title: [Very severe thrombotic thrombocytopenic purpura (TTP) after H1N1 vaccination].
abstract: BACKGROUND
  Thrombotic thrombocytopenic purpura (TTP) is a severe disease with microthrombi in various organs. The idopathic subtype is characterized by reduced ADAMTS13 activity mediated via autoantibodies against this protease. Induction of autoantibodies mechanistically is incompletely understood, but certain drugs can induce anti-ADAMTS13 antibodies through hapten mechanisms.
  
  
  METHODS
  A 56-year-old man was admitted from an external hospital because of a rapidly worsening general condition, hemolytic anemia (hemoglobin 4.17 mmol/l, hematocrit 0.19), and thrombocytopenia (22 Gpt/l) for unknown reasons. Additionally, he was found to have an elevated lactate dehydrogenase (45.37 μmol/l/s). 13 days before hospitalization he had received vaccination against H1N1. Laboratory tests revealed an increased total bilirubin (126 μmol/l), and a decreased haptoglobin level (< 0.08 g/l). The blood smear showed 24% fragmentocytes. Direct and indirect Coombs test were negative. TPP was diagnosed based on the clinical presentation and the detection of ADAMTS13 antibodies. Despite daily plasma exchange via plasmapheresis and administration of corticosteroids, there was no significant rise in platelet counts. Immunosuppression with a total of four weekly doses of rituximab (375 mg/m(2) body surface area) was added. Over the next 5 weeks, the platelet count very slowly rose. After a total of 46 sessions, plasmapheresis was ended with complete remission of the disease.
  
  
  CONCLUSIONS
  This report emphasizes the immunologic susceptibility of TTP, and suggests the potential, but not proven role of H1N1 vaccination in the pathogenesis of TTP, because no serum before vaccination was available. Severe autoantibody TTP can be successfully treated by administering rituximab in addition to standard treatment with plasmapheresis and corticosteroids.
authors.affiliation: Klinik für Innere Medizin III, Universitätsklinikum Jena, Jena, Germany. Regina.Hermann@med.uni-jena.de
authors.forename: Regina
authors.initials: R
authors.lastname: Hermann
authors.forename: Alexander
authors.initials: A
authors.lastname: Pfeil
authors.forename: Martin
authors.initials: M
authors.lastname: Busch
authors.forename: Christiane
authors.initials: C
authors.lastname: Kettner
authors.forename: Daniel
authors.initials: D
authors.lastname: Kretzschmar
authors.forename: Andreas
authors.initials: A
authors.lastname: Hansch
authors.forename: Paul
authors.initials: P
authors.lastname: La Rosée
authors.forename: Gunter
authors.initials: G
authors.lastname: Wolf
mesh_terms: D051722:ADAM Proteins / Q000276:immunology*; D000071120:ADAMTS13 Protein; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D058846:Antibodies, Monoclonal, Murine-Derived / Q000627:therapeutic use; D001323:Autoantibodies / Q000097:blood*; D003131:Combined Modality Therapy; D003937:Diagnosis, Differential; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007252:Influenza Vaccines / Q000008:administration & dosage / Q000009:adverse effects*; D007251:Influenza, Human / Q000276:immunology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D010956:Plasmapheresis; D011697:Purpura, Thrombotic Thrombocytopenic / Q000139:chemically induced* / Q000276:immunology / Q000628:therapy; D000069283:Rituximab
chemical_list: D000305:Adrenal Cortex Hormones; D058846:Antibodies, Monoclonal, Murine-Derived; D001323:Autoantibodies; D007252:Influenza Vaccines; D000069283:Rituximab; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human