Platelet Function (McCormick)

Question 1

3 fundamental building blocks for clotting

Answer 1

1) Endothelium
2) Platelets
3) Coagulation (fibrin formation)

Question 2

Injury of endothelium

Answer 2

Transient vasocontriction

Exposure of ECM

Question 3

Endothelin

Answer 3

Released by injured endothelium

causes vasoconstriction

Question 4

Charge of intact vessel luminal surface

Answer 4

negative
so repels the negative platelets
so no clot!

Question 5

Blood Plasma contact with ECM during injury

Answer 5

triggers activation of physiologic clotting with platelet adhesion molecules (GPIb, integrins)
recognizing these ECM components

Question 6

Components of extracellular matrix (ECM)

Answer 6

collagen
Fibronectin
laminin
vWF

Question 7

vWF

Answer 7

Synthesized by endothelial cells and expressed on surface of ECM

serves as vital link for platelet adherence and activation

deficit–> platelets can’t attach

Question 8

GP1B

Answer 8

Receptor on the platelets that attaches to vWF

Question 9

Sources of vWF

Answer 9

1) Endothelial cells
2) megakaryocytes–> precursors of platelets
circulate in blood and carry vWF that is circulating in the blood
3) platelet alpha granules

Question 10

vWF’s action of factor 8

Answer 10

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

Question 11

vWF factor A3 domain

Answer 11

binds to collagen of ECM

Question 12

vWF A1 domain

Answer 12

links with platelet receptor glycoprotein (GPIb) on filopodia

Question 13

Gp IIb/IIIa

Answer 13

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

Question 14

GpIb

Answer 14

attaching the initial platelets to underlying ECM via vWF

Question 15

Primary homeostasis steps

Answer 15

Adhesion
Activation (changes shape too)
Aggregation

Question 16

Fibrinogen

Answer 16

Circulates in blood and acts as a bridge between Gp IIb/IIIa on platelets filipodia for platelet aggregation

Question 17

Von Willebrand Disease

Answer 17

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

Question 18

Glanzamann thrombasthenia

Answer 18

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

Question 19

Coagulation studies (Quantitative)

Answer 19

Do or do not have enough of coagulating factor or platelets

Question 20

Coagulation studies (qualitative)

Answer 20

have enough but just not working correctly

Question 21

what releases thrombin

Answer 21

platelets

Question 22

Cytoskeletal tubular element on the outside of platelet disc

Answer 22

constricts when platelet plug is formed so the platelet plug doesn’t stick out

also forms a platform (smooth) for secondary hemostasis

Question 23

Reopro (Abcizimab)

Answer 23

Block GPIIb/IIIa receptor so aggregation doesn’t happen

induces Glanzmann thrombasthenia

Question 24

Aspirin

Answer 24

Blocks cyclooxygenase pathway that produces prostaglandins (including TxA2 which is important in aggregation)

so Aspirin makes it harder for platelets to aggregate

Question 25

Tissue factor (secondary hemostasis)

Answer 25

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

Question 26

Phospholipid platform

Answer 26

formed when platelets undergo a conformation change, exposing phospholipid-rich portion of the platelet membrane dramatically accelerates production of fibrin

Question 27

Serum

Answer 27

Whole blood allowed to clot still contains fibrinogen

Question 28

Plasma

Answer 28

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

Question 29

Quantitative Platelet Count

Answer 29

Automate analyzer

Question 30

Qualitative platelet function testing

Answer 30

Aggregation studies

Question 31

Bleeding time

Answer 31

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

Question 32

Increase platelet count by tapping into...

Answer 32

Circulating pool (blood) Marginalized platelets (pulmonary veins and spleen)

Question 33

Automated Hematology analyzers

Answer 33

Meaure Mean Platelet Volume

Question 34

Mean Platelet Volume (Quantitative)

Answer 34

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!!

Question 35

Platelet aggregation studies

Answer 35

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

Question 36

Testing Secondary Hemostasis

Answer 36

Coagulation 1) PT 2) aPTT

Question 37

When does secondary hemostasis occur?

Answer 37

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

Question 38

PT

Answer 38

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

Question 39

aPTT

Answer 39

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)

Question 40

What factors are Vitamin K dependent

Answer 40

``` Prothrombin VII (7) IX (9) X (10) 2 (thrombin/prothrombin) ```

Question 41

Platelet function

Answer 41

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

Question 42

Coumadin

Answer 42

affects extrinsic pathway

Question 43

Heparin

Answer 43

affects intrinsic pathway