Platelets and Platelet Dysfunction: Disorders and Immune Responses

Outcomes of the Session

On completion of this session you should be able to:

• Describe a number of disorders that affect platelet numbers
  and or function
• Recognise the role of the immune system in the development
  of thrombocytopenia
• Describe drug induced thrombocytopenia

Platelet Disorders

• Skin or mucosal haemorrhage
• Need to be differentiated from vascular defects
  Can be hereditary or acquired
  Patient may or may not have a normal/abnormal platelet count:

Platelet enumeration
Platelet aggregation studies

Platelet Function Agonists

Agonist
Effect
ADP
P2Y receptor activation & Ca2+ release
Thrombin
Activates PAR1 receptors and causes activation
Epinephrine
Binds to a adrenergic receptors causing
aggregation.
Collagen
Activates GPIa and GPVI causing adhesion and
degranulation
Arachidonic acid
Produced thromboxane A2 by cyclooxygenase in
platelets causing Ca2+ release

Bernard-Soulier Syndrome

• Autosomal recessive disorder
• Incidence 1 per 1,000,000
  Large circulating platelets +/ - thrombocytopenia
• Defective binding of vWF as abnormalities in GPIb
• Bleeding can be severe
• Failure of aggregation with ristocetin

Glanzmann's Thrombasthenia

Autosomal recessive
Incidence 1 per 1,000,000
CD41 (GPIIb) and CD61 (GPIlla) decreased/absent
Platelets fail to aggregate via Fib, vWF
Typical bleeding pattern for primary disorder

CD41 PerCP/CD61 PE_001 Analysis

105
CD41 PerCP-Cy5-5-A
10
03
10
Q1
Q2
0
03
Q4
-303
0
10
104
10°
-689
CD61 PE-A
Reduced levels of both CD41
(PerCP-Cy5.5) and CD61 (PE-A)
(<5%).

CD41 PerCP/CD61 PE_001 Reduced Levels

CD41 PerCP/CD61 PE_001
105
4
10
3
10
Q1
Q2
-
-263
0
10~
10-
10°
CD61 PE-A
Reduced CD41 (PerCP-Cy5.5) and
CD61 (PE-A) (5-50%).

CD41 PerCP/CD61 PE_001 Near Normal Levels

CD41 PerCP/CD61 PE_001
100
CD41 PerCP-Cy5-5-A
104
ml
Q2
103
Q1
H
Q3
4
-243
0
10
10
10°
-597
CD61 PE-A
Near normal levels of CD41
(PerCP-Cy5.5) and CD61 (PE-A)
Mutreja D, Sharma RK, Purohit A, Aggarwal M, Saxena R. Evaluation of platelet surface glycoproteins in patients with Glanzmann thrombasthenia: Association with
bleeding symptoms. Indian J Med Res [serial online] 2017 [cited 2020 Dec 24]; 145:629-34. Available from: https://www.ijmr.org.in/text.asp?2017/145/5/629/215563
0
CD41 PerCP-Cy5-5-A
-727

Immune Thrombocytopenia Purpura

• CHRONIC
  Highest incidence in females aged 15-50
  Most common cause of thrombocytopenia without anaemia
  or neutropenia
  Autoimmune, usually IgG class targeting Gpllb-Illa
  Platelet count often 10-50x109/L
• ACUTE
  Most common in children
  75% occur post vaccination/infection
  Possibly chicken pox
  Infectious mononucleosis
  Most commonly caused by immune complex formation
  Spontaneous remission occurs in 5-10% of cases

Drug Induced Thrombocytopenia

Increased risk of developing spontaneous haemorrhages
Some associated with increased thrombosis risk

• underlying mechanisms include:
  reduced platelet production due to bone marrow suppression
  insufficient megakaryocyte expansion & maturation
  impaired release of platelets
• accelerated apoptosis
• accelerated clearance of platelets from the circulation
  Non-immune
  immune-mediated
  autoimmune mechanisms