RESUMO
BACKGROUND: Entecavir (ETV) is a nucleoside analogue (NA) that is effective for treatment of chronic hepatitis B (CHB) due to its low resistance rates and potent antiviral effects. We aimed to evaluate the clinical, biochemical and virological response to ETV in patients without a prior use of nucleos(t)ide (NA-naïve) vs. those who failed prior NA use (NA-experienced) in the treatment of CHB. METHODS: Patients treated between April 2012 and December 2017 were retrospectively studied. A comparison was made between patients treated with ETV in NA-naïve Vs. NA-experienced. Complete virological response (CVR) was defined as achieving undetectable HBV-DNA level, up to 15 IU/ml, partial virological response (PVR) as 15-200 IU/ml and >200 IU/ml for no virological response (NVR) after one year of therapy. RESULTS: Overall, 148 patients were included (69 NA-naïve and 79 NA-experienced). In NA-naïve group, 51%, 17% and 32% achieved CVR, PVR and NVR vs. 17%, 9% and 75% in NA-experienced group, respectively (p < 0.001). HBsAg seroconversion was achieved in 5.8% in NA-naïve group vs. 6.3% in NA-experienced group (p = 1.00). HBeAg seroconversion was 17% in NA-naïve group and 25% in NA-experienced group (p = 0.24). There was no significant difference in alanine transaminase normalization or in mortality rate between both groups; p = 0.87 and p = 1.00 respectively. CONCLUSION: ETV therapy in CHB results in a better virological response in NA-naïve patients compared to NA-experienced. There were no differences between both groups in regards to the rate of HBsAg or HBeAg seroconversions, biochemical improvements or mortality.
Assuntos
Antivirais/uso terapêutico , Guanina/análogos & derivados , Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Adulto , Idoso , Alanina Transaminase/sangue , Antivirais/farmacologia , DNA Viral/sangue , Feminino , Guanina/farmacologia , Guanina/uso terapêutico , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/sangue , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/imunologia , Hepatite B Crônica/sangue , Hepatite B Crônica/mortalidade , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , SoroconversãoRESUMO
BACKGROUND: Early identification of a patient with infection who may develop sepsis is of utmost importance. Unfortunately, this remains elusive because no single clinical measure or test can reflect complex pathophysiological changes in patients with sepsis. However, multiple clinical and laboratory parameters indicate impending sepsis and organ dysfunction. Screening tools using these parameters can help identify the condition, such as SIRS, quick SOFA (qSOFA), National Early Warning Score (NEWS), or Modified Early Warning Score (MEWS). We aim to externally validate qSOFA, SIRS, and NEWS/NEWS2/MEWS for in-hospital mortality among adult patients with suspected infection who presenting to the emergency department. METHODS AND ANALYSIS: PASSEM study is an international prospective external validation cohort study. For 9 months, each participating center will recruit consecutive adult patients who visited the emergency departments with suspected infection and are planned for hospitalization. We will collect patients' demographics, vital signs measured in the triage, initial white blood cell count, and variables required to calculate Charlson Comorbidities Index; and follow patients for 90 days since their inclusion in the study. The primary outcome will be 30-days in-hospital mortality. The secondary outcome will be intensive care unit (ICU) admission, prolonged stay in the ICU (i.e., ≥72 hours), and 30- as well as 90-days all-cause mortality. The study started in December 2021 and planned to enroll 2851 patients to reach 200 in-hospital death. The sample size is adaptive and will be adjusted based on prespecified consecutive interim analyses. DISCUSSION: PASSEM study will be the first international multicenter prospective cohort study that designated to externally validate qSOFA score, SIRS criteria, and EWSs for in-hospital mortality among adult patients with suspected infection presenting to the ED in the Middle East region. STUDY REGISTRATION: The study is registered at ClinicalTrials.gov (NCT05172479).
