Prolonged thrombocytopenia following allogeneic hematopoietic stem cell transplantation and its association with a reduction in ploidy and an immaturation of megakaryocytes.
Prolonged thrombocytopenia is a frequent complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT); however, its pathogenesis has remained obscure. In the present study, we used flow cytometry to determine the frequency of bone marrow megakaryocytes (MKs) and MK ploidy distributions in allo-HSCT recipients with or without prolonged thrombocytopenia (n = 32 and 27, respectively) and healthy volunteers (n = 13). In addition, the expression of c-Mpl in MKs was measured. The results indicate that the proportions of MKs in marrow mononuclear cells or the percentages of CD110(+) MKs in total MKs did not significantly differ between the 3 groups; however, in a comparison of nonthrombocytopenic allo-HSCT recipients to healthy volunteers, the allo-HSCT patients who had prolonged thrombocytopenia exhibited significant shifts toward low ploidy cells (left shift), which were accompanied by a marked increase in ≤ 8N cells (P = .036 and P < .001, respectively) and significant decreases in 16N cells (P < .001 and P < .001, respectively) and ≥ 32N cells (P = .01 and P <.001, respectively). These results indicate that there were more immature MKs in allo-HSCT recipients who had prolonged thrombocytopenia, in comparison to nonthrombocytopenic allo-HSCT recipients and healthy volunteers. We conclude that prolonged thrombocytopenia and slow platelet engraftment after allo-HSCT may be related to a reduction in ploidy and an immaturation of MKs.
Zhang
Xiaohui
X
Peking University People's Hospital, Peking University Institute of Hematology, Beijing, People's Republic of China.
Fu
Haixia
H
Xu
Lanping
L
Liu
Daihong
D
Wang
Jianzhong
J
Liu
Kaiyan
K
Huang
Xiaojun
X
D000293:Adolescent; D000328:Adult; D001854:Bone Marrow Cells; D002454:Cell Differentiation; D002908:Chronic Disease; D005260:Female; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D008297:Male; D055016:Megakaryocyte Progenitor Cells / Q000166:cytology* / Q000378:metabolism; D008533:Megakaryocytes / Q000166:cytology / Q000378:metabolism; D008875:Middle Aged; D010976:Platelet Count; D011123:Polyploidy; D053628:Receptors, Thrombopoietin / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood / Q000209:etiology*; D014184:Transplantation, Homologous; D055815:Young Adult
D053628:Receptors, Thrombopoietin; C082218:MPL protein, human