Asunto(s)
Parto Obstétrico/métodos , Hemofilia A/complicaciones , Hemorragia/prevención & control , Factores de Coagulación Sanguínea/uso terapéutico , Manejo de la Enfermedad , Femenino , Hemofilia A/tratamiento farmacológico , Hemorragia/epidemiología , Humanos , Recién Nacido , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Embarazo , Complicaciones Hematológicas del Embarazo/prevención & control , RiesgoRESUMEN
Although up to 30% of babies born with haemophilia do not have a family history of the disorder, the remaining 70% are born in families where haemophilia has been diagnosed. It has been estimated that for each male with haemophilia, there are five potential female carriers. Such women will benefit from knowledge of both their genetic (mutation present or not) and phenotype (level of plasma factor activity) status. Genetic counselling services to provide information and testing, together with plasma factor measurement, should be offered where available to all women at risk of being carriers. It is critical that women know their plasma factor measurement as they may have mild haemophilia (factor 5-30%, reference range 50-150%) which requires management at times of medical and surgical procedures and following trauma. Close liaison between adult and paediatric haemophilia centres and obstetric-gynaecology units is important to ensure that clinical carers identify and address carriers' needs. Genetic testing should be performed only after a potential carrier has been counselled and supported to receive such information. There is no coercion to accept such testing. An advantage of genetic testing is to then discuss pre-implantation genetic diagnosis which is an ex-vitro form of prenatal diagnosis. This can assist couples at risk of having a child with haemophilia who wish to reduce their anxieties about reproduction. Approximately 4% of boys with haemophilia, born in countries with good maternal care, will have intracranial haemorrhage in the neonatal period. There are no high-level evidence-based guidelines for the management of delivery or of the newborn with haemophilia. Obstetricians or other birth attendants need to be advised of the possibility of delivery of a boy with haemophilia and seek support from a haemophilia specialist during the pregnancy. The mother can then be monitored and plans for delivery be developed between her medical consultants and discussed with her. It is always preferable for a carrier to know of her genetic and phenotypic status before becoming pregnant so that she is informed as to her options and requirements for safe delivery.
Asunto(s)
Asesoramiento Genético/ética , Hemofilia A/diagnóstico , Hemorragias Intracraneales/prevención & control , Complicaciones Hematológicas del Embarazo/prevención & control , Adolescente , Adulto , Niño , Preescolar , Factor IX/genética , Factor VIII/genética , Femenino , Pruebas Genéticas/ética , Hemofilia A/genética , Heterocigoto , Humanos , Lactante , Recién Nacido , Masculino , Fenotipo , Embarazo , Complicaciones Hematológicas del Embarazo/genética , Factores de RiesgoRESUMEN
Alloimmune hemolysis is a recognized but infrequent complication of solid organ transplantation, particularly where there is incompatibility within the ABO blood group system. We describe severe hemolysis due to passenger lymphocyte syndrome (PLS) in all three recipients of organs from a single donor with multiple red cell (RC) alloantibodies. The first patient, a liver transplant recipient, required augmentation of immunosuppression to treat immune hemolysis due to anti-B, -D, -C and -Cellano (k). This is the first description of PLS caused by alloantibody to the high incidence RC antigen, k. The two single lung transplant recipients developed hemolysis due to anti-D. Both required escalation of immunosuppression and early transfusion support. Three months posttransplant, all three patients have ongoing evidence of compensated hemolysis. This series highlights the potential for severe non-ABO-mediated immune hemolysis following solid organ transplantation. A positive donor RC antibody screen should prompt careful monitoring of organ recipients for hemolysis.
