Abnormal Platelet Phenotypes in Patients with Myelodysplastic Syndromes

Background:

Hemorrhage and infection are two main causes of death in patients with myelodysplastic syndromes (MDS), mainly due to thrombocytopenia and neutropenia respectively. However, it is becoming increasingly clear that platelet dysfunction can also affect the process of hemostasis and anti-infection. Several studies have evaluated platelet activation in MDS and found platelet dysfunction, but immune-related function of platelets in patients with MDS has not been investigated yet. The aim of this study was to evaluate activation function and immune-related function of platelets in MDS by testing platelet activation-associated phenotypes and immune-associated phenotypes.

Methods:

We included 29 MDS patients and 22 healthy subjects, and MDS patients were divided into different subgroups (low-risk group and high-risk group; untreated group and treated group; pre-transfusion group and post-transfusion group) according to IPSS-R score, hypomethylating agents (HMAs) therapy and platelet transfusion history to observe phenotype changes under different factors. Platelet light scatter properties, expression of CD41a, expression of activation-associated phenotypes (CD62p and CD63) and expression of immune-associated phenotypes (CD154 and TLR4) were systematically detected by multi-parameter flow cytometry (MFC). Then correlations between phenotypes and clinical indexes were analyzed.

Results:

Compared to the healthy controls, decreased expression of platelet-specific antigen CD41a was shown in MDS patients (P<0.05). No difference was found in platelet light scatter properties between MDS patients and healthy subjects (P>0.05). Significantly decreased expression frequency and intensity of activation phenotype CD63 were found in patients with MDS (P<0.05). Low-risk MDS showed lower expression frequency while high-risk MDS showed reduced mean fluorescence intensity (MFI) of CD63. Decreased expression of CD154 and TLR4 was found in MDS patients (P<0.05) which was significantly elevated after HMAs therapy (P<0.05). Particularly, high-risk MDS patients again exhibited reduced MFI of CD154 and TLR4 (P<0.05). Correlation analysis showed that the expression of activation-associated phenotypes was not significantly correlated with the severity of bleeding events, but expression of CD62p was negatively correlated with white blood cell count (WBC) (r=-0.496, P=0.006; r=-0.498, P=0.006), absolute neutrophil count (ANC) (r=-0.512, P=-0.005; r=-0.442, P=0.016), fibrinogen (FIB) (r=-0.415, P=0.025; r=-0.510, P=0.005), and D-dimer (DD) (r=-0.547, P=0.002; r=-0.601, P=0.001), and positively correlated with prothrombin time (PT) (r=0.409, P =0.028; r=0.489, P=0.007). Expression of immune-associated phenotypes was not significantly correlated with the severity of infection events (P > 0.05).

Conclusion:

MDS patients displayed defective expression of both activation- and immune-associated platelet phenotypes, with differential mechanisms between low-risk and high-risk group regarding phenotype alterations. CD62p showed clinical relevance in regard to WBC count and coagulation indexes, and HMAs treatment significantly improved CD154 and TLR4 expression on platelets. Taken together, the findings confirmed impaired platelet phenotypes in MDS which may assist in the diagnosis and identification of MDS patients.