Lec 9 Platelets Flashcards by Anna Cushing

What is normal platelet count?

150,000-350,000

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What is normal platelet lifespan?

10 days

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What percent of platelets are normally sequestered in spleen?

1/3

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

TPO = thrombopoietin

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Where is TPO synthesized?

in liver and kidney

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What controls TPO level?

megakaryocyte/platelet mass [rather than platelet count]

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What are two TPO agonists?

romiplostim

- eltrombopag

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What is mechanism of platelet adhesion?

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

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What are 4 things that happen in platelet activation?

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

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What happens in platelet aggregation?

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

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What is mech of action Abciximab?

monoclonal antibody; binds and inhibits IIb/IIIa receptor

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What are the 3 drugs that inhibit the aIIbB3 receptor?

abciximab
eptifibatide
tirofiban

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

ticlopidine
clopidogrel
prasugrel
ticagrelor

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What are clinical features seen in disorders of platelets?

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

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What happens to bleeding time in platelets disorders?

usually long

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What is inheritance of von willebrand disease?

autosomal dominant

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Wat happens in von willebrand disease?

low levels of vWF

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

long PTT due to low factor VIII

- long beleding time

What is ristocetin cofactor?

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

What is treatment for von willebrand disease?

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

What is glanzmann thrombasthenia?

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

What do you see clinically in person with glanzmann thrombasthenia?

mucocutaneous hemorrhage

How do you diagnose glanzmann thromabsthenia?

normal platelet count
long bleeding time
impaired platelet aggregation

What is treatment for glanzmann thrombasthenia?

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

What is bernard soulier syndrome?

autosomal recessive | deficiency/abnormality of GP1b --> impaired platelet adhesion

What do you see in bernard soulier?

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

What is treatment for bernard soulier?

platelet transfusion or recombinant FVIIa

WHat happens to platelts in uremia?

platelet dysfunction, anemia

What is thrombocytopenia?

decreased platelets < 150,000

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

may have pseudothrombocytopenia = platelet clumping causes falsely decreased count

At what level of platelets does spontaneous bleeding occur?

< 20,000

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

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

What is immune thrombocytopenia [ITP]?

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

What happens in chronic ITP?

have autoreactiv IgG antibodies usually against aIIbB3 seen in young women mostly; assocaited wtih other autoimmune diseases

Do you have splenomegaly in chronic ITP?

nope!

How do you diagnose ITP?

diagnosis of exclusion; bone marrow shows normal to increasd megakaryoctyes

What are treatments for ITP?

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

What happens in acute ITP?

antibodies directed against viral antigens that start to target platelets seen in young children 1-3 wks after viral illness

What is neonatal ITP?

can occur if moth has ITP since IgG crosses the placenta

What happens in DIC?

consumption of platelets

What is thrombotic thrombocytopenic puprua [TTP]?

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

What is treatment for TTP?

plasma exchange to remove antibodies