RESUMO
BACKGROUND: Prasugrel is a thienopyridine that inhibits platelet aggregation more rapidly and effectively than clopidogrel, with an increased bleeding risk. OBJECTIVE: The current study aimed to evaluate the efficacy of three nonspecific haemostatic drugs - recombinant activated factor VII (rFVIIa), tranexamic acid and desmopressin (DDAVP) - to limit blood loss after administration of prasugrel in a rabbit model of bleeding while also evaluating any prothrombotic effects. DESIGN: Randomised, placebo-controlled study. SETTING: Faculty of Medicine, University of Geneva, Switzerland, in 2013. ANIMALS: Anaesthetised and artificially ventilated rabbits (n=56). INTERVENTIONS: Animals were randomly allocated to one of five groups: control (placebo-placebo), prasugrel-placebo, rFVIIa (prasugrel-rFVIIa 150âµgâkg), tranexamic acid (prasugrel-tranexamic acid 20âmgâkg) or DDAVP (prasugrel-DDAVP 1âµgâkg). Two hours after an oral prasugrel loading dose (4âmgâkg), a stenosis and an injury were inflicted on the carotid artery to induce cyclic flow reductions (CFRs) due to thrombosis. Haemostatic drugs were administered during the ensuing observation period. MAIN OUTCOME MEASURES: Standardised hepatosplenic sections were performed to evaluate the primary endpoint of blood loss, monitored for 15âmin. Ear-immersion bleeding time and incidence of CFRs were secondary endpoints. RESULTS: Prasugrel decreased ADP-induced platelet aggregation (light transmission method) from 66â±â4% (meanâ±âSD) to 41â±â7% (Pâ<â0.001) and doubled blood loss: 10.7âg (10.1 to12.7) [median (interquartile range)] vs. 20.0âg (17.0 to 24.4), Pâ=â0.003 in the control and prasugrel-placebo groups, respectively. rFVIIa, tranexamic acid and DDAVP reduced neither hepatosplenic blood loss [19.7âg (14.0 to 27.6), 25.2âg (22.6 to 28.7) and 22.9âg (16.8 to 28.8), respectively] nor bleeding time compared with placebo. Regarding safety, rVIIa induced three or more CFRs in 5/12 rabbits, vs. 0/12 in the prasugrel-placebo group (Pâ=â0.037), whereas tranexamic acid and DDAVP did not increase them. CONCLUSION: The three studied haemostatic drugs rFVIIa, tranexamic acid and DDAVP failed to reduce prasugrel-related bleeding in this model. rFVIIa-treated rabbits were more prone to arterial thrombotic events. TRIAL REGISTRATION: NA.
Assuntos
Desamino Arginina Vasopressina/administração & dosagem , Fator VIIa/administração & dosagem , Hemorragia/induzido quimicamente , Hemorragia/tratamento farmacológico , Cloridrato de Prasugrel/toxicidade , Ácido Tranexâmico/administração & dosagem , Administração Intravenosa , Animais , Antifibrinolíticos/administração & dosagem , Avaliação Pré-Clínica de Medicamentos/métodos , Hemostáticos/administração & dosagem , Masculino , Modelos Animais , Inibidores da Agregação Plaquetária/toxicidade , Coelhos , Distribuição Aleatória , Proteínas Recombinantes/administração & dosagemRESUMO
INTRODUCTION: The most serious and challenging complication of haemophilia treatment is development of inhibitors to replacement factors VIII or IX. Innovative therapies currently being explored for patients with haemophilia and inhibitors include BAY 86-6150, a modified recombinant activated factor VII (FVIIa). Immunogenicity remains a substantial barrier in this endeavour. AIM: To present safety and efficacy results of the BAY 86-6150 study in patients with inhibitors and report detailed analysis of epitope mapping in a patient who developed anti-BAY 86-6150 antibodies. METHODS: Patients aged 12-62 years with moderate or severe haemophilia A or B were eligible for the phase 3 TRUST trial if they had a history of high-titre inhibitors. Four escalating doses of BAY 86-6150 (6.5, 20, 50, 90 µg kg-1 ) were planned with ≥10 patients per dose level. Bleeding episodes were treated with BAY 86-6150. Development of anti-BAY 86-6150 antibodies was considered a serious adverse event. RESULTS: TRUST was discontinued after one patient in the 6.5-µg kg-1 cohort developed anti-BAY 86-6150 neutralizing antibodies following three exposures. The anti-BAY 86-6150 antibodies cross-reacted with and neutralized wild-type FVIIa (WT-FVIIa). Post hoc epitope mapping using peripheral blood mononuclear cells from the responding patient found that none of the 14 peptides unique to BAY 86-6150 were recognized by the patient's T cells, but strong responses were detected against 2 WT-FVIIa peptides. CONCLUSION: In the single patient with haemophilia A who developed anti-BAY 86-6150 antibodies, results of T-cell epitope mapping indicated BAY 86-6150 was no more immunogenic than WT-FVIIa.
