RESUMO
Elective surgery in patients with congenital haemophilia with inhibitors carries a high risk of bleeding. However, inhibitor patients also have a high risk of haemarthroses and other orthopaedic complications, and surgery could improve their quality of life. Successful elective surgery has been reported in inhibitor patients under haemostatic cover with plasma-derived activated prothrombin complex concentrate (pd-aPCC) or recombinant activated factor VII (rFVIIa). Recombinant FVIIa has recently become available in Venezuela and, unlike pd-aPCC, has not been associated with an anamnestic response. The aim of this study was to assess our experience using rFVIIa as a first-line and sustained treatment in elective invasive surgical procedures at the National Haemophilia Centre in Venezuela. Surgical procedures were classified as major or minor, under haemostatic cover with rFVIIa. A total of 13 patients (12 with haemophilia A with high-responding inhibitors and one with von Willebrand's disease type 3) underwent a total of 19 surgical procedures under rFVIIa cover. Thirteen procedures were classified as major surgeries. Intraoperative haemostasis was achieved in the majority of patients. Only two patients required an additional dose of rFVIIa, at 30 min and 75 min, respectively, with good results. Postoperative haemostasis was considered effective in 16 of 18 (89%) of the procedures in haemophilia A patients. Treatment was considered to be ineffective in two patients because of excessive postoperative bleeding. Data from the study provide no safety concerns, and demonstrate that rFVIIa provides effective haemostatic cover in elective surgery in patients with inhibitors; research is ongoing to determine the optimal dose for such procedures.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Fator VIIa/uso terapêutico , Hemofilia A/tratamento farmacológico , Hemofilia A/cirurgia , Hemostasia Cirúrgica/métodos , Hemostáticos/uso terapêutico , Doença de von Willebrand Tipo 3/tratamento farmacológico , Doença de von Willebrand Tipo 3/cirurgia , Adolescente , Adulto , Inibidores dos Fatores de Coagulação Sanguínea/sangue , Criança , Pré-Escolar , Procedimentos Cirúrgicos Eletivos , Feminino , Hemofilia A/imunologia , Humanos , Masculino , Proteínas Recombinantes/uso terapêutico , Adulto Jovem , Doença de von Willebrand Tipo 3/imunologiaRESUMO
This is a non-controlled experimental prospective clinical study that evaluates the satisfactory results in the chemical synovectomy (synoviorthesis) with oxytetracycline clorhydrate (Emicine, Lab. Pfizer Ltda, Guarulhos, Sao Paulo, Brazil) in recurrence haemarthrosis in different joints, demonstrating that it is an effective method in the treatment of these recurrent haemarthrosis in haemophilia. 84 patients of whom 77 concluded the full course of treatment. 82 joints were injected. The dosage injected was 5 cm(3) of the drug (25 mg) in 5 cm(3) of anaesthesia for the knee, 2 cm(3) with 1 cm(3) of anaesthesia for the elbow and 1 cm(3) plus 1 cm(3) of anaesthesia for the ankle. These injections were administered once weekly with a reinforcement in 1 month. In case of failure the same can be administered repeatedly. Subjective parameters included pain, range of movement and use of the joint involved. Pain decreased from a mean of 6.5 to 0.9 (Likert scale). Range of movement increased from 5.9 to 9 and joint use increased from 5.9 to 9.2. Objective parameters included joint diameter and range of movement. Range of movement for flexion and extension improved from 72.2 and 149.2 to 73.7 and 167, respectively, for the knees. From 57.3 and 160 to 66.6 and 170, respectively, for the shoulder. And, from 22.7 and 10.8 to 34 and 18.6, respectively, for the ankle. This procedure has multiple advantages such as immediate therapeutic effect, short period of treatment, easy technique, much less AHF coverage (30% above coagulation level), less costly than radiocolloid treatment, which make it a perfect alternative treatment for developing countries.
