Haemostasis Lecture Part I Primary Haemostasis PDF

Haemostasis – Part I Primary Haemostasis Dr Caroline Kardeby Lecturer in Biosciences [email protected]  Aims and Objectives Aim Outline the processes involved in normal haemostasis Following this lecture you should be able to: 1. Explain the importance o...

Haemostasis – Part I Primary Haemostasis Dr Caroline Kardeby Lecturer in Biosciences [email protected]  Aims and Objectives Aim Outline the processes involved in normal haemostasis Following this lecture you should be able to: 1. Explain the importance of effective haemostasis 2. Describe the major components of haemostatic mechanisms 3. Describe the mechanisms of primary haemostasis  What is haemostasis? Haemostasis: blood (haem) stop/stand still (stasis) The 5 major components of the haemostatic system: 1. Blood vessels 2. Platelets 3. Coagulation factors 4. Coagulation inhibitors 5. Fibrinolysis The haemostasis is strictly controlled Thrombosis Bleeding Myocardial infarction Haemorrhage Stroke Legend: Blood drop Activated platelet  Primary and Secondary Haemostasis Primary haemostasis Secondary haemostasis 1. Platelets respond to the vessel wall 1. Activation of the intrinsic and injury extrinsic coagulation pathways 2. Platelets adhere to the vessel wall 2. Activation of the common pathway 3. A primary platelet plug is formed 3. Fibrin strand formation and strengthening of the platelet plug All phases are integrated and many occur simultaneously  Blood Vessels in Haemostasis The walls of arteries and veins consist of the intima, media and adventitia Intact endothelial cells of the intima are anti- thrombotic (e.g. prostacyclin and nitric oxide) Damage to the endothelium causes the underlying prothrombotic extracellular matrix to be exposed (collagen, elastin, fibronectin, actin) During injury, the vessel wall undergoes vasospasm, facilitating vasoconstriction and slowing of the blood flow  Von Willebrand Factor (vWF) vWF is a cysteine-rich glycoprotein made up of many large multimers – highly prothrombotic Endothelial cells store vWf when in their Weibel- Palade bodies (large multimers) vWF it is secreted into the plasma when endothelial cells are activated (e.g. thrombin, physical vascular damage, inflammation, etc.) Mediates platelet adhesion to the subendothelium Large multimers can be digested into smaller units and monomeric vWF by ADAMTS-13 VWF can also be stored in platelet α-granules  Platelets Thrombopoiesis – Megakaryocytes in the bone marrow (and lungs) Normal platelet count: 150 and 400 x 109/L 10 billion platelets are produced daily (1011) Spend 6-9 days in circulation before cleared in the spleen 2-3 µm diameter on blood film and appear purple Platelets require activation to facilitate Source: Thomas. 2019 Platelets 4th Edition haemostasis  Platelets Platelets contain a number of storage granules which are released upon activation 1. α-granules Contains hundreds of different proteins E.g. vWf, clotting factors, fibrinogen, PDGF 2. Dense granules (aka delta bodies) Serotonin, Ca2+, ATP, ADP 3. Lysosomes Acid hydrolase enzymes Platelets synthesise Thromboxane A2 when activated Leads vasoconstriction and further activation  Primary Haemostasis: Part I vWf in the plasma Platelets at the edge Injury to the blood Vasoconstriction of anchors to exposed of the circulation are vessel the injured vessel collagen and blood captured and bind to flow unravels vWf GPIbα  Primary Haemostasis: Part II Platelets roll and Stable adhesion Activated Integrin Platelets undergo form additional occurs. αIIbβ3 binds to irreversible shape vWF-GPIb GPVI activates by fibrinogen change (platelet-platelet interactions collagen interactions) (Lamellipodia and filopodia)  Primary Haemostasis Primary haemostasis forms a temporary and weak platelet plug Unstable and needs strengthening Secondary Haemostasis  Summary Primary haemostasis initially involves vasoconstriction of the injured blood vessel. Platelets produced by megakaryocytes bind to the injured vessel via vWF and become activated by the subendothelial matrix (i.e. collagen-GPVI activation). Platelets contain a number of storage granules that they release upon activation which contribute to haemostasis and many other functions.