title: Recipient-derived HPA-1a antibodies: a cause of prolonged thrombocytopenia after unrelated donor stem cell transplantation.
abstract: BACKGROUND
  Patients with human platelet antigen (HPA) specific antibodies in cases of neonatal alloimmune thrombocytopenia and platelet (PLT) refractoriness derive clinical benefit from the use of HPA-selected PLTs.
  
  
  METHODS
  This study describes three patients with underlying diagnoses of acute myeloid leukemia, chronic lymphocytic leukemia, and myelodysplasia, respectively, who underwent allogeneic bone marrow transplantation (BMT) with unrelated donors matched at the HLA-A, B, C, Dr, and DQ loci but who failed to achieve an adequate PLT count. Investigation using PLT immunofluorescence test, monoclonal antibody immobilization of PLT antigens assay, and genotyping revealed the presence of recipient-derived HPA-1a antibodies.
  
  
  RESULTS
  In two patients, anti-HPA-1a was detected post-BMT and in the third patient, anti-HPA-1a was detected during pre-BMT chemotherapy. Despite apparent 100% engraftment of donor cells, the patients' PLT counts failed to recover 9-10 months posttransplant. The patients remained PLT-transfusion dependent and failed to achieve satisfactory increments following random donor or HLA-matched PLT transfusions. After the identification of HPA-1a antibodies, the patients were supported by HPA-1a(-) PLTs and satisfactory posttransfusion PLT increments were obtained. These cases illustrate that HPA-1a antibodies may remain detectable for 10 months following apparently successful donor engraftment and the disappearance of recipient-derived HLA antibodies. The prolonged persistence of recipient-derived PLT-specific antibodies following BMT has to our knowledge not been described previously.
  
  
  CONCLUSIONS
  HPA-1a antibodies were associated with protracted PLT-transfusion dependence and significant hemorrhagic complications. Appropriate and timely laboratory investigation for HPA-specific antibodies followed by transfusion support with HPA-selected PLTs provided the cornerstone of the hemostatic management in these cases.
authors.affiliation: Histocompatibility& Immunogenetics, NHS Blood and Transplant, Northway, Bristol, UK. geoff.lucas@nbs.nhs.uk
authors.forename: Geoff
authors.initials: G
authors.lastname: Lucas
authors.forename: Steven
authors.initials: S
authors.lastname: Culliford
authors.forename: Frances
authors.initials: F
authors.lastname: Green
authors.forename: Gamal
authors.initials: G
authors.lastname: Sidra
authors.forename: Anthony
authors.initials: A
authors.lastname: Calvert
authors.forename: Ann
authors.initials: A
authors.lastname: Green
authors.forename: Penny
authors.initials: P
authors.lastname: Harrison
authors.forename: John
authors.initials: J
authors.lastname: Harvey
authors.forename: Dave
authors.initials: D
authors.lastname: Allen
authors.forename: David
authors.initials: D
authors.lastname: Smillie
authors.forename: Ashish
authors.initials: A
authors.lastname: Masurekar
authors.forename: David
authors.initials: D
authors.lastname: Marks
authors.forename: Nigel
authors.initials: N
authors.lastname: Russell
authors.forename: Edwin
authors.initials: E
authors.lastname: Massey
mesh_terms: D000208:Acute Disease; D000753:Anemia, Refractory / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D016824:Antigens, Human Platelet / Q000276:immunology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D016026:Bone Marrow Transplantation / Q000009:adverse effects* / Q000276:immunology; D003131:Combined Modality Therapy; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D039661:Integrin beta3; D007518:Isoantibodies / Q000096:biosynthesis / Q000276:immunology*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000276:immunology / Q000601:surgery; D008297:Male; D008875:Middle Aged; D036102:Peripheral Blood Stem Cell Transplantation / Q000009:adverse effects*; D017713:Platelet Transfusion; D011183:Postoperative Complications / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D013921:Thrombocytopenia / Q000209:etiology / Q000276:immunology* / Q000628:therapy; D014184:Transplantation, Homologous / Q000009:adverse effects* / Q000276:immunology
chemical_list: D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007518:Isoantibodies