Platelet structure and function (1)

Lecture on platelets for medical and paramedical students

1. Lecture:34 Platelets: structure and Functions Dr Shamshad

2. Objectives: Describe the structure of platelets Describe the process of thrombopoiesis Discuss the functions of platelets List common disorders of platelets.

3. Platelets/ Thrombocytes : Mediators of hemostasis Disc like of 1-4 μm diameter. Nucleus-free granulated cells. Life span: 10 days,Half life 8-12 days Synthesis: Site: Bone marrow from megakaryocytes, Megakaryocytes fragment/bud off into minute platelets either in the bone marrow or soon after entering the blood, as they pass through capillaries. Normal count: 150,000 and 300,000 /mm 3

4. Control of synthesis : Interleukins (IL3) and TPO(Thrombopoietin)/ GM-CSF(granulocyte-macrophage-colony stimulating factor) Mechanism of action: IL: stimulate the development of PHSC (progenitor hematopoietic stem cells) to committed stem cells TPO : stimulate differentiation of committed stem cells into megakaryocytes

5. Elimination: from the circulation mainly by the tissue macrophage/RE system.

6. Thrombopoiesis

7. Structure of platelet: 1 2 3 4

8. 1: Peripheral zone 1:Glycocalyx : Outermost coat Contain mucopolysaccharides & Mg 2+ dependent ATPase, plasma proteins(IgG,IgM), fibrinogen,Factor V & VIII. Function:Adsorbs plasma proteins,glycoproteins & glycolipids 2: Platelet membrane : Lipid bilayer of glycoproteins & proteoglycans Function : Maintain cytoplasmic integrity. Glycoprotein (Ia,Ib,IIa,III..) : Essential for platelets adhesion & aggregation.

9. 2 :Membrane system Function: Serves as a pathway for release of intracellular materials. Platelets factor III plays important role in activating clotting mechanism Provide increased surface areas for absorption and storage of coagulation factors from the plasma. Specific receptors: for agonists such as ADP,TxA2,Adrenaline Thrombin.

10. I :Complex open canalicular system : Made of Phospholipids S urface connected canalicular system. Invagination of plasma membrane Functions: secretion of platelet granules Uptake of plasma proteins Increased surface area during platelet activation

11. II:Dense tubular system Site for sequestration of Calcium ions & localization of enzymes required for prostaglandin synthesis Functions: Triggers platelets contraction thus causing activation of platelets Calcium also play important role as Coagulation factor(factor IV) Site of Thromboxane (TXA 2 ) synthesis

12. 3:Structural zone Network of protein filaments Submembranous cytoskeleton Contractile proteins (Actin G&F, Myosin) 3 types of microfilaments I: Microtubules : Beneath the cell membrane Maintains discoid shape of the resting platelet II: Microfilaments associated with thrombosthenin which contain Actin G & F and Myosin Meditate contractile events III: Intermediate filaments

13. 4: Organelle zone: Metabolic activity zone Internal platelet components Mitochondria Golgi apparatus and ER Granules: 3 types Alpha granules Dense Bodies Lysosomal granules

14. Function: Mitochondria and enzyme systems forms ATP & ADP ER and Golgi apparatus synthesize various enzymes , store large quantities of calcium ions. Enzyme systems synthesizes: Prostaglandins:Role in vascular & other local tissue reactions Fibrin-stabilizing factor:Important role in blood coagulation Growth factor:Multiplication & growth of vascular endothelial cells, vascular smooth muscle cells & fibroblasts that helps in repair damaged vascular walls.

15. Alpha granules Most abundant 20-200/platelet . Membrane bound oval granules Platelet Factor 4(PF4)/ anti heparin : Neutralizes heparin Coagulation Factor V & Factor VIII : Related to antigen growth factor Beta - Thromboglobulin (Beta-TG) : Promotes smooth muscle growth thus help vessel repair Platelet derived growth factor(PDGF) : Promotes smooth muscle growth & involved in atherosclerosis & lipid metabolism Thrombospondin : Promotes platelets to platelet interaction In von Willebrand disease platelets lack factor VIII related antigen .

16. Dense bodies/Delta granules: 2-10/platelet:species specific ADP : Promotes aggregation of platelets by attracting more platelets ATP : Provides energy GTP and GDP : In Signal transduction Serotonin and Histamine : Vasoconstriction. Calcium ions : Primary and secondary messenger and Regulation of platelet activation and aggregation.

17. Lysosomes C ontain enzymes called hydrolases Neutral proteases ,Acid hydrolases and Antibacterial enzymes Function: Act to digest materials brought into the platelets by endocytosis

18. Von Willebrand factor(vWF) Large multimeric protein Synthesis : In the endothelial cells and megakaryocytes Found in :Subendotheilium plasam, alpha granules of platelets, Function -Mediate platelet adhesion to the collagen in the subendothelium -Bind factor VIII to protect it from proteolysis in the plasma.

19. Structure and Function of platelet:

20. Functions of platelets On the non activated platelet cell membrane surface coat of glycoproteins repulses adherence to normal endothelium of the vessels. Injury or disruption of the continuity of the vessels causes adherence to injured areas of the vessel wall, especially to injured endothelial cells and even more so to any exposed collagen from deep within the vessel wall. It contains large amounts of phospholipids that activate multiple stages in the blood­ clotting.

21. Functions of platelets Adhesion Activation by changing its shape Secretion or release of granules Aggregation. In circulation: Checks the blood vessel continuity by endothelial lining for gaps. Formation of primary hemostatic plug. Provides surface for coagulation factors to make secondary hemostatic plug. Helps in healing injured tissue.

22. Platelets disorders Quantitative Qualitative

23. Thrombocytopenia Platelet count Symptoms 50-100,000 Prolonged bleeding following trauma <50,000 Easy bruising ,purpura following minor trauma <20,000 Spontaneous bleeding, petechiae , internal or intracranial bleeding

24. Thrombocytopenia: Causes Decreased production 1 Bone Marrow damage, aplasia, drugs, malignancy,Toxins Hepatitis Congenital defects 2 Rubella , Autosomal dominant, Fanconi anemia In effective production 3 Vit B12 and Folic acid deficiency

25. Immune 6 Drugs induced, SLE, AIDS, ITP Abnormal distribution 4 Splenomegaly ,Liver diseases, Myelofibrosis 5 Non immune :DIC,Hemolytic -uremic syndrome,TTP,HELP syndrome Increased destruction

26. Inhereted disorder of platelet functioin Defect in platelet -vessel wall interaction : vonWillebrand disease Bernard-Soulier synderome Defect in platelet- platelet interaction: Congenital afirbinogenimia Glanxmann throbasthenia Defects in platelets granules ,secretion & signal transduction: Abnormalities of granules, signal transduction defects, Defects of platelet procoagulant functions: Defect in structural/ cytoskeletal components Others

27. Thrombocytosis Causes: Myeloproliferation Essential thrombocytopenia Polycythemia vera CML Myeloid metaplasia Secondary /reactive thrombocytosis Systemic inflammation Malignancy Hemorrhage Postsplenectomy