vitamin-k-semiquinone-radical and Anemia--Aplastic

The association between acquired aplastic anemia (AA) and hepatitis/acute liver failure has been well characterized as AA temporally after the presentation of acute hepatitis. In this case series we report 2 cases of patients who present with AA occurring simultaneously with the development of acute liver failure. This is among only a few reported cases known to date in which AA occurs simultaneously with impending liver failure. More importantly, this is the first report that demonstrates the feasibility of administering immunosuppressive therapy before complete resolution of the hepatic dysfunction and with excellent results. Both of our cases avoided orthotopic liver transplantation through the use of timely immunosuppressive therapy, demonstrating the potential role of medical management to avoid transplantation in these patients. Previous studies have suggested a link between an unidentified viral process and immune dysregulation that may lead to the development of AA after acute hepatitis. These 2 cases support the rationale that in our patients the 2 disease processes may share a common etiology and encourage further research into the complex pathogenic mechanism affecting these 2 different organ systems at varying points in time.

Topics: Acute Disease; Adolescent; Anemia, Aplastic; Antilymphocyte Serum; Biopsy; Blood Coagulation Tests; Blood Transfusion; Bone Marrow; Child, Preschool; Cyclosporine; Feasibility Studies; Female; Granulocyte Colony-Stimulating Factor; Humans; Immunosuppressive Agents; Liver Failure; Liver Function Tests; Male; T-Lymphocytes; Vitamin K

Topics: Acetylcysteine; Anemia, Aplastic; Antilymphocyte Serum; Bilirubin; Child; Cyclosporine; Female; Humans; Immunosuppressive Agents; Liver Failure, Acute; Methylprednisolone Hemisuccinate; Platelet Transfusion; Prednisone; Transaminases; Treatment Outcome; Vitamin K

A human megakaryoblastic cell line (MEG-01) was investigated for the presence of protein S in culture medium and cell lysates using a specific enzyme-linked immunoassay (ELISA) and a functional assay. When 5 X 10(5) MEG-01 cells/mL was subcultured in RPMI 1640 medium with 10% fetal calf serum (FCS), the concentration of protein S antigen in the culture medium increased progressively with time from less than 8 ng/mL on day 0 to 105.6 +/- 6.0 ng/mL on day 13. Vitamin K2(1 microgram/mL) increased the production of functional protein S, whereas warfarin (1 microgram/mL) profoundly decreased the quantity and the specific activity of secreted protein S. By an indirect immunofluorescent technique, protein S antigen was detected in both MEG-01 cells and human bone marrow megakaryocytes. Immunoblot analysis of culture medium revealed two distinct bands (mol wt 84,000 and 78,000) that are identical to the doublets of purified plasma protein S. De novo synthesis of protein S was demonstrated by the presence of specific immunoprecipitable radioactivity in the medium after 5 hours of labeling of the cells with [35S]-methionine as a 84,000 mol wt protein. Plasma protein S levels of nine patients with severe aplastic anemia were not significantly different from those of normal controls. These results suggest that megakaryocytes produce functional protein S and contain the enzymes required for the carboxylation of selected glutamic acid residues, and that protein S synthesized by megakaryocytes does not represent a main source of plasma protein S.

Topics: Anemia, Aplastic; Cell Extracts; Cell Line; Culture Media; Enzyme-Linked Immunosorbent Assay; Epitopes; Fluorescent Antibody Technique; Glycoproteins; Humans; Megakaryocytes; Methionine; Molecular Weight; Precipitin Tests; Protein S; Sulfur Radioisotopes; Time Factors; Vitamin K; Warfarin

Topics: Anemia; Anemia, Aplastic; Ascorbic Acid; Blood Transfusion; Child; Corrinoids; Cortisone; Diagnosis; Humans; Iron; Rutin; Vitamin B 12; Vitamin K