Platelets Flashcards
How are platelets made? What are they? Location? Life span?
- Megakaryocyte cytoplasm elongation (pro-platelets); elongations gain granules and cytoskeleton then bud off megakaryocyte
- No nucleus and very grainy cytoplasm
- 1/3 in spleen at any time
- 8-12 day life span
TPO
(thrombopoietin)
- Made in liver (dec if liver disease) then binds receptors on mega surface –> JAK-STAT path –> proliferation and platelet formation
- When low platelet count normally have inc TPO to try to compensate BUT exception is in immune thrombocytopenia purpura when there are dec platelets and dec TPO
TPO Mimetic Drugs (2)
romiplostim and eltrombopag
Platelet Granules + Contents
More alpha than dense
- Alpha - VWF, fibrinogen, thrombospondin, fibronectin (adhesion) + Factor V, PAI-1 (coagulation factors) + platelet factor 4, PDGF, TGF-beta (growth factors)
- Dense - Ca++, serotonin, ADP, ATP (dense granules require greater activation for release)
- Lysosomes - acid hydrolases
What prevents platelet plug formation in normal state?
- Endothelial-derived factors
-
Endothelial prostacyclin PGI2 (made from same COX path as TXA2), NO (vasodilate and prevent aggregation of platelets) - Adenosine disphosphatase (or CD30) hydrolyzes trace ADP (ADP normally inc aggregation)
Primary Hemostasis Steps
- formation of platelet plug-
- 1- INJURY
- 2- Initiation/Adhesion - exposure to collagen and VWF from Weible-Palade bodies under endothelium –> platelet mono-layer
- 3 - Activation - now that platelets adhere, binding to receptors on platelet membrane –> activated membrane phospholipids –> AA –> TXA2 production and granules now released
- 4- Extension - ADP and TXA2 released from active platelets in plug bind additional platelets thru G protein receptors to recruit them (platelets aggregate via fibrinogen - GPIIbIIIa)
- 5- Stabilization - concomitant activation of thrombin stabilizes the platelet plug w/ fibrin
What receptors do collagen, VWF and fibrin bind to?
- Collagen - GP-Ia/IIa or GP-VI on platelets
- VWF binds collagen and then binds GP-Ib or GP-V or GP-IX on platelets
- Fibrin binds GPIIb/IIIa
R v L Sided Hemostasis
- L - high flow rate so few red cells incorporated; platelets more important; clots made of platelets, VWF, fibrin
- When high flow/ high sheer collagen alone cannot hold platelets so VWF-GPIb needed
- “White clots”
- R - low flow rates so coagulation components readily available; less dep on platelets; clots made of fibrin, white cells and red cells
- When low flow, VWF not needed (collagen - GPIaIIa is sufficient)
- “Red clots”
How does platelet dysfunction present clinically?
- Petechiae, purpura ecchymosis, nose bleeds, GI/GU bleed, oral bleeding (“mucocutaneous bleeding”)
- Normally bleed in lower extremities first b/c inc pressure from gravity
Bleeding Time v Closure Time
- Bleeding Time - use BP cuff and make small incision; time how long until stop bleeding (operator dependent - not used often)
- Closure Time - blood sample thru capillary tube w/ high shear rate (tube contains collagen and ADP or collagen and epinephrine)
- If normal in both … normal
- If epi prolonged but ADP normal … drug-induced
- If both prolonged … platelet problem
Platelet Aggregometry
- put plasma in cuvettes then add diff platelet aggregating agents to ea and mea light transmittance (more aggregation means more light transmittance)
VerifyNow
- meas resistance to anti-platelet meds; put whole blood from pt on a med in chamber w/ platelet agonists and fibrinogen beads and meas light transmittance change
- If still aggregate then drug not that effective
- ARU (aspirin reaction units) - use AA agonist
- PRU (p2y12 reaction units) - use ADP as agonist
- PAU (platelet aggregation units) - thrombin analog agonist
Platelet Works
- meas baseline light transmittance of pts blood then add agonist and remeasure (used by anesthesia to determine if platelets are being adequately inhibited)
Thromboelastography
- measures coagulation
- blood sample in cuvette is rotated to simulate venous flow then measure resistance in cuvette which reflects clot formation
- Tests coagulation and platelets function
Glanzmann’s thromboasthenia
- GP IIbIIIa def (no aggregation w/ fibrin)