Assuntos
Hemartrose/terapia , Oxitetraciclina/administração & dosagem , Membrana Sinovial/efeitos dos fármacos , Adolescente , Adulto , Criança , Pré-Escolar , Humanos , Lactente , Injeções Intra-Articulares , Articulações/fisiopatologia , Dor , Recidiva , Resultado do TratamentoRESUMO
The adsorption of thrombin to fibrin during clotting defines "Antithrombin I" activity. We confirmed that thrombin generation in afibrinogenemic or in Reptilase defibrinated normal plasma was higher than in normal plasma. Repletion of these fibrinogen-deficient plasmas with fibrinogen 1 (gamma A/gamma A), whose fibrin has two "low affinity" non-substrate thrombin binding sites, resulted in moderately reduced thrombin generation by 29-37%. Repletion with fibrinogen 2 (gamma'/gamma A), which in addition to low affinity thrombin-binding sites in fibrin, has a "high affinity" non-substrate thrombin binding site in the carboxy-terminal region of its gamma' chain, was even more effective and reduced thrombin generation by 57-67%. Adding peptides that compete for thrombin binding to fibrin [S-Hir53-64 (hirugen) or gamma'414-427] caused a transient delay in the onset of otherwise robust thrombin generation, indicating that fibrin formation is necessary for full expression of Antithrombin I activity. Considered together, 1) the increased thrombin generation in afibrinogenemic or fibrinogen-depleted normal plasma that is mitigated by fibrinogen replacement; 2) evidence that prothrombin activation is increased in afibrinogenemia and normalized by fibrinogen replacement; 3) the severe thrombophilia that is associated with defective thrombin-binding in dysfibrinogenemias Naples I and New York I, and 4) the association of afibrinogenemia or hypofibrinogenemia with venous or arterial thromboembolism, indicate that Antithrombin I (fibrin) modulates thromboembolic potential by inhibiting thrombin generation in blood.
Assuntos
Fibrina/biossíntese , Fibrinogênio/fisiologia , Hirudinas/análogos & derivados , Trombina/antagonistas & inibidores , Afibrinogenemia , Antitrombinas/farmacologia , Hirudinas/farmacologia , Humanos , Fragmentos de Peptídeos/farmacologia , Ligação Proteica , Protrombina/metabolismo , Trombina/biossíntese , TrombofiliaRESUMO
The purpose of this paper was to assess the effectiveness of intra-articular injected rifampicine in haemophilic patients in order to achieve synovectomy by preventing repeated intra-articular bleeding. We have used this technique in haemophilic patients previously and reported our results on 13 cases [1]. Two hundred and fifty milligrams of rifampicine was injected into the elbow and ankle joints and 500 mg was injected into knee joints with 3-10 mL of lidocaine, depending on the joint size. The injections were repeated once a week for 7 weeks. Patients were only covered with antihaemophilic factor on the day of the injection at 30% above their coagulation level. We evaluated the results using two measures: subjective reports from the patient and objective assessment by the examiner. In the subjective reports the patient graded the results from their own perspective from 1 (poor) to 10 (excellent): 1-3, poor; 4-6, fair; 7-8, good; and 9-10, excellent. In the objective reports the grading was: excellent ('dry joint', full function, no haemarthrosis, no synovitis); good (clinical improvement, synovitis, reduction of haemarthroses, full function); fair synovitis (reduction of haemarthroses, no change in function); poor synovitis (persistent haemarthroses). This paper reports on the results of 38 patients with 39 joints with more that 3 years follow up, mean 1.8 years. There were 22 knees, nine elbows and eight ankles. Subjectively, there were excellent results in 21 joints (11 knees, six elbows and four ankles) good results in 15 joints (eight knees, three elbows and four ankles), fair results in two knees and a poor result in one knee. Objectively, results obtained were excellent in 20 joints (11 knees, six elbows and three ankles); good in 17 (nine knees, three elbows and five ankles); fair in one knee and poor in one knee.
