Platelets in Health and disease

Question 1

Platelet development and release

Answer 1

Myeloid lineage, from primitive megakaryoblasts to megakaryocytes.
Polynuclear (18-32 nuclei)
Make 4000 platelets each, located near capillaries (BM sinusoids)

Question 2

What factors are associated with thrombocyopoiesis

Answer 2

stem cell factor; LIF; IL-6, IL-11; Thrombopoietin (to c-mpl receptor)

Question 3

Platelet homeostasis:

Number required,life span, how they are consumed

Answer 3

Kept at constant level
Life span: 7-10 days, drugs that block see lowered in 10 days?
Consumed: senscence or haemostasis

Question 4

Platelet ultrastructure

Answer 4

Contain:

• Electron dense granules(Ca2+, Mg2+, ATP)
• Alpha granules: Coagulation factors (fibrinogen, factor 5, Von Willebrands factor), platelet derived growth factor, TGF-B, heparin antagonist.

Question 5

Main platelet function

Answer 5

Primary haemostasis- formation of platelet plug at site of vessel injury

-Vasoconstriction; platelets activate and aggregate;

also note platelet membrane invloved in Coagulation cascade

Question 6

Platelet activation

at rest endothelium secretes NO and PGI2 to avoid platelet adhesion

Answer 6

Von Willebrand factor binds to exposed collagen ad adhere to wall through GP1B-V-IX
Then platelet integrin IIb3 binds other platelets through other proteins i.e fibrinogen. Causes release of granules

Once there is a monolayer, TA2, ADP cause further aggregation

Question 7

Thromboxane
Prostacyclin
Aspirin

Answer 7

Thromboxane: decrease in platelet cAMP- increase
Prostacyclin: increase platelet cAMP, inhibits release of granule
Aspirin: Binds irreversibly to cyclo oxeganse, decrease in TA2

Question 8

Platelet receptors to know also

Answer 8

P2Y12, clopidogrel binds
GP1B-V-IX, Von Willebrands factor
AlphaIIb Beta3, links platelets and activates, granule release (thromboxane)

Question 9

Run through again

Answer 9

Quiescence: PGI2/prostacyclin and NO, no platelets activation
Activation: Collagen exposed, TA2 and ADp bring in more platelets
Growth: PLC, PLK, PI3K support sustained activation, aIIbB3 integrin binds fibrinogen and supports aggregation

Question 10

Causes of:
reduced production
Increased destruction
Increased production

Answer 10

D. production: Viral, drugs, bone marrow failiure
I destruction: immune thrombocytopenia ITP (note some decreased production), DIC, AI, hyperslpeenism
I production: myeloproliferative neoplasms, iif bleeding corrective mechanism

Question 11

ITP treatment

note antibodies bind to and macrophages artack (predominantly in spleen) platelets

Answer 11

Prednisone, immune suppression?

Splenectomy, can use TPO-mimetics

Question 12

reduced platelet function

Answer 12

Aspirin, uraemia, hereditary defects (myelodysplasia?)