Thrombocytopenia following autologous bone marrow transplantation: evidence for autoimmune aetiology and B cell clonal involvement.
Thrombocytopenia outlasting anaemia and neutropenia is a well recognised sequel of autologous bone marrow transplantation (BMT) but the pathogenesis remains unclear. Autoimmune destruction of platelets has been suggested as a possible mechanism. We studied 5 patients who had undergone autologous BMT and were found to have persistent thrombocytopenia (< 150 x 10(9)/l) 6 months from transplantation with a normal haemoglobin level and granulocyte count. Apart from a mild reduction in the megakaryocyte numbers in one case, no other quantitative or qualitative defects of the megakaryocyte lineage were present to explain the peripheral thrombocytopenia. Two cases had positive anti-platelet autoantibodies. Immunoglobulin heavy chain gene rearrangement studies of peripheral blood and bone marrow mononuclear cells using the polymerase chain reaction showed evidence of clonal rearrangement in one of the two cases with positive anti-platelet autoantibodies. Our results support the previous reports that anti-platelet antibody-mediated destruction of platelets may play a role in the pathogenesis of post-autologous BMT thrombocytopenia. Furthermore, the demonstration of a clonal B cell expansion in one of the cases with anti-platelet antibodies suggests an aetiological link between clonal B cells, autoantibody production and thrombocytopenia.
Sivakumaran
M
M
Department of Haematology, Leicester Royal Infirmary, UK.
Hutchinson
R M
RM
Pringle
H
H
Graham
S
S
Primrose
L
L
Wood
J K
JK
Lauder
I
I
D000328:Adult; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000209:etiology* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D001792:Blood Platelets / Q000276:immunology*; D016026:Bone Marrow Transplantation / Q000009:adverse effects*; D016516:CD4-CD8 Ratio; D002455:Cell Division; D005260:Female; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia / Q000209:etiology* / Q000276:immunology; D014182:Transplantation, Autologous
D001323:Autoantibodies; D007136:Immunoglobulins