Assuntos
Antifibrinolíticos/uso terapêutico , Hemartrose/tratamento farmacológico , Hemofilia A/complicações , Rifampina/uso terapêutico , Membrana Sinovial/efeitos da radiação , Adolescente , Adulto , Antifibrinolíticos/normas , Criança , Avaliação de Medicamentos , Hemartrose/etiologia , Hemofilia A/terapia , Humanos , Injeções Intra-Articulares/métodos , Injeções Intra-Articulares/normas , Masculino , Avaliação de Resultados em Cuidados de Saúde , Satisfação do Paciente , Rifampina/normas , SinovectomiaRESUMO
Fibrinogen Caracas V is a thrombotic dysfibrinogenemia with an Aalpha 532 Ser-->Cys mutation characterized by a tight fibrin network formed of thin fibers responsible for a less porous clot than a normal one. In the present work, fibrinogen Caracas V is further characterized in order to understand the relationship between the structural defect and thrombophilia. This thrombotic disorder has been attributed to a tight fibrin network responsible for a decreased permeation of flow through the clot, leading to defective thrombus lysis due to a diminished availability of fibrinolytic enzymes to the inner fibrin surface. Correction of clot structure anomaly, by addition of dextran 40 to fibrinogen before clotting, induces an improvement in fibrin degradation that was attributed to an increase in porosity. The pulmonary embolism observed in this family has been related to an hyper rigidity of the clot, an anomaly that is also corrected by dextran. Furthermore, this abnormal fibrinogen binds more albumin than does normal fibrinogen, a phenomenon attributed to the mutation of serine in Aalpha-532 by cysteine. Therefore, this fibrinogen shows a striking similarity to the fibrinogen Dusart, allowing us to confirm that the alphaC-terminal part of fibrinogen plays an important role in fibrin structure, and to conclude that the anomaly of fibrin network observed in fibrinogen Caracas V is responsible for a deficient thrombus lysis.
Assuntos
Transtornos de Proteínas de Coagulação/fisiopatologia , Fibrinogênios Anormais/metabolismo , Albuminas/metabolismo , Substituição de Aminoácidos , Coagulação Sanguínea/efeitos dos fármacos , Coagulação Sanguínea/genética , Transtornos de Proteínas de Coagulação/sangue , Transtornos de Proteínas de Coagulação/genética , Dextranos/farmacologia , Fibrina/genética , Fibrina/metabolismo , Fibrina/ultraestrutura , Fibrinogênios Anormais/genética , Fibrinólise/efeitos dos fármacos , Fibrinólise/genética , Humanos , Microscopia Confocal , Mutação , Trombofilia/sangue , Trombofilia/genéticaRESUMO
A new dysfibrinogenemia associated with thrombophilia has been identified in a Venezuelan kindred. Thrombin and Reptilase times were prolonged and the accelerating capacity of the patient's fibrin on the t-PA-induced plasminogen activation was decreased. In addition the affinity of fibrinogen for plasminogen was diminished. Permeability and electron microscopy studies revealed that the abnormal clot was made up of thin and densely packed fibres giving rise to a reduced fibrin gel porosity. This was confirmed by turbidity studies showing a decreased fibre mass/length ratio. Affected members were heterozygous for an Aalpha 532 Ser-->Cys mutation as demonstrated by genetic analyses. This abnormal fibrinogen has been designated as Fibrinogen Caracas V. The family study showed a convincing association between the mutation and thrombotic manifestations. The thrombotic tendency may be ascribed to lack of accelerating capacity of fibrin to induce fibrinolysis caused by an abnormal clot structure with thin fibres and reduced porosity.
Assuntos
Fibrinogênios Anormais/genética , Trombose/etiologia , Adolescente , Adulto , Substituição de Aminoácidos , Coagulação Sanguínea/genética , Testes de Coagulação Sanguínea/métodos , Análise Mutacional de DNA , Saúde da Família , Feminino , Fibrina/farmacologia , Fibrina/ultraestrutura , Fibrinogênios Anormais/metabolismo , Fibrinogênios Anormais/ultraestrutura , Heterozigoto , Humanos , Radioisótopos do Iodo , Cinética , Masculino , Microscopia Eletrônica , Pessoa de Meia-Idade , Mutação/genética , Nefelometria e Turbidimetria , Linhagem , Plasminogênio/efeitos dos fármacos , Plasminogênio/metabolismo , Plasminogênio/normas , Recidiva , Análise de Sequência de DNA , Trombofilia/etiologia , Trombofilia/genética , Trombose/genética , Ativador de Plasminogênio Tecidual/farmacologiaRESUMO
Fibrinogen Caracas I is a dysfibrinogenemia with a mild bleeding diathesis and a defective wound healing. We have characterized this abnormal fibrinogen using transmission electron microscopy (TEM) in combination with turbidity and permeation studies. Turbidometric and permeability analysis showed that the abnormal fibrin had a significantly decreased mass:length ratio and fiber diameter. In addition, the permeability studies of plasma fibrin clots showed that the gel porosity of the abnormal fibrinogen was reduced. Images of the abnormal fibrin structure obtained using TEM showed that the fibers were thinner, much less branched and less ordered than normal fibers. Diminished fibrin fiber diameter and reduced fibrin gel porosity have been taken as hallmarks of thrombophilic dysfibrinogenemias. The results of the present study show that these features are not necessarily predictive of thrombophilia. Further studies performed on a larger number of dysfibrinogenemias need to be conducted in order to establish the implications of these parameters on the clinical outcome.
