Apolipoprotein E polymorphism influences orthotopic liver transplantation outcomes in patients with hepatitis C virus-induced liver cirrhosis.

BACKGROUND: Hepatitis C virus (HCV) infection is responsible for a chronic liver inflammation, which may cause end-stage liver disease and hepatocellular carcinoma. Apolipoprotein E (protein: ApoE, gene: APOE), a key player in cholesterol metabolism, is mainly synthesized in the liver and APOE polymorphisms may influence HCV-induced liver damage. AIM: To determine whether APOE alleles affect outcomes in HCV-infected patients with liver cirrhosis following orthotopic liver transplantation (OLT). METHODS: This was a cohort study in which 179 patients, both genders and aged 34-70 years, were included before or after (up to 10 years follow-up) OLT. Liver injury severity was assessed using different criteria, including METAVIR and models for end-stage liver disease. APOE polymorphisms were analyzed by quantitative real-time polymerase chain reaction. RESULTS: The APOE3 allele was the most common (67.3%). In inflammation severity of biopsies from 89 OLT explants and 2 patients in pre-transplant, the degree of severe inflammation (A3F4, 0.0%) was significantly less frequent than in patients with minimal and moderate degree of inflammation (≤ A2F4, 16.2%) P = 0.048, in patients carrying the APOE4 allele when compared to non-APOE4. In addition, a significant difference was also found (≤ A2F4, 64.4% vs A3F4, 0.0%; P = 0.043) and (A1F4, 57.4% vs A3F4, 0.0%; P = 0.024) in APOE4 patients when compared to APOE3 carriers. The fibrosis degree of the liver graft in 8 of 91 patients and the lack of the E4 allele was associated with more moderate fibrosis (F2) (P = 0.006). CONCLUSION: Our results suggest that the E4 allele protects against progression of liver fibrosis and degree of inflammation in HCV-infected patients.

[Efficacy and safety of antifibrinolytics in oncological surgery: a systematic review and meta-analysis]. / Eficácia e segurança de antifibrinolíticos em cirurgia oncológica: uma revisão sistemática e metanálise.

BACKGROUND AND OBJECTIVES: The administration of antifibrinolytics has been shown to be effective in reducing blood loss and the need for transfusions in surgeries. However, few studies have evaluated these drugs in cancer surgery. The objective was to review the efficacy and safety of the treatment with antifibrinolytics in patients who underwent oncologic surgeries. CONTENTS: An electronic bibliographic research was conducted in PubMed, OVID, MEDLINE, EMBASE, EBSCO and in the Cochrane Library data basis in order to identify randomized clinical trials performed in any type of oncologic surgery. The data evaluated were blood loss, need for transfusion and incidence of arteriovenous thromboembolism. Five randomized controlled trials evaluating 838 patients met the inclusion requirements. In the analysis of the incidence of thromboembolic events in the five RCTs, there was no statistically significant difference between the administration of tranexamic acid when compared with the placebo (OR=0.36, 95% IC: 0.11-1.19, p=0.09, I2=0%). However, when total estimated blood loss and need for blood transfusion are analyzed, the use of tranexamic acid was associated with a significant reduction over placebo (MD=-135.79, 95% CI: -179.50 to -92.08, p<0.00001, I2=68%) and (OR=0.45, 95% CI: 0.32-0.65, p<0.00001, I2=60%), respectively. CONCLUSIONS: This meta-analysis found no evidence that the administration of antifibrinolytics increases the risk of thromboembolic complications in patients submitted to oncologic surgery, and has shown evidence that it is effective in reducing total perioperative blood loss and the need for blood transfusion.

Efficacy and safety of antifibrinolytics in oncological surgery: a systematic review and meta-analysis / Eficácia e segurança de antifibrinolíticos em cirurgia oncológica: uma revisão sistemática e metanálise

