Hereditary platelet disorders Flashcards
What are the important components of platelets?
Platelet membrane glycoproteins
Platelet granules
Phospholipid surface
What are the common and uncommon clinical features of platelets disorders?
Common: Spontaneous skin purpura Mucous membrane bleeding Protracted bleeding after trauma/surgery Menorrhagia/PPH Uncommon: ICH GI Retinal GU
Above what level is bleeding considered abnormal?
When platelet count is above 30 x10^9 bleeding is considered unusual
What are some specific platelet investigations?
Platelet function analyser (PFA)
Bleeding time
Platelet aggregation
Flow cytometry
What is a PFA?
Simple rapid in vitro bleeding time, measures high shear haemostasis
Membrane is coated with collage to simulate the vessel
What is the platelet aggregation test?
An agonist is added and platelet clumps are measured with light passing through
How is flow cytometry used to diagnose platelet disorders?
Whole blood is used and complexes/platelets and microparticles are measured
specific glycoproteins are observed
How are platelet disorders classified? Which is more common?
Disorders of production
Disorders of function
Functional disorders are more common
What are the disorders of production?
All very rare and usually a part of wider problem Amegakaryocytic thrombocytopenia TAR syndrome MYH9 related disease all rare
What are the disorders of function?
Glycoprotein abnormalities
Storage pool abnormalities
Release defects
What is TAR?
Thrombocytopenia with absent radii - autosomal recessive, usually improves with age
What is CAMT?
Congenital amegakaryocytic thrombocytopenia
mutations in TPO receptor lead to aplasia
What is MYH9?
Gene in the non muscle heavy chain IIa gene
Mutations here lead to macrothrombocytopenia
Why are congenital platelet dysfunctions an issue?
There is no release from granules - gray syndrome no alpha
storage pool disease no delta
What are the 2 main plasma membrane defects?
Bernard Soulier
Glanzmanns thrombasthenia
What is Bernard Soulier?
Absence of Glp1b
It is autosomal recessive
What is the phenotype of Bernard Soulier syndrome?
Often has seven bleeding
Moderate thrombocytopenia with giant platelets
Which test is abnormal?
There is absent or reduced agglutination with ristocetin
There is absence of GP1b/IX by flow cytometry
What is Glanzmann’s thromasthenia?
Absence of Glp2b3a complex
This is normally exposed with platelets are activated and is important for binding fibrinogen or vwf
What is the phenotype?
There are 2 different types
t1: Complete deficiency - absent alpha granule fibrinogen
t2: Partial deficiency
What is Scott syndrome?
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
What is platelet type vwd?
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
What are the 3 dense granule storage pool disorders, briefly describe.
- idiopathic - reduced ADP
- Hermansky-Pudlak sydrome - oculocutaneous albinism
- Wiskott-Aldrich syndrome - X linked thrombocytopaenia
What are the alpha granules storage pool deficiencies?
Grey syndrome - absence of granules
Quebec platelet defect - abnormal aggregation of platelets with adrenaline
What are the secretary defects seen?
COX deficiency
Thromboxane synthetase deficiency
Signal transduction defects - abnormal thromboxane response
