Qualitative Platelet Disorders

Question 1

Group of disorders affecting the structure or function of platelets

Answer 1

Qualitative Platelet Disorders

Question 2

Patients with this disorder usually will have an adequate number of platelets but poor “quality” of clotting.

Answer 2

Qualitative Platelet Disorders

Question 3

Qualitative Platelet Disorders

Vascular Intima/Plasma

Answer 3

● Damaged Endothelium
● Exposed Collagen
● VWF

Question 4

Platelet Adhesion
Platelets

Answer 4

● GPIb Complex
● GPIa/IIa , GPV

Question 5

Bernard-Soulier Syndrome other name

Answer 5

Giant platelet syndrome

Question 6

Inherited disorder in which the GP Ib/IX/V complex is missing from the platelet surface or exhibits abnormal function.

Answer 6

Bernard-Soulier Syndrome (Giant platelet syndrome)

Question 7

Inability to bind to VWF accounts for the inability of platelets to adhere to exposed sub endothelium.

Answer 7

Bernard-Soulier Syndrome (Giant platelet syndrome)

Question 8

Similar manifestation to Von Willebrand Disease.

Answer 8

Bernard-Soulier Syndrome (Giant platelet syndrome)

Question 9

REMINDER ‼️‼️‼️‼️

BS Syndrome cannot be corrected by addition of normal plasma or Cryoprecipitate.

Question 10

The GPIb-Complex receptor.
● Consist of the

Answer 10

GPIbα , GPIbβ , GPIX , GPV

Question 11

GPIbα , GPIbβ , GPIX , GPV.
● These proteins are present in a ratio

Answer 11

2:2:2:1

Question 12

The most frequent forms of BSS involves defects in

Answer 12

GPIbα

Question 13

Antibody to GP Ib/V can cause

Answer 13

pseudo-BSS

Question 14

Bernard-Soulier Syndrome (Giant platelet syndrome)
Variants

Answer 14

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

Question 15

Bernard-Soulier Syndrome
Laboratory features

Answer 15

Giant Platelets

Question 16

appear larger compared to normal platelets on PBS due to a proposed tendency to spread into thin films on contact with glass.

Answer 16

Bernard-Soulier Syndrome

Question 17

BSS
platelets are unusually large and fewer in number than usual (_________________)

Answer 17

Macrothrombocytopenia

Question 18

Bernard-Soulier Syndrome
Laboratory features : Platelet aggregometry.

Answer 18

Macrothrombocytopenia and prolonged bleeding time.

Question 19

Bernard-Soulier Syndrome (Giant platelet syndrome)
Treatment: treatment of choice

Answer 19

Platelet transfusion (must be leukoreduced to
reduce alloimmunization.)

Question 20

Bernard-Soulier Syndrome (Giant platelet syndrome

REMINDER‼️‼️‼️‼️‼️

Antiplatelet therapy should be avoided

Question 21

Bernard-Soulier Syndrome (Giant platelet syndrome)
Treatment: useful for mucosal bleeding.

Answer 21

Antifibrinolytic therapy

Question 22

PLATELET AGGREGATION

PLASMA OR PLATELET GRANULES

Answer 22

● Ionized calcium
● Fibrinogen

Question 23

PLATELET AGGREGATION

PLATELETS

Answer 23

● GPIIb/IIIa receptors
● ATP/ ADP

Question 24

Glanzmann Thrombasthenia seen most frequently in populations______________________

Answer 24

high degree of consanguinity.

Question 25

Deficiency or abnormality of the GPIIb/IIIa complex.

Answer 25

Glanzmann Thrombasthenia

Question 26

GPIIb/IIIa complex complex is responsible for binding __________________

Answer 26

fibrinogen vWF fibronectin other adhesive ligands.

Question 27

Binding of GPIIb/IIIa complex to ____________ mediates the success of platelet aggregation.

Answer 27

Fibrinogen

Question 28

0-5% of normal GPIIb/IIIa complex

Answer 28

Glanzmann Thrombasthenia TYPE 1

Question 29

10-20% of normal GPIIb/IIIa

Answer 29

Glanzmann Thrombasthenia TYPE 2

Question 30

Type of GT that is Less affected by abnormal clot retraction

Answer 30

Glanzmann Thrombasthenia TYPE 2

Question 31

Glanzmann Thrombasthenia Laboratory features:

Answer 31

● Normal platelet count and morphology. ● Abnormal aggregation. Prolonged bleeding time.

