Effects of training on reticulated reactive platelets and erytrocyte fragments in patients with peripheral atherosclerosis.

Background: training is a documented effective treatment in patients affected from peripheral arterial disease (PAD). Platelet activation plays a pivotal role in atherosclerosis progression and cardiovascular events. Reticulated platelets (IPF) reflects activity of bone marrow , recently they have been associated to cardiovascular complications and atherosclerosis with unstable conditions (e.g. acute coronary syndrome). Presence of a width blood red cell distribution is considered recently as a prognostic factor for coronary artery disease, a high RDW value depends greatly on presence of red blood cells fragmentation (FRC); this parameter may depend on different conditions such as inflammation, and oxidation and is connected with different risk factors such as hypertension and diabetes. Few data can be found for patients with peripheral arterial disease on training. We aimed to evaluate the effects of aerobic training on IPF and FRC at rest and after maximal walking exercise before and after training. Methods and Results: we enrolled 12 patients with intermittent claudication. They were submitted to a 15 days aerobic training period (cycling and treadmill exercise under maximal walking capacity). IPF, MPV, PLT count and FRC were analyzed at rest, 1 hour after maximal treadmill test and after 24 hours, these evaluations were performed at the beginning and at the end of the training period. The Lab parameters were analyzed with impedentiometry, fluorimetry (oxazyne) and optical methods (Sysmex Xn-1000, Sysmex Corporation, Kobe, Japan). Walking distance was measured with treadmill (3,2 km/h, 2-10% slope), maximal test was prolonged to the maximal tolerated claudication pain. Platelets count was within normal range (216,9 ± 40 109/l ) and did not changed throughout the study; also MPV was unchanged (11,6±1,9 vs 11.45±0,8 fl ) before and after the training ; plateletcrit was slightly reduced (0,246±0,061 vs 0,282 ±0,018 %). IPF count (figure) slightly changed during maximal stress at the beginning of training with increase after 24 hours; after training the count decreased significantly (*p<0,05) at rest and 1 hour after, while it increased significantly after 24 hours (** p<0,05 vs rest ad vs 24 h-pre) but less than before training. FRC decreased after triaining (0,381±0,121 vs 0,542±0,220 %; p<0,05), maximal test slightly increased FRC after 1 hour , no significant change after 24 hours. At the end of training, absolute walking distance increased (450±180 vs 250±108 m; p<0,05). Discussion: training reduces IPF in patients with peripheral arterial disease, IPF increase after acute maximal test and this phenomenon can be attenuated by training. We also observed a reduction in FRC. Presence of FRC in these patients may be caused by mechanical forces throughout a large surface of atherosclerotic plaques fragmenting red cells, ischemia reperfusion in claudication is another mechanism that can elicit formation of FRC and in addition high oxidative stress may contribute. IPF are associated with an increase platelets activity and a higher turnover; in this pathology both these condition can be found associated with oxidative stress, inflammation and endothelial dysfunction. Training improves oxidation, inflammation and endothelium function with favorable effects on platelets activation and turnover, furthermore these parameters may influence also FRC count. Conclusion: training in PAD patients reduces IPF and FRC with potential improvement in risk profile for atherosclerosis progression and reduction of cardiovascular events. References: 1. Cesari F, Marcucci R, Gori AM, et al . Reticulated platelets predict cardiovascular death in acute coronary syndrome patients. Thrombosis and Haemostasis 2013; 109: 846-853. 2. Hoffmann JJ . Reticulated platelets: analytical aspects and clinical utility. Clin Chem Lab. 2014; 52: 1107-17. 3. Bujak K, Wasilewski J, Osadnik T, et al. Prognostic role of red blood cell distribution width in coronary artery disease: a review of the pathophysiology. Disease Markers 2015, vol 1 ; 1-12.