Platelet Function (McCormick) Flashcards
3 fundamental building blocks for clotting
1) Endothelium
2) Platelets
3) Coagulation (fibrin formation)
Injury of endothelium
Transient vasocontriction
Exposure of ECM
Endothelin
Released by injured endothelium
causes vasoconstriction
Charge of intact vessel luminal surface
negative
so repels the negative platelets
so no clot!
Blood Plasma contact with ECM during injury
triggers activation of physiologic clotting with platelet adhesion molecules (GPIb, integrins)
recognizing these ECM components
Components of extracellular matrix (ECM)
collagen
Fibronectin
laminin
vWF
vWF
Synthesized by endothelial cells and expressed on surface of ECM
serves as vital link for platelet adherence and activation
deficit–> platelets can’t attach
GP1B
Receptor on the platelets that attaches to vWF
Sources of vWF
1) Endothelial cells
2) megakaryocytes–> precursors of platelets
circulate in blood and carry vWF that is circulating in the blood
3) platelet alpha granules
vWF’s action of factor 8
grabs onto factor 8 circulating in the blood and activate endothelial cells to produce more active factor 8
maintains level and activity of factor 8 in the blood by increasing the t1/2 of factor 8 (so it stays in blood longer)
decrease in vWF –> decrease in factor 8 activity and levels
vWF factor A3 domain
binds to collagen of ECM
vWF A1 domain
links with platelet receptor glycoprotein (GPIb) on filopodia
Gp IIb/IIIa
Receptor located on filopodia of platelets
once platelets start changing shape this receptor is localized to the outside of platelets
very important b/c it grabs onto passing by platelets, causing aggregation
GpIb
attaching the initial platelets to underlying ECM via vWF
Primary homeostasis steps
Adhesion
Activation (changes shape too)
Aggregation
Fibrinogen
Circulates in blood and acts as a bridge between Gp IIb/IIIa on platelets filipodia for platelet aggregation
Von Willebrand Disease
Lack of vWF
lack of platelets recruited to initial site of injury
decrease in factor 8 in blood, so decrease in intrinsic pathway
normal platelet count
Glanzamann thrombasthenia
GpIIb/IIIa mutation
causes deficiency in aggregation so platelets can’t grab eachother anymore
does NOT effect platelet count or platelet morphology
must measure platelet aggregation
Coagulation studies (Quantitative)
Do or do not have enough of coagulating factor or platelets
Coagulation studies (qualitative)
have enough but just not working correctly
what releases thrombin
platelets
Cytoskeletal tubular element on the outside of platelet disc
constricts when platelet plug is formed so the platelet plug doesn’t stick out
also forms a platform (smooth) for secondary hemostasis
Reopro (Abcizimab)
Block GPIIb/IIIa receptor so aggregation doesn’t happen
induces Glanzmann thrombasthenia
Aspirin
Blocks cyclooxygenase pathway that produces prostaglandins (including TxA2 which is important in aggregation)
so Aspirin makes it harder for platelets to aggregate
Tissue factor (secondary hemostasis)
after platelet plug is formed, this is released by adjacent endothelial cels
starts platform of platelets producing phospholipids on their surface
this activates thrombin and polymerizes fibrinogen into fibrin
Phospholipid platform
formed when platelets undergo a conformation change, exposing phospholipid-rich portion of the platelet membrane
dramatically accelerates production of fibrin
Serum
Whole blood allowed to clot
still contains fibrinogen
Plasma
blood drawn into collection tube containing anticoagulant that prevents clotting
anticoagulation accomplished by using agent that chelates calcium
ca is essential in the coagulation cascade so if you don’t have it blood doesn’t clot
Quantitative Platelet Count
Automate analyzer
Qualitative platelet function testing
Aggregation studies
Bleeding time
Tests for defects in primary hemostasis as well as vWF disease
Are there enough platelets and are they working properly?
Does not test coagulation factors ONLY PLATELETS
Less than 8 min, less than 5 optimal
Increase platelet count by tapping into…
Circulating pool (blood)
Marginalized platelets (pulmonary veins and spleen)
Automated Hematology analyzers
Meaure Mean Platelet Volume
Mean Platelet Volume (Quantitative)
Tells us the size of the platelet (tests primary hemostasis)
If platelets are being put out at a greater rate, then more of them will be larger (younger, new)
So there will be an increase in MPV
Above 8.1 fL then too large!!
Platelet aggregation studies
Qualitative (primary hemostasis)
used to detect functional disorders of platelets
if you do a study to see platelets aggregate, and add epinephrine, ADP, collagen, arachidonic acid (prescursor to TXA2) or thrombin, it would NOT aggregate meaning problem with platelets connecting to each other
Testing Secondary Hemostasis
Coagulation
1) PT
2) aPTT
When does secondary hemostasis occur?
After the initial platelet plug has been established at the site of the endothelial injury
it involves forming larger and more stable clot by making more Fibrin from the coagulation cascade
PT
Prothrombin Time- measures amount of time blood takes to clot in the presence of certain factors
Test that is used to monitor defects in extrinsic pathway
Also used to monitor coagulants (like coumadin) in pt’s (such as pt’s who have atrial fibrillation)
Coumadin affects extrinsic pathway
aPTT
Activated partial thromboplastin time - used to monitor defects in the intrinsic pathway
Monitors heparin (anticoagulant) therapy
Heparin affects intrinsic pathway–> prolonged aPTT (means blood takes longer to clot)
What factors are Vitamin K dependent
Prothrombin VII (7) IX (9) X (10) 2 (thrombin/prothrombin)
Platelet function
Adhere to vessel wall
Activate and secrete granules
Aggregate via filapodia and fibrinogen bridges to produce platelet plug
Facilitate generation of thrombin- helps fibrinogen change to fibrin
reinforce platelet plug
Coumadin
affects extrinsic pathway
Heparin
affects intrinsic pathway
