Lecture 8 - platelets

Question 1

What is Thrombocytopoiesis ?

What is the process from a megakaryblast to forming a platelet?

What is the most important mediator for this?

lifespan?

Answer 1

Thrombocytopoiesis -formation of platelets

1. Endomiotic synchronic nuclear replication - (Megakaryoblast –> megakaryocyte containing many nucleouses)
2. Cytoplasmic granulation (granules and membrane form, lots or rna made)
3. Pro-platelets travel into blood vessels and bud of and spilt into platelets (megakaryocytes sit in BM sinusoidal endothelial cells so can easily release platelets into blood)

Mediator = thrombopoeitin

lifespan 7-10 days

Question 2

Primary haemostasis

Answer 2

Process of forming a platelet plug at site of vessel injury

1. vascularconstriciton
2. platelets need to come to site, then need to become activated
3. when they are activated they adhere to vessel wall (cytoskeleton changes shape), and form a temporary loose platelet plug
4. activated platelets release factors to recruit more platelets and form a surface for coagulation cascade

Question 3

platelet structure

Answer 3

• glycoprotein - around outside, important for platelet reactions of adhesion and aggregation to form platelet plug
• granules - ca2+, ATP, coagulation factors, growth factors ect.

Question 4

Activation pathway 1 of primary haemostasis

Answer 4

• Endothelial damage exposes collagen
• Von willibrand factor binds to collagen
• VWB can bind to platelets via Glycoprotein receptor and pulls it in and platelet becomes activated
• activated platelet has integrin exposed, and this can bind other platelets via fibrinogen molecule
• Platelets release granules with other factors to attract other platelets

Question 5

Activation pathway 2 of primary haemostasis

Answer 5

This pathway is occurring at same time as other activation pathway

• platelet adheres to collagen
• this activated prostaglandin synthesis which activated Thromboxane A2 to be released
• ADP also released
• TaA2 - triggers release of more granules and initiates aggregation
• ADP and taA2 leads to activation of coagulation and recruitment of other platelets

Question 6

How does aspirin inhibit platelet aggregation and to what extent

Answer 6

Aspirin inhibits the cyclooxygenase enzyme which helps form TaA2 enzyme
-however does not completely stop aggregation as there are other pathways of activation

Question 7

How does 2b3a receptor inhibitor block platelet aggregation and to what extent

Answer 7

Blocks this receptor and has a very potent effect as platelets cannot stick together

Question 8

What does prostacyclin vs thromboxane a2 ?

Answer 8

• will increase platelet cAMP and inhibit release of granules
• Thromboxane a2 - will decrease platelet camp and result in granule release to go onto platelet aggregation and coagulation

Question 9

What molecules are responsible in quiescence when there is no damage to blood vessels?

Answer 9

-NO and PGI2 - released from endothelium and make sure that platelet activation is suppressed

Question 10

Decreases no. of platelets in blood (thrombocytopenia)

What are factors that can decrease production of platelets?

What factors can increase destruction of platelets

Answer 10

• viral infection
• drugs
• bone marrow failure e.g leukaemia, carcinoma ect.

immune thrombocytopenia
drugs
viral infection

Question 11

What can increase the production of platelets

Answer 11

Myeloprolferative neoplasms

Question 12

Immune Thrombocytopenia
cause
symptoms
treatment -

Answer 12

Get an autoimmune response where the body makes antibodies against our own platelets and they get destroyed, can also get reduced production if get antibodies binding to megakaryocyte in the bone marrow stoping the making platelets

Symptoms - nose bleeds, bruising, previously well and no new medications

Treatment - immune suppression, if this doesn’t work then can remove spleen
-also give thrombopoetin mimics to stimualte production of platelts