Pathophysiology of Platelet Disorders

Question 1

The spleen holds about 30% of platelets, what happens if it starts to hold more than this?
• what if you remove it?

Answer 1

• Enlarged spleen may sequester platelets and cause thrombocytopenia
• Removal of spleen can cause temporary thrombocytosis

Question 2

What is found in dense granules?

Answer 2

• ADP
• Ca2+
• Serotonin
• Nucleotides

Question 3

Aside from dense granules, where can calcium be found in platelets?
• How is it released?

Answer 3

Dense Tubular System (holds calcium)

Release:
• GPCR is activated
• PHOSPHOLIPASE C (PLC) recieves signal and cleaves PIP2 to get IP3
• IP3 binds to receptor on dense tubular system and Ca2+ is released

Question 4

What is the effect of cAMP on platelets?

Answer 4

cAMP turns platelets off

Question 5

What does the platelet use to contract?

Answer 5

• Filaments made of actin and myosin allow the platelet to contract

Question 6

How does the shape of an activated platelet differ from that of a non-activated platelet?

Answer 6

Non-activated Platelet - smooth and sugar cookie-like

Activated Platelet - pseudopodia etc.

Question 7

What factor does PT (prothrombin time) measure a defect in?

Answer 7

V, VII, X, Prothrombin, fibrinogen

Question 8

What does PTT (partial thromboplastin time) measure?

Answer 8

V, VIII, IX, X, XI, XII, Prothrombin, FIbringoen

Question 9

What 2 things may cause a platelet to because activated?

Answer 9

1. Binds to vWF that is bound to subendothelial tissue (via Gp1b)
2. Binds to Collagen (via GpIa/IIa)

Question 10

How can hemophiliacs still make a primary platelet plug?

• why do they still experience severe bleeding?

Answer 10

Hemophiliacs lack factor 8 or 9

Primary plug is formed when:
• Platelet binds vWF (via Gp1b) or Collagen (via GpIa/IIa) and because activated causing dense granule release
• Dense Granules contain Fibrinogen and ADP, and platelet starts making TXA2
• ADP activates and TXA2 recruits platelets to bind fibrinogen (via GpIIb/IIIa)

Primary Plug only last 24 hrs or so without fibrinogen cross-linking

Question 11

What factors sit on the surface of endothelium or platelets?

Answer 11

Vit K dependent Factors do this: aka II, VII, IX, and X

Question 12

How does TXA2 act as a potent aggregant?

Answer 12

Turns OFF cAMP cyclization from ATP

*Remember cAMP actually DEactivates platelets

Question 13

Why does high dose asprin not work to inhibit platelet aggregation?

Answer 13

High Dose asprin will inhibit both COX-1 in endothelial cells (which produces PGI2) and COX-1 in platelets (which makes TXA2)

• Blocking both causes the functions to offset because PGI2 normally inhibits platelet aggregation

Question 14

What type of clinical signs would you expect to see from someone who was having a negative Platelet-Vessel Wall interaction?

Answer 14

Mucus Membrane Bleeding
Super Heavy Periods
Bruising
Petechiae

Question 15

T or F: a CBC is enough to tell you if you have a primary platelet defect.

Answer 15

False, CBC will only tell you about the NUMBER of platelets, it will not tell you about QUALITY of platelets or if you have a vWF issue

Question 16

What are some primary defects of platelet QUALITY that may cause Mucus membrane bleeding, Bruising, Petechiae, or Heavy Periods?

Answer 16

Glanzmann’s caused by GpIIb/IIIa defect

Bernard Soullier caused by Gp1b defect

Question 17

Would you expect someone with von Willibrand’s Disease to have a low platelet count?
• what symptoms would you expect?

Answer 17

No, they probably would have a normal platelet count

Primary Bleeding Disorder so Symptoms: 
• Mucus membrane bleeding
• Extremely heavy periods
• Petechiae
• Bruising

Question 18

Do people with hemophilia experience issues with the following?
• Mucous membrane bleeding
• Bruising

Answer 18

No, there ability to form a primary clot is fine

Question 19

Why do patients with polycythemia vera not always experience extreme thrombosis.

Answer 19

Often times they do however, the platelets they are making may be defective

Question 20

What are some things that should be in your differential for thrombocytosis?

Answer 20

• Trauma
• Malignancy
• Inflammation
• Splenectomy
• Iron Deficiency