253. Platelet Function, Formation Flashcards
NORMAL PLATELET BIOGENESIS
- what molecule stimulates platelet development
- what is unique about the way platelets develop?
- what is the function of the ____ Demarcation Membrane System?
- what is the role of the different parts of cytoskeleton?
- TPO stim platelet development at every step
- endomitosis: amplification of genetic material without division (2N -> 128N Megakaryocyte)
- Megakaryocyte Demarcation Membrane System: cytoskeleton of MK, reservoir for platelet membrane formation
- Actin-myosin interaction in MK causes proplatelet elaboration and propulsion of MK membrane
- Dynein-microtubule interaction cause proplatelet elongation and transport of granules for platelet function
PLATELET PRODUCTION AND LIFESPAN
- what is the lifespan of platelets?
- where are they made?
- where do they go from blood?
- how do platelet kinetics change in thrombocytopenia?
- effect of thrombocytopenia on endothelium
- what mutations can modulate platelet lifespan?
- 8 to 10 days
- made in bone marrow
- leave blood to liver (senescence) or spleen (sequestered)
- thrombocytopenia: decreased survival time due to increased platelet removal
- endothelium thins and develops fenestrations/pores due to thrombocytopenia (role of platelets in endothelium health)
- platelet lifespan altered by intrinsic apoptosis: BCL-2 (pro-survival: knockout = less lifespan); BH3/BAX/BAK (pro-apoptotic: knockout = more lifespan)
PLATELET FUNCTION, HEMOSTASIS
- what are the 4 functions of platelets
- what receptors bind vessel during endothelial damage
- what are the key contents in platelet granules
- how is thromboxane synthesized?
- how are additional platelets recruited during thrombus formation?
- how does the lipid bilayer change during platelet activation?
- Clot formation: adhere to damaged blood vessel, recruit additional platelets, provide a surface for coagulation to occur, clot maturation
- Provide growth factors for wound repair
- Endothelial maintenance function
- Adjuvant immune function
GpIb-IX-V binds vWF-collagen (helps roll onto endothelium)
GpIIbIIIa binds fibrinogen
Dense granules: ADP, ATP, Ca
Alpha granules: PF4, fibrinogen, Factor V, vWF
TxA2: synthesized from arachidonic acid via phospholipase A2, COX pathway
Recruitment: via ADP (platelet degranulation), TxA2 synthesis, Fibrinogen Receptor (GpIIbIIIa) activation and binding
Phospholipids: activation causes increased flippase, floppase, scramblase to express more phosphatidylserine residues on outer membrane (site of coag factor binding)
Differences between venous and arterial thromboses
- site
- extension
- factors involved
Arterial
- thrombus at site of turbulence or endothelial injury
- extends retrograde to flow
- platelets, tissue factor, fibrin
Venous
- thrombus at site of stasis
- extends in direction of flow
- RBC, fibrin, few platelets, many leukocytes, NETs, TF, microvesicles (myeloid cells are activated forming neutrophil extracellular traps = NETs)
What are 3 tests to assess qualitative platelet defects
- Platelet function analysis
- Platelet aggregation studies
- both use pt platelets, add agonist to look for clumping - Platelet flow cytometry - look at receptor defects
What are 3 common acquired platelet function defects?
- Drugs (ASPIRIN, NSAIDs)
- Uremia - metabolic byproducts inhibit platelet fx
- Dysproteinemia: liver disease with fibrin degradation products interfere with platelet-fibrinogen binding
What are 3 common hereditary platelet function defects?
- give labs and tx for each
- Bernard-Soulier Syndrome: defective GpIb/IX (vWF receptor) = platelet dysfx
- variable thrombocytopenia
- large platelets
- abnormal ristocetin aggregation, normal with other aggregates (defective vWF receptor)
- flow cytometry: decreased GpIb/IX complex
- tx: platelet transfusion (adjunct DDAVP) - Glanzmann Thrombasthemia: defective GpIIb/IIIa receptor - platelets cannot bind fibrinogen and aggregate
- global abnormal aggregation with all agonists except ristocetin
- flow cytometry: decreased GPIIb/IIIa receptors
- tx: platelet transfusion (adjunct DDAVP) - Dense Granule Storage Pool Disorder: defect in dense granules = less ADP/ATP = less aggregation
- abnormal platelet aggregation
- no dense granules on EM