ABSTRACT
Objetivo: Fornecer evidências econômicas que suportem o uso do fator VII ativado recombinante (rFVIIa) em comparação ao complexo protrombínico parcialmente ativado (CCPa) para o tratamento do episódio de sangramento leve a moderado devido a hemofilia com anticorpos inibidores no Sistema Único de Saúde (SUS). Métodos: Estudos que investigaram a eficácia clínica dos tratamentos CCPa e rFVIIa indicam diferenças entre eles na capacidade de controlar os sangramentos. A análise de custo-efetividade foi desenvolvida com base em dois modelos de árvore de decisão propostos por You et al. (2009) e Jiménez-Yuste et al. (2013). O desfecho clínico foi o percentual de pacientes que controlam o sangramento e o desfecho econômico incluiu custos médicos diretos. O horizonte de tempo variou com a gravidade da hemorragia. Os custos unitários foram obtidos do Diário Oficial da União (1 µg de rFVIIa R$ 2,09 e 1U de CCPa R$ 2,28). No modelo de You foram considerados também custos com ácido tranexâmico e centro de tratamento, extraídos da CMED (Câmara de Regulação do Mercado de Medicamentos) e do SIGTAP (Sistema de Gerenciamento da Tabela de Procedimentos), respectivamente. Resultados: O modelo de You indicou maior percentual de pacientes que tiveram o sangramento controlado com rFVIIa comparado ao CCPa (89,2% vs. 75,1%) com menor custo de tratamento (R$ 18.921 vs. R$ 28.691). Considerando Jiménez-Yuste, o percentual de pacientes com sangramento controlado também é maior com rFVIIa (79,0% vs. 61,0%), com menor custo de tratamento (R$ 63.446 vs. R$ 68.952). Conclusão: O rFVIIa é uma alternativa cost-saving para o tratamento de pacientes com hemofilia congênita com inibidores comparado ao CCPa.
Objective: To provide economic evidences that support the use of recombinant activated factor VII (rFVIIa) in comparison to activated prothrombin complex concentrate (aPCC) for the treatment of episodes of mild to moderate bleeding due to haemophilia with inhibitors in Sistema Único de Saúde (SUS). Methods: Studies that explored the clinical efficacy of aPCC and rFVIIa treatments have shown differences between them in their capacity for controlling bleeding episodes. The cost-effectiveness analysis was developed based on two decision tree models proposed by You et al. (2009) and Jiménez-Yuste et al. (2013). The clinical outcome was the percentage of patients with controlled bleeding, and the economic outcome was direct medical costs. The time horizon varied according to hemorrhage severity. Drugs unit costs were obtained from the Diário Oficial da União (1 µg of rFVIIa R$ 2.09 and 1U of aPCC R$ 2.28). In You model, also considered the costs with tranexamic acid and treatment center, extracted from CMED (Câmara de Regulação do Mercado de Medicamentos) and SIGTAP (Sistema de Gerenciamento da Tabela de Procedimentos), respectively. Results: You model showed a higher percentage of patients that controlled bleeding with rFVIIa compared to aPCC (89.2% vs. 75.1%) and with lower treatment cost (R$ 18,921 vs. R$ 28,691). Considering Jiménez-Yuste, the percentage of patients that controlled bleeding was also greater with rFVIIa (79.0% vs. 61.0%) with lower treatment cost (R$ 63,446 vs. R$ 68,952). Conclusion: rFVIIa is a cost-saving alternative for the treatment of patients with congenital haemophilia with inhibitors compared to aPCC.
Subject(s)
Humans , Cost-Benefit Analysis , Factor XIIaABSTRACT
Rectus sheath hematoma is a rare complication of anticoagulant therapy. We have described the case of a 78-year-old woman with unstable angina who developed a life-threatening rectus sheath hematoma during treatment with antiplatelet drugs and enoxaparin. The patient had underlying diseases of hypertension and triple vessels disease status post coronary artery bypass graft. She was admitted initially with an asthmatic attack. Three days later, she developed unstable angina and thus received aspirin, clopidogrel, and enoxaparin. After the fifth dose of enoxaparin, she developed progressive suprapubic pain with a newly palpable mass, anemia, hypotension, and oliguria. Abdominal computed tomography revealed a rectus sheath hematoma sized 15 cm., (about 2,000 mL by volume). Her coagulogram was normal. Despite rapid fluid resuscitation, packed red cell transfusion (1,300 mL), platelet transfusion, and protamine sulfate injection, the patient’s hemodynamic status remained unstable. Finally recombinant activated factor VII (rFVIIa) injection improved her hemodynamic status and stabilized her hemoglobin level without a thrombotic complication. This case report provides evidence of the benefit of rFVIIa use as a part of the treatment of refractory bleeding from enoxaparin.
