Lec 9 Platelets Flashcards
What is normal platelet count?
150,000-350,000
What is normal platelet lifespan?
10 days
What percent of platelets are normally sequestered in spleen?
1/3
What is the major hormone that controls thrombopoiesis + platelet production?
TPO = thrombopoietin
Where is TPO synthesized?
in liver and kidney
What controls TPO level?
megakaryocyte/platelet mass [rather than platelet count]
What are two TPO agonists?
- romiplostim
- eltrombopag
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
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
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
What is mech of action Abciximab?
monoclonal antibody; binds and inhibits IIb/IIIa receptor
What are the 3 drugs that inhibit the aIIbB3 receptor?
- abciximab
- eptifibatide
- tirofiban
What are the 4 approved antiplatelet drugs that inhibits the P2Y12 ADP receptor?
- ticlopidine
- clopidogrel
- prasugrel
- ticagrelor
What are clinical features seen in disorders of platelets?
- mucocutaneous bleeding –> epistaxis, gingival bleeding, easy bruising, menorrhagia, GI bleeding, petechiae
What happens to bleeding time in platelets disorders?
usually long
What is inheritance of von willebrand disease?
autosomal dominant
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