Question 32

Glanzmann Thrombasthenia Clinical Manifestations: Bleeding of all types;

Answer 32

Epistaxis , Ecchymosis, Hemarthrosis, Subcutaneous hematoma, Menorrhagia and GI / UT hemorrhage.

Question 33

Glanzmann Thrombasthenia Treatment: highly recommended

Answer 33

Platelet transfusion (leukoreduced)

Question 34

Glanzmann Thrombasthenia Treatment: REMINDER‼️‼️‼️‼️‼️ Anticoagulant and antiplatelet agents should be avoided.

Question 35

Glanzmann Thrombasthenia Treatment: for menorrhagia

Answer 35

Hormonal therapy (Norethindrone acetate)

Question 36

Release of Remaining Platelet granules to facilitate secondary wave of aggregation.

Answer 36

Platelet secretion

Question 37

The most common of the hereditary defects are:

Answer 37

storage pool release reaction defects

Question 38

Disorders of Platelet Secretion Platelet count is usually

Answer 38

Normal

Question 39

Disorders of Platelet Secretion Manifestations

Answer 39

● mucocutaneous hemorrhage ● hematuria ● epistaxis ● spontaneous bleeding.

Question 40

Platelet Storage Pool Diseases Dense Granule Deficiency

Answer 40

1. Hermansky-Pudlak syndrome 2. Chediak- Higashi syndrome 3. Wiskott-ALdrich syndrome 4. Thrombocytopenia-absent radius (TAR) syndrome

Question 41

Platelet Storage Pool Diseases Alpha Granule Deficiency

Answer 41

Gray platelet syndrome

Question 42

Hermansky- Pudlak Syndrome mutation

Answer 42

Autosomal recessive Chromosome 19

Question 43

Tyrosinase positive oculocutaneous albinism

Answer 43

Hermansky- Pudlak Syndrome

Question 44

Lysosomal dysfunctions

Answer 44

Hermansky- Pudlak Syndrome

Question 45

Ceroid-like depositions in the RES

Answer 45

Hermansky- Pudlak Syndrome

Question 46

Profound platelet dense granule deficiency.

Answer 46

Hermansky- Pudlak Syndrome

Question 47

Hermansky- Pudlak Syndrome ‼️‼️‼️REMINDER‼️‼️‼️‼️ ● Severe bleeding is RARE. ● But lethal hemorrhages have been reported. ● Accounts for 16% of deaths in affected patients.

Question 48

Hermansky- Pudlak Syndrome For extensive surgery and prolonged bleeding

Answer 48

administer Packed Red cells and platelets.

Question 49

Hermansky- Pudlak Syndrome hallmark

Answer 49

Swiss-cheese platelets

Question 50

consists of marked dilation and tortuosity of the surface-connecting tubular system

Answer 50

Swiss-cheese platelets

Question 51

Chediak-Higashi Syndrome mutation

Answer 51

● Autosomal recessive disorder ● Mutations in Chromosome 1

Question 52

Partial oculocutaneous albinism

Answer 52

Chediak-Higashi Syndrome

Question 53

Frequent pyogenic bacterial infections (severe immunology defects).

Answer 53

Chediak-Higashi Syndrome

Question 54

Giant lysosomal granules

Answer 54

Chediak-Higashi Syndrome

Question 55

Platelet dense granule deficiency (leads to hemorrhage).

Answer 55

Chediak-Higashi Syndrome

Question 56

Chediak-Higashi Syndrome ● Lymphocytic proliferation in the

Answer 56

liver, spleen and marrow.

Question 57

Macrophage accumulation in tissues.

Answer 57

Chediak-Higashi Syndrome

Question 58

Severe pancytopenia

Answer 58

Chediak-Higashi Syndrome

Question 59

Usually results to death in early age

Answer 59

Chediak-Higashi Syndrome

Question 60

Chediak-Higashi Syndrome REMINDER‼️‼️ Bleeding episodes may vary from mild to moderate but worsens as the platelet count decreases.

Question 61

Wiskott-Aldrich syndrome disease

Answer 61

X-linked disease

Question 62

Wiskott-Aldrich syndrome ● Affects primarily

Answer 62

Male

Question 63

Wiskott-Aldrich syndrome mutation

Answer 63

Mutations in the WAS gene on the short arm of the X chromosome. (Xp11.23

Question 64

Wiskott-Aldrich syndrome WAS gene encodes for the

Answer 64

WASp gene

Question 65

WASp gene that is found exclusively in

Answer 65

hematopoietic cells, including lymphocytes.