Abstract Background and objectives: The administration of antifibrinolytics has been shown to be effective in reducing blood loss and the need for transfusions in surgeries. However, few studies have evaluated these drugs in cancer surgery. The objective was to review the efficacy and safety of the treatment with antifibrinolytics in patients who underwent oncologic surgeries. Contents: An electronic bibliographic research was conducted in PubMed, OVID, MEDLINE, EMBASE, EBSCO and in the Cochrane Library data basis in order to identify randomized clinical trials performed in any type of oncologic surgery. The data evaluated were blood loss, need for transfusion and incidence of arteriovenous thromboembolism. Five randomized controlled trials evaluating 838 patients met the inclusion requirements. In the analysis of the incidence of thromboembolic events in the five RCTs, there was no statistically significant difference between the administration of tranexamic acid when compared with the placebo (OR = 0.36, 95% IC: 0.11‒1.19, p= 0.09, I2 = 0%). However, when total estimated blood loss and need for blood transfusion are analyzed, the use of tranexamic acid was associated with a significant reduction over placebo (MD = −135.79, 95% CI: −179.50 to −92.08, p< 0.00001, I2= 68%) and (OR = 0.45, 95% CI: 0.32‒0.65, p< 0.00001, I2= 60%), respectively. Conclusions: This meta-analysis found no evidence that the administration of antifibrinolytics increases the risk of thromboembolic complications in patients submitted to oncologic surgery, and has shown evidence that it is effective in reducing total perioperative blood loss and the need for blood transfusion.

Resumo Justificativa e objetivos: A administração de agentes antifibrinolíticos mostrou ser eficaz para reduzir a perda sanguínea e a necessidade de transfusões em cirurgias. No entanto, poucos estudos avaliaram esses agentes em cirurgias oncológicas. O objetivo foi revisar a eficácia e segurança do tratamento com antifibrinolíticos em pacientes submetidos a cirurgias oncológicas. Conteúdo: Uma pesquisa bibliográfica foi conduzida nos bancos de dados eletrônicos PubMed, OVID, MEDLINE, EMBASE, EBSCO e na Biblioteca Cochrane para identificar ensaios clínicos randomizados feitos em qualquer tipo de cirurgia oncológica. Os dados analisados foram perda sanguínea, necessidade de transfusão e incidência de tromboembolismo arteriovenoso. Cinco ensaios clínicos randomizados que avaliaram 838 pacientes atenderam aos critérios de inclusão. Na análise da incidência de eventos tromboembólicos em cinco ECR, não houve diferença estatisticamente significativa entre a administração do ácido tranexâmico, comparado ao placebo (OR = 0,36, IC 95%: 0,11-1,19, p = 0,09; I2 = 0%). No entanto, quando a perda sanguínea total estimada e a necessidade de transfusão de sangue foram analisadas, o uso do ácido tranexâmico foi associado a uma redução significativa, comparado ao placebo. (DM: -135,79, IC 95%: -179,50 a -92,08, p < 0,00001, I2 = 68%) e (OR = 0,45, IC 95%: 0,32-0,65, p < 0,00001, I2 = 60%), respectivamente. Conclusões: Esta metanálise não encontrou evidências de que a administração de antifibrinolíticos aumente o risco de complicações tromboembólicas em pacientes submetidos à cirurgia oncológica e apresentou evidências de que é eficaz para reduzir a perda sanguínea total no perioperatório e a necessidade de transfusão de sangue.

Monitoring of coagulation by intraoperative thromboelastometry of liver transplantation in a patient using warfarin - case report / Monitoração da coagulação pela tromboelastometria no intraoperatório de transplante hepático em um paciente usando varfarina - relato de caso

Abstract Introduction: Advanced hepatic disease may - in addition to the widely recognized hemorrhagic complications - occur with thrombotic events. We describe the case of a cirrhotic patient taking warfarin and whose coagulation management during liver transplantation was guided by thromboelastometry (ROTEM®). Case report: A 56 year-old male patient diagnosed with alcohol cirrhosis using warfarin (2.5 mg.day−1) for partial portal vein thrombosis with the International Normalized Ratio (INR) of 2.14. At the beginning of surgery, the ROTEM® parameters were all normal. In the anhepatic phase, EXTEM and INTEM remained normal, but FIBTEM showed reduction of amplitude after 10 min and maximum clot firmness. Finally, in the neohepatic phase, there was a slight alteration in the hypocoagulability of most of the parameters of the EXTEM, INTEM and FIBTEM, besides a notable correction of the Coagulation Time (CT) in HEPTEM compared to the CT of the INTEM. Therefore, the patient did not receive any transfusion of blood products during surgery and in the postoperative period, being discharged on the 8th postoperative day. Discussion: Coagulation deficit resulting from cirrhosis distorts INR as a parameter of anticoagulation adequacy and as a determinant of the need for blood transfusion. Thus, thromboelastometry can provide important information for patient management.

