Lecture 10: Platelets in health and disease Flashcards
What is the function of platelets?
- Angiogenesis
- Wound healing
- Inflammation
- Primary haemostasis
What are platelets derrived from?
Megakaryocytes
Write some notes on megakaryocytes:
- Located next to BM sinusoidal endothelial cells
- Filopedia extend into capillaries
- Each megakaryocytes -> 4000 platelets
- Develop multiple nuclei
Describe how platelets are formed from megakaryocytes? What are the essential factors?
- After DNA replication granules and membrane formed
- Platelets inside cytoplasm
Requires:
- Steel factor
- LIF
- IL6 & IL11
- THrombopoietin (TPO) (Lynch pin essential factor)
Whats the life span and consumption of platelets?
Life span: 7-10 days
Consumption: Senescence, Utilisation in heamostasis
Write some notes on the platelet ultrastructure:
(Things that contribute to platelet clotting)
- Submembranous filaments i.e actin (forms filopod structures (important)
2 types of granules (contain growth and clotting factors)
- Electron dense granules
- Specific Alpha granule
Whats the function of electron dense granules? what do they contain?
Key platelet reaction released and activates other platelets
Ca, Mg, ATP, ADP, serotonin
What are the function of platelet alpha granules and what do they contain?
Contain: Coagulation factors (Fibrinogen, factor V, VWF), Platelet derived growth factor, TGF beta, heparin neutralising factor, thrombospondin, etc)
Function:
- Contribute to surface coagulation reactions
- Growth factors
- Heparin reactions
What is primary heamostasis?
Primary heamostasis is the process of forming a platelet plug at the site of vessel injury
Describe an overview of primary heamostasis:
1) Initial phase of the process is vascular constriction
2) Platelets become activated and aggregate at the site of injury, forming a temporary, loose platelet plug.
Describe in more detail primary heamostasis:
1) Platelets in flowing blood - not activated
2) Vessel wall injury
3) This exposes collagen
4) Von willibrand factor binds exposed collagen
5) Activated platelets adhered to vessel wall
6) Activated platelets release factors to recruit more platelets and forma surface for coagulation cascade
7) Platelets cross link via fibrinogen-integrin
The process of platelet related clotting contains a lot of what?
Redundancy
Describe some platelet interactions in clotting:
- Exposed collagen is bound by VWF
- VWF binds factor five complex and thus platelets
- Activated platelets adhere to VWF via Integrins which are exposed following activation.
- Exposed integrins also bind other platelets via fibrinoin cross linking
- Activated platelets also release granules containing platelet agonists
What do healthy endothelial cells normally release?
Factors to stop platelet activation
Describe what happens following vessel wall injury:
Vessel wall injury, releases:
- Tissue factor -> Blood coagulation cascade -> Thrombin -> Fibrin = Contributes to stable heamostatic plug
- Collagen exposure -> Platelet adhesion and activation (releases granules and activates GPiib/iiia)
From granules: - Platelet phospholipid stimulates coagualtion cascade
- Serotonin promotes vasoconstriction
- Thromboxane stimualtes vasoconstriction AND the next step -> Platelet aggregation
= Primary haemostatic plug and together with fibrin = stable heamostatic plug
- Damaged vessel wall -> Vasoconstriction which aids primary heamostatic plug
