Platelets, Platelet Disorders

Question 1

hemostasis

Answer 1

prevention of blood loss

Question 2

4 mechanisms of hemostasis

Answer 2

1) vascular Constriction
2) Formation of Platelet Plug
3) Formation of a blood clot (coagulation)
4) growth of fibrous tissue to close a vessel hole permanently

Question 3

Vasoconstriction

Answer 3

• contractile response of vascular smooth muscle
  •Sensory impulses from traumatized vessel
  •Stimulation of smooth muscle via perivascular nerves results in spasm
  •Thromboxane A2 released from platelet dense granules
  •May be sufficient to close arterioles and small arteries

Question 4

thrombus

Answer 4

stable clot

Question 5

primary hemostasis

Answer 5

platelet aggregation
-vessel injury -> platelet adherence -> activation -> hemostatic plug
(within seconds)

Question 6

secondary hemostasis

Answer 6

blood coagulation
-hemostatic plug ->fibrin strands -> thrombus -> clot contraction
(minutes-hours)

Question 7

thrombopoiesis

Answer 7

CFU-Meg->Megakaryocyte->thrombocyte

-IL3, thrombopoietin, GM-CSF, SCF

Question 8

megakaryocyte

Answer 8

• giant cells with multiple copies of DNA in nucleus

- edges break off to form platelets

Question 9

platelets

Answer 9

-2-4micrometres in diameter
-lack nuclei -> can’t synthesize new proteins
-live ~10days -> drug consequences
-old plateletes are removed by macrophages in the spleen
aka thrombocytes
-mostly circulate in blood, some stored in spleen
-150,000-400,00/microliter of blood

Question 10

hyalomere

Answer 10

outside concentric zone of platelet; microtubules maintain shape and contraction

Question 11

granulomere

Answer 11

inside concentric zone of platelet; 3 types of granules (release prohemostatic and anti-hemostatic substances); few mitochondria

Question 12

platelet adhesion

Answer 12

• at site of endothelial injury

- mediated by integrins (GlycoProtein receptors)

Question 13

integrins

Answer 13

integral membrane receptor proteins
aka GlycoProtein receptors
-receptor binding activates platelets

Question 14

GP lalla

Answer 14

GlycoProtein receptor, binds collagen beneath the vascular bed

Question 15

GP IbIX

Answer 15

GlycoProtein receptors, binds von willebrand factor on extra-vascular smooth muscle cells

Question 16

activated platelets

Answer 16

• change shape (spherical -> stellate) and discharge granule contents
• serotonin-> local vasoconstriction
• ADP -> activates other platelets -> amplification
• adhesion activates phospholipase A2 in platelet membrane _> activates other platelets
• activation exposes GP IIbIIIa receptors ->aggregation

Question 17

phospholipase A2

Answer 17

in platelet membrane -> activates other platelets -> amplification

Question 18

aspirin

Answer 18

• inhibits platelet activation and aggregation

- irreversible inhibitor of cyclooxygenase enzymes (COX-1)

Question 19

NSAIDS

Answer 19

• non-steroidal anti-inflammatory drugs (e.g. ibuprofen)

- reversible COX inhibitors

Question 20

acetaminophen

Answer 20

• tylenol/ paracetamol

- elevated transaminase indicates liver toxicity

Question 21

platelet aggregation

Answer 21

• Mediated by fibrinogen receptors (GP IIbIIIa)

* GP IIbIIIa receptors become exposed during activation

Question 22

Bernard-Soulier syndrome

Answer 22

-defective vWf receptor (GPIb-IX) -> inactive platelets

Question 23

Glanzmann’s disease

Answer 23

defective fibrinogen receptor (GPIIb-IIIa) -> no aggregation

Question 24

antagonists for thrombosis

Answer 24

Abciximab and Eptifibatide bind to GPIIbIIIa and compete with fibrinogen.They prevent platelet aggregation

Question 25

plavix

Answer 25

binds/blocks ADP-receptor preventing ADP-activation | aka Clopidogrel

Question 26

Thrombocytopenia

Answer 26

decrease in platelets; < 150,000/ μl of blood - purpura, petechia, hemorrhage - positive tourniquet test is >20 petechiae in area of 3cm diameter of cubital fossa - increases bleeding time (normal is 2-6min)

Question 27

purpura

Answer 27

bleeding under the skin causing a purple or red discoloration)

Question 28

petechiae

Answer 28

minor bleeds under skin),

Question 29

Primary thrombocytopenic purpura

Answer 29

unknown cause

Question 30

Secondary thrombocytopenic purpura:

Answer 30

due to a known cause: aspirin overdose, aplastic anemia, malignancies infiltrating BM, infections like dengue fever (hemorrhagic fever).

Question 31

thrombocytosis

Answer 31

- increase in platelets: >400,000 / μl of blood - thrombotic (clotting) events- stroke, heart attacks, pulmonary embolism - may happen after splenectomy bc fewer platelets are removed from circulation - gangrene

Question 32

eptifibatide

Answer 32

- protein in rattlesnake | - inhibits GPIIbIIIa -> decrease in aggregation

Question 33

GPIIbIIIa

Answer 33

fibrinogen receptor, normally hidden but get exposed when platelets are activated

Question 34

thromboxane A2

Answer 34

produced by activated platelets and has prothrombotic properties