Early administration of fibrinogen concentrate in patients with polytrauma with thromboelastometry suggestive of hypofibrinogenemia: A randomized feasibility trial

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.

Pediatric liver transplantation with ex-situ liver transection and the application of the human fibrinogen and thrombin sponge in the wound area / Transplante hepático pediátrico com transecção hepática ex-situ e aplicação da esponja de fibrinogênio e trombina humana na área cruenta

ABSTRACT Background: Surgical strategy to increase the number of liver transplants in the pediatric population is the ex-situ liver transection (reduction or split). However, it is associated with complications such as hemorrhage and leaks. The human fibrinogen and thrombin sponge is useful for improving hemostasis in liver surgery. Aim: Compare pediatric liver transplants with ex-situ liver transection (reduction or split) with or without the human fibrinogen and thrombin sponge. Methods: Was performed a prospective analysis of 21 patients submitted to liver transplantation with ex-situ liver transection with the application of the human fibrinogen and thrombin sponge in the wound area (group A) and retrospective analysis of 59 patients without the sponge (group B). Results: The characteristics of recipients and donors were similar. There were fewer reoperations due to bleeding in the wound area in group A (14.2%) compared to group B (41.7%, p=0.029). There was no difference in relation to the biliary leak (group A: 17.6%, group B: 5.1%, p=0.14). Conclusion: There was a lower number of reoperations due to bleeding of the wound area of ​​the hepatic graft when the human fibrinogen and thrombin sponge were used.

RESUMO Racional: Estratégia cirúrgica para aumentar o número de transplantes hepáticos na população pediátrica é a transecção hepática ex-situ (redução ou split). No entanto, ela está associada com complicações, tais como hemorragia e fístulas. A esponja de fibrinogênio e trombina humana é útil para melhorar a hemostasia nas operações hepáticas. Objetivo: Comparar transplantes hepáticos pediátricos com transecção hepática ex-situ (redução ou split) com ou sem a esponja de fibrinogênio e trombina humana. Métodos: Foi realizada análise prospectiva de 21 pacientes submetidos ao transplante de fígado com transecção hepática ex-situ com a aplicação da esponja de fibrinogênio e trombina humana na área cruenta (grupo A) e análise retrospectiva de 59 pacientes sem a esponja (grupo B). Resultados: As características dos receptores e doadores eram semelhantes. Observou-se menor número de reoperações devido à hemorragia na área da cruenta no grupo A (14,2%) em comparação com o grupo B (41,7%, p=0,029). Não houve diferença em relação à fístula biliar (grupo A: 17,6%, grupo B: 5,1%, p=0,14). Conclusão: Houve menor número de reoperações por sangramento da área cruenta do enxerto hepático quando a esponja de fibrinogênio e trombina humana foi utilizada.

A randomized, double blind trial of prophylactic fibrinogen to reduce bleeding in cardiac surgery / Estudo randômico e duplo-cego de profilaxia com fibrinogênio para reduzir o sangramento em cirurgia cardíaca / Estudio aleatorizado y doble ciego de profilaxis con fibrinógeno para reducir el sangrado en cirugía cardíaca

BACKGROUND AND OBJECTIVES: Postoperative bleeding has a great clinical importance and can contribute to increased mortality and morbidity in patients undergoing coronary artery bypass graft surgery. In this prospective, randomized, double-blind study, we evaluated the effect of prophylactic administration of fibrinogen concentrate on post-coronary artery bypass graft surgery bleeding. METHODS: A total of 60 patients undergoing coronary artery bypass surgery were randomly divided into two groups. Patients in the fibrinogen group received 1 g of fibrinogen concentrate 30 min prior to the operation, while patients in the control group received placebo. Post-operative bleeding volumes, prothrombin time, partial thromboplastin time, INR, hemoglobin and transfused blood products in both groups were recorded. A strict red blood cell transfusion protocol was used in all patients. RESULTS: There were no significant differences between intra-operative packed red blood cells infusion in the studied groups (1.0 ± 1.4 in fibrinogen group, and 1.3 ± 1.1 in control group). Less postoperative bleeding was observed in the fibrinogen group (477 ± 143 versus 703 ± 179, p = 0.0001). Fifteen patients in the fibrinogen group and 21 in the control group required post-op packed red blood cells infusion (p = 0.094). No thrombotic event was observed through 72 h after surgery. CONCLUSION: Prophylactic fibrinogen reduces post-operative bleeding in patients undergoing coronary artery bypass graft. .

