3 PLATLETS BY DR QAZI

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Platelets ( Thrombocytes ) Throm = clot BY DR QAZI IMTIAZ RASOOL

OBJECTIVES: 

OBJECTIVES 1.Describe the structure and functions 2.Describe the thrombopoiesis 3. Discuss the role of platelet in coagulation

PLATELETS=small plates: 

PLATELETS=small plates cytoplasmic fragments ,colorless, smallest of formed elements staining shows an blue- outer region and purple granular center Circular/oval, biconcave discs ,Non-nucleated, extensive invagination of cell membrane 2-5  m in diameter. Vol. 5.8 μ mm 3 2. in clusters , 250.000/ mm 3 life span is 7-10 days. 3.60-75% circulate , 30% and graveyard( spleen). 4. (~ 4,000 Platelets / Megakaryocyte ) Produce 200,000,000,000/day

The cytoplasm: 

The cytoplasm contains ;- Contractile proteins : actin and myosin ( thromboasthenia ) which contract if activated skeleton of microtubules , peripheral microvesicles Glycogen granules utilized for energy production Lysosomes containing lysosomal granules hydrolytic enzymes. ER ,Golgi apparatus which store large quantities of Ca ++ ions. Mitochondria are capable of forming ATP and ADP.

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7. Enzyme system that synthesizes PG local, TxA2 , leukotrienes hormones those cause vascular and local tissue reactions. 8. 2 types of granules 1.Dense granules which contain ATP, ADP, serotonin and Ca ++ ,5 -HT,PL,TG,cholesterol 2.Specific ( α ) granules : contain fibrinogen, heparin antagonist, (PF 3+4) platelet derived growth factor (PDGF), 9.Lot of receptors Surface contains membrane bound receptors (GP Ib / IIb / IIIa ) mediate surface adhesion reactions, aggregation reactions interact with coagulation proteins

Genesis : 

Stem cell Developmental pathway Hemocytoblast Megakaryoblast Promegakaryocyte Megakaryocyte Platelets Genesis HEMOCYTOBLASTS (stem cells)is regulated by hormone thrombopoietin , -TPO synthesis is static and binds to the surface of megakaryocytes and platelets -Produced by liver -Negatively feedbck to regulates free TPO Megakaryocytes : gaint cell 35-160 μ m in the bone marrow Larger fragments shrinkand become platelets pseudopods provide amoeboid movement & phagocytosis PHSC+CSC+ STAG E 1 STAG E 2 STAG E 3

Role of Platelets: 

Role of Platelets

Role of Platelets: 

Role of Platelets Damage to endothelium allows platelets to bind to exposed collagen von Willebrand factor increases bond by binding to both collagen & platelets Platelets stick to collagen & release ADP , serotonin , & thromboxane A 2 platelet release reaction

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VON WILLEBRAND DISESE

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Platelet Aggregation 1.. During activation, a receptor for fibrinogen becomes exposed on the platelet membrane. 2. Activated platelets release: Fibrinogen ADP/ATP vWF Seratonin Factor V Ca 2 + Factor VIII Platelet derived growth factor (PDGF) ~ promotes healing Platelet factor IV – prevents formation of active thrombin inhibitor from heparin and anti-thrombin III. a -granules dense core granules

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Activated platelets induces large - morphological changes -are essential because several of the cascade reactions take place on the surface of these platelet( membrane lipids rearrange) phosphatidyl serine which is usually on the inner membrane of the platelet , flips out to outer membrane where binding prothrombin . Activated platelets unactivated fully activated phosphatidyl serine

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Platelet Plug Formation Note;-Platelets not involved in clotting are kept inactive by NO and Prostacyclin scereted by endothelial cells

Functions: 

Functions Coagulation Anticoagulation Thrombolysis Inflammation Wound Healing secrete clotting factors, growth factors for endothelial repair, and vasoconstrictors in broken vessels 2. Form temporary platelet plugs 3. Dissolve old blood clots 4. Phagocytize bacteria,viruses , carbon particles 5. Attract WBCs to sites of inflammation

