PLATELET DYSFUNCTION IN PATIENTS WITH MDS AND ITP

Background. Hemorrhagic complications are frequent and among the leading causes of death in patients with myelodysplastic syndromes (MDS). Not only thrombocytopenia, but also platelet function abnormalities contribute to bleeding tendency of MDS patients. However, no published studies comprehensively evaluated several parameters of platelet function, including the measurement of the platelet levels of cyclic AMP (cAMP), which is an effective inhibitor of platelet function. In this case-control study, we aimed to comprehensively assess in vitro platelet function of patients with MDS of any IPSS risk category. Methods. Patients diagnosed as MDS according to WHO guidelines and two control groups, primary Immune ThrombocytoPenia (ITP) patients and healthy subjects were consecutively recruited. Platelet aggregation and secretion in platelet rich plasma (PRP) with platelet count >150x109/L were induced by adenosine diphosphate (ADP) (2µM), epinephrine (5µM), thrombin receptor-activating peptide (TRAP) (10µM), synthetic reactive peptide (SRP) (4 ng/mL), collagen reactive peptide (CRP) 0.1µg/mL , Horm collagen (2µg/mL) and arachidonic acid (AA) (1 mM) and measured by lumi-aggregometry. In addition, the effect of Prostaglandin E1 (PGE1) (0.1µM) was tested in collagen-induced platelet aggregation. Intraplatelet cAMP content was measured by an ELISA assay in extracts of PRP containing theophylline (1 mM), incubated with PGE1 (1 or 0.1 µM) or Tyrode’s buffer alone for 2 minutes. Differences among the three groups were analyzed by Kruskal-Wallis and Dunn's multiple comparisons test. Results. 32 MDS (male=22), 26 ITP (male=12) patients, and 54 healthy subjects (male=26) were enrolled. Platelet aggregation measured in PRP samples induced by all agonists was significantly lower in MDS patients than in healthy control group, but there was no difference between ITP and healthy subjects. The platelet aggregates formation induced by collagen was significantly decreased in presence of PGE1 (0.1uM) in all groups. The extent of decrease was significantly higher in MDS patients than in the other two groups while Intraplatelet cAMP production induced by PGE1 (0.1uM and 1 uM) were similar in MDS patients, ITP patients and healthy controls. Conclusion: MDS patients showed dysfunctional platelets while ITP patients showed relatively normal function platelets.