Assuntos
Fator VIIa/uso terapêutico , Hemofilia A/imunologia , Proteínas Recombinantes/uso terapêutico , Adolescente , Adulto , Criança , Fator VIIa/administração & dosagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/administração & dosagem , Adulto JovemRESUMO
Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole blood (WB) clot formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes containing 3·2% citrate and corn trypsin inhibitor 18·3 µg/ml. WB [mean platelet count 22 × 10(9) /l (range 0-42)] was spiked in vitro with buffer, donor platelets (+40 × 10(9) /l), rFVIIa (1 or 4 µg/ml), fibrinogen (1 or 3 mg/ml), or combinations of rFVIIa and fibrinogen. Coagulation profiles were recorded by tissue factor (0·03 pmol/l) activated thromboelastometry. Coagulation in ITP was characterized by a prolonged clotting time (CT, 1490 s (mean)) and a low maximum velocity (MaxVel, 3·4 mm × 100/s) and maximum clot firmness (MCF, 38·2 mm). Fibrinogen showed no haemostatic effect, whereas rFVIIa reduced the CT and increased the MaxVel. The combination of fibrinogen and rFVIIa revealed a significant synergistic effect, improving all parameters (CT 794 s, MaxVel 7·9 mm × 100/s, MCF 50·7 mm) even at very low platelet counts. These data suggest that rFVIIa combined with fibrinogen corrects the coagulopathy of ITP even at very low platelet counts, and may represent an alternative to platelet transfusion.
Assuntos
Coagulação Sanguínea/efeitos dos fármacos , Fator VIIa/farmacologia , Fibrinogênio/farmacologia , Agregação Plaquetária/efeitos dos fármacos , Contagem de Plaquetas , Púrpura Trombocitopênica Idiopática/sangue , Adulto , Idoso , Avaliação Pré-Clínica de Medicamentos , Sinergismo Farmacológico , Fator VIIa/administração & dosagem , Feminino , Fibrinogênio/administração & dosagem , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Técnicas In Vitro , Masculino , Pessoa de Meia-Idade , Plasma Rico em Plaquetas , Púrpura Trombocitopênica Idiopática/tratamento farmacológico , Púrpura Trombocitopênica Idiopática/terapia , Receptores Fc/uso terapêutico , Proteínas Recombinantes de Fusão/uso terapêutico , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/farmacologia , Tromboelastografia , Trombina/biossíntese , Tromboplastina/farmacologia , Trombopoetina/uso terapêuticoRESUMO
BACKGROUND: As a potent anticoagulant agent, rivaroxaban exposes a risk of bleeding. An effective way to reverse its effects is needed. Objectives were to study efficacy and safety of recombinant activated factor VII (rFVIIa) and prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of an overdose of rivaroxaban in a rabbit model of bleeding and thrombosis. METHODS: First, a dose-ranging study assessed the minimal rivaroxaban dose that increased bleeding. Then, 48 anesthetized and ventilated rabbits were randomized into four groups: control (saline), rivaroxaban (rivaroxaban and saline), rFVIIa (rivaroxaban and rFVIIa), and PCC (rivaroxaban and PCC). The Folts model was applied: a stenosis and an injury were carried out on the carotid artery, inducing thrombosis, detected as cyclic flow reductions, which were recorded over 20 min. Then the following were measured: ear