warfarin and Anemia--Aplastic

A 44-year-old Japanese man having aplastic anemia (AA)-paroxyamal nocturnal hemoglobinuria (PNH) syndrome was referred to our hospital because of purpuras due to thrombocytopenia in July 1994. He suffered from pneumonia after admission, complicated with cerebral, splenic, and left renal infarction. Pulmonary infaction was also confirmed by perfusion lung scan. He had a plasma plasminogen (PLG) functional activity of 54.4% with a normal level of PLG antigen. The gel isoelectrofocusing pattern of the plasminogen derived from the patient showed 10 normal bands and 10 additional doublet bands with slightly higher isoelectric points than the normal components. Abnormal PLG is converted by urokinase to an inactive two-chain plasmin molecule. These findings were similar to those of a case with dysplasminogenemia (PLG Tochigi) reported by Aoki et al. He was given warfarin for the prevention of thrombosis in December 1994. As of October 1995, these was no recurrence of thrombosis. The cause of thrombosis in the present case have been the association with PNH, predisposition to PLG Tochigi, or the complication of pneumonia. This is the first report of AA/PNH syndrome associated with dysplasminogenemia.

Topics: Adult; Anemia, Aplastic; Anticoagulants; Hemoglobinuria, Paroxysmal; Humans; Male; Plasminogen; Pneumonia; Syndrome; Thrombosis; Warfarin

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: Acetaminophen; Anemia, Aplastic; Anticoagulants; Aspirin; Blood Platelets; Bone Marrow; Capillary Fragility; Drug Hypersensitivity; Drug Synergism; Hemorrhagic Disorders; Hemostasis; Heparin; Heparin Antagonists; Humans; Indenes; Platelet Adhesiveness; Purpura; Thrombocytopenia; Vascular Diseases; Warfarin

Topics: Anemia, Aplastic; Blood Coagulation; Blood Transfusion; Erythropoiesis; Erythropoietin; Female; Fluoxymesterone; Humans; Iron; Iron Isotopes; Kidney; Kidney Failure, Chronic; Liver; Liver Function Tests; Long-Term Care; Male; Prothrombin Time; Warfarin