Assuntos
Sepse , Síndrome de Resposta Inflamatória Sistêmica , Adulto , Humanos , Estudos de Coortes , Serviço Hospitalar de Emergência , Mortalidade Hospitalar , Estudos Multicêntricos como Assunto , Escores de Disfunção Orgânica , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Curva ROC , Sepse/diagnósticoRESUMO
Hemophilia A is an X chromosome-linked recessive disorder resulting in defective or deficient factor VIII (FVIII) molecules, which, in its severe form, is a life-threatening and crippling hemorrhagic disease. Infusion of homologous FVIII to patients with severe hemophilia A results, in 25% of patients, in the emergence of alloantibodies against FVIII (inhibitors)( ref. 1) that inhibit FVIII procoagulant activity by steric hindrance of the interaction of FVIII either with stabilizing molecules, with molecules essential for its activity or with activating molecules. Here, we report on the proteolysis of FVIII by alloantibodies of two patients with severe hemophilia A, demonstrating a previously unknown mechanism by which FVIII inhibitors may prevent the pro-coagulant function of FVIII. The kinetic parameters of FVIII hydrolysis indicate a functional role for the catalytic immune response in the inactivation of FVIII in vivo. The characterization of alloantibodies against FVIII as site-specific proteases may provide new approaches to the treatment of FVIII inhibitors.
Assuntos
Anticorpos Catalíticos/metabolismo , Endopeptidases/metabolismo , Fator VIII/imunologia , Hemofilia A/imunologia , Isoanticorpos/metabolismo , Anticorpos Catalíticos/imunologia , Anticorpos Catalíticos/isolamento & purificação , Ligação Competitiva , Endopeptidases/imunologia , Endopeptidases/isolamento & purificação , Fator VIII/antagonistas & inibidores , Fator VIII/metabolismo , Hemofilia A/enzimologia , Humanos , Hidrólise , Imunoglobulina G/imunologia , Imunoglobulina G/isolamento & purificação , Imunoglobulina G/metabolismo , Isoanticorpos/imunologia , Isoanticorpos/isolamento & purificação , Cinética , Fator de von Willebrand/metabolismoRESUMO
Study of the normal human factor VIII/von Willebrand factor reveals a macromolecular glycoprotein composed of apparently identical subunits. This purified glycoprotein has procoagulant, antigen, and von Willebrand factor activities. In three patients with a variant of the von Willebrand's disease syndrome, their factor VIII/von Willebrand factor protein was present in normal amounts and had normal procoagulant and antigen activities; however, this protein was deficient in both carbohydrate and von Willebrand factor activity. The carbohydrate portion of the factor VIII/von Willebrand factor glycoprotein is of major importance in its interactions with platelets or the blood vessel wall, or both.
Assuntos
Fatores de Coagulação Sanguínea/análise , Doenças de von Willebrand/sangue , Fator de von Willebrand/análise , Antígenos , Carboidratos/análise , Glicoproteínas/sangue , Relação Estrutura-Atividade , Fator de von Willebrand/imunologia , Fator de von Willebrand/fisiologiaRESUMO
BACKGROUND: Fever in children is a common presenting complaint during health visits. Parents frequently have concerns about fever and perceive it as a disease rather than a symptom of illness. Parent's practice of home managing of fever varies according to their background and experience. OBJECTIVE: To explore parents' perception and practice in home management of fever in their preschool children in Riyadh, Saudi Arabia (SA). MATERIALS AND METHODS: This is a cross-sectional study. Data were collected from 250 parents attending three main family medicine centers at King Abdul-Aziz Medical City, Riyadh, SA, using self-administered questionnaire. RESULTS: Most of the parents (64%) defined fever correctly and 56% identified high fever. Almost all the parents (95%) believed fever is harmful, and febrile convulsion was the most concerned complication of fever (74%), followed by loss of consciousness, dehydration, brain damage, and hearing loss. Most of the parents (82%) touch their children to confirm fever, 68% use oral thermometer, and 63% use axillary thermometer. Most parents (84%) applied cold compression, 75% gave their children nonprescribed fever medication, 61% gave their children plenty of fluids, and 64% took their children to the doctor right away. Almost one-third of participants reported having difficulty either in choosing fever medicine or giving the proper dose and frequency. No difference in knowledge or practice was found in relation to difference in demographic characteristics of participants. CONCLUSION: Results of this study indicate poor knowledge and practice in regard to parent's management of febrile children, overuse of nonprescribed fever medication, and possible waste of health resources.
