Qualitative Platelet Disorders Flashcards
Group of disorders affecting the structure or function of platelets
Qualitative Platelet Disorders
Patients with this disorder usually will have an adequate number of platelets but poor “quality” of clotting.
Qualitative Platelet Disorders
Qualitative Platelet Disorders
Vascular Intima/Plasma
● Damaged Endothelium
● Exposed Collagen
● VWF
Platelet Adhesion
Platelets
● GPIb Complex
● GPIa/IIa , GPV
Bernard-Soulier Syndrome other name
Giant platelet syndrome
Inherited disorder in which the GP Ib/IX/V complex is missing from the platelet surface or exhibits abnormal function.
Bernard-Soulier Syndrome (Giant platelet syndrome)
Inability to bind to VWF accounts for the inability of platelets to adhere to exposed sub endothelium.
Bernard-Soulier Syndrome (Giant platelet syndrome)
Similar manifestation to Von Willebrand Disease.
Bernard-Soulier Syndrome (Giant platelet syndrome)
REMINDER ‼️‼️‼️‼️
BS Syndrome cannot be corrected by addition of normal plasma or Cryoprecipitate.
The GPIb-Complex receptor.
● Consist of the
GPIbα , GPIbβ , GPIX , GPV
GPIbα , GPIbβ , GPIX , GPV.
● These proteins are present in a ratio
2:2:2:1
The most frequent forms of BSS involves defects in
GPIbα
Antibody to GP Ib/V can cause
pseudo-BSS
Bernard-Soulier Syndrome (Giant platelet syndrome)
Variants
1.Normal surface expression of GPIb complex but impaired functionality.
2. Mutations that affect binding domains that cause poor binding.
3.Antibody to GP Ib/V can cause pseudo-BSS, causes a non- functional complex
Bernard-Soulier Syndrome
Laboratory features
Giant Platelets
appear larger compared to normal platelets on PBS due to a proposed tendency to spread into thin films on contact with glass.
Bernard-Soulier Syndrome
BSS
platelets are unusually large and fewer in number than usual (_________________)
Macrothrombocytopenia
Bernard-Soulier Syndrome
Laboratory features : Platelet aggregometry.
Macrothrombocytopenia and prolonged bleeding time.
Bernard-Soulier Syndrome (Giant platelet syndrome)
Treatment: treatment of choice
Platelet transfusion (must be leukoreduced to
reduce alloimmunization.)
Bernard-Soulier Syndrome (Giant platelet syndrome
REMINDER‼️‼️‼️‼️‼️
Antiplatelet therapy should be avoided
Bernard-Soulier Syndrome (Giant platelet syndrome)
Treatment: useful for mucosal bleeding.
Antifibrinolytic therapy
PLATELET AGGREGATION
PLASMA OR PLATELET GRANULES
● Ionized calcium
● Fibrinogen
PLATELET AGGREGATION
PLATELETS
● GPIIb/IIIa receptors
● ATP/ ADP
Glanzmann Thrombasthenia seen most frequently in populations______________________
high degree of consanguinity.
Deficiency or abnormality of the GPIIb/IIIa complex.
Glanzmann Thrombasthenia
GPIIb/IIIa complex complex is responsible for binding __________________
fibrinogen
vWF
fibronectin
other adhesive ligands.
Binding of GPIIb/IIIa complex to ____________ mediates the success of platelet aggregation.
Fibrinogen
0-5% of normal GPIIb/IIIa complex
Glanzmann Thrombasthenia
TYPE 1
10-20% of normal GPIIb/IIIa
Glanzmann Thrombasthenia
TYPE 2
Type of GT that is Less affected by abnormal clot
retraction
Glanzmann Thrombasthenia
TYPE 2
Glanzmann Thrombasthenia
Laboratory features:
● Normal platelet count and morphology.
● Abnormal aggregation. Prolonged bleeding time.
Glanzmann Thrombasthenia
Clinical Manifestations: Bleeding of all types;
Epistaxis , Ecchymosis, Hemarthrosis,
Subcutaneous hematoma, Menorrhagia and
GI / UT hemorrhage.
Glanzmann Thrombasthenia
Treatment: highly recommended
Platelet transfusion (leukoreduced)
Glanzmann Thrombasthenia
Treatment:
REMINDER‼️‼️‼️‼️‼️
Anticoagulant and antiplatelet agents should be avoided.
Glanzmann Thrombasthenia
Treatment: for menorrhagia
Hormonal therapy (Norethindrone acetate)
Release of Remaining Platelet granules to facilitate secondary wave of aggregation.
Platelet secretion
The most common of the hereditary defects are:
storage pool
release reaction defects
Disorders of Platelet Secretion
Platelet count is usually
Normal
Disorders of Platelet Secretion
Manifestations
● mucocutaneous hemorrhage
● hematuria
● epistaxis
● spontaneous bleeding.
Platelet Storage Pool Diseases
Dense Granule Deficiency
- Hermansky-Pudlak syndrome
- Chediak- Higashi syndrome
- Wiskott-ALdrich syndrome
- Thrombocytopenia-absent
radius (TAR) syndrome
Platelet Storage Pool Diseases
Alpha Granule Deficiency
Gray platelet syndrome
Hermansky- Pudlak Syndrome mutation
Autosomal recessive
Chromosome 19
Tyrosinase positive oculocutaneous albinism
Hermansky- Pudlak Syndrome
Lysosomal dysfunctions
Hermansky- Pudlak Syndrome
Ceroid-like depositions in the RES
Hermansky- Pudlak Syndrome
Profound platelet dense granule deficiency.
