Prolonged Isolated Thrombocytopenia (PIT) Is Associated with Platelet Aggregation, Which Is Affected By Endothelial Progenitor Cells (EPCs) Following Allo-HSCT
Authors: Zhang Xiao Hui , Zhou Shi-yuan , Feng Fei-er , Han Wei , Chen Huan , Xu Lan-ping , Huang Xiao Jun 
Published: October 2019

Introduction

Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is an effective treatment for malignant hematological diseases, but prolonged isolated thrombocytopenia (PIT) following allo-HSCT seriously decreases patient survival after transplantation. PIT was defined as a platelet count <100×109/L for more than 3 months after HSCT, recovery of all other cell counts, and no apparent cause for thrombocytopenia(Zhang XH et al, Biol Blood Marrow Transplant, 2011). Endothelial progenitor cells (EPCs) are a minor subpopulation of peripheral blood mononuclear cells with surface expression of both endothelial and stem cell (CD34) lineage antigens. These cells were able to promote vasculogenesis at sites of ischemia in vitro. Recent research has shown that EPCs inhibit platelet aggregation by secreting prostacyclin (PGI2) (Abou-Saleh et al., Circulation, 2009). However, to our knowledge, there is no research regarding the relationship between EPCs and PIT after allo-HSCT. We hypothesize that PIT after allo-HSCT is associated with an abnormal increase of EPCs, which might secret high levels of PGI2 and inhibit platelet activation and aggregation.

Methods and results

We enrolled 78 patients who underwent allo-HSCT in our department due of various types of hematological malignancies, of which 38 patients were suffering from PIT and 40 were matched controls.

In the patients suffering from PIT after allo-HSCT, a significantly higher percentage of BM EPCs percent were found compared with the control group (0.041%±0.022% v 0.021%±0.012%, p <0.05) at +3 months after allo-HSCT. However, when the PIT patients were classified into subgroups according to the PLT count at +3 month after allo-HSCT, the difference only existed in patients with lower platelet counts (PLT<50 x 109/L) and controls (0.052%±0.025 v 0.021%±0.012%, p<0.05), but there was no significant difference between the subgroups of PIT patients.

Then, we tested whether PGI2 levels had the same tendency as the EPCs. We found that in PIT patients, the serum PGI2 levels seemed to be higher than in the control group, but the difference did not reach statistical significance (379.23±43.41 pg/ml v 234.75±38.49 pg/ml, p=0.08). However, when classified into subgroups, serum PGI2 levels of patients with lower platelet counts were significantly higher than those of the controls (433.32±76.43 pg/ml v 234.75±38.49 pg/ml, p<0.05).

We also measured platelet aggregation and activation in the two groups. We found that platelet aggregation and activation (measured by CD62P and PAC-1, respectively) in PIT patients were significantly lower than in the control group (PLT aggregation: 21.2%± 5.5% v 29.2% ±8.7%, p <0.05; PLT activation-PAC-1: 21.6%± 7.3% v 28.7% ±8.3%, p <0.05; PLT activation-CD62P: 43.7%± 8.3% v 38.9% ±9.4%, p =0.22). However, when further classified into subgroups, none of the groups showed significant differences.

Conclusion

Patients suffering PIT after allo-HSCT have a higher percentage of BM EPCs, higher serum PGI2 levels and lower platelet activation and aggregation. These data might lead to new insight into the mechanism of PIT following allo-HSCT, and provide a potential avenue for treatment for PIT after allo-HSCT.

Disclosures: No relevant conflicts of interest to declare.