RESUMO
The Factor VIII/von Willebrand factor protein was characterized in two unrelated patients with von Willebrand's disease in whom procoagulant and Factor VIII/von Willebrand factor antigen levels were normal. In both patients evidence of an abnormal protein was observed on crossed antigen-antibody electrophoresis. In one patient the Factor VIII/von Willebrand factor protein eluted from Sepharose 4B in a position and distribution identical to normal with normal levels of procoagulant activity and antigen. However, the partially purified Factor VIII/von Willebrand factor protein had markedly reduced von Willebrand factor activity in a ristocetin assay. In the second patient the peak of Factor VIII/von Willebrand factor protein, antigen, and procoagulant activity eluted from a Sepharose 4B column with an estimated molecular weight of approximately half that of normal. This protein had no von Willebrand factor activity. In both patients the reduced Factor VIII/von Willebrand factor protein subunit was indistinguishable from normal on polyacrylamide gel electrophoresis. These studies indicate that in some patients with von Willebrand's disease there is a qualitative defect of the Factor VII/von Willebrand factor protein; the total amount of protein, antigen, and procoagulant activity are normal while the von Willebrand factor activity is deficient.
Assuntos
Transtornos de Proteínas de Coagulação , Hemofilia A/imunologia , Doenças de von Willebrand , Doenças de von Willebrand/sangue , Anticorpos , Antígenos , Testes de Coagulação Sanguínea , Precipitação Química , Cromatografia em Gel , Quimotripsina , Contraimunoeletroforese , Eletroforese em Gel de Poliacrilamida , Feminino , Fibrinogênio/metabolismo , Humanos , Masculino , Adesividade Plaquetária , Agregação Plaquetária/efeitos dos fármacos , Ristocetina/farmacologia , Doenças de von Willebrand/genéticaRESUMO
We have investigated and characterized the abnormalities in four unrelated patients with von Willebrand's disease (vWd) who have (a) enhanced ristocetin-induced platelet aggregation (RIPA) at low ristocetin concentrations, (b) absence of the largest plasma von Willebrand factor (vWf) multimers, and (c) thrombocytopenia. The platelet-rich plasma of these patients aggregates spontaneously without the addition of any agonists. When isolated normal platelets are resuspended in patient plasma spontaneous aggregation occurs; however, the patients' plasmas did not induce platelet aggregation of normal washed formalinized platelets. When the patients' platelets are suspended in normal plasma, spontaneous aggregation is not observed. The spontaneous platelet aggregation (SPA) is associated with dense granule secretion as measured by ATP release and alpha granule release as measured by beta-thromboglobulin and platelet factor 4 release. The SPA is totally inhibited by 5 mM EDTA, prostaglandin I2, and dibutryl cyclic AMP, while it is only partially inhibited by 1 mM EDTA, acetylsalicylic acid, or apyrase. A monoclonal antibody directed against glycoprotein Ib (GPIb) and/or a monoclonal antibody against the glycoprotein IIb/IIIa (GPIIb/IIIa) complex totally inhibits the SPA. The vWf was isolated from the plasma of one of these patients. The purified vWf induced platelet aggregation of normal platelets resuspended in either normal or severe vWd plasma, but the vWf did not induce platelet aggregation of normal platelets resuspended in afibrinognemic plasma. Sialic acid and galactose quantification of the patient's vWf revealed approximately a 50% reduction compared with normal vWf. These studies indicate that a form of vWd exists, which is characterized by SPA that is induced by the abnormal plasma vWf. The SPA is dependent on the presence of plasma fibrinogen, and the availability of the GPIb and the GPIIb/IIIa complex. In this variant form of vWd the abnormal vWf causes enhanced RIPA, SPA, and thrombocytopenia.
