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Lecture:34
Platelets: structure and Functions
Dr Shamshad
Objectives:
1. Describe the structure of platelets
2. Describe the process of thrombopoiesis
3. Discuss the functions of platelets
4. List common disorders of platelets.
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 /mm3
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
● Elimination:from the circulation mainly by the tissue
macrophage/RE system.
Thrombopoiesis
Structure of platelet:
1
2
3
4
1:Peripheral zone
1:Glycocalyx :Outermost coat
Contain mucopolysaccharides & Mg2+ 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.
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.
I:Complex open canalicular system: Made of Phospholipids
Surface connected canalicular system.
Invagination of plasma membrane
Functions:
➔ secretion of platelet granules
➔ Uptake of plasma proteins
➔ Increased surface area during
➔ platelet activation
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 (TXA2) synthesis
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
4:Organelle zone: Metabolic activity zone
Internal platelet components
Mitochondria
Golgi apparatus and ER
Granules: 3 types
1) Alpha granules
2) Dense Bodies
3) Lysosomal granules
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.
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.
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.
Lysosomes
Contain enzymes called hydrolases
Neutral proteases ,Acid hydrolases and Antibacterial enzymes
Function:
Act to digest materials brought into the platelets by endocytosis
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.
Structure and Function
of platelet:
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.
Functions of platelets
1. Adhesion
2. Activation by changing its shape
3. Secretion or release of granules
4. 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.
Platelets disorders
Quantitative Qualitative
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
Thrombocytopenia: Causes
Decreased
production
1
Bone Marrow damage, aplasia, drugs,
malignancy,Toxins Hepatitis
Congenital defects2
Rubella , Autosomal dominant,
Fanconi anemia
In effective production3
Vit B12 and Folic acid
deficiency
Immune6 Drugs induced, SLE, AIDS, ITP
Abnormal distribution4
Splenomegaly,Liver diseases,
Myelofibrosis
5 Non immune :DIC,Hemolytic -uremic
syndrome,TTP,HELP syndrome
Increased
destruction
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
Thrombocytosis
Causes:
➢ Myeloproliferation
➢ Essential thrombocytopenia
➢ Polycythemia vera
➢ CML
➢ Myeloid metaplasia
➢ Secondary /reactive thrombocytosis
➢ Systemic inflammation
➢ Malignancy
➢ Hemorrhage
➢ Postsplenectomy

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Platelet structure and function (1)

  • 1. Lecture:34 Platelets: structure and Functions Dr Shamshad
  • 2. Objectives: 1. Describe the structure of platelets 2. Describe the process of thrombopoiesis 3. Discuss the functions of platelets 4. 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 /mm3
  • 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.
  • 8. 1:Peripheral zone 1:Glycocalyx :Outermost coat Contain mucopolysaccharides & Mg2+ 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 Surface 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 (TXA2) 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 1) Alpha granules 2) Dense Bodies 3) 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 Contain 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.
  • 21. 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.
  • 22. Functions of platelets 1. Adhesion 2. Activation by changing its shape 3. Secretion or release of granules 4. 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.
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  • 28. 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
  • 29. Thrombocytopenia: Causes Decreased production 1 Bone Marrow damage, aplasia, drugs, malignancy,Toxins Hepatitis Congenital defects2 Rubella , Autosomal dominant, Fanconi anemia In effective production3 Vit B12 and Folic acid deficiency
  • 30. Immune6 Drugs induced, SLE, AIDS, ITP Abnormal distribution4 Splenomegaly,Liver diseases, Myelofibrosis 5 Non immune :DIC,Hemolytic -uremic syndrome,TTP,HELP syndrome Increased destruction
  • 31. 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
  • 32. Thrombocytosis Causes: ➢ Myeloproliferation ➢ Essential thrombocytopenia ➢ Polycythemia vera ➢ CML ➢ Myeloid metaplasia ➢ Secondary /reactive thrombocytosis ➢ Systemic inflammation ➢ Malignancy ➢ Hemorrhage ➢ Postsplenectomy