Glanzmann thrombasthenia

1. Glanzmann Thrombasthenia
DR. VI JAY DIHORA

2. Normal Physiology-Production and Number
of Platelet
Platelets are normally made in the bone marrow from
progenitor cells known as megakaryocytes.
Normal platelet lifespan is 10 d. Every day, 1/10 of
platelet pool is replenished.
Normal platelet count is between 150,000 and
450,000/mm3

3. Platelet Production
Platelet production is regulated by thrombopoietin
(TPO).
Thrombopoietin binds to the surface of
megakaryocytes and platelets--
 only free TPO stimulates platelet production
 Therefore, platelet mass negatively regulates free TPO and
further platelet production

4. Platelet Plug Formation
Adhesion - Platelets stick to injured vessel wall.
Aggregation - Platelets stick to each other via
fibrinogen bridges.
Secretion - Platelets release granular contents and
potentiate clotting

5. STRUTURE
Mucopolysacch.
coat
Granules
Dense core
granules
Mucopolysacch. Coat: Glycoprotein content which are
important for interaction of platelets with each other or
aggregating agents.
-  Granules : express the adhesion molecule P-selectin
and CD63. these are transfereed to the membran after
synthesis
- Dense core : contain ADP and ATP, ionazed calcium
,Histamine and Serotonine

6. PLATELETS ADHESION
Adhesion of platelet to subendothelial collagen.
Dependent on the VW factor (Von Willebrand
part of Fact VIII). Also dependent on
glyoproteins.

8. Membrane Phospholipid

Arachidonic acid
 Cyclo-oxygenase
Thromboxane synthetase 
Thromboxane A2
Thromboxane A2: Potentiase aggregation
and vasoconstrictor.
Aggregation: Release ADP+thromboxane
A2 aggregation. This is followed by more
secration secondary aggregation.
platelet mass or plug.

9. Primary Hemostasis: Platelet adhesion
GPIb
EC
Sub Endo
glycoprotein Ib (GPIb) –
platelet receptor for VWF

10. Primary Hemostasis: Platelet
aggregation
EC EC
Fibrinogen
GPIIbIIIa
GPIIbIIIa – platelet receptor for
fibrinogen

11. Classification of platelet disorders
Quantitative disorders
Production
– Reduced
Infiltration (e.g. tumor)
Aplasia (e.g. chemicals)
Congenital (e.g. Wisskot aldrich syn)
– Ineffective
Megaloblastic anemia,
myelodysplasia,
Destruction
– Immune
Autoantibody e.g. ITP
Alloantibody
– HIT
– Consumption
DIC
TTP
Mechanical
Hemodilution
Qualitative disorders
• Inherited
– Bernard-Soulier
– Glanzmann’s
– Storage pool disease
(ChediakHigashi, WiscottAldrich, Gray
Platelet Syndrome)
• Acquired
– Drugs (e.g. ASA)
– Uremia, Post-bypass
– Primary marrow disorders; MDS,
Dysproteinemias

13. Glanzmann Thrombasthenia
Is inherited in an autosomal recessive manner.
The genes of both of these proteins are on
chromosome 17.
Different genetic mutations of either GP IIb or
IIIa genes result in a heterogeneity of
thrombasthenia phenotype.
Carrier detection in GT is important to control the
disease in family members.
Can be acquired as an autoimmune disorder

14. PATHOGENESIS
Platelet glycoprotein IIb/IIIa (GP IIb/IIIa)
complex is deficient or present but
dysfunctional.
Defect in the GP IIb/IIIa complex leads to
defective platelet aggregation and
subsequent bleeding.
Aggregation of PLTs occurs in response to
ristocetin, but not to other agonists
such as ADP, thrombin, collagen or
epinephrine.

15. Severity
Glanzmann Thrombasthenia has three categories of
severity, depending on the importance of the platelet
deficiency in Glycoprotein IIb/IIIa.
• Type 1 (Severe): A level less than 5% of
normal
• Type II (Less severe): A level between 5%
and 20% of normal
• Type III (Least severe): A variant of
Thrombasthenia with levels of more than
50% of normal, but with major abnormalities
in the way platelets aggregate

16. Symptoms
purpura
Menorrhagia
Mucosal bleeding
Brain hemorrhages
epistaxis
gingival bleeding
gastrointestinal bleeding
postpartum bleeding
increased bleeding post-operatively

17. DIAGNOSIS
Normal PLT count and morphology.
Greatly prolonged bleeding time.
Absence of PLT aggregation in response
to ADP,collagen,epinephrine or thrombin
(Platelet aggregation test)
Flow cytometry (CD 41,CD 61).
Studies of GP IIb/IIIa receptors on the PLT
membrane.

18. Aggregation of thrombocytes (platelets). Platelet rich human blood
plasma (left vial) is a turbid liquid. Upon addition of ADP, platelets
are activated and start to aggregate, forming white flakes (right vial)

19. Treatment
- Dental hygiene lessens gingival bleeding
- Avoidance of antiplatelet agents such as aspirin and other anti-inflammatory
drugs (NSAIDs) such as ibuprofen and naproxen, and
anticoagulants
- Iron or folate supplementation
- Antifibrinolytic drugs such as tranexamic acid or ε-aminocaproic
acid
- Desmopressin (DDAVP) does not normalize the bleeding time in
Glanzmann's thrombasthenia but anecdotally improves hemostasis
- Hormonal contraceptives to control excessive menstrual bleeding
- Platelet transfusions (only if bleeding is severe; risk of
platelet alloimmunization)
- Recombinant factor VIIa
- Hematopoietic stem cell transplantation (HSCT) for severe
recurrent hemorrhages