Assuntos
Agregação Plaquetária , Doenças de von Willebrand/sangue , Fator de von Willebrand/análise , Antígenos/análise , Fator VIII/análise , Fator VIII/imunologia , Fibrinogênio/metabolismo , Galactose/análise , Glicoproteínas/metabolismo , Humanos , Proteínas de Membrana/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Glicoproteínas da Membrana de Plaquetas , Ristocetina/farmacologia , Ácidos Siálicos/análise , Trombocitopenia/etiologia , Doenças de von Willebrand/classificação , Doenças de von Willebrand/complicaçõesRESUMO
OBJECTIVE: To evaluate whether HLA-B35 influences progression to AIDS in HIV-seropositive subjects with haemophilia. DESIGN: Retrospective (before 1985) and prospective (after 1985) follow-up of a group of French haemophiliacs. METHODS: We studied 144 seropositive patients with moderate or severe haemophilia A or B or von Willebrand's disease. Enzyme-linked immunosorbent assay was used to screen patient sera for total HIV antigen and core p24 antigen antibodies. All patients were typed for HLA A, B and C antigens in the same laboratory. Time of seroconversion was estimated to be the mid-point between the last seronegative test and the first seropositive test. AIDS-free survival curves were constructed using the Kaplan-Meier estimate and differences in survival analysed using the Mantel-Cox test. The Cox proportional hazards model was used to adjust for confounding variables. RESULTS: Median follow-up after seroconversion was 8.7 years (range, 3.5-10.7 years). By the end of the study, six HLA-B35-positive patients and 12 HLA-B35-negative patients had progressed to AIDS. Individuals with HLA-B35 showed a significantly faster rate of progression to AIDS over the follow-up period than HLA-B35-negative individuals (hazard ratio, 2.72; P = 0.037). After adjusting for type and severity of haemophilia, CD4 cell count at first seropositive test, age at seroconversion, and zidovudine treatment before AIDS, the hazard ratio was 2.74 (P = 0.045). CONCLUSION: HLA-B35 is a risk factor for more rapid progression to AIDS in subjects with haemophilia.
Assuntos
Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/imunologia , HIV-1 , Antígeno HLA-B35 , Hemofilia A/complicações , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adolescente , Adulto , Idoso , Criança , Pré-Escolar , França/epidemiologia , Soropositividade para HIV , HIV-1/imunologia , Hemofilia A/imunologia , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores de TempoRESUMO
The selective detection of hybridomas producing monoclonal antibodies against tissue-plasminogen activators (t-PA) by means of a solid-phase fibrin immunoassay (SOFIA) is described. The screening method is based on the specific and high affinity binding of t-PA for fibrin solid phase. This, as in the physiological fibrin-t-PA interaction, provides a molecular structure conserving its antigenic and functional properties. The solid-fibrin-state support is prepared by thrombin proteolysis of fibrinogen coupled to a poly-glutaraldehyde activated polyvinylchloride plate. This procedure avoids fibrinogen desorption and provides a uniform fibrin network onto which t-PA from crude extracts or purified preparations, can be specifically absorbed. The fibrin-t-PA solid-phase support is able to fix anti-t-PA antibodies which can be subsequently revealed by a second enzyme- or radiolabelled anti-mouse Ig antibody. The results demonstrate the effectiveness of the SOFIA method for the selection of hybridomas producing anti-t-PA antibodies against different epitopic determinants of t-PAs.