JUSTIFICATIVA E OBJETIVO: a hemorragia no período pós-operatório é de grande importância clínica e pode contribuir para o aumento da morbidade e mortalidade em pacientes submetidos à cirurgia de revascularização coronária. Nesse estudo prospectivo, randômico e duplo-cego, avaliamos o efeito da administração profilática de concentrado de fibrinogênio sobre o sangramento após cirurgia de revascularização coronária. MÉTODOS: no total, 60 pacientes submetidos à cirurgia de revascularização coronária foram randomicamente divididos em dois grupos. Os pacientes do grupo fibrinogênio receberam 1 g de concentrado de fibrinogênio 30 minutos antes da operação, enquanto os doentes do grupo controle receberam placebo. Os volumes de sangramento no pós-operatório, tempo de protrombina, tempo de tromboplastina parcial, INR, hemoglobina e hemoderivados transfundidos em ambos os grupos foram registrados. Um protocolo de conduta rigoroso para transfusão de hemácias foi usado em todos os pacientes. RESULTADOS: não houve diferenças significantes entre as infusões de concentrados de hemácias nos grupos estudados (1,0 ± 1,4 no grupo fibrinogênio e 1,3 ± 1,1 no grupo controle). O grupo fibrinogênio apresentou menos sangramento no pós-operatório (477 ± 143 versus 703 ± 179, p = 0,0001). Quinze pacientes do grupo fibrinogênio e 21 do grupo controle precisaram de infusão de concentrado de hemácias no pós-operatório (p = 0,094). Evento trombótico não foi observado durante 72 h após a cirurgia. CONCLUSÃO: profilaxia com fibrinogênio reduz o sangramento no período pós-operatório de pacientes submetidos à revascularização coronária. .

JUSTIFICACIÓN Y OBJETIVOS: la hemorragia en el período postoperatorio es de gran importancia clínica y puede contribuir al aumento de la morbimortalidad en pacientes sometidos a cirugía de revascularización del miocardio. En este estudio prospectivo, aleatorizado y doble ciego, evaluamos el efecto de la administración profiláctica del concentrado de fibrinógeno sobre el sangrado después de la cirugía de revascularización del miocardio. MÉTODOS: en total, 60 pacientes sometidos a cirugía de revascularización del miocardio fueron aleatoriamente divididos en 2 grupos. Los pacientes del grupo fibrinógeno recibieron 1 g de concentrado de fibrinógeno 30 min antes de la operación, mientras que los del grupo control recibieron placebo. Los volúmenes de sangrado en el postoperatorio, tiempo de protrombina, tiempo de tromboplastina parcial, INR, hemoglobina y hemoderivados transfundidos en ambos grupos fueron registrados. En todo los pacientes se usó un protocolo de conducta riguroso para la transfusión de hematíes. RESULTADOS: no hubo diferencias significativas entre las infusiones de concentrados de hematíes en los grupos estudiados (1 ± 1,4 en el grupo fibrinógeno y 1,3 ± 1,1 en el grupo control). El grupo fibrinógeno presentó menos sangrado en el postoperatorio (477 ± 143 versus 703 ± 179, p = 0,0001). Quince pacientes del grupo fibrinógeno y 21 del grupo control necesitaron infusión de concentrado de hematíes en el postoperatorio (p = 0,094). Ningún evento trombótico fue observado durante 72 h después de la cirugía. CONCLUSIÓN: la profilaxis con fibrinógeno reduce el sangrado en el período postoperatorio de pacientes sometidos a revascularización del miocardio. .

Fibrinogen and thrombin concentrations are critical for fibrin glue adherence in rat high-risk colon anastomoses

OBJECTIVE: Fibrin glues have not been consistently successful in preventing the dehiscence of high-risk colonic anastomoses. Fibrinogen and thrombin concentrations in glues determine their ability to function as sealants, healers, and/or adhesives. The objective of the current study was to compare the effects of different concentrations of fibrinogen and thrombin on bursting pressure, leaks, dehiscence, and morphology of high-risk ischemic colonic anastomoses using fibrin glue in rats. METHODS: Colonic anastomoses in adult female Sprague-Dawley rats (weight, 250-350 g) treated with fibrin glue containing different concentrations of fibrinogen and thrombin were evaluated at post-operative day 5. The interventions were low-risk (normal) or high-risk (ischemic) end-to-end colonic anastomoses using polypropylene sutures and topical application of fibrinogen at high (120 mg/mL) or low (40 mg/mL) concentrations and thrombin at high (1000 IU/mL) or low (500 IU/mL) concentrations. RESULTS: Ischemia alone, anastomosis alone, or both together reduced the bursting pressure. Glues containing a low fibrinogen concentration improved this parameter in all cases. High thrombin in combination with low fibrinogen also improved adherence exclusively in low-risk anastomoses. No differences were detected with respect to macroscopic parameters, histopathology, or hydroxyproline content at 5 days post-anastomosis. CONCLUSIONS: Fibrin glue with a low fibrinogen content normalizes the bursting pressure of high-risk ischemic left-colon anastomoses in rats at day 5 after surgery. .