ABSTRACT
BACKGROUND: Congenital factor VII (FVII) deficiency is a rare hemorrhagic disorder that can cause excessive bleeding during and after surgery in affected patients. The recombinant form of activated factor VII (rFVIIa, NovoSeven(R) from Novo Nordisk, Bagsvaerd, Denmark), which was developed as a second-generation bypassing agent, has recently been used in the management of bleeding for patients with congenital FVII deficiency. METHODS: We reviewed the results of 8 surgical procedures in 5 patients with congenital FVII deficiency at the Kyung Hee University Hospital, Gangdong, Seoul, Korea, between January 2008 and June 2010. We administrated rFVIIa preoperatively in six patients and postoperatively in five patients. RESULTS: Between January 2008 and June 2010 at our center, 8 operations were performed successfully and no complications were observed in the 5 patients with congenital FVII deficiency. The median level of FVII activity was 2% (range, 0.6-7%). Four orthopedic procedures, 1 tonsillectomy, and 3 dental extractions were performed. The median duration of hospitalization was 8.5 days (range, 0-15 days). rFVIIa was administered at all procedures, except the dental extraction that was performed using only antifibrinolytic agents without any replacement. No bleeding or thrombogenic complications were observed in any case. CONCLUSION: Patients with congenital FVII deficiency who require surgery can be treated efficiently and safely with rFVIIa or antifibrinolytic agents. rFVIIa was well tolerated and maintained effective hemostasis and showed good clinical outcome after the major surgery.
Subject(s)
Humans , Antifibrinolytic Agents , Factor VII , Factor VIIa , Hemorrhage , Hemorrhagic Disorders , Hemostasis , Hospitalization , Korea , Orthopedic Procedures , Recombinant Proteins , TonsillectomyABSTRACT
PURPOSE: Uncontrolled bleeding is a leading cause of death in multiple-injury patients. It is very difficult to control hemorrhage due to microvascular injury in soft tissue by surgery or vascular intervention. Thus, hemostatic agents such as recombinant activated coagulation factor VII (rFVIIa) have become popular with regard to reducing transfusion volumes and correcting the hemorrhage-associated coagulopathy. METHODS: From March 2007 to January 2010 we used rFVIIa in 15 multiple-injury patients. Transfused packed red blood cell (pRBC) volume was compared before and 6 h after administration of rFVIIa. Complete blood count, prothrombin time and activated partial thromboplastin time were also checked. RESULTS: Mortality rate correlated strongly with initial severity of coagulopathy. Transfused pRBC volumes per hour were reduced significantly after rFVIIa (p=0.01), and coagulopathy was also significantly corrected. Thromboembolic events such as acute myocardial infarction and cerebrovascular attack, a fatal complication of rFVIIa, did not occur. CONCLUSION: The administration of rFVIIa can correct hemorrhage associated coagulopathy and reduce pRBCs transfusion volume. A quick decision regarding the administration of rFVIIa is needed for a more favorable outcome in multiple-injury patients with hemorrhagic shock.
Subject(s)
Humans , Blood Cell Count , Cause of Death , Erythrocytes , Factor VII , Factor VIIa , Hemorrhage , Hemostasis , Multiple Trauma , Myocardial Infarction , Partial Thromboplastin Time , Prothrombin Time , Recombinant Proteins , Shock, HemorrhagicABSTRACT
PURPOSE: Uncontrolled bleeding is a leading cause of death in multiple-injury patients. It is very difficult to control hemorrhage due to microvascular injury in soft tissue by surgery or vascular intervention. Thus, hemostatic agents such as recombinant activated coagulation factor VII (rFVIIa) have become popular with regard to reducing transfusion volumes and correcting the hemorrhage-associated coagulopathy. METHODS: From March 2007 to January 2010 we used rFVIIa in 15 multiple-injury patients. Transfused packed red blood cell (pRBC) volume was compared before and 6 h after administration of rFVIIa. Complete blood count, prothrombin time and activated partial thromboplastin time were also checked. RESULTS: Mortality rate correlated strongly with initial severity of coagulopathy. Transfused pRBC volumes per hour were reduced significantly after rFVIIa (p=0.01), and coagulopathy was also significantly corrected. Thromboembolic events such as acute myocardial infarction and cerebrovascular attack, a fatal complication of rFVIIa, did not occur. CONCLUSION: The administration of rFVIIa can correct hemorrhage associated coagulopathy and reduce pRBCs transfusion volume. A quick decision regarding the administration of rFVIIa is needed for a more favorable outcome in multiple-injury patients with hemorrhagic shock.
Subject(s)
Humans , Blood Cell Count , Cause of Death , Erythrocytes , Factor VII , Factor VIIa , Hemorrhage , Hemostasis , Multiple Trauma , Myocardial Infarction , Partial Thromboplastin Time , Prothrombin Time , Recombinant Proteins , Shock, HemorrhagicABSTRACT
El factor VII activado recombinante (rFVIIa, NovoSeven®) ha sido utilizado en el tratamiento de los sangramientos en los pacientes hemofílicos con inhibidores. También ha sido usado para el tratamiento de los sangramientos no controlados asociados con trauma o cirugía. Se describe el tratamiento con rFVIIa en 7 pacientes no hemofílicos con un amplio rango de eventos hemorrágicos: 3 a quienes se les realizó trasplante hepático y presentaron sangramiento postrasplante sin respuesta al tratamiento convencional; 1 con aplasia medular severa y hemorragia retiniana; 1 con enfermedad de Rendú-Osler-Weber, quien tuvo un sangramiento gastrointestinal severo; y 1 paciente con manifestaciones hemorrágicas cutáneas y pulmonares debido a una enfermedad viral. La dosis de rFVIIa utilizada fue entre 90_100 µg/kg de peso, tanto para el tratamiento profiláctico como terapéutico. El rFVII activado alcanzó una hemostasia efectiva en todos los casos. Consideramos que el FVII activado puede ser aplicado cuando la combinación de los hemoderivados y los avances quirúrgicos han fallado en el control de los sangramientos que ponen en peligro la vida.
