Platelets

Question 1

How are platelets produced?

Answer 1

Fragmentation of Megakaryoctes

Question 2

What is the precursor to a megakaryocyte?

Answer 2

A megakaryoblast.

Question 3

Why is TPO low in patients with high platelet counts?

Answer 3

Platelets have a receptor for TPO and remove it from circulation.

Question 4

What platelet surface glycoprotein facilitates adhesion to collagen?

Answer 4

Glycoprotein Ia

Question 5

What glycoprotein is deficient in Bernard-Soulier syndrome?

Answer 5

Glycoprotein Ib

Question 6

What is Bernard-Soulier syndrome?

Answer 6

Mild to moderate mucocutaneous bleeding disorder caused by one of a series of mutations to platelet glycoprotein Ib or GPIX, part of the Ib/IX/V von Willebrand factor receptor complex. The disorder is a defect of platelet adhesion.

Question 7

What glycoproteins are defective in Glanzmann’s thrombasthenia?

Answer 7

Mutations in Glycoprotein IIb or IIIa.

Question 8

What is Glanzmann’s thrombasthenia?

Answer 8

Severe mucocutaneous bleeding disorder caused by one or a series of mutations in GP IIb and or IIIa. Normal GP IIb/IIIa recognizes and binds the arginine-glycine-aspartate peptide sequence receptor complex found in fibrinogen and von Willebrand factor. Glanzmann’s thrombasthenia causes a defect of fibrinogen-dependent platelet aggregation.

Question 9

What are the three types of storage granules contained within the platelets?

Answer 9

1. Dense
2. α
3. Lysosomes

Question 10

What is contained within the α granules?

Answer 10

1. VWF
2. PDGF
3. clotting factors

Question 11

What is contained within the dense granules?

Answer 11

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

Question 12

What is contained within the lysosomes?

Answer 12

Hydrolytic enzymes

Question 13

How are platelet surface antigen known?

Answer 13

HPA-Human Platelet Antigen

Question 14

What are the three categories of platelet action?

Answer 14

Adhesion, aggregation, and release reactions. There is also amplification.

Question 15

Which GP acts to allow direct platelet adhesion to collagen?

Answer 15

GPIa

Question 16

What is the function of VWF?

Answer 16

1. VWF is involved in shear dependent platelet adhesion to vessel wall and to other platelets.
2. It also carries Factor VIII

Question 17

Where is VWF synthesized?

Answer 17

1. Platelets

2. Megakaryocytes

Question 18

Where is VWF stored?

Answer 18

1. Weibel-Palade bodies

2. α granules of platelets

Question 19

How is the VWF stored in Weibel-Palade bodies released?

Answer 19

In the form of large and ultra large multimers the most adhesive and reactive form of VWF.

Question 20

What cleaves these very adhesive very adhesive ULVWF multimers?

Answer 20

A VWF cleaving metalloprotease ADAMTS

Question 21

How is platelet aggregation achieved?

Answer 21

By cross-linking of platelets through active GPIIb/IIIa receptors with fibrinogen bridges

Question 22

What role does ADP released from dense granules play in platelet aggregation?

Answer 22

Plays a major role in positive feedback promoting platelet activation.

Question 23

What role does TXA2 play in platelet aggregation?

Answer 23

TXA2 is the second major platelet positive feedback loop molecule and is important in secondary amplification of platelet activation to form a stable platelet aggregate.

Question 24

What are the natural inhibitors of platelet function?

Answer 24

1. N.O
2. Prostacylin
3. The Ectonucleotidase CD39 (ADPase)

Question 25

How does a megakaryocyte divide?

Answer 25

By endomitosis. Nucleus divides cell does not

Question 26

After splenectomy what happens to platelet count.

Answer 26

At first increases sharply then falls back down to a normal number

Question 27

Where is calcium in platelets stored?

Answer 27

Dense tubular system which is analogous to ER

Question 28

Are dense granular Ca2+ and neucleotides available for platelet metabolic needs?

Answer 28

NO

Question 29

What is the primary function of platelets?

Answer 29

Form the primary hemostatic plug

Question 30

What is VWF role during formation of haemostatic plug?

Answer 30

Bind GPIb on platelet to subendothelial connective tissue.

Question 31

What is the function of ADP during haemostatic plug?

Answer 31

Secreted ADP activates platelets as well as recruits other platelets to the site of injury.

Question 32

What does secretion of ADP essentially lead to?

Answer 32

Aggregation

Question 33

What subsequently happens at the site of aggregation?

Answer 33

Formation of a fibrin clot.

Question 34

What is a secondary function of VWF?

Answer 34

Under a certain amount of shear stress it can facilitate platelet aggregation.

Question 35

How do platelets aggregate together?

Answer 35

The GpIIb/IIIa receptor on one platelets binds to FIBRINOGEN on 2 platelets

Question 36

What are the two molecules that generally govern the activity of platelets?

Answer 36

Ca2+ and cAMP

Question 37

High cAMP affects platelets how?

Answer 37

Turn off the cell.

Question 38

What are the 2 most potent activators of platelets?

Answer 38

Thrombin and Thromboxane A2 (TXA2)

Question 39

How does prostacyclin (PGI2) affect platelets?

Answer 39

Potent inhibitor of platelet activation via increasing cAMP

Question 40

What are the causes of thrombocytopenia?

Answer 40

1. Failure of production 2. Increased consumption 3. Sequestration 4. Dilution

Question 41

Causes of Bone Marrow failure?

Answer 41

1. Cytotoxic drugs 2. Radiation therapy 3. Aplastic Anemia 4. Myelodysplastic syndromes 5. Myelofibrosis/infiltration diseases 6. MM 7. Megaloblastic anemia 8. HIV infection

Question 42

What are the causes of selective Megakaryocyte depression?

Answer 42

1. Drug toxicity 2. Viral infection 3. Congenital mutation of c-MPL receptor 4. Congenital absent radii 5. May-Hegglin anomaly 6. Wiscott-Aldrich syndrome

Question 43

What are the causes of Increased destruction-Immune of platelets?

Answer 43

1. Autoimmune-idiopathic, SLE, CLL/lymphoma 2. Infection-H pylori, HIV, other viral malaria 3. Drug induced-Heparin quinine, quinidine 4. Post transfusion 5. Feto-maternal alloimmune thrombocytopenia

Question 44

Thropbopoietin (TPO)

Answer 44

1. Hormone Made in liver and kidney 2. Regulates Megakaryocytopoiesis. 3. Has receptors on Megakaryocytes and Platelets

Question 45

What is not ordinarily recommended in patients with ITP?

Answer 45

Platelet transfusion

Question 46

What are the treatment for ITP?

Answer 46

1. Corticostreoids 2. High dose IVIg 3. Immunosuppression 4. Rituximab 5. Thrombopoietin receptor agonists 6. Splenectomy 7. IV anti-D immunoglobulin 8. Stem cell transplant

Question 47

What are the causes of reactive thrombocytosis?

Answer 47

1. Acute Trauma, surgery, blood loss, chronic iron deficiency 2. Splenectomy 3. Infections: Osteomyelitis, tuberculosis 4. Inflammatory disease: rheumatoid arthritis, chronic ulcerative colitis, vasculitis 5. Malignancy: carcinoma, Hodgkin's disease