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Thrombocytosis : It is the increase in the number of platelets, this occurs physiologically in pregnancy and after hemorrhage. Thrombocytopenia : It is the decrease in the number of platelets, this occurs after aplastic anemia, pernicious anemia, and during menstruation. Thromboathenia : It is the decrease in the functions of platelets. How low is too low? 150,000 - 50,000: no symptoms 50,000 - 20,000: first symptoms 20,000-10,000: potentially life-threatening <10,000: risk for spontaneous intracranial hemorrhage

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Physical Signs Bleeding Easy bruising Petechiae Bruising with mild trauma Bruising without trauma Petechiae - a Ecchymoses - b Hematoma - c Epistaxis - nosebleed History of recurrence Gingival bleeding Hematuria , hemoptysis , hematemesis Relatively uncommon presenting features Menorrhagia

LAB TESTS IN DISORDERS OF PRIMARY HEMOSTASIS: 

LAB TESTS IN DISORDERS OF PRIMARY HEMOSTASIS Platlet count PT PTT Bleeding time Vascular disorder Normal Normal Normal Normal or abnormal Thrombocytopenia Decreased Normal Normal Abnormal Platlet Dysfunction Usually Normal Normal Normal Normal or Abnormal

PLATELET DISORDERS: 

PLATELET DISORDERS Quantitative Thrombocytopenia Thrombocytosis Qualitative Morphologic abnormalities Macrothrombocytes Microthrombocytes Hypogranular or agranular platelets

THROMBOCYTOPENIA: 

THROMBOCYTOPENIA result from Abnormal platelet distribution Deficient platelet production Increased platelet destruction Platelet dysfunction

Platelet satellitism: 

Platelet satellitism - Platelet ribbon platelets to white cells Bernard Soulier ( Giant Platelets)

Thrombocytosis Too many platelets: 

Thrombocytosis Too many platelets Primary - i.e. myeloproliferative syndromes Diseases include Essential Thrombocythemia , Polycythemia Vera These platelets are both hyper- and hypo-functional May lead to thrombosis and/or bleeding Secondary - i.e. reactive Causes include inflammation, infection, bleeding, iron deficiency Treat the underlying cause. Usually does not lead to thrombosis

Differential Diagonosis: 

Differential Diagonosis 1. Pseudothrombocytopenia 2 . ↓ Production- suggested by: other cytopenias normal sized/small platelets suggest a reduced bone marrow response to need 3. ↑ Destruction- suggested by: microangiopathic blood picture (fragmented RBCs, high LDH) Large platelets on smear Associated autoimmune disease

Aspirin inhibits the cyclooxygenase (COX) in the eicosanoid pathways that generate PG and TXA2 : 

Aspirin inhibits the cyclooxygenase ( COX) in the eicosanoid pathways that generate PG and TXA2 1. TXA2 , produced by the platelets,for aggregation, aspirin reduces both aggregation and coagulation. 2. Importantly, low doses of aspirin cause a steady-state ↓ in platelet COX but not endothelial-cell COX, 3. so the formation of prostacyclin —the PG that opposes aggregation—is not impaired.

FIBRINOGEN BLOCKERS: 

FIBRINOGEN BLOCKERS contrast to aspirin,, the oral anticoagulants, and heparin, which prevent clotting,5 TH drug— plasminogen activators— dissolves a clot after it is formed. 2. Use of such drugs is termed thrombolytic therapy 3 . I.V. of recombinant t-PA or a proteolytic drug called streptokinase within 3-6 hours after M.I . significantly reduces myocardial damage and mortality. 4. Recombinant t-PA has also been effective in reducing brain damage following a stroke caused by blood-vessel occlusion

“NO ALCOHOLIC WORTH HIS SALT HAS NORMAL PLATELETS” : 

“NO ALCOHOLIC WORTH HIS SALT HAS NORMAL PLATELETS”