Platelet Function (McCormick) Flashcards
Thrombopoietin
a cytokine produced by liver and kidney
regulates platelet production and differentiation of megakaryocytic
What factors can regulate the process of platelet formation
any factor that is converting the common myeloid progenitor into megakaryocyte: TBO thrombopoietin SCF Stem cell factor IL-3 GM-CSF
what is the normal concentration of platelets in peripheral blood and lifespan of these platelets
150,000-450,000 x 10E9/L
7-10 days
Where are marginalized or sequestered platelets found?
sinusoids in spleen and in the pulmonary vasculature
List the platelet components
Glycoprotein R Tubulin mts actin/myosin proteins alpha granules dense-core granules
Function of glycoprotein R on platelet
external surface to bind to vWF
Function of tubulin mt on platelets
encircle disk forming inner skeleton
Function of actin/myosin proteins on platelets
contractile proteins in center- important for platelet plug
What are in the alpha granules of platelets
vWF, platelet factor IV, TGF-B1, PDGF, factors V and XIII and fibrinogen
What are in the dense-core granules of platelets
ADP, serotonin, histamine, epinephrine, and Ca2+ (procoagulants)
3 general steps of platelet formation
Adhesion
Activation
Aggregation
Describe the events in Adhesion of platelets
vWF is exposed to to injury to endothelium(via shearing, cytokines or hypoxia), the GpIb R on platelets bind to vWF
Describe the events in Activation of platelets
The binding to vWF causes G protein intracell cascade
mediated via PLC and Ca2+ influx to initiate the “release rxn of platelets”
What is included in the “release rxn” of platelets?
exocytosis of dense storage granule contents
exocytosis of alpha granule contents
production of TXA2
Thrombin will cause changes in cytoskeleton of platelets to form filpodia
Describe the events in Aggregation of platelets
Release of ADP, serotonin, TXA2 and Ca2+ activates this cascade
the binding of vWF and R activatre platelet aggregation
GpIIb/IIIa Receptors on platelet surface bind fibrinogen to make bridges
what is the role of thrombin in platelet formation
activates factor XI which will facilitate the interaction of intrinsic and extrinsic pathways
difference of clot and platelet
clot will retract to form a plug via interaction of actin and myosin in center of platelet
define hemostasis
balance of blood for optimal tissue perfusion
basically the balance of procoagulants and anticoagulants in blood
What is the bleeding time test and what can it tell you about a patient
cut patient, test how long it takes for bleeding to stop. normal within 8 min optimal 5 min
tells you about disorders in primary hemostasis like vWF disease
What are platelet aggregation studies and what can they tell you about a patient
measure aggregation in presence of pro-aggregant
functionality of qualitative platelet disorders
Platelet factor 4- what can this test tell you about a patient
measures release of PF4 from alpha granules of platelets.
detects functional or qualitative platelet disorders
What is Von Willebrand disease
vWF normally is a carrier protein for factor VII and acts as an adhesive surface for platelets at vascular injury site
defects result in bleeding tendencies
5 fundamental steps of clotting
Vessel Injury: endothelial damage Primary hemostasis: platelet function Secondary hemostasis: coagulation-fibrin Anti-thrombosis: clotting inhibition Fibrinolysis: breakdown-removal of clot
3 fundamental building blocks for a clot
endothelium, platelets, coagulation (fibrin formation)
What occurs in response to endothelial injury
Endothelin is released to cause vasoconstriction
contact with underlying ECM causes activation of clotting and platelet adhesion
what is vWF role in circulating blood
binds to factor VIII thus increasing its time circulating
Which domain of vWF binds to ECM and which to the platelet glycoprotein R
A3 binds to collagen on ECM and A1 binds GP1b on filopodia
where is fibrinogen found? role in clotting?
circulates in blood- forms bridge between filopodia of platelets
Glanzmann thrombasthenia
when the platelets can’t grab onto eachother in clot formation. Problem with GpIIb/IIIa complex
do patients with VW disease have lower platelet count?
no does not affect quantity.
What is the drug Reopro used for?
blocks GpIIb/IIIa therefore blocking platelet plug formation.
How does aspirin prevent clot formation
inhibits conversion of AA into TXA2 which is a stimulator of clotting
What is the phospholipid platform and when does it form?
platelets when activated expose phospholipid-rich portion of membrane and this acts to accelerate fibrin production 100-1000 fold. Secondary Hemostasis
How do we obtain serum from blood draw?
whole blood allowed to clot then centrifuge down and take supernatant(serum) from top (red top)
How do we obtain plasma from blood draw?
blood is drawn into tube with anticoagulant that prevents clotting, then centrifuged and supernatant is plasma (blue top)
What is a common anticoagulant for plasma samples/?
Sodium citrate. citrate will bind Ca2+ and prevents its coagulation activity (blue top)
purple top uses EDTA for anticoagulant
Two types of categories to test primary hemostasis
quantitative platelet count(automated analyzer)
qualitative platelet function testing- aggregation studies
What is an automated analyzer that is used in testing form problems in primary hemostasis
laser light scattering- measure the report Mean Platelet Volume
Difference between appearance of young platelets vs old
younger platelets are larger and more functional
how can you test for glanzmann thrombasthenia?
aggregation studies. no response to eli, ADP, collagen and AA or thrombin
Tests to monitor coagulation
Prothrombin time
activated Partial Thromboplastin Time (aPTT)