Assuntos
Anticorpos Monoclonais , Epitopos/imunologia , Fibrina , Imunoensaio/métodos , Ativadores de Plasminogênio/imunologia , Animais , Anticorpos Monoclonais/fisiologia , Especificidade de Anticorpos , Sítios de Ligação de Anticorpos , Ligação Competitiva , Fibrinogênio/metabolismo , Glutaral , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Ativadores de Plasminogênio/metabolismo , Cloreto de Polivinila , SuínosRESUMO
SCID mice were grafted with human PBL (hu-PBL-SCID) from healthy or haemophilia A donors. Those containing human and no murine Ig in their plasma, were injected with 100 U VIII:Ag of a plasma derived (pd) FVIII or recombinant deleted Factor VIII (FVIII deltaII) and with 10 microg of tetanus toxoid as control immunogen. The frequency and the intensity of the humoral specific responses were measured in 253 mice humanized with PBL from 13 different donors. There was no significant difference in the frequency or intensity of the anti-FVIII immune responses to pd FVIII and FVIII deltaII. Neutralizing antibodies were only detected in the plasma of mice humanized with cells from haemophiliacs having FVIII inhibitors in their blood. The immune responses observed in hu-PBL-SCID mice correlated with the immune status of the corresponding human donor.
Assuntos
Fator VIII/imunologia , Adulto , Animais , Formação de Anticorpos , Fator VIII/antagonistas & inibidores , Feminino , Hemofilia A/sangue , Hemofilia A/terapia , Humanos , Imunização , Masculino , Camundongos , Camundongos SCID , Pessoa de Meia-Idade , Proteínas Recombinantes/imunologia , Toxoide Tetânico/imunologia , Transplante HeterólogoRESUMO
Intravenous immunoglobulin (IV Ig) is useful in most patients with spontaneous factor VIII:C (FVIII:C) inhibitors, but some complete failures also are observed. Among patients responding to this therapy, decreases in FVIII:C autoantibody titer occurs within 24-48 hours and may lead to suppression of inhibitor activity. The prolonged response observed in some cases suggest an effect on autoantibody synthesis. The immediate decrease in FVIII:C inhibitory activity after IV Ig infusion indicates a direct interaction between IV Ig and the autoantibody. This effect is reproducible in vitro by mixing the patient's plasma and Ig at an appropriate molar ratio, which differs in each patient. Similarly, incubation of Ig with F(ab)'2 fragments of a patient's IgG and Ig reproduces inhibition, and this result indicates that the interaction is mediated by antigen binding sites (epitopes) on the immunoglobulins. The suggestion is that an idiotype- anti-idiotype mechanism must be at work. The origin of such anti-idiotypes in Ig prepared from pooled plasma of several thousand blood donors is unclear. The F(ab)'2 fragments were prepared from individual blood donors and tested in similar experiments with F(ab)'2 fragments of three distinct spontaneous FVIII:C inhibitors. The plasma level of anti-idiotypic antibodies reacting with FVIII:C inhibitors varied according to age and gender.
Assuntos
Autoanticorpos/análise , Fator VIII/imunologia , Imunoglobulinas Intravenosas/uso terapêutico , Anticorpos Anti-Idiotípicos/análise , Anticorpos Anti-Idiotípicos/imunologia , Doenças Autoimunes/terapia , HumanosRESUMO
Factor VIII/von Willebrand factor antigen (VIII R:Ag) has been localized in human endothelial cells by an immunoperoxidase method and electron microscopy. Specific antibodies against VIII R:Ag were isolated from monospecific rabbit antisera by an immunoadsorbant. Fab fragments were prepared and coupled to peroxidase. Native human endothelial cells from umbilical cord veins were incubated with the Fab conjugates. Peroxidase labeling was seen on the plasma membrane, in vesicles, and in the Golgi apparatus. In order to eliminate nonspecific antibody internalization, the same procedure was reproduced on fixed endothelial cells and similar localization was observed. Staining was only found when specific VIII R:Ag Fab conjugates were used. All the controls were devoid of labeling, thus the peroxidase reaction product localized in the Golgi cisternae is specific for VIII R:Ag and suggests VIII R:Ag synthesis in endothelial cells.
