The effect of Desferasirox in expression of Adhesion molecules in Neutrophils and Monocytes, in the Platelets Activacion and in the Atherothrombosis in Patients with Mielodisplastic Syndrome (MDS) and iron Overload.
Authors: Caparros Isabel , Garcia-Delgado Regina , Campos Arturo , Rosell Ana , de Llano Ma Paz Queipo , de la Torre Santiago , Ramirez Gemma , Entrena Laura , Conde Eulogio , Del Castillo Santiago 
Published: October 2019

Abstract 1346

Poster Board I-368

Introduction

The interaction of leukocytes, platelets and vascular endothelial plays a fundamental role in the development of the arteriosclerotic injuries. This initial interaction is caused by P-selectin. This P-selectin is expressed on the surface of activated platelets and its recipient, ligand 1 of the glycoprotein P-selectin (PSGL-1) of the monocytes and granulocytes. In this interaction the microparticles derived from platelets, leukocytes and endothelial cells play a role fundamentally too. Platelets microparticles are formed by a phenomenon of vesiculation of the activated platelets by agonists as the thrombin, the collagen, among others. They induce the adherence of monocytes and granulocytes to endothelial. Besides, they amplify all signs that will give rise to an increase of the activity of adhesion molecules which will culminate in the expression of the tissue factor and its transformation into a procoagulant surface. As we know, the iron contributes to oxidative changes in tissues through the Fenton's reaction, which generates free radicals that would affect the activation of platelets through the reduction of types derived from the nitric acid.

Objective

To evaluate the effect of desferasirox in the activation of platelets and the development of atherothrombotic factors in patients with MDS and iron overload secondary to transfusions.

Patients and methods

16 patients with MDS and iron overload secondary to transfusion, as well as 15 healthy controls were included. Chelation treatment was administered with 20 mg / kg / a day of desferasirox to 8 patients, 30 mg / kg / a day to 4 patients, 10 mg / kg / a day to 3 of them (2 for gastrointestinal toxicity and 1 for renal toxicity) and one withdrew the treatment due to ocular toxicity. They all received treatment at least one month. They were studied at the beginning of the treatment with desferasirox and after the treatment (ferritin 1000-1200), biomarkers of platelets activation (expression of anexin-V and P-selectin), the expression of adhesion molecules in monocytes and granulocytes (VCAM-1, ICAM-1, E-selectin, PSGL-1 and b1-integrin) and the percentage of interactions monocytes-platelets.

Results

The patients with MDS and iron overload presented basal values of platelets activation and of expression of adhesion molecules above the healthy controls. The patients treated with desferasirox that obtained a decrease in their ferritin figures (10/16) presented statistically significant reductions of the scoreboards of platelets activation with the consistent improvement of the membrane damage in the vascular endothelial.

Conclusions

It seems that a suitable chelating of the iron in the patients with MDS and iron overload reduces platelets activation and different parameters of activation in monocytes and granulocytes that would contribute to the tissue damage in the vascular endothelial. Other additional studies will be necessary to correlate these changes with the long-term morbidity, the mortality and quality of life in this population of patients.

Disclosures

No relevant conflicts of interest to declare.