RESUMEN
UNLABELLED: Essentials Patients with cirrhosis have hemostatic changes, which may contribute to a risk of thrombosis. This in vitro study compares clot formation and structure between patients and healthy subjects. Clot formation is delayed in patients; ultimately, however, clot permeability is decreased. The thrombogenic structure of fibrin clots may contribute to the thrombotic risk in cirrhosis. ABSTRACT: Background and Objectives Patients with cirrhosis can be at risk of thrombotic complications due to an imbalance between hemostatic components. However, little is known on how the disease affects clot generation or how alterations in the structure of fibrin clots may affect the hemostatic function of these patients. Methods We investigated the formation and structure of clots generated with plasma and purified fibrinogen of 42 patients with cirrhosis. Clots generated with plasma and fibrinogen of 29 healthy volunteers were studied for comparison. Clot formation and structure were assessed by turbidity, permeation studies, confocal laser and scanning electron microscopy (SEM). The extent of fibrinogen oxidation was assessed by measuring the carbonyl content of purified fibrinogen samples. Results Tissue factor and thrombin-induced clotting of plasma was delayed in patients. The clotting rate was also decreased, but change in turbidity, fibrin density and fiber thickness were largely comparable to healthy volunteers. Conversely, clot permeability was significantly decreased in patients. When clots were generated with purified fibrinogen, differences in clot formation and structure similar to those in plasma were found. The carbonyl content was increased in patient fibrinogen and correlated with disease severity and clot permeability. Conclusions Delayed clot formation in cirrhosis ultimately results in decreased clot permeability. Similar alterations in clots generated with purified fibrinogen suggest that modifications of the molecule are (partly) responsible. Taken together, these findings are indicative of hypercoagulable features of clots of patients with cirrhosis, which may explain the increased risk of thrombosis associated with this condition.
Asunto(s)
Coagulantes/química , Fibrinógeno/química , Fibrosis/sangre , Adulto , Coagulación Sanguínea , Pruebas de Coagulación Sanguínea , Factor XIII/química , Femenino , Fibrina/química , Voluntarios Sanos , Hemostasis , Hemostáticos , Humanos , Masculino , Malondialdehído/sangre , Microscopía Confocal , Microscopía Electrónica de Rastreo , Persona de Mediana Edad , Oxígeno/química , Permeabilidad , Trombosis/sangreAsunto(s)
Factor VIII/administración & dosificación , Factor VIII/farmacología , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Hemostasis/efectos de los fármacos , Trombina/biosíntesis , Adulto , Factor VIII/farmacocinética , Factor VIII/uso terapéutico , Hemofilia A/metabolismo , Humanos , Masculino , Adulto JovenRESUMEN
BACKGROUND: Mechanical pressure is increasingly applied as a means to prevent or treat keloid scars. AIM: The aim of this study is to analyze the long-term efficacy of our custom-molded pressure-adjustable earclips to prevent keloid recurrence after surgical excision. METHODS: Using our custom-molded earclip, 88 patients who had undergone ear surgery for keloid scars were treated for 12 h a day for 6-18 months. The mean follow-up was 6.5 years. The primary outcome was the recurrence of keloids with patient satisfaction being the secondary outcome as assessed by Patient and Observer Scale (POSAS). RESULTS: Keloid scars did not recur in 70.5% of treated patients. The Fitzpatrick scale, which classifies human skin by type, was significantly different between the recurrence and nonrecurrence group. Differences in other patient characteristics were not found between both groups. All parameters mentioned in the POSAS patient scale drastically improved after therapy. There were no severe side effects observed after the therapy. CONCLUSION: Our pressure-adjustable earclip model is an effective tool in the prevention of ear keloid recurrence and is associated with high patient satisfaction. Its benefits should prompt further studies on its value as an adjuvant therapy to surgery in keloid treatment. LEVEL OF EVIDENCE: Level III on the Evidence Rating Scale for Therapeutic Studies.
Asunto(s)
Enfermedades del Oído/cirugía , Oído Externo/cirugía , Queloide/cirugía , Microcirugia/métodos , Procedimientos de Cirugía Plástica/instrumentación , Adulto , Diseño de Equipo , Femenino , Estudios de Seguimiento , Humanos , Masculino , Presión , Estudios Retrospectivos , Instrumentos Quirúrgicos , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Optimal hemostatic management during orthotopic liver transplantation (OLT) remains a challenge. The cause of bleeding during OLT is multifactorial, and may include hemostatic imbalance. Fibrinogen concentrates are increasingly being used to control perioperative bleeding during OLT. However, administration is based on arbitrary thresholds of fibrinogen levels. Importantly, studies on fibrin clot structure during OLT are lacking. OBJECTIVE: We determined the hemostatic efficacy of fibrinogen concentrate in correcting the fibrin structure. METHODS: Plasma samples taken at various times during OLT from 15 patients and 15 healthy controls were spiked with 1 g L(-1) fibrinogen concentrate or saline. Turbidity, fibrin fiber density and permeability of the fibrin clots were assessed. RESULTS: Clotting rate and turbidity were significantly decreased at the start of surgery, and decreased even further during surgery. Addition of fibrinogen significantly increased the clotting rate and turbidity at all time points, but did not normalize it. Fibrin density was significantly reduced after reperfusion as compared with the density at the start of surgery and in healthy controls. Fibrin density improved significantly after addition of fibrinogen in samples taken at the start of surgery and after reperfusion. The severely impaired polymerization and decreased density after reperfusion were accompanied by significantly increased permeability of the clot as compared with the start of surgery and in controls, which was completely restored after addition of fibrinogen. CONCLUSIONS: Ex vivo addition of fibrinogen concentrate during OLT substantially improves the structural properties of the fibrin clot, which, particularly after reperfusion, shows hypocoagulable features. These data support the use of fibrinogen concentrate to control bleeding complications during OLT.
