Lec 9 Platelets

Question 1

What is normal platelet count?

Answer 1

150,000-350,000

Question 2

What is normal platelet lifespan?

Answer 2

10 days

Question 3

What percent of platelets are normally sequestered in spleen?

Answer 3

1/3

Question 4

What is the major hormone that controls thrombopoiesis + platelet production?

Answer 4

TPO = thrombopoietin

Question 5

Where is TPO synthesized?

Answer 5

in liver and kidney

Question 6

What controls TPO level?

Answer 6

megakaryocyte/platelet mass [rather than platelet count]

Question 7

What are two TPO agonists?

Answer 7

• romiplostim

- eltrombopag

Question 8

What is mechanism of platelet adhesion?

Answer 8

• platelets adhere to exposed subendothelium matrix via GP1b receptors
• vWf binds GP1b and mediates adhesion of platelets ot subendothelium

Question 9

What are 4 things that happen in platelet activation?

Answer 9

• changes shape from flat disk to sphere
• releases vWF, serotonin, and ADP from a granules and dense bodies
• releases TXA2 –> aggregating agent and vasoconstrictor
• conformational change of GPIIb/IIIa so it can bing fibrinogen and vWF

Question 10

What happens in platelet aggregation?

Answer 10

platelets aggregate via fibrinogen or vWF bridges between their IIb/IIIa receptors

results in formation of platlelt plug and epxosure of platelet phospholipids which become platform for coagulation factor reactions

Question 11

What is mech of action Abciximab?

Answer 11

monoclonal antibody; binds and inhibits IIb/IIIa receptor

Question 12

What are the 3 drugs that inhibit the aIIbB3 receptor?

Answer 12

• abciximab
• eptifibatide
• tirofiban

Question 13

What are the 4 approved antiplatelet drugs that inhibits the P2Y12 ADP receptor?

Answer 13

• ticlopidine
• clopidogrel
• prasugrel
• ticagrelor

Question 14

What are clinical features seen in disorders of platelets?

Answer 14

• mucocutaneous bleeding –> epistaxis, gingival bleeding, easy bruising, menorrhagia, GI bleeding, petechiae

Question 15

What happens to bleeding time in platelets disorders?

Answer 15

usually long

Question 16

What is inheritance of von willebrand disease?

Answer 16

autosomal dominant

Question 17

Wat happens in von willebrand disease?

Answer 17

• low levels of vWF

Question 18

What happens to PT, PTT, bleeding time in VWD?

Answer 18

• long PTT due to low factor VIII

- long beleding time

Question 19

What is ristocetin cofactor?

Answer 19

causes platelets to agglutinate in presence of normal vWF; sensitive test to detect low VWD

Question 20

What is treatment for von willebrand disease?

Answer 20

• give DDAVP = desmoporessin –> causes release of vWF from endothelial cells
• infusion of factor VIII

Question 21

What is glanzmann thrombasthenia?

Answer 21

autosomal recessive
quantitative/qualitative abnormality of aIIbB3 platelet receptor = blocks platelet aggregation

Question 22

What do you see clinically in person with glanzmann thrombasthenia?

Answer 22

mucocutaneous hemorrhage

Question 23

How do you diagnose glanzmann thromabsthenia?

Answer 23

• normal platelet count
• long bleeding time
• impaired platelet aggregation

Question 24

What is treatment for glanzmann thrombasthenia?

Answer 24

hep B vaccine, oral hygeine, avoid trauma, platelet transfusion for serious hemorrhage

Question 25

What is bernard soulier syndrome?

Answer 25

autosomal recessive

deficiency/abnormality of GP1b –> impaired platelet adhesion

Question 26

What do you see in bernard soulier?

Answer 26

• long bleeding time
• giant platelets
• thrombocytopenia [low PC]

Question 27

What is treatment for bernard soulier?

Answer 27

platelet transfusion or recombinant FVIIa

Question 28

WHat happens to platelts in uremia?

Answer 28

platelet dysfunction, anemia

Question 29

What is thrombocytopenia?

Answer 29

decreased platelets < 150,000

Question 30

Why do you need to do peripheral smear if CBC comes back with low PC?

Answer 30

may have pseudothrombocytopenia = platelet clumping causes falsely decreased count

Question 31

At what level of platelets does spontaneous bleeding occur?

Answer 31

< 20,000

Question 32

What are some causes of impaired bone marrow production of platelets?

Answer 32

• aplastic anemia
• B12 or folate deficiency
• myelophthisis
• drug induced
• alcohol
• infection –> HIV, CMV, hepatitis, B19 parvovirus

Question 33

What is immune thrombocytopenia [ITP]?

Answer 33

premature removal of antibody coated platelets by macrophages, primariyl in spleen

Question 34

What happens in chronic ITP?

Answer 34

have autoreactiv IgG antibodies usually against aIIbB3

seen in young women mostly; assocaited wtih other autoimmune diseases

Question 35

Do you have splenomegaly in chronic ITP?

Answer 35

nope!

Question 36

How do you diagnose ITP?

Answer 36

diagnosis of exclusion; bone marrow shows normal to increasd megakaryoctyes

Question 37

What are treatments for ITP?

Answer 37

• steroids
• IV Ig
• splenectomy
• win-rho antibody in Rh+
• rituximab

Question 38

What happens in acute ITP?

Answer 38

antibodies directed against viral antigens that start to target platelets

seen in young children 1-3 wks after viral illness

Question 39

What is neonatal ITP?

Answer 39

can occur if moth has ITP since IgG crosses the placenta

Question 40

What happens in DIC?

Answer 40

consumption of platelets

Question 41

What is thrombotic thrombocytopenic puprua [TTP]?

Answer 41

disorder of antibodies agaisnt ADAMTS-13 that normally breaks down multimers of vWF –> result is uncontrolled platelet aggregation + microagnipathic hemolysis

Question 42

What is treatment for TTP?

Answer 42

plasma exchange to remove antibodies