Assuntos
Antígenos/análise , Fatores de Coagulação Sanguínea/imunologia , Endotélio/imunologia , Fator VIII/imunologia , Fator de von Willebrand/imunologia , Membrana Celular/imunologia , Fator VIII/análise , Complexo de Golgi/imunologia , Humanos , Técnicas Imunoenzimáticas , Fragmentos Fab das Imunoglobulinas , Lisossomos/imunologia , Veias UmbilicaisRESUMO
UNLABELLED: Interferon (alpha-IFN) exerts a modulating effect on the immune system. Kupffer cells of the liver play an important immunological role by their uptake of various agents and particles, including colloids. We sought to discover if alpha-IFN could enhance the colloid uptake function of the Kupffer cells. The effect of alpha-IFN therapy on radioisotope scans of the liver was studied in 20 patients with chronic liver disease due to hepatitic C virus (HCV) infection who received therapy at a dose of 3 million IU for 6 mo, in another 20 patients who received the same therapy for 12 mo and in matched control groups (10 patients with HCV infection for each study group) who did not receive alpha-IFN. METHODS: A 99mTc-sulfur colloid scan of the liver was obtained for each group before and after therapy and, for control subjects, at the start and end of the study periods. The liver-to-spleen geometric mean ratio of colloid uptake was assessed. RESULTS: In the first study group, the mean rate of improvement in the liver-to-spleen ratio was 48% in 70% of patients, compared to 8% in 20% of controls (p < 0.05). In the second study group, mean liver-to-spleen ratio was 88% in 85% of patients, compared to 12% in 40% of controls (p < 0.001). CONCLUSION: Alpha-IFN therapy appears to enhance the colloidal uptake function of Kupffer cells, which adds a new dimension to the immunomodulatory effect of interferon.
Assuntos
Hepatite C/diagnóstico por imagem , Interferon-alfa/uso terapêutico , Fígado/diagnóstico por imagem , Doença Crônica , Hepatite C/terapia , Humanos , Cintilografia , Baço/diagnóstico por imagem , Coloide de Enxofre Marcado com Tecnécio Tc 99mRESUMO
A cooperative study between the 37 centers of the French Hemophilia Study Group was undertaken to establish the prevalence of inhibitor patients in the French hemophilia population. The prevalence reported in the literature varies widely from 3.6% to 17.5%. Some of the studies are dealing with a small number of patients and inhibitor patients are reported either to the total number of hemophiliacs or to the severely affected ones. The French study provided information concerning 3,435 hemophiliacs and showed a prevalence of 6.2% for the overall population. Prevalence of inhibitors was found to be 7% in the population of hemophilia A patients and 12.8% in the population of severely affected ones. The prevalence of inhibitors in the population of hemophilia patients was 2% and 4% in the population of severely affected hemophilia B patients. The cooperative study also showed that 47.5% of inhibitors are detected before 10 years of age and that 82% of inhibitor patients are high responders. Analysis of inhibitor detection in patients under the age often showed that there was a peak in the population of 2 years old children. Although not comparable to the present study the high incidence of inhibitors with ultrapurified and recombinant FVIII reported in previously untransfused patient may be borne in mind.
