Crosstalk Flashcards
Which two lipids on the plasma membranes that are -vely charged?
PS & PE
What happens to PS and PE in activated platelets?
Flip to face outwards towards ECF
What are 2 activators for platelets?
Thrombin
Collagen
What is Scott Syndrome?
Bleeding episodes but normal platelet counts, aggregation & clotting factors
What causes Scott Syndrome?
Altered phospholipid composition of outer plasma membrane after platelet activations (lack of PS & PE)
Where do Scott Syndrome patients have mutations?
TMEM16F
What is TMEM16F?
Membrane channel protein for chloride ions & lipid scramblase
What is TMMEM16F triggered by?
Strong platelet activation (thrombin & collagen)
What is lipid scramblase?
Allows lipid to move from one side of the lipid bilayer to the other
What are the 3 platelet granules?
Lysosomes
Dense granules
Alpha granules
What 5 things do alpha granules release?
Coagulation factors
Chemokines
Regulators of growth & angiogenesis
Immunologic molecules
Adhesion molecules
What is PF4?
Platelet specific CXC chemokine
Where is PF4 contained?
Alpha granules
What does PF4 form a homo-tetramer with?
Band of +vely charged aas on its surface
What does PF4 bind to?
-vely charged molecules eg heparin, glycosaminoglycans, Gla-domain on PC
What can PF4 stimulate?
APC formation (clot inhibition)
Clot formation but only in a narrow range
What can heparin treatment induce?
heparin induced thrombocytopenia (HIT)
What does HIT cause?
Antibody development against complexes of PF4 & heparin
What do HIT antibodies cause?
Platelet & EC activation & enhanced thrombus formation
destruction of platelets resulting in low platelet numbers
What happens when platelets and neutrophils interact?
trigger TF expression
What is the role of ADAMTS13?
Cleaves A2 domain of VWF in fluid shear stress
What happens in a loss of ADAMTS13?
Thrombotic thrombocytopenic purpura (TTP)
Too long vWF
How is TTP treated?
Plasma exchange (PEX) -> removal of autoantibodies against ADAMTS13 & replaces ADAMTS13
What do patients with hereditary TTP have a high risk of?
TIA & stroke at a young age