Fibrinógeno-trombina como tratamiento puente en un caso de hemoptisis masiva / Fibrinogen-thrombin as bridge therapy in massive hemoptysis

Se presenta el caso de una paciente joven con hemoptisis masiva por tuberculosis que no pudo ser controlada de forma efectiva con la inserción de un catéter Fogarty por un fibrobroncoscopio. Ante esto y el alto riesgo de asfixia o desangramiento, se decidió infundir fibrinógeno-trombina a través de un catéter, introducido por el fibrobroncoscopio; con esto se logró controlar el sangrado, intubarla con un tubo orotraqueal de doble luz y estabilizarla para remitirla a otra institución, donde fue sometida a lobectomía y se le proporcionó tratamiento antituberculoso. La infusión de fibrinógeno-trombina podría considerarse como una opción terapéutica transitoria, de tipo puente, mientras se practica el manejo definitivo.

This article presents the case of a young woman with massive hemoptysis (1,000 mL in 6 hours) due to tuberculosis, which could not be controlled by insertion of a Fogarty catheter through a fiber-optic bronchoscope. Because of asphyxia and persistent bleeding risk we instilled fibrinogen-thrombin through a fiber-optic bronchoscope inserted catheter, achieving bleeding cessation and permitting the placing of a double-lumen oro-tracheal tube. Later on, the patient underwent lobectomy and anti-tuberculosis treatment. The fibrinogen-thrombin could be considered as a bridge, transitory measure for massive hemoptysis, while definitive treatment could be established.

Estandarización de la técnica para la dosificación de Fibrinógeno por interpolación con la curva del Timol en donadores sanos / Standardization of the technical for the dosification of fibrinogen by interpolation with the curve of tinol in healthy donors

El fibrógeno es un factor indispensable en la coagulación sanguínea y se polimeriza por medio de la heparina, no se forma trombina y la sangre se hace incoagulable, aumenta en infecciones agudas, exceptuando la fiebre tifoidea. Enfermedades como las del hígado y la malnutrición, pueden disminuir los niveles de fibrinógeno, así también este puede subir si se presenta alguna condición inflamatoria como artritis reumatoide, neumonía aguda y enfermedad coronaria 2,3. Por lo anteriormente mencionado, se resaltó la importancia en la determinación de la concentración fibrinógeno, principalmente en pacientes con enfermedades vasculares, angiopatías o bien pacientes con historia de sangrados o tromboembolias, por esta razón se estandarizó esta prueba, considerando el establecimiento del rango de referencia, mediante una prueba de fácil ejecución; además, se planteó que el tiempo, la temperatura de almacenamiento del plasma y la hemólisis, tienen efecto en la determinación de las concentraciones de fibrinógeno utilizando esta curva

Haemostasis with cryoprecipitate in patients undergoing surgery for severe von Willebrand disease.

BACKGROUND: There are limited data on the management of haemostasis in patients with severe von Willebrand disease undergoing major surgery. Data on the use of cryoprecipitate in this setting are even more limited. In many developing countries cryoprecipitate is often the only available source of factor replacement. The minimum factor levels required for maintaining haemostasis after surgery have never been carefully evaluated. METHODS: Data from 3 patients with severe von Willebrand disease who underwent 4 major surgical procedures at our institution, using lower than standard recommended doses of cryoprecipitate were analysed for adequacy of factor replacement and complications. RESULTS: The average preoperative cryoprecipitate infusion was 22.5 i.u. of factor VIII/kg (range: 15-25). The bleeding time done by the modified Ivy method, 30 minutes after infusion, was normal in all these patients. The average cryoprecipitate support for days 1-3 was 16.5 i.u. of factor VIII/kg/day (range: 12.5-25) and for days 4-10 was 12.4 i.u. of factor VIII/kg/day (range: 8.3-16). The mean duration of factor replacement was 12 days (range: 7-17). Two patients had delayed bleeding, one on day 3 attributed to the inadvertent use of a non-steroidal anti-inflammatory drug and the second on day 10 which was probably secondary to septicaemia. Bleeding resolved in both these patients as soon as the precipitating factors were relieved. CONCLUSION: The total amount of factor replaced in our patients is approximately half of what would have been used if the usual recommendations were followed. The data suggests that lower doses of cryoprecipitate could be adequate for major surgery and wound healing in severe von Willebrand disease. This will lead to lowering of costs and reducing the risk of transfusion-associated virus infection.

