Lecture 7 - Platelets; Development, Morphology and Function

Question 1

Stages of Platelet Production - Megakaryopoiesis

Answer 1

Starts as megakaryoblast
Then promegakaryocyte
Then megakaryocyte
Lastly platelet

Question 2

Megakaryocyte

Answer 2

Platelet forming
Typical megakaryocyte is seen with platelets budding off the periphery
Granular cytoplasm fragments, resulting in the formation of platelets

Question 3

Morphology of Platelets

Answer 3

Mature platelets:
Size - 1-4 microns
Shape - discoid
Appearance - palely basophilic with several punctate basophilic granules
Lifespan of platelets in circulation - ~9.5 days

Question 4

Ultrastructure of Platelets

Answer 4

Platelets contain different types of granules that can be morphologically identified using transmission electron microscopy
These granules contained 'preformed' substances
Alpha granules
- fibrinogen
- FV
- vWf
- PF4
Dense (bodies) granules
- ADP
- Ca2+
Also
- mitochondria
- canalicular system
- mictrotubules

Question 5

Biochemistry of Platelet

Answer 5

Platelets are capable of generating substances which influence platelet function
E.g. the Arachidonic acid pathway which produces Thromboxane A2 which promotes aggregation
A key enzyme in this pathway is cyclooxygenase that converts arachidonic acid to prostaglandin G2 and PGH2
Cyclooxygenase is inhibited by a wide range of drugs that will consequentially impair platelet function

Question 6

Functions of Platelets

Answer 6

Role in 'primary haemostasis'
Forms a haemostatic plug
Acts to stem blood loss
Several stages
- adhesion 
- release reaction
- aggregation

Question 7

Platelet Plug - Adhesion

Answer 7

First stage of plug formation
Injury to blood vessel exposes collagen
Platelets bind to collagen-bound vWf in the sub-endothelium via GP Ib-V-IX
Collagen binding induces platelet activation
Causes changes in
- platelet biochemistry
- platelet shape (discoid to spherical)

Question 8

Platelet Plug - Release Reaction

Answer 8

Release of granule contents to the surrounding environment
- dense bodies
- alpha granules
Creates a local prothrombotic/procoagulant environment
Activated platelets also have increased production of Thromboxane A2

Question 9

Platelet Plug - Recruitment and Aggregation

Answer 9

Release of prothrombotic/procoagulant substances promotes recruitment of additional platelets
Further aggregation
- platelets bridged via vWf and fibrinogen
-> formation of primary haemostatic plug

Question 10

What are the problems with using automated analysis when measuring platelets?

Answer 10

Large platelets may not be distinguished from small RBC

Large platelets/micro aggregates of platelets not recognised by analysers

Question 11

Disorders of Platelets

Answer 11

Disorders of platelet number:
- thrombocytosis (increased)
- thrombocytopenia (decreased)
Disorders of platelet function:
- thrombopathy

Question 12

Primary vs Secondary Thrombocytosis

Answer 12

Primary
- ~20% of cases
- due to clonal expansion
- ‘haematopoietic neoplasm’ (myeloproliferative disorder)
- a.k.a. essential thrombocythemia (overproduction of every cell)
Secondary
- ~80% of cases
- due to cytokine stimulated production by bone marrow
- many causes

Question 13

Pathological Mechanisms of Thrombocytopenia

Answer 13

Decreased production
- via bone marrow destruction
Sequestration
- via splenomegaly
Increased destruction
- antibody mediated destruction
- via immune mediated thrombocytopenia

Question 14

Clinical Consequences of Thrombocytopenia

Answer 14

<100 x 10^9/L - may haemorrhage esp. with trauma, surgery

<20 x 10^9/L - commonly haemorrhage

Question 15

Bernard-Soulier Syndrome

Answer 15

Autosomal recessive disorder
Deficiency platelet surface receptor GP Ib defect (part of GP-Ib-V-IX)
Leads to decreased platelet-vWF binding 
Then leads to ineffective aggregation
Giant platelets evident