The recombinant activated factor VII (rFVIIa, NovoSeven®) has been used in the treatment of bleedings in hemophilic patients with inhibitors. It has also been used for treating uncontrolled bleedings associated with trauma or surgery. The treatment with rFVIIa in 7 non-hemophilic patients with a wide range of hemorrhagic events is described: 3 that underwent liver transplant and presented posttransplant without response to the conventional treatment; 1 with severe medullary aplasia and retinal hemorrhage; 1 with Rendú-Osler-Weber's disease that had severe gastrointestinal bleeding; and 1 patient with cutaneous and pulmonary hemorrhagic manifestations due to a viral disease. The dose of rFVIIa used was between 90 and 100 µg/kg of weight, both for the prophylactic and therapeutic treatment. The activated rFVII reached an effective hemostasis in all cases. We consider that the activated FVII may be applied when the combination of hemoderivatives and the surgical advances have failed in the control of bleedings endangering life.
Subject(s)
Humans , Male , Adolescent , Adult , Female , Child , Middle Aged , Factor VIIa/therapeutic use , Telangiectasia, Hereditary Hemorrhagic/complications , Telangiectasia, Hereditary Hemorrhagic/drug therapy , Liver Transplantation/adverse effects , Liver Transplantation/methodsABSTRACT
El Factor VII activado recombinante (rFVIIa Novoseven, Novonordisk, Dinamarca) ha sido usado con éxito en el tratamiento de las hemorragias en pacientes hemofílicos con inhibidores, en la deficiencia congénita del FVII y en la tromboastenia de Glanzmann. Además, se ha planteado su uso en pacientes no hemofílicos con anticuerpos adquiridos contra el FVIII (hemofilia adquirida) y otros trastornos de la función plaquetaria como el síndrome de Bernard Soulier (SBS). Administrado en dosis farmacológicas aumenta la generación de trombina sobre las plaquetas activadas y puede ser beneficioso en otros trastornos caracterizados por sangramiento profuso e inadecuada generación de trombina como en las trombocitopenias. Ha sido usado en hemorragias secundarias a alteraciones de la función hepática y en el trauma severo. Su utilización en pacientes con enfermedad de Rendú Osler-Weber y sangramientos severos es una indicación nueva, teniendo en cuenta la activación de la coagulación en el sitio especifico de la lesión. Se reporta la respuesta favorable de un paciente con sangramiento digestivo severo con peligro para la vida en quien se utilizó rFVII en dosis de 90ìg/Kg hasta completar 3 dosis en 24 horas; se detuvo la hemorragia y se confirmó su carácter hemostático potente en sangramientos incontrolables.
The recombinat activated factor VII (rFVIIa Novoseven, Novonordisk, Denmark) has been successfully used in the treatment of hemorrhages in hemophilic patients with inhibitors, in the congenital deficiency of FVII and in Glanzmann's thromboasthenia. Besides, its use has been recommended in non-hemoplilic patients with acquired antibodies against FVIII (acquired hemophilia) and in other disorders of the platelet function as Bernard Soulier Syndrome (SBS). When it is administered at pharmacological doses, it increases the generation of thrombin on the activated platelet, and it may be benefitial in other disorders characterized by profuse bleeding and inadequate generation of thrombin, such as the thrombocytopenias. It has been used in hemorrhages secondary to alterations of the liver function and in severe trauma. Its administration to patients with Rendú Osler Weber's disease and severe bleedings is a new indication, taking into account the activation of coagulation in the specific site of the lesion. It is reported the favorable response of a patient with severe digestive bleeding endangering his life that received rFVII at doses of 90 µg/kg until completing 3 doses in 24 hours. The hemorrhage stopped and its potent hemostatic character in uncontrollable bleedings was confirmed.
Subject(s)
Humans , Male , Middle Aged , Factor VIIa/therapeutic use , Telangiectasia, Hereditary Hemorrhagic/drug therapy , Liver Transplantation/adverse effectsABSTRACT
Recombinant activated factor VII (rFVIIa, NovoSeven (R)) was initially developed for the treatment of bleeding in patients with hemophilia having antibodies against factor VIII or IX, and factor VII deficiency. Although the precise mode of action is still elusive and there are just several hypotheses, recently case reports have suggested a role of rFVIIa in the management of intractable or life-threatening bleeding in some non-hemophilic patients who do not respond to conventional treatments. We report the successful use of rFVIIa in a pediatric patient with intractable gastrointestinal bleeding.