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1.
ABCD (São Paulo, Impr.) ; 29(4): 236-239, Oct.-Dec. 2016. tab, graf
Article in English | LILACS | ID: biblio-837538

ABSTRACT

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.


Subject(s)
Humans , Child , Fibrinogen/administration & dosage , Surgical Sponges , Liver Transplantation , Surgical Wound/drug therapy , Hepatectomy/methods , Liver/surgery , Thrombin/administration & dosage , Prospective Studies , Retrospective Studies
3.
Clinics ; 69(4): 259-264, 4/2014. tab, graf
Article in English | LILACS | ID: lil-705782

ABSTRACT

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. .


Subject(s)
Animals , Female , Colon/surgery , Fibrin Tissue Adhesive/therapeutic use , Fibrinogen/administration & dosage , Ischemia/prevention & control , Thrombin/administration & dosage , Tissue Adhesives/therapeutic use , Anastomosis, Surgical , Collagen/analysis , Colon/blood supply , Colon/pathology , Hydroxyproline/analysis , Ischemia/etiology , Pressure , Rats, Sprague-Dawley , Reproducibility of Results , Risk Factors , Treatment Outcome , Wound Healing
4.
ABC., imagem cardiovasc ; 26(4): 289-307, out.-dez. 2013. ilus, tab
Article in English, Spanish, Portuguese | LILACS | ID: lil-705125

ABSTRACT

Pseudoaneurismas são complicações vasculares cada vez mais frequentes numa época em que a Medicina Intervencionista avança e mostra um significativo aumento dos seus procedimentos, sejam eles diagnósticos ou terapêuticos. Esta revisão busca definir essa patologia de maneira adequada, mostrando suas complicações, discorrendo sobre as várias formas de diagnóstico (clinico, US, Tomografia Computadorizada, Ressonância Magnética e Angiografia), bem como os vários tipos de tratamento propostos, (Expectante, Cirúrgico, por Compressão, Endovascular, com Injeções de Trombina e Salina). Este artigo, revendo os vários tipos de tratamento, avalia suas indicações, contraindicações e complicações, dando ênfase ao tratamento percutâneo com injeção de trombina.


Psudoaneurysms are vascular complications increasingly common at a time when the interventionist medicine progresses and shows a significant increase of its procedures, whether diagnostic or therapeutic. This review seeks to define this condition appropriately, showing its complications, discussing the various forms of diagnosis (Clinical, US, CT, MRI and Angiography), as well as the various types of treatment proposed (Expectant, Surgical, by Compression, Endovascular, with Injections of Thrombin and Salina); this article, reviewing the various types of treatment, assesses their indications, contraindications and complications, emphasizing the percutaneous treatment with thrombin injection.


Los pseudoaneurismas son complicaciones vasculares cada vez más frecuentes en una época en que la Medicina Intervencionista avanza y muestra un significativo aumento de sus procedimientos, sean ellos diagnósticos o terapéuticos. Esta revisión busca definir dicha patología de manera adecuada, mostrando sus complicaciones, reflexionando sobre las distintas formas de diagnóstico (clínico, US, Tomografía Computada, Resonancia Magnética y Angiografía), así como también los distintos tipos de tratamiento propuestos, (Expectante, Quirúrgico, por Compresión, Endovascular, con Inyecciones de Trombina y Salina). Este artículo, reviendo los distintos tipos de tratamiento, evalúa sus indicaciones, contraindicaciones y complicaciones, dando énfasis al tratamiento percutáneo con inyección de trombina


Subject(s)
Humans , Vascular Diseases/complications , Vascular Diseases/mortality , Aneurysm, False/therapy , Aneurysm, False , Thrombin/administration & dosage , Angiography/methods , Angiography
5.
Rev. bras. cardiol. invasiva ; 21(1): 18-22, jan.-mar. 2013. tab
Article in Portuguese | LILACS | ID: lil-674483

