Pathophysiology of Platelet Disorders Flashcards
The spleen holds about 30% of platelets, what happens if it starts to hold more than this?
• what if you remove it?
- Enlarged spleen may sequester platelets and cause thrombocytopenia
- Removal of spleen can cause temporary thrombocytosis
What is found in dense granules?
- ADP
- Ca2+
- Serotonin
- Nucleotides
Aside from dense granules, where can calcium be found in platelets?
• How is it released?
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
What is the effect of cAMP on platelets?
cAMP turns platelets off
What does the platelet use to contract?
• Filaments made of actin and myosin allow the platelet to contract
How does the shape of an activated platelet differ from that of a non-activated platelet?
Non-activated Platelet - smooth and sugar cookie-like
Activated Platelet - pseudopodia etc.
What factor does PT (prothrombin time) measure a defect in?
V, VII, X, Prothrombin, fibrinogen
What does PTT (partial thromboplastin time) measure?
V, VIII, IX, X, XI, XII, Prothrombin, FIbringoen
What 2 things may cause a platelet to because activated?
- Binds to vWF that is bound to subendothelial tissue (via Gp1b)
- Binds to Collagen (via GpIa/IIa)
How can hemophiliacs still make a primary platelet plug?
• why do they still experience severe bleeding?
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
What factors sit on the surface of endothelium or platelets?
Vit K dependent Factors do this: aka II, VII, IX, and X
How does TXA2 act as a potent aggregant?
Turns OFF cAMP cyclization from ATP
*Remember cAMP actually DEactivates platelets
Why does high dose asprin not work to inhibit platelet aggregation?
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
What type of clinical signs would you expect to see from someone who was having a negative Platelet-Vessel Wall interaction?
Mucus Membrane Bleeding
Super Heavy Periods
Bruising
Petechiae
T or F: a CBC is enough to tell you if you have a primary platelet defect.
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
What are some primary defects of platelet QUALITY that may cause Mucus membrane bleeding, Bruising, Petechiae, or Heavy Periods?
Glanzmann’s caused by GpIIb/IIIa defect
Bernard Soullier caused by Gp1b defect
Would you expect someone with von Willibrand’s Disease to have a low platelet count?
• what symptoms would you expect?
No, they probably would have a normal platelet count
Primary Bleeding Disorder so Symptoms: • Mucus membrane bleeding • Extremely heavy periods • Petechiae • Bruising
Do people with hemophilia experience issues with the following?
• Mucous membrane bleeding
• Bruising
No, there ability to form a primary clot is fine
Why do patients with polycythemia vera not always experience extreme thrombosis.
Often times they do however, the platelets they are making may be defective
What are some things that should be in your differential for thrombocytosis?
- Trauma
- Malignancy
- Inflammation
- Splenectomy
- Iron Deficiency