Asunto(s)
Sistema del Grupo Sanguíneo ABO/inmunología , Eritrocitos/inmunología , Hemólisis/inmunología , Isoanticuerpos/inmunología , Trasplante de Hígado/efectos adversos , Trasplante de Pulmón/efectos adversos , Incompatibilidad de Grupos Sanguíneos/inmunología , Femenino , Humanos , Isoanticuerpos/análisis , Linfocitos/inmunología , Masculino , Persona de Mediana Edad , Síndrome , Donantes de TejidosRESUMEN
The prevalence of hepatitis C virus (HCV) infection in adult patients with a congenital bleeding disorder (CBD) approaches 95% and is a major cause of morbidity and mortality. Histological examination of the liver remains the cornerstone of management decisions in patients without a CBD. The reluctance to perform liver biopsies in patients with a CBD has been a major limitation in the management of these patients. We are currently the only haemophilia centre in Australasia performing liver biopsies in patients with a CBD for the purpose of guiding prognostic and therapeutic decisions. We report here the results of our centre's experience with transjugular liver biopsy (TJLB) in patients with a CBD. An adequate specimen for histological assessment was attained from all of the patients. There were no major complications recorded. Patients were hospitalized for < or = 48 h for haemostasis prophylaxis. The diagnostic specimen obtained from patients was integral in guiding their future management. We suggest that with a coordinated multidisciplinary approach, TJLB can be performed in patients with a CBD.
Asunto(s)
Trastornos de la Coagulación Sanguínea/patología , Hepatitis C/complicaciones , Hígado/patología , Adulto , Biopsia/métodos , Trastornos de la Coagulación Sanguínea/complicaciones , Trastornos de la Coagulación Sanguínea/congénito , Femenino , Hepatitis C/patología , Humanos , Venas Yugulares , Masculino , Persona de Mediana Edad , PronósticoRESUMEN
In patients with hemophilia A who have an inhibitor to factor (F)VIII measured by Bethesda assay, enzyme-linked immunosorbent assay (ELISA) can also be used to detect the inhibitor. In some studies non-inhibitory antibodies were also detected by ELISA in many patients who were negative by Bethesda assay. Our aim was to investigate whether there is a higher detection rate of FVIII antibodies by ELISA compared with Bethesda assay. We also compared outcomes using three different preparations of recombinant FVIII (rFVIII) to coat the microtiter plates for ELISA. Inhibitor detection by ELISA generally agreed with the Bethesda method. Only four of 26 patients with no clinical suspicion of an inhibitor and with no detectable inhibitor by Bethesda assay showed a non-inhibitory antibody by ELISA, and three of these were only weakly positive. Patients with severe hemophilia A and the intron 22 inversion (n = 21) did not show a higher incidence of non-inhibitory antibodies compared with those without that mutation. Finally, we found that the formulation of rFVIII has a small effect on ELISA performance, mainly in detection of low-level antibody. The results of the present study are in contrast to and fail to confirm previously published reports showing a higher incidence of non-inhibitory antibodies in hemophilia A.
Asunto(s)
Autoanticuerpos/inmunología , Epítopos/inmunología , Factor VIII/inmunología , Hemofilia A/inmunología , Adulto , Autoanticuerpos/sangre , Preescolar , Inversión Cromosómica , Ensayo de Inmunoadsorción Enzimática , Factor VIII/análisis , Factor VIII/genética , Humanos , Epítopos Inmunodominantes/inmunología , Intrones , Persona de Mediana Edad , Fragmentos de Péptidos/análisis , Proteínas Recombinantes/análisisRESUMEN
Factor VIII inhibitors have previously been classified as type I or type II using complex experiments that study the time course of inactivation of factor VIII and the effect of varying the antibody concentration. Classification may be important to better understand inhibitor behaviour in vivo. To determine the most reliable method of classifying the kinetics of factor VIII inactivation, we studied 11 patients with haemophilia A, comprising five severe, three mild and three acquired cases, and compared the classification obtained from plasma dilution studies and time-course studies. The plasma dilution studies showed two distinctly different patterns: a steep slope with complete FVIII:C inactivation at high antibody concentrations for type I inhibitors and a FVIII:C plateau with incomplete inactivation for type II inhibitors. Six type I (four severe, one mild and one acquired) and two type II (one mild and one acquired) inhibitors were classified using either plasma samples or purified and concentrated IgG, while the remaining were undetermined owing to insufficient available plasma. In contrast, the time-course studies could not discriminate between these groups. We recommend that plasma dilution studies be used for the classification of in vitro kinetics of factor VIII inhibitors.
