Hereditary platelet disorders

Question 1

What are the important components of platelets?

Answer 1

Platelet membrane glycoproteins
Platelet granules
Phospholipid surface

Question 2

What are the common and uncommon clinical features of platelets disorders?

Answer 2

Common:
Spontaneous skin purpura
Mucous membrane bleeding
Protracted bleeding after trauma/surgery
Menorrhagia/PPH
Uncommon:
ICH
GI 
Retinal 
GU

Question 3

Above what level is bleeding considered abnormal?

Answer 3

When platelet count is above 30 x10^9 bleeding is considered unusual

Question 4

What are some specific platelet investigations?

Answer 4

Platelet function analyser (PFA)
Bleeding time
Platelet aggregation
Flow cytometry

Question 5

What is a PFA?

Answer 5

Simple rapid in vitro bleeding time, measures high shear haemostasis
Membrane is coated with collage to simulate the vessel

Question 6

What is the platelet aggregation test?

Answer 6

An agonist is added and platelet clumps are measured with light passing through

Question 7

How is flow cytometry used to diagnose platelet disorders?

Answer 7

Whole blood is used and complexes/platelets and microparticles are measured
specific glycoproteins are observed

Question 8

How are platelet disorders classified? Which is more common?

Answer 8

Disorders of production
Disorders of function
Functional disorders are more common

Question 9

What are the disorders of production?

Answer 9

All very rare and usually a part of wider problem
Amegakaryocytic thrombocytopenia
TAR syndrome
MYH9 related disease
all rare

Question 10

What are the disorders of function?

Answer 10

Glycoprotein abnormalities
Storage pool abnormalities
Release defects

Question 11

What is TAR?

Answer 11

Thrombocytopenia with absent radii - autosomal recessive, usually improves with age

Question 12

What is CAMT?

Answer 12

Congenital amegakaryocytic thrombocytopenia

mutations in TPO receptor lead to aplasia

Question 13

What is MYH9?

Answer 13

Gene in the non muscle heavy chain IIa gene

Mutations here lead to macrothrombocytopenia

Question 14

Why are congenital platelet dysfunctions an issue?

Answer 14

There is no release from granules - gray syndrome no alpha

storage pool disease no delta

Question 15

What are the 2 main plasma membrane defects?

Answer 15

Bernard Soulier

Glanzmanns thrombasthenia

Question 16

What is Bernard Soulier?

Answer 16

Absence of Glp1b

It is autosomal recessive

Question 17

What is the phenotype of Bernard Soulier syndrome?

Answer 17

Often has seven bleeding

Moderate thrombocytopenia with giant platelets

Question 18

Which test is abnormal?

Answer 18

There is absent or reduced agglutination with ristocetin

There is absence of GP1b/IX by flow cytometry

Question 19

What is Glanzmann’s thromasthenia?

Answer 19

Absence of Glp2b3a complex

This is normally exposed with platelets are activated and is important for binding fibrinogen or vwf

Question 20

What is the phenotype?

Answer 20

There are 2 different types

t1: Complete deficiency - absent alpha granule fibrinogen
t2: Partial deficiency

Question 21

What is Scott syndrome?

Answer 21

Very rare defect of platelet procoagulant activity
Lack of FVa and Xa binding sites - PT complex does not form
Platelet adhesion, activation and aggregation is completely normal

Question 22

What is platelet type vwd?

Answer 22

Pseudo vwd
there is mutation in the vwf binding domain of GP1ba which leads to spontaneous binding of vwf
there is n increased risto-induced agglutination - RIPA

Question 23

What are the 3 dense granule storage pool disorders, briefly describe.

Answer 23

1. idiopathic - reduced ADP
2. Hermansky-Pudlak sydrome - oculocutaneous albinism
3. Wiskott-Aldrich syndrome - X linked thrombocytopaenia

Question 24

What are the alpha granules storage pool deficiencies?

Answer 24

Grey syndrome - absence of granules

Quebec platelet defect - abnormal aggregation of platelets with adrenaline

Question 25

What are the secretary defects seen?

Answer 25

COX deficiency
Thromboxane synthetase deficiency
Signal transduction defects - abnormal thromboxane response