realizó cirugía torácica electiva, con el objetivo de evaluar la eficacia del ácido épsilon aminocaproico (AEAC) en cuanto a la disminución del sangramiento posoperatorio y las transfusiones homólogas en este período, así como describir sus posibles reacciones indeseables. Se encontró que la cantidad de sangre colectada en el posoperatorio fue significativamente menor en el grupo tratado con AEAC que en el control tanto a las 6 como a las 24 horas de finalizada la intervención. Las unidades de glóbulos transfundidas en el transoperatorio fueron semejantes en los 2 grupos, pero la cantidad de glóbulos administrados en el posoperatorio resultó significativamente menor en el grupo estudio, al igual que la proporción de pacientes que necesitó transfusión homóloga en este grupo. No se hallaron diferencias entre ambos grupos en cuanto a las reacciones indeseables(AU)

A randomized, prospective and comparative clinicotherapeutic trial was conducted as part of a non-observational study that included 60 patients who underwent elective thoracic surgery in order to evaluate the effectiveness of epsilon aminocaproic acid (EACA) in connection with the decrease of postoperative bleeding and homologous transfusions in this period, as well as to describe its potential undesirable reactions. It was found that the quantity of blood collected in the postoperaive period was much lower in the group treated with EACA than in the control group, both at 6.00 and at 24.00 hrs postintervention. The units of red blood cells transfunded in the transoperative period were similar in both groups, but the quantity of red blood cells administered in the postoperative was significantly lower in the study group, as well as the proportion of patients requiring homologous transfusions in this group. There were no differences between both groups as for undesirable reactions(AU)

The Effect of Aminocaproic Acid and Prednisolone in the Traumatic Hyphema

It is recognized that rebleeding of traumatic hyphema may predispose patients to several complications including decreased visual acuity. We reviewed the medical records of 92 patients(92 eyes) with the diagnosis of nonperforating traumatic hyphema. The relative efficiencies of Aminocaproic acid and systemic Predisolone for reducing rate of rebleeding and their side effects were evaluated under the statistical analysis. Fourty-seven patients received an oral dosage of 50 mg/kg of Aminocaproic acid every 4 hours for 5 days(up to a maximum 30 gm/day), and fourty-five patients took an oral dosage of 0.6 mg/kg of Prednisolone daily in two devided doses. The frequency of rebleeding was not statistically significantly different between the aminocaproic acid treated group(4.3%, 2/47 patients) and the prednisolone treated group(6.7%, 3/45 patients). The developing rates of their acute adverse reaction were statistically different between the aminocaproic acid treated group(44.7%, 21/47 patients) and the prednisolone treated group(20%, 9/45 patients).

Compatible Stability of Moxifloxacin Hydrochloride and Sodium Chloride Injection with Four Kinds of Antihemorrhagic Drugs / 中国药房

OBJECTIVE:To observe the compatibility of moxifloxacin hydrochloride and sodium chloride injection with four kinds of antihemorrhagic drugs(etamsylate injection,aminomethylbenzoic acid injection,vitamin K1 injection,and aminocaproic acid injection).METHODS:The concentration of moxifloxacin in the mixture of Moxifloxacin Hydrochloride and sodium chloride injection with four kinds of antihemorrhagic drugs at 25℃ and 37 ℃ were determined by UV-spectrophotometry and dual wavelength spectrophotometry within 8 h.The changes of the mixture in appearance and pH were also observed.RESULTS:The mixture of moxifloxacin hydrochloride and sodium chloride injection with four kinds of antihemorrhagic drugs experienced no obvious changes in both contents of moxifloxacin and pH and appearance.CONCLUSION:The mixture of moxifloxacin hydrochloride and sodium chloride injection with four kinds of antihemorrhagic drugs was stable in contents of moxifloxacin and property.However,further studies remain to be done to investigate whether there are changes in the contents of the other four injections.

A Clinical Study of Traumatic Hyphema

Traumatic hyphema accounts for about 6.7% of ocular trauma and its visual threatening associated ocular injuries are commotio retinae, retinal detachment, macular hole. cataract and rebleeding. The authors reviewed the medical records of 98 patients (98 eyes) having been admitted to the Joongang Gil Hospital between March 1989 and February 1991 with the diagnosis of nonperforating traumatic hyphema. Prospective study was performed as to the effect of epsilon-aminocaproic acid (EACA) in the clearance time of blood clot in the anterior chamber and the frequency of rebleeding. The avlrage clearance time of blood clot was significantly longer in the EACA treated group (5.8 days) than in the control group (3.5 days)(t-Test P0.05).

A study on the prevention of secondary hemorrhage after traumatic hyphemas by intravenous aminocaproic acid / 第二军医大学学报

To evaluate the efficacy of intravenous administration of aminocaproic acid in pre-venting secondary hemorrhage after traumatic hyphemas. Methods: 60 patients with traumatic hyphemaswere random separated into two groups: (1 ) Routine treated group: 31 patients received intramuscular ad-ministration of adrenosin or dicynone and oral administration of steroids t (2) Arninocaproic acid treatedgroup: 29 patients received aminocaproic acid in an intravenous drip. Results: The incidence of secondaryhemorrhage in the amin0caproic acid treated group was much lower than that in the routine treated group(P