Hemostasis

Platelets or thrombocytes Fragments of megakaryocytes, a large cell in the bone marrow- 60 micrometer in diameter One megakaryocyte gives about 1000 platelets 1-4 micrometer diameter 150,000 – 300,000 per cmm of blood No nuclei Actin & myosin molecules for contraction Special contractile protein Thrombosthenin Thrombopoietin→↑ Megakaryocytes & Platelets production in the bone marrow

Megakaryocyte

Megakaryocyte

Platelets or thrombocytes Residual ER and Golgi complex synthesize enzymes and store Ca++ Fibrin stabilizing factor (FSF) production Mitochondria form ADP & ATP Prostaglandin, Thromboxane A2 -local hormones produced ADP and Thromboxane A2 activate Platelets Growth factor for growth & multiplication of Endothelial cells Vascular smooth muscle cells Fibroblasts

Platelets or thrombocytes Glycocalyx on the cell membrane Repulsive for normal endothelium Adhesive to damaged endothelial cells and collagen fibers Cell membrane contains Phospholipid involved in blood coagulation Half life = 8 - 12 days Removed from circulation by macrophages mostly in spleen and liver

Hemostasis Prevention of blood loss Four processes Vascular constriction Formation of platelets plug Formation of blood clot Fibrous organization of clot

Vascular constriction Local myogenic spasm due to direct trauma to smooth muscles of the vessels Local vasoconstrictors From the traumatized tissue and platelets e.g. thromboxane A2 and Serotinin Nervous reflexes Due to pain & other sensory signals from the traumatized tissue Vascular constriction is very strong when the vessel is severely damaged Most effective in smaller vessels Can significantly reduce blood loss for 20-30 minutes

Formation of platelets plug Contact with damaged vascular cells or Collagen Swelling Form spiked processes, Irregular shape Many pseudopodia Release of sticky substances by contraction Stick to each other, Collagen, von Willebrand factor etc.

Formation of platelets plug Contraction and release of active substances Secretion of ADP & thromboxane A2 (TXA2) Both activate more and more platelets A positive feedback cycle is initiated that forms a platelet plug and seals the hole within 1 minute

Platelet Plug formation

Formation of platelets plug The platelet plug must be limited in size and extent Plug should be limited to the damaged area only Prevention of blocking the whole vessel Prostacyclin, produced by endothelial cells is a strong inhibitor of platelet plug formation It stops the +ve feed back cycle of plug formation

Formation of platelets plug Initially loose plug but successfully blocks small openings in the capillary wall Later on plug is invaded by fibrin meshwork in the clotting process for permanent repair Important in day to day small damages in the capillary walls Process may actually result in formation of additional endothelial cell membrane due to fusion of platelets and endothelial cells thereby closing the small holes in endothelial cells . Failure of plug formation in thrombocytopenia causes Purpura

Thrombocytopenic purpura Very low platelets count Tendency to bleed more Many small purplish blotches in the skin Count may be as low as 50,000/cmm Count below 10,000/cmm is lethal Idiopathetic thrombocytopenia Antibodies formed against platelets Treatment Platelets transfusion from a fresh blood Fresh whole blood

Blood coagulation Conversion of fluid state of blood into semisolid state by activation and interaction of pro-coagulants in the blood Set in motion with formation of the platelet plug Many steps involving > 30 plasma factors Proteins (made in the liver), Vitamin K necessary for the synthesis of the liver proteins Ca++

Formation of blood clot Starts earlier (15-20 seconds) if trauma is severe and late (1-2 minutes) if trauma is trivial The activating factors are Traumatized vessel wall or surrounding tissue Platelets Plasma proteins Clotting completes in 3-6 minutes Clot retracts after 20 minutes

Blood coagulation Last three phases of critical importance Prothrombin activator is formed Which converts prothrombin  thrombin Which converts fibrinogen  fibrin Fibrin threads form a meshwork which traps blood cells and seals the hole until permanent repair

RBCs Trapped in Clot

Fibrous organization of clot Within a few hours clot is invaded by fibroblasts which form connective tissue all through the clot. The process is promoted by growth factor secreted by platelets. Complete fibrous organization of the clot within about 1-2 weeks.

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