RESUMO
The objective of the present study was to evaluate factors of the plasma kallikrein system in patients with acute nonlymphoblastic leukemia (ANLL), and compare the results to a normal control group. A prospective study was performed in the Tertiary Health Care Institution, Hemocentro, Campinas State University, Campinas, Sao Paulo, Brazil. Thirty-five patients, diagnosed as ANLL between 1988 and 1991, were considered for participation. Eleven patients were not elegible, according to the exclusion criteria: infection/septicemia, previous treatment of blood transfusion. The study was performed with 24 ANLL patients, average age 34 years (16-69 years), 14 men and 10 women. Nineteen healthy volunteers, workers from the Hematology Center, average age 32 years (21-59 years), 11 men and 8 women, were the control group. Plasmatic prekallikrein, C1-inhibitor, alpha 2-macroglobulin, activated partial thromboplastin time, prothrombin time, factor XII, factor XI, factor V and prealbumin were measured. Plasmatic prekallikrein (p=0.02) and prealbumin (p=0.03) were significantly decreased, and prothrombin time increased (p=0.003) in the patient group when compared to the control. Significant correlation (r=0.49, critical value=0.43, p<0.05) between prekallikrein and prealbumin, and between prothrombin time and factor V (r=0.54, critical value=0.44, p<0.05) was demonstrated in the patient group. No correlation was found between parameters analysed and circulant blast count or leukemia subgroups. Statistical analysis was performed by the Willcoxon test. Correlation between the parameters was also verified. These results suggest activation of the contact system or impaired liver synthesis in patients with ANLL, and could contribute to disease complications.
Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Tempo de Protrombina , Proteínas Sanguíneas/análise , Leucemia Mieloide Aguda/sangue , Tempo de Tromboplastina Parcial , alfa-Macroglobulinas/análise , Fator V/análise , Fator XI/análise , Fator XII/análise , Pré-Albumina/análise , Pré-Calicreína/análise , Contagem de Células , Proteínas Inativadoras do Complemento 1/análise , Estudos ProspectivosRESUMO
OBJECTIVE: To test if serially sampled determinations of the contact system proteins and factor V have prognostic value for death in patients who develop the systemic inflammatory response syndrome. DESIGN: Prospective, observational study with sequential measurements in an inception cohort. SETTING: Medical intensive care unit (ICU) in a community hospital. PATIENTS: Over a 1-yr period, a population base sample of 23 patients was selected from all ICU admissions who met established criteria for the systemic inflammatory response syndrome. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Components of the contact system, factor XII, prekallikrein, high-molecular-weight kininogen, factor XI, alpha 2-macroglobulin-kallikrein complexes and factor V values were measured in plasma samples collected serially (day of admission, and at 2, 12, 24, 48 and/or 72 hrs or at discharge). Data were analyzed to determine if admission values or serially obtained values within 48 hrs were useful in predicting outcome. Fourteen patients survived and nine died. At admission, in all patients, assay values indicated that prekallikrein, high-molecular-weight kininogen, and factor V were significantly lower than normal (as observed in a range of 20 to 23 healthy adults), alpha 2-macroglobulin-kallikrein complexes were higher than normal, while concentrations of factor XII and factor XI were in the normal range. No differences were detected in the admission values between survivors and nonsurvivors, nor between patients with positive or negative blood cultures. However, subsequent values demonstrated a difference in values between survivors and nonsurvivors. Survivors showed improvement in high molecular weight kininogen values and higher than normal factor V values, as compared with nonsurvivors. CONCLUSIONS: Low or persistently low serial factor XII, high-molecular-weight kininogen and factor V values are associated with a poor prognosis, whereas high or increasing values of factor XII, high-molecular-weight kininogen, prekallikrein, and factor V all correlate with a favorable outcome.
Assuntos
Fator V/análise , Síndrome de Resposta Inflamatória Sistêmica/sangue , Idoso , Coagulação Sanguínea , Fator XI/análise , Fator XII/análise , Humanos , Cininogênios/sangue , Pré-Calicreína/análise , Prognóstico , Estudos Prospectivos , Sobreviventes , Síndrome de Resposta Inflamatória Sistêmica/mortalidade , alfa-Macroglobulinas/análiseRESUMO
Prekallikrein (PK), a zymogen of the contact system, and its activation products, kallikrein (KAL), KAL-inhibitor complexes and fragments containing KAL epitope(s) have been detected in human plasma by immunoblotting with a monoclonal anti-human plasma PK antibody, MAb 13G11. Detection of antigen-MAb 13G11 complexes with peroxidase-conjugated anti-IgG showed that the two variants of PK (85- and 88-kDa) are the only major antigen species in normal, non-activated plasma. Upon plasma activation with kaolin, the intensity of the PK bands decreased with formation of complexes of KAL with C1 inhibitor (C1 INH) and alpha 2-macroglobulin (alpha 2 M) identical to those formed by the purified proteins. Immunoblots of normal plasma showed good correlation between the PK detected and the amount of plasma assayed. Increasing amounts of KAL incubated with a constant volume of PK-deficient plasma showed increasing amounts of KAL and of KAL-C1 INH and KAL-alpha 2 M complexes. Complexes of KAL-antithrombin III (ATIII) and the ratio of KAL-alpha 2 M/KAL-C1 INH were higher in activated C1 INH-deficient plasmas than in activated normal plasmas. Protein resolution by 3-12% gradient SDS-PAGE and epitope detection with [125I]MAb 13G11 showed four KAL-alpha 2 M species and a 45-kDa fragment(s) in both surface-activated normal plasma and complexes formed by purified KAL and alpha 2 M. Immunoblots of activated plasma also showed bands at the position of KAL-C1 INH and KAL-ATIII complexes. When alpha 1-antitrypsin Pittsburgh (alpha 1-AT. Pitts) was added to plasma before activation, KAL-alpha 1-AT. Pitts was the main complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Assuntos
Western Blotting/métodos , Pré-Calicreína/análise , Anticorpos Monoclonais , Proteínas Inativadoras do Complemento 1 , Humanos , Calicreínas/antagonistas & inibidores , Calicreínas/sangue , alfa-MacroglobulinasRESUMO
Surface-mediated reactions of clotting were compared in 21 black children with homozygous sickle cell disease, 12 age-matched controls, and 15 adults. Both the coagulant and antigen titers of Hageman factor (factor XII) were decreased in asymptomatic patients compared with those in the control groups. These findings were associated with slight but significant reductions in the plasma titers of prekallikrein and high molecular weight kininogen. A further decrease from the initially low titers of these contact factors was observed during vaso-occlusive crises. Additionally, we observed a disparate relationship between Hageman factor coagulant activity and its antigen titers. These data provide evidence for reduction of the contact factors in patients with homozygous sickle cell disease.