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Haematology > Platelets > Flashcards

Platelets Flashcards

1
Q

How are platelets produced?

A

Fragmentation of Megakaryoctes

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2
Q

What is the precursor to a megakaryocyte?

A

A megakaryoblast.

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3
Q

Why is TPO low in patients with high platelet counts?

A

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

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4
Q

What platelet surface glycoprotein facilitates adhesion to collagen?

A

Glycoprotein Ia

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5
Q

What glycoprotein is deficient in Bernard-Soulier syndrome?

A

Glycoprotein Ib

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6
Q

What is Bernard-Soulier syndrome?

A

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.

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7
Q

What glycoproteins are defective in Glanzmann’s thrombasthenia?

A

Mutations in Glycoprotein IIb or IIIa.

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8
Q

What is Glanzmann’s thrombasthenia?

A

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.

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9
Q

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

A
  1. Dense
  2. α
  3. Lysosomes
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10
Q

What is contained within the α granules?

A
  1. VWF
  2. PDGF
  3. clotting factors
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11
Q

What is contained within the dense granules?

A
  1. ATP
  2. ADP
  3. Serotonin
  4. Calcium
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12
Q

What is contained within the lysosomes?

A

Hydrolytic enzymes

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13
Q

How are platelet surface antigen known?

A

HPA-Human Platelet Antigen

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14
Q

What are the three categories of platelet action?

A

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

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15
Q

Which GP acts to allow direct platelet adhesion to collagen?

A

GPIa

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16
Q

What is the function of VWF?

A
  1. VWF is involved in shear dependent platelet adhesion to vessel wall and to other platelets.
  2. It also carries Factor VIII
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17
Q

Where is VWF synthesized?

A
  1. Platelets

2. Megakaryocytes

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18
Q

Where is VWF stored?

A
  1. Weibel-Palade bodies

2. α granules of platelets

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19
Q

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

A

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

20
Q

What cleaves these very adhesive very adhesive ULVWF multimers?

A

A VWF cleaving metalloprotease ADAMTS

21
Q

How is platelet aggregation achieved?

A

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

22
Q

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

A

Plays a major role in positive feedback promoting platelet activation.

23
Q

What role does TXA2 play in platelet aggregation?

A

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.

24
Q

What are the natural inhibitors of platelet function?

A
  1. N.O
  2. Prostacylin
  3. The Ectonucleotidase CD39 (ADPase)
25
Q

How does a megakaryocyte divide?

A

By endomitosis. Nucleus divides cell does not

26
Q

After splenectomy what happens to platelet count.

A

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

27
Q

Where is calcium in platelets stored?

A

Dense tubular system which is analogous to ER

28
Q

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

A

NO

29
Q

What is the primary function of platelets?

A

Form the primary hemostatic plug

30
Q

What is VWF role during formation of haemostatic plug?

A

Bind GPIb on platelet to subendothelial connective tissue.

31
Q

What is the function of ADP during haemostatic plug?

A

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

32
Q

What does secretion of ADP essentially lead to?

A

Aggregation

33
Q

What subsequently happens at the site of aggregation?

A

Formation of a fibrin clot.

34
Q

What is a secondary function of VWF?

A

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

35
Q

How do platelets aggregate together?

A

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

36
Q

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

A

Ca2+ and cAMP

37
Q

High cAMP affects platelets how?

A

Turn off the cell.

38
Q

What are the 2 most potent activators of platelets?

A

Thrombin and Thromboxane A2 (TXA2)

39
Q

How does prostacyclin (PGI2) affect platelets?

A

Potent inhibitor of platelet activation via increasing cAMP

40
Q

What are the causes of thrombocytopenia?

A
  1. Failure of production
  2. Increased consumption
  3. Sequestration
  4. Dilution
41
Q

Causes of Bone Marrow failure?

A
  1. Cytotoxic drugs
  2. Radiation therapy
  3. Aplastic Anemia
  4. Myelodysplastic syndromes
  5. Myelofibrosis/infiltration diseases
  6. MM
  7. Megaloblastic anemia
  8. HIV infection
42
Q

What are the causes of selective Megakaryocyte depression?

A
  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
43
Q

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

A
  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
44
Q

Thropbopoietin (TPO)

A
  1. Hormone Made in liver and kidney
  2. Regulates Megakaryocytopoiesis.
  3. Has receptors on Megakaryocytes and Platelets
45
Q

What is not ordinarily recommended in patients with ITP?

A

Platelet transfusion

46
Q

What are the treatment for ITP?

A
  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
47
Q

What are the causes of reactive thrombocytosis?

A
  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

Haematology (16 decks)

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