Evidence for the presence of a kininogen-like species in a case of total deficiency of low and high molecular weight kininogens

Low and high molecular weight kininogens (LK and HK), containing 409 and 626 amino acids with masses of ~65 and 120120 kDa after glycosylation, respectively, are coded by a single gene mapped to the human chromosome 3 by alternative splicing of the transcribed mRNA. The NH2-termini Glu(1)-Thr(383) region, identical in LK and HK, contains bradykinin (BK) moieties Arg(363)-Arg(371). LK, HK and their kinin products Lys-BK and BK are involved in several biological processes. They are evolutionarily conserved and only 7 patients, all apparently normal, have been reported to lack them. In one of these patients (Williams'trait), a codon mutation (Arg(178) r stop) has been blamed for the absence of LK and HK. However, using Western blots with 2 monoclonal anti-HK antibodies, one that recognizes the region common to LK and HK and the other that recognizes only HK, I detected ~110-kDa bands in the plasma of this LK/HK-deficient patient vs ~120-kDa bands in normal human and ape plasmas. With polyclonal anti-Lys-BK antibody, which strongly detects BK eleaved at its COOH-terminus in purified HK, I detected ~110-kDa bands in the normal and the deficient plasmas. Western blots with a monoclonal anti-prekallikrein (PK) antibody showed that surface activation of PK and distribution of PK activation products, both dependent on HK, were similar in these plasmas. These findings suggest that a mutant gene yielded a kininogen-like species possibly involving aberrant mRNA splicing - structurally different from normal HK, but apparently with the capacity to carry out seemingly vital HK functions.

Exposure to acellular blood products and risk of HIV infection in hemophiliacs from Belo Horizonte, Brazil

Results of a HIV prevalence study conducted in hemophiliacs from Belo Horizonte, Brazil are presented. History of exposure to acellular blood components was determined for the five year period prior to entry in the study, which occurred during 1986 and 1987. Patients with coagulations disorders (hemophilia A = 132, hemophilia B = 16 and coagulation disorders other than hemophilia = 16) were transfused with liquid cryoprecipitate, locally produced, lyophilized cryoprecipitate, imported from Säo Paulo (Brazil) and factor VIII and IX, imported from Rio de Janeiro (Brazil), Europe, and United States. Thirty six (22%) tested HIV seropositive. The univariate and multivariate analysis (logistic model) demonstrated that the risk of HIV infection during the study period was associated with the total units of acellular blood components transfused. In addition, the proportional contribution of the individual components to the total acellular units transfused, namely a increase in factor VIII/IX and lyophilized cryoprecipitate proportions, were found to be associated with HIV seropositivity. This analysis suggest that not only the total amount of units was an important determinant of HIV infection, but that the risk was also associated with the specific component of blood transfused

Presencia de inhibidores del tiempo tromboplastina parcial activada (TTPA): repercusión clínica en pacientes obstétricas / Presence of thromboplastin time partial activated (TTPA): clinical repercussion in obstetrical patients

El tiempo de tromboplasina parcial activado con caolin (TTPA) es un ensayo cualitativo utilizado para evidenciar defectos de algún factor de la vida intrínseca de la coagulación o para descartar la presencia de algún inhibidor circulante. El anticoagulane lúpico (AL) forma parte de un grupo de varios autoanticuerpos con potencial patogénico en distintas ramas médicas, principalmente reumatología, hematología y geinecoobstericia. En esta última área, el AL se ha asociado a diferentes repercusiones obstétricas. El objetivo de este estudio fue determinar los principales eventos obstétricos asociados a pacientes con anticoagulantes circulantes identificados por TTPA con caolin. Noventa y seis pacientes fueron incluidas, en el estudio de casos-control. El grupo I (n=48) casos y el grupo II (n=48) controles, fueron seleccionadas de una misma población y fuente de información. Los casos fueron incluidos por presentar prolongación de más de 4 segundos del TTPA activado con caolin con respecto a un testigo, con falta de corección con plasma normal. Una hoja-registro de captación de datos fue diseñada especialmente para el estudio. La comparabilidad de ambos grupos fue establecida al no encontrarse diferencias significativas entre variables consideradas basales. El grupo de casos presentó una frecuencia mayor de aborto habiatual, muerte neonatal y fenómenos trombóticos. Esta relación de cuadros autoinmunológicos con pérdida fetal recurrente y accidentes tromboembólicos ha sido descrita consistentemente en la literatura. De han descrito al respecto una gama de anormalidades inmunológicas incluyendo anticuerpos alticardiolipina positivos y VDRL falsamente positivo. La incidencia en nuestro país de etas entidades es desconocida. Estas observaiones inciden sobre la necesidad de una superación metodológica. Se concluye que el reconocimiento de estos procesos autoimunes en relación al campo de la ginecología y obstetricia puede abrir nuevas perspectivas en eldiagnóstico y tratamiento de entidades como aborto habitual, tromboembolias y retardo del crecimiento intrauterino.