immersion bleeding time, clotting times, anti-Xa activity, thrombelastometric parameters, and thrombin generation test. Ultimately, a hepatosplenic section was performed and the total amount of blood loss after 15 min was evaluated as primary endpoint. RESULTS: Rivaroxaban increased blood loss (17 g [8-32] vs. 7 g [5-18] for control (median [range]), P = 0.0004), ear bleeding time, clotting times, thrombelastographic clotting time, and decreased thrombin generation. In contrast, rFVIIa decreased ear bleeding time (92 s [65-115] vs. 140 s [75-190], P < 0.02), but without efficacy on blood loss. PCC and rFVIIa decreased activated partial thromboplastin time as well as thrombelastographic clotting time. Regarding safety, neither rFVIIa nor PCC increased cyclic flow reductions. CONCLUSION: rFVIIa and PCC partially improved laboratory parameters, but did not reverse rivaroxaban induced-bleeding.
Assuntos
Anticoagulantes/antagonistas & inibidores , Fator VIIa/uso terapêutico , Morfolinas/antagonistas & inibidores , Protrombina/uso terapêutico , Tiofenos/antagonistas & inibidores , Anestesia , Animais , Anticoagulantes/farmacologia , Tempo de Sangramento , Testes de Coagulação Sanguínea , Pressão Sanguínea/efeitos dos fármacos , Temperatura Corporal/efeitos dos fármacos , Relação Dose-Resposta a Droga , Fator VIIa/administração & dosagem , Hemorragia/sangue , Fígado/irrigação sanguínea , Masculino , Monitorização Fisiológica , Morfolinas/farmacologia , Protrombina/administração & dosagem , Coelhos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Respiração Artificial , Rivaroxabana , Baço/irrigação sanguínea , Tiofenos/farmacologia , Tromboelastografia , Trombina/biossíntese , Trombose/sangue , Trombose/tratamento farmacológicoRESUMO
IMPORTANCE OF THE FIELD: Improving the pharmacodynamics of protein drugs has the potential to improve the care and the quality of life of patients suffering from a variety of diseases. AREAS COVERED IN THIS REVIEW: Four approaches to improve protein drugs are described: PEGylation, amino acid substitution, fusion to carrier proteins and encapsulation. A new platform technology based on the binding of proteins/peptides to the outer surface of PEGylated liposomes (PEGLip) is then presented. Binding of proteins to PEGLip is non-covalent, highly specific and dependent on an amino acid consensus sequence within the proteins. Association of proteins with PEGLip results in substantial enhancement of the pharmacodynamic properties of proteins following administration. This has been demonstrated in preclinical studies and clinical trials with coagulation factors VIII and VIIa. It has also been demonstrated in preclinical studies with granulocyte colony-stimulating factor. A mechanism is presented that explains the improvements in hemostatic efficacy of PEGLip-formulated coagulation factors VIII and VIIa. WHAT THE READER WILL GAIN: The reader will gain an understanding of the advantages and disadvantages of each of the approaches discussed. TAKE HOME MESSAGE: PEGLip formulation is an important new approach to improve the pharmacodynamics of protein drugs. This approach may be applied to further therapeutic proteins in the future.
