Background: Bleeding complications can have serious outcomes in patients with myelodysplastic syndromes (MDS) and are usually related to thrombocytopaenia. In a recent work we demonstrated that platelets from MDS have impaired capacity to respond to agonist stimulation and exposed more phosphatidylserine (PS) than those from healthy controls whichever their platelet count was (Martin et al, Thromb Haemost., 2013;109:909-19). The exposure of PS in the outer layer of cell membranes supports coagulation through enhanced formation of the tenase (factors IXa, VIIIa and X) and prothrombinase (factors Xa, Va and prothrombin) complexes and thrombin generation. So, the possibility exists that these processes are increased in these patients.Objectives: The aim of this work was to study whether thrombus formation and thrombin generation is impaired in MDS patients with normal platelet count employing global coagulation tests thromboelastrometry (ROTEM) and Calibrated Automated Thrombogram (CAT).Methods: Thirty-one MDS patients with normal platelet count and twenty healthy controls were included. Citrated blood was centrifuged at 152 g 10 min at 23°C for obtaining platelet rich plasma (PRP) and at 1,500 g for 15 min at 23°C for platelet-poor plasma (PPP). For ROTEM and CAT experiments, PRP was adjusted to a platelet count of 25 x 109/L. Aliquots for ROTEM assay were tested within the two hours after obtaining blood samples. For CAT experiments, adjusted PRP and PPP aliquots were stored at -70ºC until analysis.Kinetics of clot formation, non-activated ROTEM was performed on adjusted PRP. Clotting time (CT, time from start of measurement until initiation of clotting [in seconds], alpha angle, which reflects the rate of fibrin polymerisation (tangent to the curve at 2-mm amplitude [in degrees]), and maximum clot firmness, which reflects the maximum tensile strength of the thrombus (MCF, [in mm]), were recorded.Thrombin generation was measured in adjusted PRP without any trigger and in PPP with 1 pM tissue factor and 4 µM phospholipids (PPP-Reagent LOW, Thrombinoscope BV, Maastricht, The Netherlands) as trigger. Endogenous thrombin potential (ETP, the total amount of thrombin generated over time); the lag time (the time to the beginning of the explosive burst of thrombin generation); the peak height of the curve (the maximum thrombin concentration produced); and the time to the peak were evaluated.Platelet activation was determined by PAC1 (BD, Madrid, Spain) binding after stimulation with 100 μM thrombin receptor-activating peptide 6 (TRAP, Bachem, Switzerland) and surface PS through Annexin-V binding and flow cytometry analyses.Results: Platelets from MDS patients had a reduced response to TRAP stimulation (control= 12016+6384 arbitrary units; MDS= 5829+3704 arbitrary units) and exposed more PS than controls (control= 362.1+80.5 MF; MDS= 378.5+173.5 MF).ROTEM experiments showed kinetic parameters corresponding to a hipocoagulable profile (CT: control= 550+95 sec, MDS= 922+216 sec, p<0.01; alpha angle control= 62.8+4.3, MDS= 47.5+6.0, p<0.05; A5: control= 29.8+3.2, MDS= 24.2+5.8, p<0.05 whereas MCF was similar to controls (control= 46.7+3.1mm, MDS= 47.5+4.3 mm).In order to evaluate whether the impaired clot formation was due to a reduction in plasma-associated thrombin generation, CAT experiments were performed in PPP samples. No differences were found between MDS patients and control group (ETP: control=1223.4+257.8 nMxmin, MDS= 1224.4+344 .1 nMxmin; peak: control= 279.5+54.7nM, MDS= 265.9+64.1 nM). On the other hand, when thrombin generation experiments were performed in adjusted PRP, ETP and peak values were lower than in control group (ETP: control=1574.8+430.5 nMxmin, MDS= 1167.4+354 nMxmin,p<0.05; peak: control= 225.6+82.9 nM, MDS= 266.9+92.2 nM, p<0.05).Conclusions: Platelet dysfunction might be resposible of bleeding complications observed in patients with MDS with normal platelet counts. Increment in PS exposure on platelet surface did not seem to compensate impairment in platelet function. DisclosuresNo relevant conflicts of interest to declare.