Assuntos
Transtornos de Proteínas de Coagulação/patologia , Fibrinogênios Anormais/química , Fibrinogênios Anormais/ultraestrutura , Transtornos de Proteínas de Coagulação/genética , Feminino , Fibrina/ultraestrutura , Fibrinogênios Anormais/genética , Hemorragia/genética , Humanos , Análise dos Mínimos Quadrados , Microscopia Eletrônica , Porosidade , Cicatrização/genéticaRESUMO
Dietary experiments, performed in metabolic wards, gave rise to predictive regression equations relating changes of plasma cholesterol concentration to the intake of fatty acids of the diet. It has been established that polyunsaturated fatty acids diminish and most saturated fatty acids increase plasma cholesterol concentration. This information led to expect that dietary use of palm oil may induce an unfavorable plasma lipoprotein profile. This has not been the case as shown in various dietary experiments. The reasons for this discrepancy is discussed. The influence of palm oil enriched diets on prothrombotic variables show that platelets are not affected in their function during prolonged dietary intervention. It is important to continue research on the effects of palm oil based diet on plasma fibrinogen, factor VII. There is still discordant information in this field.
Assuntos
Arteriosclerose/etiologia , Gorduras na Dieta/farmacologia , Hipercolesterolemia/induzido quimicamente , Óleos de Plantas/farmacologia , Trombose/etiologia , Adulto , Animais , Arteriosclerose/prevenção & controle , Criança , Colesterol/sangue , Dieta Aterogênica , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/efeitos adversos , Fator VII/análise , Comportamento Alimentar , Feminino , Fibrinogênio/análise , Óleos de Peixe/farmacologia , Humanos , Ácido Linoleico , Ácidos Linoleicos/administração & dosagem , Ácidos Linoleicos/farmacologia , Lipoproteínas/sangue , Masculino , Óleo de Palmeira , Óleos de Plantas/administração & dosagem , Óleos de Plantas/efeitos adversos , Óleos de Plantas/química , Agregação Plaquetária/efeitos dos fármacos , Coelhos , População Rural , Óleo de Girassol , Trombose/prevenção & controle , Triglicerídeos/sangue , População Urbana , VenezuelaRESUMO
The majority of bleeding episodes in patients who have hemophilia occur within the musculoskeletal system, primarily in the joints, but approximately 30% occur within the muscles. Iliopsoas muscle bleeding episodes are often large in volume, causing muscular function inhibition, angular deformities, and nerve involvement. Recurrent hemorrhages are common (14.2%) and neural involvement is as high as 37%. Three hundred patients are being observed in the authors' hemophilia center, 63 of whom have suffered 127 hemorrhages. Absolute bed rest and long term factor replacement are the mainstay of therapy. The experiences of physicians in other countries are appendixed to this article.
Assuntos
Hematoma/etiologia , Hemofilia A/complicações , Doenças Musculares/etiologia , Músculos Psoas , Humanos , América Latina , Recidiva , Resultado do TratamentoRESUMO
We describe six new cases of a hemorrhagic diathesis induced by contact with Lonomia achelous caterpillars. Onset of clinical bleeding varied between a few hours and 10 days post-exposure. Laboratory coagulation tests showed prolonged PT, PTT and ThT; normal platelets and a marked decrease of fibrinogen, factor V, plasminogen and factor XIII (including its subunits A and S). Factors VII, II and alfa 2 anti-plasmin were variably affected. In addition, activation of the fibrinolytic system and the generation of a procoagulant effect could also be demonstrated. Two cases developed severe hemorrhagic diathesis and one of them died of a cerebral hemorrhage. Different aspects of this rare syndrome are discussed in relation to its complex physiopathology and the variability observed in all clinical and laboratory manifestations. Therapeutic recommendations and some possible hazards following replacement transfusions are also considered.