Assuntos
Diálise/métodos , Falência Hepática/terapia , Transplante de Fígado/efeitos adversos , Doença Aguda , Adulto , Diálise/mortalidade , Feminino , Encefalopatia Hepática/mortalidade , Encefalopatia Hepática/terapia , Humanos , Falência Hepática/mortalidade , Transplante de Fígado/fisiologia , Masculino , Pessoa de Meia-IdadeRESUMO
The presence of alloantibodies may play a role in accelerated or acute humoral rejection. Different therapeutic strategies based on a removal of anti donor antibodies and prevention of their resynthesis have been used in the management of transplant rejection episodes. Immunoadsorption with staphylococcal protein A, a method to selectively remove immunoglobulin G, may represent a new treatment to reverse humoral rejection in kidney transplantation. From 1991 to January 1996, such a method was used in 23 patients in whom an acute humoral rejection developed over a mean period of 14.1 +/- 9.5 days after operation. Twenty-two patients had been transplanted from living donors and one from a cadaveric donor. The ages ranged from 23 to 58 years (mean, 34 +/- 10 years). All transplants were performed according to a negative direct crossmatch. Basic immunosuppression included cyclosporine, steroids, azathioprine, and antilymphocyte globulin or monoclonal antibodies (OKT3). Rejection was diagnosed on the basis of hematochemical tests, Doppler ultrasonography, and kidney biopsy. Only steroid and monoclonal and polyclonal antibody resistant rejections with > 165% positive direct crossmatches against the donor were treated with Protein A immunoabsorption. The procedure used is based on the treatment of 2-3 plasma volumes for the first 2 days and then every other day until a negative crossmatch is obtained, together with improvement in clinical status (mean treatments, 7.3 +/- 4.5 [range, 4-23]; mean duration of treatment, 12.3 +/- 10.2 days [range, 3-44]). From the start of treatment, azathioprine is replaced by cyclophosphamide at a dose of 1-2 mg/kg/day. During treatment, a remarkable fall in immunoglobulin G levels is achieved on the first day, whereas immunoglobulin M titers remain constant, with a slight decrease in serum albumin. Immediately after treatment, a negative crossmatch was found in 22 (95.6%) of 23 patients. In six patients (26%), graft function did not recover, and one patient (4.3%) died. Preliminary results show that immunoabsorption with staphylococcal protein A may be an effective support in the treatment of humoral acute rejection, particularly when it is performed as soon as an early diagnosis of humoral rejection is made. In fact, such treatment has a highly selective adsorption, allows treatment of large volumes of plasma, and can achieve a rapid decrease in the titer of circulating immunoglobulins.
Assuntos
Rejeição de Enxerto/terapia , Técnicas de Imunoadsorção , Transplante de Rim/efeitos adversos , Transplante de Rim/imunologia , Doença Aguda , Adulto , Formação de Anticorpos , Creatinina/sangue , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/imunologia , Humanos , Imunoglobulina G/isolamento & purificação , Isoanticorpos/isolamento & purificação , Transplante de Rim/fisiologia , Pessoa de Meia-Idade , Proteína Estafilocócica AAssuntos
Transplante de Rim , Doadores de Tecidos , Adolescente , Adulto , Cadáver , Criança , Pré-Escolar , Ciclosporina/efeitos adversos , Ciclosporina/uso terapêutico , Família , Feminino , Rejeição de Enxerto/tratamento farmacológico , Rejeição de Enxerto/epidemiologia , Sobrevivência de Enxerto , Hospitais Universitários , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Incidência , Lactente , Transplante de Rim/mortalidade , Transplante de Rim/fisiologia , Masculino , Estudos Retrospectivos , Cidade de Roma , Taxa de Sobrevida , Fatores de TempoAssuntos
Derivação Arteriovenosa Cirúrgica , Bioprótese , Prótese Vascular , Diálise Renal/instrumentação , Veia Safena/transplante , Braço/irrigação sanguínea , Derivação Arteriovenosa Cirúrgica/efeitos adversos , Bioprótese/efeitos adversos , Prótese Vascular/efeitos adversos , Humanos , Perna (Membro)/irrigação sanguíneaRESUMO
Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100-150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 +/- 26 mg/dl compared to 351 +/- 65 mg/dl at baseline in the IMA-treated patients and 139 +/- 18 mg/dl compared to 359 +/- 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.
Assuntos
Hiperlipoproteinemia Tipo II/terapia , Lipoproteínas LDL/sangue , Plasmaferese/métodos , Adulto , Colesterol/sangue , Angiografia Coronária , Doença das Coronárias/sangue , Doença das Coronárias/prevenção & controle , Sulfato de Dextrana , Feminino , Humanos , Hiperlipoproteinemia Tipo II/sangue , Imunoadsorventes , Lipoproteínas LDL/química , Lipoproteínas LDL/imunologia , Masculino , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: Immunoadsorption (IMA) and dextran sulfate adsorption (DSA) are two methods for selective extracorporeal elimination of low-density lipoproteins which are known as LDL apheresis. Their influence on haemostasis until now is widely unknown. DESIGN: The effects of both LDL apheresis procedures on the coagulation and fibrinolytic systems were compared amongst five patients treated with IMA and four patients who received a DSA therapy. SUBJECTS: All patients with severe heterozygous familial hypercholesterolaemia were participants in a long-term LDL apheresis programme with treatments every 1-2 weeks. INTERVENTION: Combined anticoagulation with heparin and citrate in IMA, and also heparin exclusively in DSA were used for the extracorporeal circulation. MEASURES: Blood samples were taken immediately before and after a single LDL apheresis and five times during the weekly interval until the next therapy. RESULTS: DSA had a significantly greater effect on standard clotting tests than IMA at the end of plasma therapy despite identical dosages of heparin. DSA caused a considerable reduction of the coagulation factors V, VIII:C, vWF:Ag, XI, XII, and prekallikrein by 48-99% at the end of apheresis treatment whereas only factor VIII:C showed a marked decrease of 72% after IMA. All abnormalities of the global coagulation tests and of most clotting factors were restored 1 day after treatment in both procedures followed by a moderate rebound phenomenon of single coagulation factors during the next few days in IMA-treated patients. CONCLUSION: DSA exerts a more profound effect on the coagulation system than IMA by a substantial co-elimination of various clotting factors in addition to the desired removal of atherogenic lipoproteins.
Assuntos
Coagulação Sanguínea/fisiologia , Remoção de Componentes Sanguíneos/métodos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/terapia , Lipoproteínas LDL/sangue , Adsorção , Adulto , Sulfato de Dextrana , Feminino , Fibrinólise/fisiologia , Humanos , Técnicas de Imunoadsorção , Masculino , Pessoa de Meia-IdadeAssuntos
Transplante de Rim/fisiologia , Complicações na Gravidez/fisiopatologia , Aborto Espontâneo , Azatioprina/uso terapêutico , Cesárea , Ciclosporina/uso terapêutico , Feminino , Retardo do Crescimento Fetal/etiologia , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Transplante de Rim/imunologia , Prednisona/uso terapêutico , Gravidez , Resultado da GravidezRESUMO
Extracorporeal procedures for selective removal of low-density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column-regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous-flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57-year-old male with drug-resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4-5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A-I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug-resistant familial hypercholesterolemia without or with concomitant hypertriglyceridemia.