ABSTRACT

INTRODUÇÃO: A injeção de trombina guiada por ultrassom (IT) é uma opção para o tratamento de pseudoaneurisma da artéria femoral. No entanto, o resultado dessa técnica em pacientes com síndrome coronária aguda (SCA) pode ser comprometido pelo uso de medicações antitrombóticas. Também, o extravasamento de trombina para a circulação sistêmica pode causar aumento de eventos tromboembólicos. MÉTODOS: Foram selecionados todos os pacientes admitidos com SCA que apresentaram pseudoaneurisma da artéria femoral após procedimento percutâneo, tratados com IT, entre janeiro de 2007 e julho de 2011. Características clínicas e laboratoriais, resultado do tratamento e complicações foram avaliados. RESULTADOS: Analisamos 23 pacientes, com idade de 67,1 ± 14,2 anos, 60,9% eram do sexo feminino, com índice de massa corporal de 28,4 ± 4,7 kg/m², e 52,2% eram diabéticos. À apresentação, 87% tinham SCA sem supradesnivelamento do segmento ST e o restante, infarto do miocárdio com supradesnivelamento do segmento ST. Entre os pacientes avaliados, 70% foram submetidos a intervenção coronária percutânea. Todos os pacientes estavam em uso de ácido acetilsalicílico, 78,3% utilizaram inibidores da P2Y12 e 39,1%, inibidores da glicoproteína IIb/IIIa. A IT foi eficaz em ocluir o pseudoaneurisma em 100% dos casos (96,7% após a primeira injeção), sem embolia distal, infecção local ou necessidade de correção cirúrgica em nenhum caso. Não houve infarto, acidente vascular cerebral ou revascularização não-programada. Houve um óbito por choque cardiogênico, 22 dias após a IT, no segundo dia após cirurgia eletiva de revascularização miocárdica. CONCLUSÕES: O tratamento de pseudoaneurisma da artéria femoral com IT é um método seguro e eficaz em pacientes com SCA.


BACKGROUND: Ultrasound-guided thrombin injection (TI) is an option for the treatment of femoral artery pseudoaneurysm. Nevertheless, the result of this technique in patients with acute coronary syndrome (ACS) may be compromised by the use of antithrombotic drugs. In addition, thrombin extravasation to systemic circulation could potentially cause an increase in thromboembolic events. METHODS: Patients admitted with ACS who developed femoral artery pseudoaneurysm after a percutaneous procedure and treated by TI between January 2007 and July 2011 were included. Clinical and laboratory characteristics, treatment results and complications were evaluated. RESULTS: We evaluated 23 patients with mean age of 67.1 ± 14.2 years, 60.9% were women, with body mass index of 28.4 ± 4.7 kg/m² and 52.2% were diabetics. At presentation, 87% had non-ST elevation ACS and the remaining had ST elevation myocardial infarction. Of the evaluated patients, 70% were submitted to percutaneous coronary intervention. All patients were receiving aspirin, 78.3% used P2Y12 inhibitors and 39.1% used glycoprotein IIb/IIIa inhibitors. TI was successful in occluding the pseudoaneurysm in 100% of cases (96.7% after the first injection), without distal embolization, local infection or need of surgical correction. There were no cases of myocardial infarction, stroke or unscheduled revascularization. There was one death due to cardiogenic shock 22 days after TI, on the second post-operative day after an elective coronary artery bypass graft surgery. CONCLUSIONS: Treatment of femoral artery pseudoaneurysm by TI is a safe and effective procedure in patients with ACS.


Subject(s)
Humans , Male , Female , Adult , Middle Aged , Femoral Artery/physiopathology , Aneurysm, False/physiopathology , Aneurysm, False/therapy , Acute Coronary Syndrome/complications , Acute Coronary Syndrome/physiopathology , Thrombin/administration & dosage , Cardiac Catheterization , Heparin/administration & dosage , Percutaneous Coronary Intervention/methods , Platelet Aggregation Inhibitors , Ultrasonography, Interventional/methods
6.
Biomédica (Bogotá) ; 33(1): 28-33, ene.-mar. 2013.
Article in Spanish | LILACS | ID: lil-675128

ABSTRACT

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.


