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Cardiovascular > Hemostasis - Platelet Function > Flashcards

Hemostasis - Platelet Function Flashcards

1
Q

platelet morphology and function

A

resting platelets are discoid, anucleate cells 2-3 uM in diameter

form by budding or retraction from megakaryocyte proplatelet processes in bone marrow myeloid sinuses and other tissues

microtubule coil helps maintain platelet discoid shape

upon activation, platelet changes shape from discoid to round and then with many projections

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2
Q

canalicular sytstem

A

provides easy release of granule contentss and excess platelet membrane during shape change

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3
Q

phases of platelet activation

A

adhesion - binding to subendothelial matrix

activation - change from quiescent state to promote hemostasis

secretion - release of granule contents

aggregation - binding to other platelets through active GPIIbIIIa

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4
Q

process of injury that activates platelets

A

i) Collagen exposure
ii) Exposure of von Willebrand factor that binds platelet receptors
iii) Thrombin generation
iv) Decreased endothelial production of CD39 ecto-ADPase
v) Endothelin release (vasoconstriction)

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5
Q

agonists that cause platelet activation

A

ADP, thromboxane A2, collagen, thrombin, epinephrine

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6
Q

i) Endothelium-dependent platelet inhibitors such as Prostacyclin (PGI2)

A

stimulates platelet cyclic AMP and Nitric Oxide (Endothelium-Derived Relaxing Factor (EDRF), which stimulates cyclic GMP

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7
Q

consequence of platelet activation

A

a. Platelet shape change
b. Thromboxane A2 generation and release
c. Release of granule contents – recruits and activates additional platelets
d. Inside-out signaling presenting the active fibrinogen binding form of GPIIbIIIa receptors on the platelet surface.
e. Exposure of an anionic phospholipid surface on the outer leaflet of the plasma membrane which promotes the assembly of factor tenase and prothrombinase complexes.

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8
Q

Thromboxane A2

A

produced by activated platelets is a potent agonist for platelet activation and aggregation.

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9
Q

Aspirin

A

acetylates cyclooxygenase and irreversibly inhibits its activity immediately upon exposure within the portal circulation

affects function for the life of the platelet – return to normal requires 7-10 days when a significant number of new platelets appear in the circulation

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10
Q

dense granule contents

A

ADP

ATP

Serotonin

Pyrophosphate

Calcium

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11
Q

alpha granule contents

A

Platelet Factor-4

beta-Thromboglobulin

Platelet-Derived Growth Factor

Fibrinogen

Factor V

vWF

High Molecular Weight Kininogen

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12
Q

GP IIb/IIIa receptor

A

mediates platelet aggregation when activated

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13
Q

fibrinogen

A

the most important multivalent adhesive glycoprotein that can bridge two activated platelets (on a molar basis) but other ligands such as von Willebrand factor can also serve this function

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14
Q

platelet function tests

A

Peripheral smear – count, size, granules

Bleeding time

Point of care instruments:

a. Platelet function analyzer PFA-100® - a screening test for platelet function
b. Accumetrics VerifyNow® - for therapeutic drug monitoring
c. Thromboelastography – aspirin and thienopyridine drug monitoring
d. Other assays

Clot retraction

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15
Q

platelet aggregation studies

A
  • *Optical nephelometry** – uses platelet rich plasma
  • gold standard assay, but cumbersome for routine screening and clinical monitoring

Electrical impedance - whole blood

agonists: ADP, epinephrine, collagen, arachidonic acid, Ristocetin

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16
Q

clinical manifestations of platelet dysfunction

A

mucocutaneous bleeding, petechiae, purpura, epistaxis, gingival bleeding, menorrhagia

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17
Q

Bernard-Soulier Syndrome

A

GP Ib/IX (vWF Receptor) defect

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18
Q

Glanzmann’s Thrombasthenia

A

GP IIb/IIIa Complex defect

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19
Q

delta-Storage Pool Disease

A

Dense Body Deficiency

20
Q

alpha-Storage Pool Disease (Gray Platelet Syndrome)

A

Alpha Granule Deficiency

21
Q

Scott Syndrome

A

Decreased platelet surface acidic phospholipid expression

22
Q

Quebec Syndrome

A

Multimerin defect; alpha-granule and procoagulant activity defect

23
Q

Stimulus-response coupling defects

A

Heterogeneous; defects of cyclooxygenase, G-couple proteins or calcium response

24
Q

acquired disorders of platelet function.