Resumo Introdução: A doença hepática avançada pode, além das complicações hemorrágicas amplamente reconhecidas, ocorrer com eventos trombóticos. Descrevemos o caso de um paciente cirrótico em uso de varfarina, cujo manejo da coagulação durante o transplante de fígado foi guiado por tromboelastometria (ROTEM®). Relato de caso: Paciente do sexo masculino, 56 anos, diagnosticado com cirrose alcoólica, recebendo varfarina (2,5 mg.dia−1) para trombose parcial da veia porta, com razão normalizada internacional (INR) de 2,14. No início da cirurgia, os parâmetros ROTEM® estavam todos normais. Na fase não hepática, EXTEM e INTEM permaneceram normais, mas FIBTEM mostrou redução da amplitude após 10 min e firmeza máxima do coágulo. Por fim, na fase neo-hepática houve uma ligeira alteração da hipocoagulabilidade na maioria dos parâmetros de EXTEM, INTEM e FIBTEM, além de uma correção notável do tempo de coagulação (CT) de HEPTEM em comparação com o CT de INTEM. Portanto, o paciente não recebeu transfusão de hemoderivados durante a cirurgia e no período pós-operatório, obteve alta no oitavo dia de pós-operatório. Discussão: O déficit de coagulação resultante da cirrose distorce o INR como um parâmetro da adequação da anticoagulação e como um determinante da necessidade de transfusão de sangue. Portanto, a tromboelastometria pode fornecer informações importantes para o manejo do paciente.

[Monitoring of coagulation by intraoperative thromboelastometry of liver transplantation in a patient using warfarin - case report]. / Monitoração da coagulação pela tromboelastometria no intraoperatório de transplante hepático em um paciente usando varfarina ­ relato de caso.

INTRODUCTION: Advanced hepatic disease may - in addition to the widely recognized hemorrhagic complications - occur with thrombotic events. We describe the case of a cirrhotic patient taking warfarin and whose coagulation management during liver transplantation was guided by thromboelastometry (ROTEM®). CASE REPORT: A 56 year-old male patient diagnosed with alcohol cirrhosis using warfarin (2.5mg.day-1) for partial portal vein thrombosis with the International Normalized Ratio (INR) of 2.14. At the beginning of surgery, the ROTEM® parameters were all normal. In the anhepatic phase, EXTEM and INTEM remained normal, but FIBTEM showed reduction of amplitude after 10min and maximum clot firmness. Finally, in the neohepatic phase, there was a slight alteration in the hypocoagulability of most of the parameters of the EXTEM, INTEM and FIBTEM, besides a notable correction of the Coagulation Time (CT) in HEPTEM compared to the CT of the INTEM. Therefore, the patient did not receive any transfusion of blood products during surgery and in the postoperative period, being discharged on the 8th postoperative day. DISCUSSION: Coagulation deficit resulting from cirrhosis distorts INR as a parameter of anticoagulation adequacy and as a determinant of the need for blood transfusion. Thus, thromboelastometry can provide important information for patient management.

Treatment of Severe Refractory Hematuria due to Radiation-Induced Hemorrhagic Cystitis with Dexamethasone.

Treatment of pelvic neoplasms with radiotherapy may develop sequelae, especially RHC. An 85-year-old male patient was admitted to a hospital emergency with gross hematuria leading to urinary retention and was diagnosed with RHC. The urinary bladder was probed, unobstructed, and maintained in continuous three-way saline irrigation. During 45 days of hospitalization, the patient underwent two cystoscopic procedures for urinary bladder flocculation, whole blood transfusions, and one platelet apheresis. None of these interventions led to clinical resolution. As the patient hematological condition was deteriorating, dexamethasone (4 mg i.v., bolus of 6/6, 12/12, and 24 h during five days) and epoetin alpha (1000 IU, 1 ml, s.c., for four weeks) were administered which led to the remission of the urinary bleeding. Dexamethasone therapy may be considered for RHC, when conventional treatments are not effective or are not possible, avoiding more aggressive interventions such as cystectomy.