Assuntos
Química Farmacêutica/métodos , Fator VIII/administração & dosagem , Fator VIIa/administração & dosagem , Fator Estimulador de Colônias de Granulócitos/administração & dosagem , Lipossomos/síntese química , Proteínas/administração & dosagem , Animais , Anticoagulantes/administração & dosagem , Avaliação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Humanos , Lipossomos/administração & dosagem , Modelos Biológicos , Modelos Moleculares , Polietilenoglicóis/administração & dosagem , Polietilenoglicóis/química , Proteínas/químicaRESUMO
Massive bleeding is a dreaded complication of biventricular mechanical assistance implantation. Its origin is multifactorial. Blood products transfusion associated with correction of coagulopathy are sometimes insufficient. We report two cases of massive bleeding after a Thoratec biventricular assistance implantation. After surgical haemostasis failure and despite the correction of coagulation disorders, a major bleeding persisted, so these patients received a single injection of 90 microg/kg of rFVIIa. This allowed in both cases a significant reduction of the bleeding and the restoration of normal haemodynamic conditions. This treatment was not complicated by any thrombotic accident.
Assuntos
Fator VIIa/uso terapêutico , Coração Auxiliar , Hemostáticos/uso terapêutico , Hemorragia Pós-Operatória/tratamento farmacológico , Choque Hemorrágico/tratamento farmacológico , Adulto , Anticoagulantes/efeitos adversos , Aprotinina/administração & dosagem , Aprotinina/uso terapêutico , Transfusão de Sangue , Transfusão de Sangue Autóloga , Tamponamento Cardíaco/cirurgia , Cardiomiopatia Dilatada/complicações , Cardiomiopatia Dilatada/cirurgia , Terapia Combinada , Quimioterapia Combinada , Emergências , Fator VIIa/administração & dosagem , Feminino , Coração Auxiliar/efeitos adversos , Hemostáticos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Miocardite/complicações , Norepinefrina/uso terapêutico , Hemorragia Pós-Operatória/induzido quimicamente , Hemorragia Pós-Operatória/etiologia , Hemorragia Pós-Operatória/terapia , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Choque Cardiogênico/tratamento farmacológico , Choque Cardiogênico/etiologia , Choque Cardiogênico/cirurgia , Choque Hemorrágico/etiologia , Choque Hemorrágico/terapia , Tromboelastografia , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/uso terapêuticoRESUMO
Glanzmann thrombasthenia is a rare congenital platelet disorder characterized by spontaneous mucocutaneous bleeding and severe bleeding complications during major surgery. This report centres on the perioperative haemostatic management of a patient with Glanzmann thrombasthenia undergoing elective major abdominal surgery. The treatment regimen was based mainly on recombinant activated factor VII, fibrinogen, and factor XIII, reducing platelet transfusion to a minimum. No red blood cell transfusions were needed perioperatively. For haemostatic monitoring, routine laboratory tests were sufficient.
Assuntos
Antifibrinolíticos/uso terapêutico , Fator VIIa/uso terapêutico , Fibrinolisina/uso terapêutico , Histerectomia , Transfusão de Plaquetas , Medicação Pré-Anestésica , Trombastenia/terapia , Ácido Tranexâmico/uso terapêutico , Adulto , Antifibrinolíticos/administração & dosagem , Testes de Coagulação Sanguínea , Perda Sanguínea Cirúrgica , Transfusão de Sangue Autóloga , Volume Sanguíneo , Terapia Combinada , Soluções Cristaloides , Procedimentos Cirúrgicos Eletivos , Fator VIIa/administração & dosagem , Feminino , Fibrinolisina/administração & dosagem , Comunicação Interventricular/complicações , Doenças das Valvas Cardíacas/complicações , Humanos , Hipertensão Pulmonar/complicações , Soluções Isotônicas/administração & dosagem , Assistência Perioperatória/métodos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/uso terapêutico , Trombastenia/complicações , Trombastenia/tratamento farmacológico , Ácido Tranexâmico/administração & dosagemRESUMO
Blood components are a limited and expensive resource, and transfusions may cause serious side effects. Drug treatment is an option to reduce the need for transfusions related to surgery. Tranexamic acid reduces transfusion requirements after total hip and knee arthroplasty, and after various cardiac surgical procedures. Desmopressin does not reduce the need for transfusions after surgery in patients with normal preoperative hemostasis. Treatment with recombinant factor VIIa may be considered in patients with massive hemorrhage caused by blunt trauma, post-partum hemorrhage, cardiac surgery, and in uncontrolled bleeding in surgery in general.
