Recipient-derived HPA-1a antibodies: a cause of prolonged thrombocytopenia after unrelated donor stem cell transplantation.
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.
Lucas
Geoff
G
Histocompatibility& Immunogenetics, NHS Blood and Transplant, Northway, Bristol, UK. geoff.lucas@nbs.nhs.uk
Culliford
Steven
S
Green
Frances
F
Sidra
Gamal
G
Calvert
Anthony
A
Green
Ann
A
Harrison
Penny
P
Harvey
John
J
Allen
Dave
D
Smillie
David
D
Masurekar
Ashish
A
Marks
David
D
Russell
Nigel
N
Massey
Edwin
E
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
D016824:Antigens, Human Platelet; C061248:ITGB3 protein, human; D039661:Integrin beta3; D007518:Isoantibodies