Subject(s)
Adult , Female , Humans , Aprotinin/therapeutic use , Factor XIII/therapeutic use , Fibrin Tissue Adhesive/therapeutic use , Fibrinogen/therapeutic use , Hemostatic Techniques , Hemoptysis/therapy , Thrombin/therapeutic use , Antitubercular Agents/therapeutic use , Aprotinin/administration & dosage , Balloon Occlusion , Bronchoscopy/methods , Catheters , Combined Modality Therapy , Cholangiopancreatography, Endoscopic Retrograde/instrumentation , Drug Combinations , Emergencies , Fiber Optic Technology , Factor XIII/administration & dosage , Fibrin Tissue Adhesive/administration & dosage , Fibrinogen/administration & dosage , Hemoptysis/etiology , Hemoptysis/surgery , Hemostatic Techniques/instrumentation , Intubation, Intratracheal/instrumentation , Pneumonectomy , Thrombin/administration & dosage , Tuberculosis, Pulmonary/complications , Tuberculosis, Pulmonary/drug therapy , Tuberculosis, Pulmonary/surgery
7.
Pesqui. vet. bras ; 32(1): 83-92, Jan. 2012. ilus, tab
Article in English | LILACS | ID: lil-614735

ABSTRACT

This study was conducted to investigate the activation ability of the platelet-rich plasma (PRP) by pharmacological agents, as well as to verify the need or not of this activation for therapeutic use. The PRP was obtained from four healthy crossbred geldings aged 13 to 16 years (15±1years), and was processed for observation and quantification of the platelet morphology by using the transmission electron microscopy. All PRP samples were activated with 10 percent calcium chloride (CaCl2) solution, pure bovine thrombin or associated with CaCl2. The control (pure PRP) was not pharmacologically activated. In the pure PRP samples, 49 percent of the platelets were classified as state of activation uncertain, 41 percent as resting, 9 percent as fully activated and 1 percent as irreversibly damaged. Treatment with 10 percent CaCl2 provided a distribution of 54 percent platelets in state of activation uncertain, 24 percent as fully activated, 20 percent as resting, and 2 percent as irreversibly damaged. The platelet morphology of the bovine thrombin treated samples did not fit into classification adopted, as showing irregular shape with emission of large filamentous pseudopods, appearance of ruptured and whole granules in the remaining cytoplasm and extracellular environment. There was effect of the treatment on the platelet morphology (P=0.03). The 10 percent CaCl2 is an adequate platelet-activating agent. However, in cases the use of PRP under its liquid form is necessary, the use of pure PRP is recommended, since besides presenting an adequate percentage of fully activated platelets it also has significant amount of the resting type, which can be activated by substances found in the injured tissue.


O objetivo desse estudo foi investigar a capacidade de ativação do plasma rico em plaquetas (PRP) por substâncias farmacológicas, assim como verificar a necessidade ou não dessa ativação para uso terapêutico. O PRP foi obtido de quatro equinos mestiços hígidos, machos castrados, com 13 a 16 anos (15±1anos) de idade, e processado para observação e quantificação da morfologia plaquetária mediante a utilização da microscopia eletrônica de transmissão. Todas as amostras de PRP foram ativadas com cloreto de cálcio (CaCl2) a 10 por cento, trombina bovina pura ou associada a CaCl2. O controle (PRP puro) não foi ativado farmacologicamente. Nas amostras de PRP puro, 49 por cento das plaquetas foram classificadas como ativação incerta, 41 por cento em repouso, 9 por cento totalmente ativada e 1 por cento com dano irreversível. O tratamento com CaCl2 a 10 por cento proporcionou uma distribuição de 54 por cento de plaquetas com ativação incerta, 24 por cento totalmente ativada, 20 por cento em repouso, e 2 por cento como com dano irreversível. Amostras tratadas com trombina bovina apresentaram morfologia plaquetária que não se enquadraram na classificação adotada, apresentando forma irregular com emissão de grandes pseudópodes filamentosos, aspecto de rompimento e grânulos inteiros no citoplasma remanescente e meio extracelular. Houve efeito do tratamento sobre a morfologia plaquetária (P=0,03). O CaCl2 a 10 por cento é um adequado agente ativador de plaquetas. Entretanto, nos casos onde se faz necessário o uso de PRP na forma mais líquida, recomenda-se o uso do PRP puro, que além de apresentar uma adequada porcentagem de plaquetas totalmente ativadas, também possui importante quantidade do tipo em repouso, que pode ser ativado por substâncias presentes no tecido lesionado.