Assuntos
Antifibrinolíticos/administração & dosagem , Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue , Hemostáticos/administração & dosagem , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Aprotinina/administração & dosagem , Transfusão de Sangue Autóloga , Desamino Arginina Vasopressina/administração & dosagem , Fator VIIa/administração & dosagem , Humanos , Proteínas Recombinantes/administração & dosagem , Procedimentos Cirúrgicos Operatórios/métodos , Ácido Tranexâmico/administração & dosagem , Reação TransfusionalAssuntos
Transfusão de Sangue Autóloga/legislação & jurisprudência , Transfusão de Sangue/legislação & jurisprudência , Aprotinina/administração & dosagem , Transfusão de Sangue/ética , Transfusão de Sangue/normas , Ensaios Clínicos como Assunto , Coagulantes/administração & dosagem , Eritropoetina/administração & dosagem , Fator VIIa/administração & dosagem , Hemodiluição , Hemostáticos/administração & dosagem , Humanos , Consentimento Livre e Esclarecido , Cuidados Pré-Operatórios , EspanhaRESUMO
No disponible
Assuntos
Humanos , Aprotinina/administração & dosagem , Transfusão de Sangue/legislação & jurisprudência , Transfusão de Sangue Autóloga/legislação & jurisprudência , Transfusão de Sangue/ética , Transfusão de Sangue/normas , Ensaios Clínicos como Assunto , Coagulantes/administração & dosagem , Eritropoetina/administração & dosagem , Fator VIIa/administração & dosagem , Hemodiluição , Hemostáticos/administração & dosagem , Cuidados Pré-Operatórios , Espanha , Consentimento Livre e EsclarecidoRESUMO
The Consensus Document on Alternatives to Allogenic Blood Transfusion (AABT) has been drawn up by a panel of experts from 5 scientific societies. The Spanish Societies of Anesthesiology (SEDAR), Critical Care Medicine and Coronary Units (SEMICYUC), Hematology and Hemotherapy (AEHH), Blood Transfusion (SETS) and Thrombosis and Hemostasis (SETH) have sponsored and participated in this Consensus Document. Alternatives to blood transfusion have been divided into pharmacological and non-pharmacological, with 4 modules and 12 topics. The main objective variable was the reduction of allogenic blood transfusions and/or the number of transfused patients. The extent to which this objective was achieved by each AABT was evaluated using the Delphi method, which classifies the grade of recommendation from A (supported by controlled studies) to E (non-controlled studies and expert opinion). The experts concluded that most of the indications for AABT were based on middle or low grades of recommendation, "C", "D", or "E", thus indicating the need for further controlled studies.
Assuntos
Hemorragia/terapia , Ácido Aminocaproico/administração & dosagem , Ácido Aminocaproico/efeitos adversos , Ácido Aminocaproico/uso terapêutico , Antifibrinolíticos/administração & dosagem , Antifibrinolíticos/efeitos adversos , Antifibrinolíticos/uso terapêutico , Aprotinina/administração & dosagem , Aprotinina/efeitos adversos , Aprotinina/uso terapêutico , Perda Sanguínea Cirúrgica/prevenção & controle , Substitutos Sanguíneos/administração & dosagem , Substitutos Sanguíneos/efeitos adversos , Substitutos Sanguíneos/uso terapêutico , Transfusão de Sangue Autóloga , Coloides/administração & dosagem , Coloides/efeitos adversos , Coloides/uso terapêutico , Soluções Cristaloides , Desamino Arginina Vasopressina/administração & dosagem , Desamino Arginina Vasopressina/efeitos adversos , Desamino Arginina Vasopressina/uso terapêutico , Medicina Baseada em Evidências , Fator VIIa/administração & dosagem , Fator VIIa/efeitos adversos , Fator VIIa/uso terapêutico , Hematínicos/administração & dosagem , Hematínicos/efeitos adversos , Hematínicos/uso terapêutico , Hemodiluição , Hemorragia/tratamento farmacológico , Hemostáticos/administração & dosagem , Hemostáticos/efeitos adversos , Hemostáticos/uso terapêutico , Humanos , Ferro/administração & dosagem , Ferro/efeitos adversos , Ferro/uso terapêutico , Soluções Isotônicas/administração & dosagem , Soluções Isotônicas/efeitos adversos , Soluções Isotônicas/uso terapêutico , Recuperação de Sangue Operatório , Hemorragia Pós-Operatória/tratamento farmacológico , Pré-Medicação , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Proteínas Recombinantes/administração & dosagem , Proteínas Recombinantes/efeitos adversos , Proteínas Recombinantes/uso terapêutico , Ácido Tranexâmico/administração & dosagem , Ácido Tranexâmico/efeitos adversos , Ácido Tranexâmico/uso terapêuticoRESUMO
