Disorders of Primary Haemostasis

Question 1

What is the source of platelets?

Answer 1

Megakaryocyte

Question 2

What are the characteristics of platelets?

Answer 2

1. platelet count → 1.5 - 4x10^(11)/L
2. New platelets are larger and have a higher density than old platelets
3. Circulation life span is 7-12 days
4. Platelet survival is determine by peripheral platelet count of radiaoactively labelled platelets
5. Removal of platelets is mainly by spleen > liver > BM = lymph nodes

Question 3

What do the alpha granules of the platelet contain?

Answer 3

Coagulation proteins
1. Clotting factor V
2. Protein S
3. Plasminogen activatior inhibitor (PAI)
4. Series of adhesive plasma proteins: fibrinogen, fibronectin, VWF, vitronectin and thrombospondin

Question 4

What do the delta granules of the platelet contain?

Answer 4

1. Serotonin
2. ADP
3. ATP
4. Phosphate
5. Calcium

Question 5

What is the difference between the shapes of a resting platelet vs an activated platelet?

Answer 5

Restign platelets are smooth and disc shaped, activated platelets have an irregular shape with many protruding pseudopodia

Question 6

What is the function of platelet receptors?

Answer 6

1. Hemostasis
2. Inflammation
3. Antimicrobial host defense
4. Tumor growth

Question 7

What are some examples of platelet receptors?

Answer 7

1. Integrins
2. Thrombin receptor
3. ADP receptor
4. Prostaglandin receptor
5. Lipid and chemokine receptor

Question 8

What are the receptors for collagen?

Answer 8

GPIa-IIa
GPIIb-IIIa
GPIV

Question 9

What are the receptors for vWF?

Answer 9

GPIb-IX-V
GPIIb-IIIa

Question 10

What are the receptors for fibrinogen?

Answer 10

GPIIb-IIIa

Question 11

What are the receptors for fibronectin?

Answer 11

GPIc-IIa
GPIIb-IIIa

Question 12

What are the receptors for thrombospondin?

Answer 12

Vitronectin receptor
GPIV

Question 13

What happens after a signal on GPIb-IX-V?

Answer 13

Signal on GPIb-IX
- Transferred to the cytoplasm
- Activates GPIIb-IIIa
- Fibrinogen binding

Question 14

What does fibrinogen depend on?

Answer 14

Calcium

Question 15

What is atherothrombosis?

Answer 15

Characterized by sudden atherosclerotic plaque disruption (rupture/erosion) leading to platelet activation and thrombus formation.

Plaque rupture -> embolization -> microvascular obstruction

Question 16

What is the link between thrombosis and inflammation?

Answer 16

Platelets modulate leukocyte adhesion at sites of inflammation by
1. Inducing a pro-inflammatory, pro-adhesive state in endothelial cells and leukocytes
2. Providing a bridge between the endothelium and leukocytes

Question 17

What is are examples of acquired causes of platelet function defects?

Answer 17

1. Uremia
2. Myeloproliferative disorder
3. Acute leukemia
4. Antiplatelet Ab
5. Liver disease

Question 18

What are examples of inherited causes of platelet function defects?

Answer 18

1. Platelet adhesion (BSS)
2. Agonist receptors
3. Signaling pathways
4. Secretion
5. Aggregation (Glanzmann)
6. Platelet-coagulant protein interaction

Question 19

What are the causes of thrombocytopenia? (EXAM)

Answer 19

1. Reduced production
2. Increased removal

Question 20

What are the disorders of platelet secretion?

Answer 20

1. Alpha granule storage disease (Gray Platelet Syndrome)
   - rare congenital bleeding disorder caused by a reduction/absence of the platelet a-granules in blood platelets or of the proteins contained in these granules
   - under microscopic analysis standard stain, no a-granules in platelets
2. Hermansky Pudlak syndrome
   - dense granule deficiency in platelets
   - decreased aggregation and secretion with multiple agonists
   - defective pigmentation (albinism)

Question 21

What is the treatment for Hermansky Pudlak syndrome?

Answer 21

• no cure, treatment for chronic hemorrhages only
• therapy with vit E and antidiretic Demopressin
• lifelong UV protection
• avoid anticoagulants like aspirin

Question 22

What are the different quantitative platelet disorders?

Answer 22

1. Idiopathic Thrombocytopenic Purpura (ITP)
2. Disseminated Intravascualar Coagulation (DIC)
3. Thrombotic Thrombocytopenic Purpura (TTP)
4. Hemolytic Uremic Syndrome (HUS)

Question 23

What is idiopathic thrombocytopenic purpura and what causes it?

Answer 23

Autoimmune disease where blood doesn’t clot normally and is caused by Ab against platelets

Question 24

What is Disseminated Intravascualar Coagulation (DIC) triggered by? What are the clinical manifestations?

Answer 24

• triggered by inflammation, infection or cancer
• blood clots throughout body blocks small BV
• low platelet count, low fibrinogen level, high D-dimers (FGB degradation products)
• prolonged aPTT and PT

Question 25

What is Thrombotic Thrombocytopenic Purpura (TTP) caused by? What is the pathophysiology? What is the treatment?

Answer 25

Caused by infections such as HIV - extensive microscopic clots which can cause kidney, heart and brain damage - lack of ADAMTS13 enzyme leads to OVERACTIVE BLOOD CLOTTING Treatment: - plasma transfusion to replace ADAMTS13 - NO PLATELET TRANSFUSION

Question 26

What is Hemolytic Uremic Syndrome (HUS) caused by? What is the pathophysiology? clinical manifestations? What is the treatment?

Answer 26

Caused by infection such as E.coli species tht produces toxic substances (Shiga toxin) acute kidney failure due to damage to the very small blood vessels of the kidney → destruction of RBC Low RBC count (anemia), Low platelet count (thrombocytopenia) Treatment: RBC & PLT transfusion

Question 27

What are drugs that affect platelet function?

Answer 27

1. Clopidogrel (ADP receptor agonist) - Leads to an irreversible blockage of the ADP receptor on the platelet membrane 2. Aspirin (cyclooxygenase inhibitor) - Anti-clotting effect and is used long term - low doses to prevent MI, strokes, and blood clot - low doses may be given immediately after MI to reduce the risk of another MI or death of cardiac tissue 3. Eptifibatide (GPII/III antagonist) - antiplatelet drug tht selectivelyblocks the platelet GP-IIbIIIa receptor