Subject(s)
Animals , Horses/metabolism , Calcium Chloride/administration & dosage , Calcium Chloride/therapeutic use , Platelet-Rich Plasma , Microscopy, Electron, Transmission/veterinary , Thrombin/administration & dosage
8.
Korean Journal of Radiology ; : S45-S55, 2012.
Article in English | WPRIM | ID: wpr-23432

ABSTRACT

Major vascular complications related to pancreatitis can cause life-threatening hemorrhage and have to be dealt with as an emergency, utilizing a multidisciplinary approach of angiography, endoscopy or surgery. These may occur secondary to direct vascular injuries, which result in the formation of splanchnic pseudoaneurysms, gastrointestinal etiologies such as peptic ulcer disease and gastroesophageal varices, and post-operative bleeding related to pancreatic surgery. In this review article, we discuss the pathophysiologic mechanisms, diagnostic modalities, and treatment of pancreatic vascular complications, with a focus on the role of minimally-invasive interventional therapies such as angioembolization, endovascular stenting, and ultrasound-guided percutaneous thrombin injection in their management.


Subject(s)
Humans , Diagnostic Imaging , Embolization, Therapeutic/methods , Hemostasis, Endoscopic , Hemostatics/administration & dosage , Pancreatitis/complications , Stents , Thrombin/administration & dosage , Ultrasonography, Interventional , Vascular Diseases/diagnosis , Vascular Surgical Procedures/methods
9.
Rev. chil. cardiol ; 30(1): 65-70, 2011.
Article in Spanish | LILACS | ID: lil-592045

ABSTRACT

Los Seudoaneurimas (SA) iatrogénicos de la arteria femoral, se han vuelto más frecuentes debido al aumento en la complejidad de los procedimientos que requieren introductores cada vez de mayor diámetro, asociado a terapias anticoagulantes y/o antiagregantes de largo plazo. El tratamiento estándar de este tipo de lesiones fue por mucho tiempo la cirugía, sin embargo, han aparecido nuevas opciones menos invasivas, como el seguimiento activo, la compresión guiada bajo ultrasonido o la inyección de trombina bajo visión ecográfica Asimismo, se han estudiado cuales son los factores -ya sea asociados a los pacientes o a las técnicas de punción o hemostasia-, que aumentan las posibilidades de desarrollar SA. Esto ha permitido el desarrollo de dispositivos de tipo "sello arterial" como elementos preventivos. El presente trabajo tiene por objetivo revisar los factores de riesgo asociados al desarrollo de SA, las medidas de prevención -incluido el uso de "sellos arteriales en ciertos pacientes-, así como las opciones terapéuticas disponibles actualmente para el manejo de pacientes con este tipo de lesiones.


Subject(s)
Humans , Aneurysm, False/diagnosis , Aneurysm, False/therapy , Femoral Artery/injuries , Iatrogenic Disease , Aneurysm, False/etiology , Aneurysm, False/prevention & control , Diagnosis, Differential , Risk Factors , Thrombin/administration & dosage , Ultrasonography, Doppler, Color
10.
Article in English | IMSEAR | ID: sea-39292

ABSTRACT

OBJECTIVE: Report the successful treatment of iatrogenic pseudoaneurysm of the brachial artery with the percutaneous ultrasonographically guided thrombin injection (PUGTI). MATERIAL AND METHOD: The pseudoaneurysm was caused by an accidental puncture into a native brachial artery instead of the venous side of an arteriovenous fistula during hemodialysis. The aneurysmal sac had a large size with a short neck, vulnerable to intra-arterial thrombosis and distal artery embolization during the thrombin glue injection. RESULTS: This procedure was secured by using color duplex ultrasonography (CDU) for the accurate positioning of the needle and the assessment of the optimal dosage of the injected bovine thrombin. After the procedure, an elastic compression was applied at the injection site to prevent the reentry of blood flow into the aneurysmal sac. The flow in the aneurysmal sac completely disappeared in seven days after the treatment. The 4-month follow-up demonstrated the complete resolution of the aneurysmal sac. CONCLUSION: Percutaneous injection of bovine thrombin under ultrasound guidance is possible as one of the minimal invasive procedures to treat the pseudoaneurysm of the extremity artery.