Assuntos
Fator IX/imunologia , Fator VIII/imunologia , Hemofilia A/imunologia , Isoanticorpos/sangue , Criança , Pré-Escolar , França/epidemiologia , Humanos , Lactente , PrevalênciaRESUMO
Two approaches were used to identify and characterize the presence of tissue plasminogen activator (t-PA) in megakaryocytes and platelets. We investigated the fibrinolytic activity of human megakaryocytes (MK) and platelets. The presence of t-PA antigen in megakaryocytes and platelets was demonstrated using immunocytochemical techniques and polyclonal or monoclonal antibodies specific for t-PA. When cells were applied to fibrin plates, lysis zones developed around isolated human megakaryocytes, whereas no fibrinolytic activity appeared when either intact washed platelets or platelet lysate were deposited. After SDS-PAGE of platelet and MK extracts (Triton X-100) immunoblotting and peroxidase staining identified t-PA antigen in several bands. Zymographic analysis of SDS-PAGE carried out on fibrin film overlays identified one or two zones corresponding to free or complexed t-PA. These results indicate that t-PA is present in platelets as well as in the precursor cells, however, in platelets, t-PA may not be immediately available for plasminogen activation and fibrin degradation. From our findings and from previous work of others, it appears that platelets may either activate or inhibit the fibrinolytic system. Therefore the conditions of plasminogen activation by platelet t-PA and plasmin inhibition by platelet alpha 2-antiplasmin or other inhibitors have to be precised before the role of platelets in clot dissolution is understood. The physiological role of platelets in fibrinolysis and clot dissolution remains unclear. In 1953, the antifibrinolytic activity of blood platelets was demonstrated and in the early 1960's a fibrinolytic activity, increasing with platelet concentration in the experimental system, was shown.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Plaquetas/enzimologia , Megacariócitos/enzimologia , Ativador de Plasminogênio Tecidual/análise , Eletroforese em Gel de Poliacrilamida , Fibrinólise , Humanos , Immunoblotting , Técnicas Imunoenzimáticas , Ativador de Plasminogênio Tecidual/sangueRESUMO
Two patients with a severe von Willebrand's disease characterized by no detectable factor VIII related antigen in their plasma received transfusions of cryoprecipitate. The bleeding time was corrected for a short period of time and returned to its pretransfusional value although the other parameters of the disease were still corrected. Electrophoretic and immunologic properties of factor VIII related antigen infused were determined serially after transfusion. Modifications of these properties occurred progressively after transfusion. The half disappearance time of F. VIII R.A. was determined and found to be considerably shorter than in hemophilic recipients. This study suggests an alteration in vivo of F. VIII R.A. infused into von Willebrand recipients.
Assuntos
Fator VIII/imunologia , Doenças de von Willebrand/imunologia , Adulto , Antígenos/análise , Transfusão de Sangue , Criança , Fator VIII/uso terapêutico , Feminino , Meia-Vida , Humanos , Imunoeletroforese Bidimensional , Masculino , Doenças de von Willebrand/terapia , Fator de von Willebrand/análiseRESUMO
Two monoclonal antibodies raised against FVIII/von Willebrand protein were used in an immunoradiometric assay (IRMA) to measure this antigen in normal plasma and plasma of patients with different forms of von Willebrand's disease. The first antibody, an IgG1, was used to coat polystyrene tubes, the second one, an IgG2a, iodinated and used in the second step. Both antibodies inhibit ristocetin induced platelet agglutination and react strongly with platelets, megakaryocytes and endothelial cells. The IRMA test using these antibodies showed greater sensitivity than that using rabbit polyclonal anti VIIIRAg antibodies. A good correlation between the two tests was nevertheless found when VIIIRAg was measured in the majority of patient's plasma. However 5 patients from 3 different families showed more antigenic material in the rabbit antibody IRMA than in the monoclonal antibody IRMA. It is suggested therefore that the monoclonal antibodies identify part of the VIIIR:Ag molecule showing structural abnormalities in these vWd patients, these structural changes remaining undetected by the polyclonal antibodies.
Assuntos
Antígenos/análise , Fator VIII/imunologia , Radioimunoensaio/métodos , Doenças de von Willebrand/diagnóstico , Animais , Anticorpos Monoclonais/imunologia , Fator VIII/análise , Humanos , Camundongos , Coelhos , Doenças de von Willebrand/sangue , Doenças de von Willebrand/imunologia , Fator de von WillebrandRESUMO
The plasminogen activators (PA) and cell types responsible for the fibrinolytic activity of isolated human glomeruli were studied by an indirect spectrophotometric method for plasminogen activation and immunohistological techniques with specific antibodies. Our results indicate that human glomeruli possess the ability to release both tissue-type PA (t-PA) and urokinase (UK). This has been shown for t-PA by quenching its fibrin-dependent activity with rabbit anti-t-PA antibodies and for UK by quenching its fibrin-independent activity with goat anti-UK antibodies. On the other hand, immunohistochemical analysis performed with a murine monoclonal antibody to plasma-t-PA and goat polyclonal antibodies to UK allowed the exclusive localization of t-PA in the endothelial cell lining of the glomerular flocculus and UK in the cytoplasma of glomerular epithelial cells. In addition, arachidonic acid and CaCl2 were shown to enhance glomerular fibrinolytic activity by stimulating the release of either UK or t-PA, respectively. This particular distribution and regulation of glomerular PA's may be important in the physiopathology of the intra and extracapillary fibrin deposits observed in several glomerulopathies.
