| Abstract |
Inflammatory Bowel Diseases (IBD) constitute chronic recurrent inflammatory disorders of the digestive tract. Current theory of pathogenesis suggests that these disorders are due to an aberrant immune response of the intestinal mucosa against bacterial or other environmental antigens in a genetic predisposed person. The most crucial inductive factor of intestinal inflammation is the immune system. Nevertheless, a series of non-immune cells like PLT, emerge in late clinical trials as significant IBD inflammatory regulators.
Main PLT role in human body is the preservation of haemostasis, surveying endothelial barrier in vessels and promoting clot formation in cases where the barrier is breached. PLT in IBD are in highly active state, which occurs in the mesenteric microcirculation of the patient where they are exposed to a series of inflammatory agents. Plenty PLT changes have been described in IBD, including morphological [reduction of MPV, increase of PDW, PCT and granular content, loss of discoid shape and acquisition of pseudopodia], increase in their absolute number, microparticles release (PDMPs) and increased PLT agglutination to form complexes like PLT-PLT and PLT-leukocyte (PLA), all of which are connected with the PLT activation by inflammatory agonists.
This thesis studied: (1) the change in quantitative PLT parameters such as the absolute number, PCT, PDW and MPV in IBD patients when compared to a control group consisting of healthy controls (HC). (2) The correlation of these values with clinical and laboratory activity indices in IBD, but also with anemic and red blood cells parameters in the same patients. (3) The concentration of activation products in patients’ plasma, such as the total MPs, the monocyte derived MPs (MDMPs) and mostly the platelet derived MPs (PDMPs), and their comparison with the ones from the HC group. (4) The evaluation of the MPs subtypes ability to bind to the molecule of annexin both in IBD patients and HC. (5) The possible relationship between studied MPs and clinical, laboratory characteristics of the disease in IBD.
The IBD patients showed decreased hematocrit (Hct), hemoglobin (Hb), MCV and ferritin and increased number of PLT, erythrocyte distribution width (RDW), PDW, PCT, soluble transferrin receptor (sTfR) and its index compared to HC. The absolute number of PLT in IBD patients was associated with all anemia indices (Hct, Hb, MCV, RDW, ferritin, sTfR and sTfR index), except for vitamin B12 and folate, as well as with disease activity indices (CRP, SCCAI score, CDAI score). Other PLT- related parameters (MPV, PDW, PCT) were correlated with the Hb and sTfR, but with no other red cell, anemic and disease activity parameter. Multivariate analysis revealed a linear relationship between PLT number and RDW, ferritin, sTfR index and CRP and inverse correlation between PLT and Hb.
Τotal and annexin (+) MDMPs were statistically elevated and annexin (-) total and PDMPs reduced in IBD patients compared to HC. Annexin (+) / (-) ratio in all types of MPs were significantly increased in IBD patients compared to HC. Clinically active IBD patients demonstrated higher levels of annexin (+) total MPs, total MPs and total, annexin (+) and (-) PDMPs compared to inactive patients and higher levels in the majority of the counted MPs compared to HC. The annexin (-) PDMPs were the most statistically significant increased MPs on the comparison between active and inactive IBD patients. Total and annexin (-) PDMPs correlated to nearly all disease activity indices.
The results of this study indicate that the absolute PLT number correlates with iron deficiency and disease activity indices. Control of the inflammation and iron deficiency regulation can lead to reversal of thrombocytosis in IBD patients. On the other hand, the majority of circulating MPs and their subtypes are significantly elevated in active IBD patients compared to HC. Annexin (-) PDMPs revealed the greater significance between active and non-active IBD patients. The annexin (+) / (-) ratio of all cell MPs subtypes has been proven the most consistent differentiating index between IBD patients and HC. Consequently, MPs and in particular PDMPs are likely to be key players in the pathogenesis and clinical manifestations of IBD.
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