Platelets

Dr. Niranjan Murthy H L Asst Prof of Physiology ESIC-MC & PGIMSR, Bangalore

 Small, granulated bodies that aggregate at the site of injury Non-nucleated Half-life of 8-12 days Count- 1.5 to 4 lakhs/mm of blood Synthesis- from megakaryoblasts in marrow

Thrombopoiesis
Pluripotent stem cell Committed stem cell
GM-CSF Thrombopoietin

Megakaryoblast

Megakaryocyte
platelets

Megakaryocytes
Giant cells- 35-160m in diameter Multinucleated Forms 1000 platelets Platelets formed by pinching off of cytoplasm Fragmentation is thought to occur in pulmonary capillaries

Thrombopoietin
Produced in kidney and liver
Cause megakaryocyte maturation Bound to platelets

Platelet morphology
Non-nucleated, Colorless disc, 2-4 m in diameter Cell membrane: 20 nm in thickness Microtubules with invaginated cell membrane form an intricate canalicular system Phospholipids important in initiation of coagulation Receptors for ADP, vWF, collagen, fibrinogen, thrombin

Glycocalyx: -net negative charges due to sialic acid -Minimizes adhesion - rich in agonist receptors Surface connected canalicular system: -Internal reservoir of membrane -Storage reservoir of membrane glycoproteins -Route of granule release on activation Cytoskeleton: -Includes membrane skeleton, actin & intermediate filaments and microtubules -Change of shape -Extrusion of granules

Structure of platelet

 Cytoplasm: contains actin, myosin, glycogen, lysosomes, golgi apparatus, endoplasmic reticulum, few mitochondria and granules Dense granules- contain non-proteins like ATP, ADP, Serotonin, Ca2+ Alpha granules- contain proteins like PDGF, vWF, factor V, fibrinogen, PF4 ADP- plays a role in platelet aggregation vWF- platelet adhesion & regulate factor VIII levels

Functions of platelets
1. 2. 3. 4. 5. Hemostasis Coagulation of blood Clot retraction Phagocytosis Storage and transport- serotonin & histamine

 Platelet adhesivenessto exposed collagen Adhesive ligands: vWF, collagen, Fibrinogen

gpIb/V/IX interact with subendothelial vWF

Deceleration of platelets

Collagen and 2 interact

 Platelet activation- by binding of vWF & collagen and thrombin releases granules. Platelet secretion- occurs in association with activation; ADP, vWF, Fibrinogen & Ca2+ Platelet aggregation- by ADP, Ca2+, thrombin, fibrinogen & vWF

Platelet activators
1. vWF: multimeric glycoprotein; act via gp Ib 2. Collagen: activation via gp IV interaction and adhesion via 2 3. Thrombin: act via PAR (protease activated receptors) 4. ADP: act via purinergic receptors; present in dense granules; Clopidogrel inhibits ADP associated aggregation

5. Epinephrine: acts via 2 receptors and TXA2 ; stimulates secretion and aggregation 6. Thromboxane A2: Arachidonic acid derivative via cyclo-oxygenase pathway; vasoconstrictor; Aspirin

Inhibitors of Platelet activation

1. Generation of negative regulating molecules a. platelets- cAMP b. Endothelium- PGI2, NO, Heparin 2. Endothelial barrier 3. Generation of ecto-ADPase by endothelial cells which neutralize ADP 4. Tendency of blood flow to wash away thrombin 5. Brief half-life of TXA2 (30sec)

Thrombocytopenia: Bone marrow depression Hypersplenism Viral infections Idiopathic Thrombocytosis: Splenectomy Epinephrine administration

Purpura
Def: Small punctate bleeding below skin and mucosa caused due to capillary defects &/or platelet defects Types: i) Non-thrombocytopenic purpura ii) Idiopathic thrombocytopenic purpura iii) Thrombasthenia

Petechiae

Tests for bleeding disorders

1. Platelet count 2. Bleeding time i) Duke method 1-5mins ii) Ivy method 5-11mins 3. Capillary fragility test <10 petechiae 4. Platelet aggregation test 5. Platelet adhesiveness test 6. Clot retraction time- begins within 30secs,50% in 1hr, 100% within 18-24hrs

Hemostasis
Injury to vessel Constriction of injured vessel- vasospasm Platelet adhesion Platelet activation and aggregation Temporary platelet plug formation Activation of clotting factors Fibrin network True clot

Clot retraction: Due to activation of acto-myosin complex Reduces to 40% of size in 5-30 mins Minimizes size of clot Brings the cut ends of vessel nearer

 Cycloxygenase inhibitors- Aspirin Purine receptor inhibitors- Clopidogrel Role in prevention of coronary thrombosis