Assuntos
Glomérulos Renais/enzimologia , Ativadores de Plasminogênio/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Ativador de Plasminogênio Tipo Uroquinase/metabolismo , Ácido Araquidônico , Ácidos Araquidônicos/farmacologia , Cloreto de Cálcio/farmacologia , Endotélio/enzimologia , Epitélio/enzimologia , Imunofluorescência , Humanos , Taxa Secretória/efeitos dos fármacosRESUMO
Factor VIII or factor IX replacement is frequently impossible in inhibitor-developing hemophiliacs, because of the level of the inhibitor titer. Activated prothrombin complex concentrates are one of the available options to treat the bleeding episodes in such patients. However, the efficacy of these products and the associated thrombogenic risk, particularly in prolonged administration such as employed during surgeries, are important concerns for hemophilia care providers. We performed a multicenter retrospective study to evaluate the use of FEIBA (Factor Eight Bypassing Activity) in France, and data is presented on 433 bleeding episodes, including surgical procedures, concerning 60 patients from 15 hemophilia centers. The efficacy was judged as good or excellent in 352 episodes (81.3%), poor in 73 episodes (16.9%) and non-existent in 8 episodes (1.8%). Minor and major surgical procedures were successfully performed using FEIBA as a second-line therapy after human or porcine factor VIII, and in some occasions FEIBA was utilized as the only substitution product. The tolerance was assessed as good in 428 episodes (98.8%), but in 5 cases adverse effects were reported. Only 3 patients out of 52 regularly evaluated (5.8%) were HIV-seropositive, and for two of them the seroconversion occurred prior to the first use of FEIBA. In contrast, 80.4% of the patients were HCV-seropositive. An anamnestic response after the administration of FEIBA was noted in 31.5% of cases. This study points out the main features of the use of FEIBA in France, and particularly the low HIV seroprevalence in the patients treated. The good efficacy and the excellent tolerance still confer to this product a place to consider in the therapeutic options for the treatment of inhibitor-developing hemophiliacs or in acquired hemophilia.
Assuntos
Fatores de Coagulação Sanguínea/uso terapêutico , Fator IX/imunologia , Fator VIII/imunologia , Hemofilia A/tratamento farmacológico , Hemofilia B/tratamento farmacológico , Adolescente , Adulto , Anticorpos/sangue , Fatores de Coagulação Sanguínea/efeitos adversos , Criança , França , Hemofilia A/sangue , Hemofilia A/imunologia , Hemofilia B/sangue , Hemofilia B/imunologia , Humanos , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Fifteen previously untreated patients (Pups) with severe haemophilia B (factor IX activity < or = 2 U/dl) only treated with one brand of plasma-derived high purity factor IX concentrate (FIX LFB) were studied. Age at first injection varied from 1 to 137 months and follow-up since this first injection from 21 to 86 months (median: 35). Cumulative exposure days (CED) were from 4 to over 100 (median: 26). Among these 15 Pups only one developed an inhibitor. Mutation analysis performed in all patients showed total gene deletion in the patient with inhibitor, partial gene deletion in another one, and missense mutations in 9 families. Mutation was not found in one patient. Actually, according to the data already published, only two patients were at high risk for inhibitor development in our population. Our study, although rather small, confirms the previously reported low incidence of inhibitors in haemophilia B. Large studies on incidence of FIX inhibitors are indeed difficult to perform, due to both the overall small number of severe haemophilia B patients and the low incidence of FIX inhibitors. Consequently, the impact of bias, such as prevalence of different types of gene defects in a given population, is major. Therefore, any study, dealing with incidence of FIX inhibitors in severe haemophilia B should report, for each patient, the type of gene defect.