A

Uremia – metabolic byproducts inhibit platelet function in Myeloproliferative Disorders

Post-Cardiac Bypass - artificial surfaces activate and cause “spent platelets”

Dysproteinemia – plasma immunoglobulin paraprotein receptor interference

Antiplatelet antibodies – interfere with platelet receptors

Liver disease with fibrin degradation product (fdp) interferes with binding of fibrinogen with platelet receptor

Drugs

25
Q

ecto-ADPase (CD39)

A

normally expressed by endothelial cells, which removes ADP and ATP nucleotides from the local fluid environment

26
Q

platelet products in atherogenesis

A

CD40 ligand

interleukin-1beta

P-selectin

platelet factor 4

ROS

F2-isoprostanes

tissue factor

chemokines, cytokines

matrix metalloproteinases

27
Q

CD40 ligand in atherogenesis

A

endothelial cell expression of chemokines, tissue factor, cell adhesion molecules, and ROS

28
Q

interleukin-1beta in atherogenesis

A

endothelial cell activation, cell adhesion, chemokine production

29
Q

P-selectin in atherogenesis

A

adhesion to endothelial cells and monocytes

30
Q

platelet factor 4 in atherogenesis

A

macrophage differentiation, endothelial cell E-selectin

31
Q

ROS in atherogenesis

A

scavenges nitric oxide, prevents thrombus disaggregation, lipid peroxidation, F2-isoprostanes

32
Q

F2-isoprostanes in atherogenesis

A

activates platelets, modulates cell adhesion

33
Q

tissue factor in atherogenesis

A

promotes thrombosis

34
Q

chemokines and cytokines in atherogenesis

A

leukocyte recruitment and inflammation

35
Q

matrix metalloproteinases in atherogenesis

A

plaque destabilization

36
Q

NSAIDs

A

inhibits cyclooxygenase reversibly, platelet function returns after drug levels fall

use of NSAIDs can interfere with therapeutic antiplatelet aspirin effect

37
Q

Thienopyridines: clopidigrel (Plavix®)

A

P2Y12 ADP receptor blocking agent which may be used in conjunction with aspirin in patients with stroke and coronary artery disease

the drug must be metabolized to the active form; some persons resistant

38
Q

Ticlopidine (Ticlid®)

A

ADP receptor blocking agent use associated with increased incidence of Thrombotic Thrombocytopenic Purpura (TTP) in 1:2000-4000 cases

39
Q

Prasugrel, Ticagrelor

A

efficacious new ADP receptor blocking agents

may be used in patients who have resistance to clopidogrel

40
Q

Abciximab (ReoPro®)

A

humanized murine monoclonal Fab monoclonal antibody that binds to and inhibits GP IIb/IIIa function

used in cardiovascular catheter interventions

also consider: Eptifibatide, tirofiban

41
Q

Dipyridamole (Persantine®)

A

inhibits adenosine uptake, acts on PLA2 and causes increased platelet cAMP, which leads to inhibited function

42
Q

GP IIb/IIIa

A

fibrinogen/vWF (aggregation)

43
Q

GP Ib-V-IX

A

vWF (adhesion)

44
Q

GP Ia-IIa

A

collagen (adhesion)

45
Q

GP VI

A

collagen (activation)

46
Q

isoprostane

A

bioactive molecule that is formed due to inflammation and increases platelet activation

Cardiovascular (46 decks)

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