Question 66

WASp gene plays a crucial role

Answer 66

actin cytoskeleton remodeling.

Question 67

Wiskott-Aldrich syndrome Wiskott-Aldrich syndrome Classic form of WAS

Answer 67

Eczema-thrombocytopenia immunodeficiency syndrome

Question 68

Wiskott-Aldrich syndrome Eczema-thrombocytopenia immunodeficiency syndrome characterized by

Answer 68

● Immune dysfunction (susceptibility to bacterial, viral and fungal infections). ● Microthrombocytopenia ● Severe Eczema. ● Bleeding episodes (mod-severe).

Question 69

Wiskott-Aldrich syndrome Platelet characteristics in WAS

Answer 69

1. Decreased platelet dense granules. 2. Platelets are small- Microthrombocytes

Question 70

Wiskott-Aldrich syndrome Other instances where small platelets are hallmark features:

Answer 70

TORCH Infections TORCH (toxoplasma, other agents rubella virus cytomegalovirus herpesvirus) infections

Question 71

Wiskott-Aldrich syndrome Thrombocytopenia in WAS is due to:

Answer 71

1. Ineffective thrombocytopoiesis. 2. Increased platelet sequestration. 3. Increased platelet destruction.

Question 72

Wiskott-Aldrich syndrome Treatment:

Answer 72

- Splenectomy - Platelet transfusions - Bone marrow transplantations

Question 73

Congenital absence of radial bones

Answer 73

Thrombocytopenia with absent radii syndrome (TAR)

Question 74

Cardiac and skeletal abnormalities

Answer 74

Thrombocytopenia with absent radii syndrome (TAR)

Question 75

Thrombocytopenia ● Structural defects of platelet dense granules.

Answer 75

Thrombocytopenia with absent radii syndrome (TAR)

Question 76

Gray platelet syndrome ● mutation in the

Answer 76

NBEAL2 gene (614169) on chromosome 3p21.

Question 77

Characterized by the specific absence of morphologically recognizable alpha granules.

Answer 77

Gray platelet syndrome

Question 78

Virtually absent Alpha granules in platelets

Answer 78

Gray platelet syndrome

Question 79

But they do contain vacuoles and small alpha granules precursors.

Answer 79

Gray Platelet Syndrome

Question 80

Gray platelet syndrome ● Platelet alpha granules are the

Answer 80

Storage site for proteins

Question 81

Gray platelet syndrome These proteins are either:

Answer 81

a. stored in megakaryocytes. b. Present in the plasma and taken up by the platelets.

Question 82

How many alpha granules are present in platelet

Answer 82

50-80 alpha granules

Question 83

Primarily responsible for the granular appearance of platelets

Answer 83

50-80 alpha granules

Question 84

Gray platelet syndrome Manifestations:

Answer 84

Lifelong mild bleeding tendencies. ● Moderate thrombocytopenia ● Fibrosis of the marrow ● Large platelets with gray appearance on a wright-stained smear

Question 85

Virtually absent Alpha granules in platelets.

Answer 85

Gray platelet syndrome

Question 86

But they do contain vacuoles and small alpha granules precursors.

Answer 86

Gray platelet syndrome

Question 87

Gray platelet syndrome Membranes and precursors have

Answer 87

P-selectin and GPIIB/IIIA expressions.

Question 88

Gray platelet syndrome Increased levels of

Answer 88

Platelet factor 4 and B-thromboglobulin in the plasma.

Question 89

Platelet factor 4 and B-thromboglobulin in the plasma are usually stored in

Answer 89

alpha granules of platelets.

Question 90

Gray platelet syndrome Treatment & Management

Answer 90

- Platelet transfusions - Cryoprecipitates - Desmopressin acetate

Question 91

a rare disorder in which both alpha and dense granules are deficient. Inherited in an autosomal dominant manner

Answer 91

Alpha-Dense storage pool deficiency-

Question 92

autosomal dominant bleeding disorder, this results to a deficiency in multimerin. Many alpha granules are degraded by proteases.

Answer 92

Quebec Platelet disorder

Question 93

multimeric protein that is stored complexed with factor V in the alpha granules of platelets.

Answer 93

Multimerin