Asunto(s)
Autoanticuerpos/clasificación , Inhibidores de Factor de Coagulación Sanguínea/clasificación , Factor VIII/inmunología , Hemofilia A/sangre , Adulto , Anciano , Autoanticuerpos/análisis , Inhibidores de Factor de Coagulación Sanguínea/farmacocinética , Pruebas de Coagulación Sanguínea , Factor VIII/genética , Femenino , Humanos , Inmunoglobulina G/inmunología , Isoanticuerpos/clasificación , Masculino , Persona de Mediana Edad , MutaciónRESUMEN
There are many challenging problems related to bleeding and anticoagulation in cardiac surgery. Practical guidelines, which are based on available evidence, can help to direct management issues of post-bypass bleeding, perioperative anticoagulation and the use of haemostatic agents. The patient's bleeding history is the most useful preoperative screening test of haemostasis. The input of a haematologist is often valuable in a number of areas, such as preoperative assessment of patients with a significant history of bleeding, or past history of heparin-induced thrombocytopenia, a lupus anticoagulant, or recent venous thromboembolism. Cardiothoracic surgeons, anaesthetists, perfusionists and haematologists can ensure 'best practice' by being actively involved in the development of 'local' transfusion and anticoagulation guidelines, hospital transfusion committee policies, and audits.
RESUMEN
The anticoagulant effect of warfarin should be kept at an international normalised ratio (INR) of about 2.5 (desirable range, 2.0-3.0), although a higher level may be better in a few clinical conditions. The risk of bleeding increases exponentially with INR and becomes clinically unacceptable once the INR exceeds 5.0. Warfarin therapy should be continued for around six weeks for symptomatic calf vein thrombosis, and for 3-6 months after proximal deep vein thrombosis (DVT) that occurs after surgery or limited medical illness. Therapy for six months or longer could be considered for DVT occurring without an obvious precipitating factor, proven recurrent venous thromboembolism (VTE), or if there are continuing risk factors. Oral anticoagulants prevent ischaemic stroke in atrial fibrillation (AF). Maximum efficacy requires an INR > 2.0, but some benefit remains at an INR of 1.5-1.9. Patients aged over 75 years are at greatest risk of intracranial bleeding during warfarin therapy for AF, and the target INR may be reduced to 2.0-2.5, or perhaps as low as 1.5-2.0, in such patients. Warfarin should be withheld if it is more likely to cause major bleeding than to protect from stroke (e.g., in young people with isolated AF where the annual baseline risk of stroke is < 1%). In patients with AF, aspirin is less effective than warfarin (much less effective after such patients have had a stroke or transient cerebral ischaemia). In people with prosthetic heart valves, an INR of 2.5-3.5 is probably sufficient for bileaflet or tilting disc valves, but a higher target INR is necessary for caged ball or caged disc valves. The addition of aspirin (100 mg/day) further decreases the risk of embolism but increases the risk of gastrointestinal bleeding.
Asunto(s)
Anticoagulantes/uso terapéutico , Warfarina/uso terapéutico , Anciano , Anciano de 80 o más Años , Anticoagulantes/efectos adversos , Fibrilación Atrial/complicaciones , Humanos , Persona de Mediana Edad , Accidente Cerebrovascular/prevención & control , Trombosis/tratamiento farmacológico , Trombosis/prevención & control , Warfarina/efectos adversosRESUMEN
The conditions for activation transmission across a region of extracellular space was demonstrated in two-dimensional preparations with results consistent with those previously seen in the one-dimensional fiber studies. In addition, one sees changes in action potential morphology which occur in the tissue nearest the connective-tissue border as well as changes in conduction velocity along the border. These results hinge on an adequate representation of the connective-tissue region achieved by careful implementation of the boundary conditions in the intracellular and interstitial spaces and the expansion of the connective-tissue discretization to a "double-tier network" description. Through a series of simulations, a clear dependence on fiber orientation is illustrated in the efficacy to transmit activation. The collision of a front with an embedded connective-tissue region was also examined. The results revealed that fibers aligned normal to a planar stimulus would more greatly disrupt the advancement of a planar front. Such pronounced disruptions have been shown to be proarrhythmic in the literature. The increasing evidence of the ability of connective tissue to transmit activation has implications in understanding spread of activation through infarcted tissues and through the healthy ventricular wall in the presence of connective-tissue sheets.