Asunto(s)
Coagulación Sanguínea/efectos de los fármacos , Pérdida de Sangre Quirúrgica/prevención & control , Fibrina/metabolismo , Fibrinógeno/farmacología , Hemostáticos/farmacología , Trasplante de Hígado/efectos adversos , Adulto , Anciano , Pruebas de Coagulación Sanguínea , Estudios de Casos y Controles , Factor XIII/metabolismo , Femenino , Fibrina/química , Humanos , Masculino , Persona de Mediana Edad , Permeabilidad , Polimerizacion , Porosidad , Factores de TiempoRESUMEN
An unbalance between the platelet-adhesive protein von Willebrand factor (VWF) and its cleaving protease ADAMTS13 is a risk factor for thrombosis. Here, we assessed levels and functionality of VWF and ADAMTS13 in patients undergoing off-pump lung transplantation. We analyzed plasma of 10 patients and distinguished lung transplantation-specific effects from those generally accompanying open-chest surgeries by comparing results with 11 patients undergoing off-pump coronary bypass graft (CABG) surgery. Forty healthy volunteers were included for reference values. VWF antigen levels as well as the VWF ristocetin cofactor activity/VWF antigen ratio increased during lung transplantation and after CABG surgery. An increase in VWF propeptide levels was paralleled by a decrease in ADAMTS13 activity. This was more pronounced during lung transplantation. Similarly, the capacity of plasma to support platelet aggregation under shear flow conditions in vitro was more increased during lung transplantation. The proportion of high molecular weight VWF multimers was elevated in both groups without evidence for ultra-large VWF. VWF's collagen binding activity remained unchanged. In conclusion, a hyperactive primary hemostatic system develops during lung transplantation resulting both from a pronounced (functional) increase of the VWF molecule and decrease of ADAMTS13. This may increase the risk of platelet thrombosis within the allograft.
Asunto(s)
Proteínas ADAM/sangre , Hemostáticos , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/efectos adversos , Trombosis/etiología , Factor de von Willebrand/metabolismo , Proteína ADAMTS13 , Adulto , Estudios de Casos y Controles , Puente de Arteria Coronaria , Femenino , Estudios de Seguimiento , Rechazo de Injerto , Supervivencia de Injerto , Humanos , Masculino , Persona de Mediana Edad , Adhesividad Plaquetaria , Complicaciones Posoperatorias , Pronóstico , Factores de Riesgo , Trombosis/metabolismo , Trombosis/patologíaRESUMEN
Emerging evidence indicates that various haemostatic components can regulate the progression of liver disease. Thrombin-activatable fibrinolysis inhibitor (TAFI) possesses anti-inflammatory properties besides its anti-fibrinolytic function. Here, we investigated the contribution of TAFI to the progression of disease in murine models of chronic and acute liver failure. Chronic carbon tetrachloride (CCL4) administration induced liver damage and fibrosis both in TAFI knockout (TAFI-/-) mice and wild-type controls. Smooth muscle actin-α (α-SMA) content of liver tissue was significantly increased after 1 and 3 weeks, and pro-collagen α1 expression was significantly increased after 3 and 6 weeks in TAFI-/- mice. TAFI-/- mice showed significantly elevated levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) after 3 weeks of CCL4. Neutrophil influx was significantly increased in TAFI-/- mice after 6 weeks of CCL4. No difference in hepatic fibrin deposition between TAFI-/- and wild-types was observed. After acetaminophen intoxication, necrosis was significantly increased in TAFI-/- mice at 24 hours (h) after injection. AST and ALT levels were decreased at 2 and 6 h after acetaminophen injection in TAFI-/- mice, but were significantly higher in the TAFI-/- mice at 24 h. Similarly, hepatic fibrin deposition was decreased at 6 h in TAFI-/- mice, but was comparable to wild-types at 24 h after injection. In conclusion, TAFI deficiency results in accelerated fibrogenesis and increased liver damage in murine models of chronic and acute liver disease, which may be related to increased inflammation.