Subject(s)
Aneurysm, False/etiology , Brachial Artery/diagnostic imaging , Hemostatics/administration & dosage , Humans , Injections, Intra-Arterial , Male , Middle Aged , Renal Dialysis/adverse effects , Thrombin/administration & dosage , Ultrasonography, Interventional
12.
Indian Heart J ; 2003 Jul-Aug; 55(4): 365-7
Article in English | IMSEAR | ID: sea-5536

ABSTRACT

The formation of pseudoaneurysm in the femoral artery after cardiac catheterization is a well-recognized complication occurring in 1%-4% of cases. It is traditionally managed surgically and has a high morbidity. Prolonged ultrasound-guided compression of the neck of the pseudoaneurysm, and ultrasound-guided injection of thrombin into the aneurysm are newer modalities of treatment especially for small aneurysms. We describe the case of a giant pseudoaneurysm of the right femoral artery, post-arteriography, which was successfully managed with ultrasonographically guided percutaneous thrombin injection.


Subject(s)
Aged , Aneurysm, False/drug therapy , Femoral Artery/diagnostic imaging , Cardiac Catheterization/adverse effects , Hemostatics/administration & dosage , Humans , Injections, Intra-Arterial , Male , Thrombin/administration & dosage
13.
Rev. argent. transfus ; 26(1): 79-84, ene.-mar. 2000. tab
Article in Spanish | LILACS | ID: lil-288441

ABSTRACT

El número de pacientes bajo tratamiento anticoagulante oral se ha incrementado notablemente en los últimos años al incorporarse la población de pacientes con fibrilación auricular crónica. Su manejo se ha facilitado al contar actualmente con reactivos comerciales sensibles y calibrados. No obstante este avance, las complicaciones hemorrágicas siguen siendo uno de los peligros de este tratamiento. En nuestra experiencia, las hemorragias mayores se correlacionan sobre todo con la intensidad de la anticoagulación y la duración del tratamiento. También la variabilidad del RIN (Razón Internacional Normatizada) (la desviación del RIN del rango deseado) puede asociarse con mayor sangrado. La necesidad de ajustar la dosis con pruebas de laboratorio, los controles frecuentes, la interacción con otras medicaciones, la estrecha ventana terapéutica y la alta variación en la relación dosis-respuesta, hacen surgir la necesidad de nuevos agentes antitrombóticos, igualmente eficaces, pero que permitan prescindir del ajuste por el laboratorio. Inhibidores de trombina de bajo peso molecular disponibles por vía oral están actualmente en período de prueba y constituirían una alternativa al tratamiento con antagonistas de vitamina K.


Subject(s)
Humans , Administration, Oral , Anticoagulants/administration & dosage , Anticoagulants/therapeutic use , Embolism/complications , Hemorrhage/complications , Pregnancy Complications, Hematologic , Heart Valve Prosthesis/adverse effects , Thrombin/administration & dosage , Vitamin K/administration & dosage , Acenocoumarol/therapeutic use , Heparin/therapeutic use , Ischemic Attack, Transient , Quality of Life , Risk Factors
14.
Arq. bras. oftalmol ; 58(5): 354-6, out. 1995.
Article in Portuguese | LILACS | ID: lil-260460

ABSTRACT

Neste trabalho, mostramos o desenvolvimento de adesivo tecidual fibrínico para uso em perfurações corneanas experimentais. Nesse adesivo a concentração de trombina é de 1,5mg por ml de solução, o que leva a um tempo médio de solidificação da cola de 5,6 segundos, bastante adequado para esse tipo de perfuração.


Subject(s)
Cornea/injuries , Fibrin Tissue Adhesive/therapeutic use , Tissue Adhesives/therapeutic use , Wounds, Stab/surgery , Cryopreservation , Hemostatics/administration & dosage , Thrombin/administration & dosage , Whole Blood Coagulation Time
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