Hermansky- Pudlak Syndrome
Hermansky- Pudlak Syndrome
‼️‼️‼️REMINDER‼️‼️‼️‼️
● Severe bleeding is RARE.
● But lethal hemorrhages have been reported.
● Accounts for 16% of deaths in affected patients.
Hermansky- Pudlak Syndrome
For extensive surgery and prolonged bleeding
administer Packed Red cells and platelets.
Hermansky- Pudlak Syndrome hallmark
Swiss-cheese platelets
consists of marked dilation and tortuosity of the surface-connecting tubular system
Swiss-cheese platelets
Chediak-Higashi Syndrome mutation
● Autosomal recessive disorder
● Mutations in Chromosome 1
Partial oculocutaneous albinism
Chediak-Higashi Syndrome
Frequent pyogenic bacterial infections (severe immunology defects).
Chediak-Higashi Syndrome
Giant lysosomal granules
Chediak-Higashi Syndrome
Platelet dense granule deficiency (leads to hemorrhage).
Chediak-Higashi Syndrome
Chediak-Higashi Syndrome
● Lymphocytic proliferation in the
liver, spleen and marrow.
Macrophage accumulation in tissues.
Chediak-Higashi Syndrome
Severe pancytopenia
Chediak-Higashi Syndrome
Usually results to death in early age
Chediak-Higashi Syndrome
Chediak-Higashi Syndrome
REMINDER‼️‼️
Bleeding episodes may vary from mild to moderate but worsens as the platelet count decreases.
Wiskott-Aldrich syndrome disease
X-linked disease
Wiskott-Aldrich syndrome
● Affects primarily
Male
Wiskott-Aldrich syndrome mutation
Mutations in the WAS gene on the short arm
of the X chromosome. (Xp11.23
Wiskott-Aldrich syndrome
WAS gene encodes for the
WASp gene
WASp gene that
is found exclusively in
hematopoietic cells, including lymphocytes.
WASp gene plays a crucial role
actin cytoskeleton remodeling.
Wiskott-Aldrich syndrome
Wiskott-Aldrich syndrome
Classic form of WAS
Eczema-thrombocytopenia immunodeficiency syndrome
Wiskott-Aldrich syndrome
Eczema-thrombocytopenia immunodeficiency syndrome characterized by
● Immune dysfunction (susceptibility to bacterial, viral and fungal infections).
● Microthrombocytopenia
● Severe Eczema.
● Bleeding episodes (mod-severe).
Wiskott-Aldrich syndrome
Platelet characteristics in WAS
- Decreased platelet dense granules.
- Platelets are small- Microthrombocytes
Wiskott-Aldrich syndrome
Other instances where small platelets are hallmark
features:
TORCH Infections
TORCH (toxoplasma, other agents rubella virus
cytomegalovirus herpesvirus) infections
Wiskott-Aldrich syndrome
Thrombocytopenia in WAS is due to:
- Ineffective thrombocytopoiesis.
- Increased platelet sequestration.
- Increased platelet destruction.
Wiskott-Aldrich syndrome
Treatment:
- Splenectomy
- Platelet transfusions
- Bone marrow transplantations
Congenital absence of radial bones
Thrombocytopenia with absent radii syndrome (TAR)
Cardiac and skeletal abnormalities
Thrombocytopenia with absent
radii syndrome (TAR)
Thrombocytopenia
● Structural defects of platelet dense granules.
Thrombocytopenia with absent
radii syndrome (TAR)
Gray platelet syndrome
● mutation in the
NBEAL2 gene (614169) on chromosome 3p21.
Characterized by the specific absence of morphologically recognizable alpha granules.
Gray platelet syndrome
Virtually absent Alpha granules in platelets
Gray platelet syndrome
But they do contain vacuoles and small alpha granules precursors.
Gray Platelet Syndrome
Gray platelet syndrome
● Platelet alpha granules are the
Storage site for proteins
Gray platelet syndrome
These proteins are either:
a. stored in megakaryocytes.
b. Present in the plasma and taken up by the platelets.
How many alpha granules are present in platelet
50-80 alpha granules
Primarily responsible for the granular appearance of platelets
50-80 alpha granules
Gray platelet syndrome
Manifestations:
Lifelong mild bleeding tendencies.
● Moderate thrombocytopenia
● Fibrosis of the marrow
● Large platelets with gray appearance on a wright-stained
smear
Virtually absent Alpha granules in platelets.
Gray platelet syndrome
But they do contain vacuoles and small alpha granules precursors.
Gray platelet syndrome
Gray platelet syndrome
Membranes and precursors have
P-selectin and GPIIB/IIIA expressions.
Gray platelet syndrome
Increased levels of
Platelet factor 4 and B-thromboglobulin in the
plasma.
Platelet factor 4 and B-thromboglobulin in the
plasma are usually stored in
alpha granules of platelets.
Gray platelet syndrome
Treatment & Management
- Platelet transfusions
- Cryoprecipitates
- Desmopressin acetate
a rare disorder in which both alpha and dense granules are deficient. Inherited in an autosomal dominant manner
Alpha-Dense storage pool deficiency-
autosomal dominant bleeding disorder, this results to a deficiency in multimerin. Many alpha granules are degraded by proteases.
Quebec Platelet disorder
multimeric protein that is stored complexed with
factor V in the alpha granules of platelets.
Multimerin