Relacín entre el bibrinógeno y el metabolismo lipidico en diabéticos no dependientes de insulina

El objetivo de este trabajo fue determinar los niveles de fibrinogeno en sujetos diabéticos no dependientes de insulina (DMNID) con y sin enfermedad arterial coronaria (EAC) y en sujetos controles, así como su interrelación con los lípidos, lipoproteínas y aproteínas. No se encontraron significativas en los valores de fibrinógeno entre los sujetos normo e hipercolesterolemicos, normo e hipergliceridemicos, con c-HDL- normales o bajas, con Apo Al normales o bajas y con Apo B normales o altas. En el grupo con hipercolesterolemia, los diabéticos sin EAC presentaron niveles mas altos de fibrinogeno que los diabeticos con EAC (p<0.01). En el grupo con TG normales, los diabeticos sin EAC tuvieron niveles mas altos de fibrinogeno que los diabeticos con EAC (p<0.05). En el grupo con c-LDL normales, los diabeticos sin EAC tuvieron niveles más altos de fibrinógeno que los controles (p<0.01)y que los diabéticos con EAC (p<0.05). En conclusión, en este estudio no encontramos interacciones entre los niveles de fibrinógeno y lípidos, lipoproteínas más elevadas de fibrinógeno que con EAC y del grupo con c-HDL bajas donde los diabeticos sin EAC tuvieron niveles más altos de fibrinógeno que los controles y que los diabeticos con EAC.

Injeçäo intra-bleb de sangue autólogo no tratamento da hipotonia persistente / Intrableb injection of autologous blood for the treatment of persistent hypotony

Apresenta-se o resultado preliminar da hipotonia persisitente pós-trabeculectomia, com danos cório-retinianos, feito com a injeçäo intra-vesicular de sangue atólogo. O procedimento é de simples execuçäo, baixa morbidade, e capaz de melhorar o estado anátomo-funcional de 75 por cento dos olhos, podendo ser repetido se uma primeira tentativa fracassa

Fibrinogeno, lipidos, enfermedad arterial coronaria y diabetes mellitus no insulino dependiente

El objetivo fue determinar si elevados niveles de fibrinogeno están asociados con diabetes o enfermedad arterial coronaria (EAC) en pacientes con diabetes Mellitus No insulino dependiente (DMNID) y examinar la relación entre niveles de fibrinógeno y control glucémico. Fueron comparados los niveles de fibrinógeno, lipoproteínas y otros factores de riesgo en 164 sujetos con DMNID y 35 sujetos controles; y entre los sujetos diabéticos en aquellos con (n=38) y sin (n=126) EAC. La correlación entre los niveles de fibrinógeno y la fructosamina fue investigada en los diabéticos. Los sujetos con DMNID tuvieron niveles más altos de apolipoproteina B(p<0.02) y cociente Apolipoproteína B/ Apolipoproteina Al (p<0.05). La mayor edad (P>0.001). El sexo masculino (p<0.01) y la hipertensión arterial (p>0.001), predominaron en los diabéticos frente a los controles. Los sujetos diabéticos con EAC tuvieron la apolipoproteína al mas bajo y al cociente Apolipoproteína B/Apolipoproteína al maselevada que aquellos sin EAC. El porcentaje de obesidad abdominal fue menor en los sujetos con EAC que en aquellos sin EAC (p<0.046). No encontramos diferencias significativas en los niveles de fibrinógeno entre los diabéticos en general y los controles. Los diabéticos sin EAC tuvieron niveles de fibrinogeno más altos en promedio que aquellos con EAC (p<0.05) tampoco se encontró correlación significativa entre fibrinógeno y control metabólico. En conclusión, en este estudio no se demostró que sujetos con DMNID tuvieron niveles más altos de fibrinógeno que los sujetos controles. El fibrinogeno no se asoció con EAC en los sujetos DMNID y tampoco se encontró asociación entre niveles de fibrinógeno y control glucémico.

Congenital afibrinogenaemia.

A case of congenital afibrinogenaemia in a young female child is described. She had haemorrhagic tendency since birth in the form of markedly prolonged umbilical bleeding and easy bruising afterwards. Two of her brothers had bleeding tendencies, one died shortly after birth due to uncontrollable umbilical bleeding and other died at the age of 12 years from internal haemorrhage. The family study indicates the mode of inheritance to be probably autosomal recessive. The principal laboratory findings are complete non-coagulability of blood, grossly abnormal coagulation tests, zero ESR value, failure to detect fibrinogen by heat coagulation or chemical precipitation tests and biuret reaction and correction of thrombin time after fibrinogen infusion.