Indisputably, liver transplantation is among the most technically challenging operations in current practice and is compounded by significant coagulopathy and portal hypertension. Recombinant human coagulation factor VIIa (rFVIIa) is a new product that was initially described to treat bleeding in hemophilia patients. We present in this paper 10 liver transplants in Jehovah's Witness patients using this novel product at University of Southern California-University Hospital. The subject population included nine males and one female with an average age of 50 years. Six patients underwent cadaveric and four live donor liver transplantation. Surgeries were conducted following our established protocol for transfusion-free liver transplantation, which includes preoperative blood augmentation, intraoperative blood salvage, acute normovolemic hemodilution, and postoperative blood conservation. Factor rFVIIa was used at a dose of 80 microg/kg intravenously just prior to the incision in all patients, and a second intraoperative dose was used in 3 patients. All living donor liver transplantation (LDLT) recipients did well and were discharged uneventfully with normal liver functions. Two of the six cadaveric recipients died. One patient died intraoperatively from acute primary graft nonfunction, and the other died 38 hours postoperatively from severe anemia. This report suggests factor rFVIIa might have a much broader application in surgery in the control of bleeding associated with coagulopathy.
Assuntos
Coagulantes/uso terapêutico , Fator VIIa/uso terapêutico , Testemunhas de Jeová , Transplante de Fígado/métodos , Adulto , Idoso , Anemia/etiologia , Transfusão de Sangue Autóloga/métodos , Volume Sanguíneo , Cadáver , Causas de Morte , Coagulantes/administração & dosagem , Fator VIIa/administração & dosagem , Feminino , Hemodiluição/métodos , Humanos , Cirrose Hepática/cirurgia , Doadores Vivos , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes , Religião e Medicina , Deficiência de alfa 1-Antitripsina/cirurgiaRESUMO
Recent studies in humans have shown that tissue factor on the surface of endothelial cells, monocytes, or subendothelial structures sparks plasmatic coagulation. In vivo, there is no functional separation of an "endogenous" and "exogenous" pathway of the coagulation cascade. However, global laboratory tests run along such pathways due to preincubation with specific activators and, hence, allow localization of inherited coagulation defects. Coagulation inhibitors such as antithrombin or activated protein C are accelerated in their activity by cell surface glycoproteins and almost completely inactivate procoagulant activity in the microcirculation. Antithrombin binds to endothelial glycosaminoglycans and then significantly increases anticoagulant activity. Protein C is activated by the thrombin-thrombomodulin-complex and inactivates factors V a and VIII a, respectively. Additionally, activated protein C has a profibrinolytic effect. Both systems physiologically counteract the procoagulant transformation of endothelial and monocyte cell surfaces which occurs in critically ill patients due to induction of tissue factor, suppression of thrombomodulin, and removal of glycosaminoglycans from the cell surface. The distinction of static and dynamic coagulation disorders is useful since static disorders seldom require therapeutic interventions although global laboratory tests may continuously deteriorate. Dynamical disorders are symptoms of an underlying disease, and consumption coagulopathy with disseminated fibrin deposition and oozing occurs when coagulation turnover cannot be stopped. Antithrombin substitution is a well documented therapeutic option along with fresh frozen plasma and erythrocyte concentrate transfusion for blood substitution. Recent case reports in patients with irreversible bleeding complications favour the application of a recombinant factor VII concentrate. A rising perspective to decrease the use of heterologous blood and blood products may be intraoperative plasma retransfusion. The quality of such plasma undergoing consecutive filtration steps has to be clinically studied. The application of a synthetic platelet substitute, the "plateletsome", containing platelet glycoproteins led to significantly improved haemostasis without generating systemic procoagulant activity. In a far future, procoagulant cell surface transformation may be influenced by topic application of inhaled thrombomodulin loaded liposomes or by sense or antisense oligonucleotides inducing thrombomodulin expression or suppressing tissue factor expression, respectively.
