Platelet Changes in Cases of Iron Overload(IO)

Study Overview
=================
Brief Summary
-----------------
Iron demand: The average daily demand to fit the cell biological metabolism is balanced between intake and lost which about 1-2 mg.

Detailed Description
-----------------
Iron demand: The average daily demand to fit the cell biological metabolism is balanced between intake and lost which about 1-2 mg. One unit of packed red blood cells contains approximately 200-250 mg of iron.Thus, patients who arereceiving an average of 2 to 4 units of blood monthly willhave an iron intake of 5000to 10 000 mg of iron per year. Iron overload(IO) A condition in which the body takes up and stores more iron than it needs from any cause. Iron overload constitutes a major problem in patients receivingregular blood transfusion. Patients with β-thalassemia,sickle cell anemia, and congenital and refractory anemiasonchronic transfusion programs accumulate iron in variousbody organs. Untreated iron overload will eventually lead todamage of the liver, endocrine organs, and most seriously theheart(1).Acquired platelet function defect might be one of thecomplications of iron overload. This could occur indirectlythrough the effect of iron load on the liver and other organsor might occur due to effect of iron load on platelet functiondirectly. Dleteriouscomlications contributed by chemical reactive deregulated iron may affect cellular homeostasis systematically lead to tissue and organ damage when this toxicity occurred in blood cells ,alteration of peripheral hematological profile concerning erythrocyte,leucocyte and Platelet. On the other hand, acquired platelet function defects are classified broadly into defects that are intrinsic or extrinsic to the platelets. Acquired platelets defect are due to medications, medical conditions, underlying hematologic diseases, and are more frequent than inherited causes of platelets defects.(2) Platelet function is also influenced by changes in membranefluidity that has an important role in the expressionof platelet receptors and in modulating the activity ofproteins like phospholipase C or proteinkinase C(3). Ithas been shown (4) that changes in membrane fluidityare associated to altered aggregation/agglutination functionof freshly prepared platelets. The platelet aggregationresponse is modified by monovalent cations (whichalter fibrinogen binding) and monovalent anions thatenhance hydroxyl radicals production of platelets inducing platelet activation (5) Reactive oxygen species(ROS) are involved in integrin aIIbb3 activation(6,7). Moreover, bursts of ROS are generated in platelets exposed to thrombin (8). We herein report the case of a patient with acquired plateletfunction defect associated with iron overload as a consequenceof chronic blood transfusion. Therefore, we emphasizethe necessity of further studies to confirm directcorrelation between iron overload as a causative agent andplatelets dysfunction. And we recommend screening forplatelet function in patients receiving chronic blood transfusionaiming at possible prevention of any life-threateningbleeding. One of the most commonly used laboratorymarkers to early characterize platelet functionis the mean platelet volume (MPV). Increasedplatelet volume mayindicate its greater content ingranules, showing a platelet activation also betteraggregation and more reactive than the ordinarysize one. Limited study and the inconsistent resultare available regarding the platelet function studyin IO complicated condition. Higher MPV wasidentified in heterozygous beta-thalassemiapatientswith no correlation with cardiovascular-relatedrisks(9). However, but in line with this study, adefect in platelet aggregation indicated by ahyporeactivityof platelet after induction withADP, ristocetin, and collagen was showed in majorthalassemia children patients with an iron overloadcondition(10). The decreased MPV showed in a highdose iron treatment group of this study impliesthe eventual toxic effect of iron accumulation toplatelet function. Still, specific platelet functionmarker analysis i.e. P-selectin, fibrinogen receptor,and the CD40 ligand is imperative to be exploredto understand the fundamental notion of how IOaffects the platelet functionality. Platelets were affected by iron overloadindicated by differential platelet indices i.e.platelet count, mean platelet volume, plateletcrit,and platelet distribution width (figure1). Asignificant effect of iron treatment was showedin mean platelet volume among groups, applyingANOVA, [F (2, 17) = 4.263, P = 0.031]. Post hoccomparisons using the Tukey's test indicated thatthe mean platelet volume for the high dose irontreatment (2.5+0.5) was significantly lower (P =0.02) than the low dose iron treatment group (3.7+0.7). However, the mean platelet volume of thecontrolgroup (3.1 +0.9) did not significantly differfrom the low and the high iron treatment groups. low mean platelet volume following acquired platelet function attenuation was evidenced by iron overload directing that platelet was also affected blood component. In study ,theexpiremental mice model was established by a law and high dose of iron dextran intraperitoneally. High dose iron treatment showed asignificantly lower mean platelet volume (MPV) The result showed that the IO decrease the MPV.

Official Title
-----------------
Platelet Changes in Cases of Iron Overload(IO)

Conditions
-----------------
Platelet Changes in Cases of Iron Overload

Intervention / Treatment
-----------------
* Diagnostic Test: blood test


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients around age of 6 to 18 years Patients with thalassemia disease Exclusion Criteria: - Patients less than 6 years and more than 18 years. Patients with sever inflammatory disease. Patients with any malignant disease. Patients take steroid or bone marrow suppression drugs. Patients with aplastic anemia or pancytopenia.

Ages Eligible for Study
-----------------
Minimum Age: 1 Month
Maximum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| platelet count in iiron overload<br> | Diagnostic Test: blood test<br>* complete blood count and platelet function<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Changes in Cases of Iron Overload(IO) | Platelet Changes in Cases of Iron Overload(IO) | 1 year |