The most convincing evidence for the participation of platelets in arterial thrombosis in humans comes from studies of platelet activation in patients with acute coronary syndromes (ACS) and from trials of antiplatelet drugs. Both strongly support the concept that repeated episodes of platelet activation over the thrombogenic surface of a vulnerable plaque may contribute to the risk of death from coronary causes. However, the relation of in vivo platelet activation and adverse clinical events to results of platelet function tests remains largely unknown. A valuable marker of in vivo platelet activation should be specific, unaltered by pre-analytical artefacts and reproducibly measured by easily performed methods. This article describes current biomarkers of platelet activation in ACS, reviews their advantages and disadvantages, discusses their potential pitfalls, and demonstrates emerging data supporting the positive clinical implications of monitoring in vivo platelet activation in the setting of ACS.

BackgroundAcute myeloid leukemia (AML) is both more common and with more biologically aggressive phenotype in the elderly. Allogenic stem cell transplantation (allo-SCT) is the best treatment option in fit patients. Either HLA-matched unrelated donor (MUD) or haploidentical (Haplo) donor are possible alternative for patients in need.MethodsWe retrospectively compared non-T-cell-depleted Haplo (n = 250) to 10/10 MUD (n = 2589) in AML patients ≥ 60 years.ResultsMedian follow-up was 23 months. Disease status at transplant differs significantly between the two groups (p < 10−4). Reduced intensity conditioning (RIC) was administrated to 73 and 77% of Haplo and MUD, respectively (p = 0.23). Stem cell source was the bone marrow (BM) in 52% of the Haplo and 6% of MUD (p < 10−4). Anti-thymocyte globulin (ATG) was most frequently used in MUD (p < 10−4) while post-Tx cyclophosphamide (PT-Cy) was given in 62% of Haplo. Engraftment was achieved in 90% of the Haplo vs 97% of MUD (p < 10−4). In multivariate analysis, no significant difference was found between Haplo and MUD for acute (a)graft versus host disease (GVHD) grade II–IV, relapse incidence (RI), non-relapse mortality (NRM), leukemia free survival (LFS), graft-versus-host-free-relapse free survival (GRFS), and overall survival (OS). Extensive chronic (c)GVHD was significantly higher for MUD as compared to Haplo (HR 2, p = 0.01, 95% CI 1.17–3.47). A propensity score analysis confirmed the higher risk of extensive cGVHD for MUD without differences for other outcomes.ConclusionsAllo-SCT from both Haplo and MUD are valid option for AML patients ≥ 60 years of age with similar results. Transplantation from MUD was associated with higher extensive cGVHD. Our findings suggest that Haplo is a suitable and attractive graft source for patients≥ 60 with AML in need of allo-SCT.

BackgroundAllogenic hematopoietic stem cell transplantation (allo-SCT) is the most effective post-remission treatment for adults with high-risk acute lymphoblastic leukemia (ALL). The aim of the study was to analyze results of unmanipulated haploidentical allo-SCT (haplo-SCT) for adults with ALL and to identify prognostic factors.MethodsWe performed a retrospective analysis on 208 adults transplanted in EBMT centers from 2007 to 2014.ResultsMedian age at haplo-SCT was 32 years and median follow-up, 31 months. Forty-four percent of the patients were in first complete remission (CR1). Stem cell source was the bone marrow (BM) for 43% and peripheral blood (PB) for 57% of patients. Myeloablative conditioning (MAC) was used for 66% and reduced intensity regimen (RIC) for 34% of patients. GVHD prophylaxis was based on post-transplant cyclophosphamide (PT-Cy) for 118 (57%) or on anti-thymocyte-globulin (ATG) for 90 (43%) plus standard prophylaxis. One hundred eighty-four (92%) patients achieved engraftment. Cumulative incidence (CI) of grade II–IV acute-graft-versus-host-disease (GVHD) was 31%, grade III–IV 11%, and chronic GVHD 29%. Non-relapse mortality (NRM) and relapse-incidence (RI) were 32 and 37%, respectively. Overall survival (OS), leukemia-free survival (LFS), and GVHD-free, relapse-free-survival (GRFS) at 3 years were 33, 31, and 26%. For patients in CR1, OS, LFS, and GRFS were 52, 47, and 40%, respectively. Disease status was the main factor associated with transplant outcomes. Use of BM was independently associated with improvement in NRM, acute GVHD, GRFS, LFS, and OS.ConclusionsUnmanipulated haplo-SCT may be considered a valid option for adult patients with high-risk ALL lacking HLA identical donor preferably in early disease status.Electronic supplementary materialThe online version of this article (doi:10.1186/s13045-017-0480-5) contains supplementary material, which is available to authorized users.

BackgroundLow high‐density lipoprotein (HDL) levels are major predictors of cardiovascular (CV) events, even in patients on statin treatment with low‐density lipoprotein (LDL) at target. In animal models HDLs protect LDL from oxidation and blunt platelet activation. Our study aimed to examine whether HDL levels are related to in vivo oxidative stress and platelet activation, as determinants of atherothrombosis.Methods and ResultsUrinary 8‐iso‐PGF2α and 11‐dehydro‐TXB2, in vivo markers of oxidative stress and platelet activation, respectively, were measured in 65 coronary heart disease (CHD) normocholesterolemic patients with HDL ≤35 mg/dL, and in 47 CHD patients with HDL >35 mg/dL. The 2 eicosanoids were also measured before and after an intensive exercise program in sedentary people (n=18) and before and after fenofibrate treatment in otherwise healthy subjects with low HDL (n=10). Patients with HDL ≤35 mg/dL showed significantly higher urinary 8‐iso‐PGF2α (median [25th to 75th percentiles]: 289 [189 to 380] versus 216 [171 to 321] pg/mg creatinine, P=0.019) and 11‐dehydro‐TXB2 (563 [421 to 767] versus 372 [249 to 465] pg/mg creatinine, P=0.0001) than patients with higher HDL. A direct correlation was found between urinary 8‐iso‐PGF2α and 11‐dehydro‐TXB2 in the entire group of patients (ρ=0.77, P<0.0001). HDL levels were inversely related to both 8‐iso‐PGF2α (ρ=−0.32, P=0.001) and 11‐dehydro‐TXB2 (ρ=−0.52, P<0.0001). On multiple regression, only 8‐iso‐PGF2α (β=0.68, P<0.0001) and HDL level (β=−0.29, P<0.0001) were associated with urinary 11‐dehydro‐TXB2 excretion, independent of sex, age, smoking, hypertension, diabetes, previous myocardial infarction, total cholesterol, LDL, and triglycerides. Both intensive exercise and fenofibrate treatment significantly reduced the 2 eicosanoids in healthy subjects, in parallel with an HDL increase.ConclusionsA low HDL phenotype, both in CHD patients and in healthy subjects, is associated with increased lipid peroxidation and platelet activation. These data provide novel insight into the mechanisms linking low HDL with increased CV risk.