Life threatening bleeding in a case of autoantibody-induced factor VII deficiency

Department of Laboratory Medicine, Kumamoto University School of Medicine, Japan.
International Journal of Hematology (Impact Factor: 1.92). 02/1999; 69(2):129-32.
Source: PubMed


A male patient presented with life-threatening bleeding induced by autoantibody-induced factor VII (F.VII) deficiency. This patient had macroscopic hematuria, skin ecchymosis, gastrointestinal bleeding, and a neck hematoma that was causing disturbed respiration. He developed acute renal failure and acute hepatic failure, probably due to obstruction of the ureters and the biliary tract, respectively. Although activated partial thromboplastin time was normal, prothrombin time (PT) was remarkably prolonged at 71.8 seconds compared to 14.0 seconds in a normal control. Both the immunoreactive level of F.VII antigen and the F.VII activity of the patient's plasma samples were < 1.0% of normal. Although an equal part of normal plasma was added to the patient's plasma, PT was not corrected. The patient's plasma inhibited F.VII activity. These findings suggested the presence of a plasma inhibitor for F.VII. After administration of large doses of methylprednisolone, PT was gradually shortened and plasma levels of F.VII increased over time. Bleeding, acute renal failure, and acute hepatic failure improved markedly following the steroid treatment. These observations suggest that life-threatening bleeding can be induced by autoantibody-induced F.VII deficiency and that immunosuppressive therapy using large doses of steroid can be successful in inhibiting the production of the autoantibody.

9 Reads
  • [Show abstract] [Hide abstract]
    ABSTRACT: Acquired coagulation factor antibodies are either alloantibodies or autoantibodies. Alloantibodies are formed when the body reacts to an external antigen. Commonly, alloantibodies arise when a patient who has a congenital clotting factor deficiency is infused with a blood product. Alternately, patients exposed to a coagulation protein from a different species may develop alloantibodies to the animal protein that cross-reacts with their own protein. On the other hand, autoantibodies develop spontaneously in people without pre-existing factor deficiencies and without exposure to an external antigen. These antibodies may neutralize function of a clotting factor, promote rapid clearance of a clotting factor from the blood, or alter the clotting factor in such a way that the protein-antibody complex acquires a unique function. This review focuses on recent reports of autoantibodies directed against fibrinogen, prothrombin, factor V, factor VII, factor X, and von Willebrand factor, in which these various activities of autoantibodies are illustrated.
    Current Opinion in Hematology 10/1999; 6(5):323-8. DOI:10.1097/00062752-199909000-00009 · 3.97 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We recently observed a patient with acquired inhibitor-induced F.VII deficiency whose plasma level of F.VII was < 1.0%. However, the biochemical nature of the inhibitor has not yet been clarified. In the present study, we purified the F.VII inhibitor from the patient's plasma by using activated F.VII (F.VIIa)-conjugated gel and characterized the inhibitor. The results showed that the inhibitor comprised two kinds of antibodies: one was eluted with EDTA (antibody 1) and the other with glycine-HCl buffer (pH 2.3) (antibody 2) from the F.VIIa affinity gel. SDS-polyacrylamide gel electrophoresis (SDS-PAGE) and immunoblotting analysis of these inhibitors demonstrated that both antibodies had features of immunoglobulin G1 (IgG1) with kappa and lambda-light chains. Antibody 1 bound to the immobilized F.VIIa with a high affinity in the presence of calcium ion, while antibody 2 bound to the F.VIIa very weakly and the binding was independent of calcium ion. Immunoblotting analysis demonstrated that antibody 1 bound to the light chain of F.VIIa after reduction with 2-mercaptoethanol, while it did not react with either the gamma-carboxyglutamic acid (Gla)-domainless light chain of F.VIIa or the heavy chain with the protease domain. Antibody 1 markedly inhibited the activity of tissue factor-F.VIIa complex. Based on these observations, it is suggested that F.VIIa autoantibody (antibody 1) recognizes the calcium-dependent conformation within or near the Gla domain and inhibits F.VIIa activity by interacting with the light chain.
    Thrombosis and Haemostasis 01/2000; 83(1):60-4. · 4.98 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: A 65-year-old man was admitted to another hospital with a life-threatening brain haemorrhage, and laboratory examinations on admission revealed prolonged prothrombin time with normal activated partial thromboplastin time. To establish the cause of his abnormal coagulation, he was referred to our clinic. Neither the patient nor his family had any previous history of bleeding symptoms. His liver function was within normal limits but coagulation tests showed increased plasma activities of factors II, VIII, IX, X, with reduced activities of factors V and VII. The activity of factor VII was less than 2% but no inhibitor of factor VII was detected in the plasma. We concluded that the patient had a rare congenital isolated factor VII deficiency although he had not shown earlier bleeding problems, presumably because of compensation for the factor VII deficiency by enhanced activities of components of the extrinsic coagulation pathway, factors II, VIII, IX and X.
    The Journal of international medical research 12/2000; 28(6):318-23. DOI:10.1177/147323000002800609 · 1.44 Impact Factor
Show more