Asunto(s)
Tejido Conectivo/fisiología , Corazón/fisiología , Modelos Cardiovasculares , Potenciales de Acción , Simulación por Computador , Electrofisiología , Espacio Extracelular/fisiología , Humanos , Matemática , Potenciales de la MembranaRESUMEN
BACKGROUND: Inhibitory antibodies which neutralise factor VIII develop in 10-20% of individuals with inherited haemophilia A and rarely as autoantibodies in normal individuals to cause acquired haemophilia. The antibodies are directed against human factor VIII but cross-react to varying degrees with porcine factor VIII. Porcine factor VIII can be used for treatment in individuals with low cross-reactivity. AIMS: To determine the cross-reactivity of factor VIII inhibitors between human factor VIII and porcine factor VIII, in a population of patients with inherited and acquired haemophilia A. Also, to determine whether patients with inherited haemophilia and inhibitors have a higher incidence of factor VIII gene inversion in intron 22. METHODS: Samples and data sheets from 43 patients with inherited and ten with acquired haemophilia were submitted from hospitals in Australia and New Zealand. Inhibitor levels to human and porcine factor VIII were measured by the Bethesda method in 39 with inherited and nine with acquired haemophilia A. RESULTS: Of 39 patients with inherited haemophilia A, cross-reactivity was 0% in 17 patients, 1-19% in six, 20-39% in 11 and 40-80% in five. In six of nine patients with acquired haemophilia cross-reactivity was < or = 7%. In inherited severe haemophilia A, the frequency of the intron 22 inversion was not greater in 37 study patients than in 28 patients without an inhibitor. CONCLUSIONS: Many patients in Australia and New Zealand with inhibitors to human factor VIII presently show a low or absent level of cross-reactivity to porcine factor VIII. These may respond to treatment with this concentrate at least in the short term. There remains a group of patients with high cross-reactivity who will respond only to recombinant factor VIIa or prothrombin complex concentrates.
Asunto(s)
Inhibidores de Factor de Coagulación Sanguínea/inmunología , Factor VIII/inmunología , Factor VIII/uso terapéutico , Hemofilia A/terapia , Animales , Australia , Inversión Cromosómica , Reacciones Cruzadas , Factor VIII/genética , Humanos , Nueva Zelanda , Índice de Severidad de la Enfermedad , PorcinosAsunto(s)
Autoanticuerpos/análisis , Mucopolisacaridosis I/inmunología , Hemorragia Posoperatoria/etiología , Trombocitopenia/inmunología , Adulto , Deficiencia de Antitrombina III , Cofactor II de Heparina/deficiencia , Humanos , Masculino , Mucopolisacaridosis I/complicaciones , Tiempo de Tromboplastina Parcial , Trombocitopenia/complicaciones , Derivación VentriculoperitonealAsunto(s)
Hemofilia A/terapia , Adulto , Animales , Niño , Costos y Análisis de Costo , Factor VIII/administración & dosificación , Factor VIII/economía , Factor VIII/inmunología , Factor VIIa/administración & dosificación , Femenino , Predicción , Terapia Genética , Infecciones por VIH/transmisión , Hemofilia A/genética , Hemofilia A/inmunología , Heterocigoto , Humanos , Masculino , Diagnóstico Prenatal , Protrombina/administración & dosificación , Porcinos , Reacción a la TransfusiónRESUMEN
Patients with HIV infection may present with symptoms and/or signs of anaemia, neutropenia or thrombocytopenia at all stages, including seroconversion.
Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/complicaciones , Infecciones por VIH/complicaciones , Enfermedades Hematológicas/etiología , Infecciones Oportunistas Relacionadas con el SIDA/terapia , Anemia/etiología , Anemia/terapia , Transfusión Sanguínea , Femenino , Infecciones por VIH/terapia , Enfermedades Hematológicas/terapia , Humanos , Masculino , Neutropenia/etiología , Púrpura Trombocitopénica Trombótica/etiología , Púrpura Trombocitopénica Trombótica/terapia , Trombocitopenia/etiología , Trombocitopenia/terapia , Tromboembolia/etiología , Tromboembolia/terapiaRESUMEN
OBJECTIVE: To examine the management of haemophilia A in Australia and to compare it with international trends. METHODS: Six haemophilia centres treating most patients in Victoria, New South Wales and South Australia were surveyed in 1993 by means of a written questionnaire followed by an "on site" interview. RESULTS: The centres were treating 739 patients; 234 (32%) had severe haemophilia. Factor VIII inhibitors were present in 5.9% of all patients and in 19% of those with severe disease. Twenty-three per cent were human immunodeficiency virus (HIV) antibody-positive and 74% were hepatitis C virus (HCV) antibody-positive. The main treatment was "on demand" therapy for acute bleeds (average use of factor VIII: 1350 IU/kg per year for children; and 780 IU/kg per year for adults). Prophylactic therapy was used in only 17 patients, with doses of 3000-4500 IU/kg per year. One million IU was used for three patients with high titre inhibitors who had "tolerising" therapy. While most developed countries have a factor VIII supply of 2-5 IU per capita, the total supplied to the States represented 1.46 IU per capita, while use at the centres represented 1.1 IU per capita. CONCLUSION: Because supply of factor VIII is limited, use was less than half that recommended internationally. Shortage of factor VIII has compromised prophylactic therapy and virtually prevented "tolerising" therapy.
Asunto(s)
Hemofilia A/terapia , Enfermedad Aguda , Adolescente , Adulto , Niño , Tolerancia a Medicamentos , Factor VIII/análisis , Factor VIII/antagonistas & inhibidores , Factor VIII/provisión & distribución , Factor VIII/uso terapéutico , Seropositividad para VIH/sangre , Hemartrosis/tratamiento farmacológico , Hemartrosis/prevención & control , Hemofilia A/sangre , Hemofilia A/tratamiento farmacológico , Hemofilia A/prevención & control , Hemorragia/tratamiento farmacológico , Hemorragia/prevención & control , Hepacivirus/inmunología , Anticuerpos Antihepatitis/análisis , Terapia de Infusión a Domicilio , Humanos , Nueva Gales del Sur , Australia del Sur , Encuestas y Cuestionarios , VictoriaRESUMEN
Between 1987 and 1991 we performed Yttrium-90 (Y-90) silicate radionuclide synovectomies on 40 joints of 20 haemophiliac patients with haemophilic arthropathy. All were male, their mean age was 31 yr and 15 of the 20 (75%) were HIV antibody positive. The number of joint bleeds and amount of factor (VIII and IX) replacement given in the 6 months pre- and 6 and 12 months post-radionuclide synovectomy was compared. Y-90 silicate synovectomy was shown significantly to reduce both the number of joint bleeds (P < 0.001) and factor usage (P < 0.001) in the 6 months after the procedure, a result maintained up to 12 months. Depot methyl prednisolone was co-administered with Y-90 but thought unlikely to contribute to joint response beyond 6 months. The reduction of joint bleeds and factor usage was even more dramatic in the 6- to 12-month period post-synovectomy although this was not reflected by the P value (P < 0.001). The reduction of joint bleeds and factor consumption post-synovectomy was most obvious in elbow joints, although the other joints as a group showed a significant reduction. Patients who were HIV antibody positive showed considerable improvement up to 12 months post-treatment, both in reduction of joint bleeds and as a consequence factor consumption. This improvement was seen to a lesser extent in the smaller HIV-negative group.