Assuntos
Transtornos da Coagulação Sanguínea , Coagulação Sanguínea , Transfusão de Sangue , Procedimentos Cirúrgicos Operatórios , Coagulação Sanguínea/fisiologia , Transtornos da Coagulação Sanguínea/classificação , Transtornos da Coagulação Sanguínea/etiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Transtornos da Coagulação Sanguínea/terapia , Fatores de Coagulação Sanguínea , Transfusão de Sangue Autóloga , Ensaios Clínicos Controlados como Assunto , Estado Terminal , Coagulação Intravascular Disseminada , Fator VIIa/administração & dosagem , Fator VIIa/uso terapêutico , Hemostasia , Humanos , Microcirculação , Transfusão de PlaquetasRESUMO
Liver transplantation is associated with excessive blood loss. In order to identify factors influencing blood loss and to provide a basis for a pilot study to evaluate recombinant activated factor VII as a haemostatic agent, a retrospective study was performed in 164 consecutive patients with cholestatic or noncholestatic liver disease, who underwent orthotopic liver transplantation at a single centre between 1989 and 1996. Transfusion of allogeneic and autologous (cell saver) blood was used as a measurement of blood loss. Transfusion requirements were associated with age, gender, primary disease, Child-Pugh classification, serum levels of activated partial thromboplastin time, antithrombin III, urea and creatinine, platelet number, year of transplantation, length of cold ischaemia time and autologous blood transfusion. Of these variables, Child-Pugh classification (P = 0.001), urea (P = 0.0007), year of transplantation (P = 0.002), cold ischaemia time (P = 0.01) and autologous blood transfusion (P < 0.0001) were independent predictors of transfusion requirements by multivariate analysis. Thus, blood loss and transfusion requirements depend primarily on the severity of liver disease, quality of the donor liver, experience of the transplantation team and use of autologous (cell saver) blood transfusion. These findings emphasize the need for appropriate drug therapy and a critical reappraisal of current transfusion policy.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Transfusão de Sangue Autóloga , Transplante de Fígado , Adulto , Coagulação Sanguínea/efeitos dos fármacos , Fator VIIa/administração & dosagem , Feminino , Humanos , Masculino , Proteínas Recombinantes/administração & dosagem , Estudos RetrospectivosRESUMO
Activated recombinant human coagulation factor VII (rFVIIa) is a promising new therapeutic agent for patients with hemophilia A or B with inhibitors who experience serious bleeding episodes or who need coverage during surgical procedures. This open-label, uncontrolled, emergency-use study evaluated the efficacy and safety of rFVIIa in 11 hemophiliac patients and 1 FVII-deficient patient with life-threatening intracranial hemorrhage previously unresponsive to one or more alternative therapies. rFVIIa effectively controlled intracranial hemorrhage in 10 of the 12 patients. Patients with hemophilia A or B received an average of 96.9 rFVIIa injections over 14.7 days with a mean total administration of 153.3 mg, corresponding to 8.1 mg/kg. Most reported adverse events were considered to be unrelated to rFVIIa therapy. These findings suggest that rFVIIa is an effective and well-tolerated therapeutic option in the management of central nervous system bleeding in patients with hemophilia A or B with inhibitors.