Platelets and Hemostasis- Lecture Flashcards
_ is the mechanism by which bleeding comes to an end after vessel injury –> clot formation
Hemostasis is the mechanism by which bleeding comes to an end after vessel injury –> clot formation
3 broad steps of hemostasis
- Blood vessel constriction
- Platelet plug formation (primary hemostasis)
- Fibrin formation (secondary hemostasis)
Platelets are fragments of _
Platelets are fragments of megakaryocyte cytoplasm
Thrombopoiesis is the process by which _
Thrombopoiesis is the process by which megakaryocytes bud off fragments of their cytoplasm
The hormonal regulator of platelet production is _
The hormonal regulator of platelet production is thrombopoietin
_ is a platelet count under 150,000
Thrombocytopenia is a platelet count under 150,000
* Can lead to excess bleeding
_ is a platelet count > 400,000
Thrombocytosis is a platelet count > 400,000
* This can lead to excess clotting
Platelet structure can be divided into two sections _ and _
Platelet structure can be divided into two sections granulomere and hyalomere
The granulomere contains the _
The granulomere contains the alpha and dense granules
The hyalomere contains the _
The hyalomere contains the cytoskeletal fibers which allow the platelet to contract
4 factors secreted by the alpha granules
Alpha granules secrete:
1. PDGF
2. PF4
3. vWF
4. P-selectin
4 factors secreted by the dense granules
Dense granules secrete:
1. Serotonin
2. ADP
3. ATP
4. Calcium
vWF is secreted by _ granules
vWF is secreted by alpha granules
The platelet has a GPIb receptor for binding _
The platelet has a GPIb receptor for binding vWF during the adhesion stage
The platelet has a GPIIb/IIIa receptor for binding _
The platelet has a GPIIb/IIIa receptor for binding fibrinogen during the aggregation step
The platelet has a P2Y12 receptor that for binding _
The platelet has a P2Y12 receptor that for binding ADP during aggregation
What prevents platelets from adhering to the blood vessels under normal conditions without injury?
Endothelial cells!
- Secretion of products that prevent platelets from activating:
* Prostacyclin
* Nitric oxide
* Endothelial ADPase - Hide collagen and vWF beneath their surface
When blood vessel injury occurs, collagen becomes exposed and binds vWF; platelets can then start to stick to the site of injury by grabbing onto vWF with their _ receptors
When blood vessel injury occurs, collagen becomes exposed and binds vWF; platelets can then start to stick to the site of injury by grabbing onto vWF with their GPIb receptors
After vWF – GPIb binding occurs we next get _
After vWF – GPIb binding occurs we next get platelet granule release
* Alpha granules
* Dense granules
* Thromboaxane A2
* Coagulation factors
Platelets also change their shape to increase their surface area
Now (during platelet activation stage) platelets express their _ receptors to attract more platelets and get ready to aggregate
Now (during platelet activation stage) platelets express their GPIIb/IIIa receptors to attract more platelets and get ready to aggregate
* Thrombin also activates platelet membrane receptors
In order for platelets to aggregate and form the soft platelet plug, we need binding between _ receptors and _
In order for platelets to aggregate and form the soft platelet plug, we need binding between GPIIb/IIIa receptors and fibrinogen
After the soft platelet plug is created, the next step is the _ , which turns _ into _ to form a strong network between platelets and stabilizes the clot
After the soft platelet plug is created, the next step is the coagulation cascade, which turns fibrinogen into fibrin to form a strong network between platelets and stabilizes the clot
Clotting factors are really special enzymes called _ that activate more downstream factors
Clotting factors are really special enzymes called serine proteases that activate more downstream factors
Factor I is _
Factor I is fibrinogen
Factor II is _
Factor II is (pro)thrombin
Factor III is _
Factor III is tissue factor
Thrombin activates factors _ , _ , _ and _
Thrombin activates factors V , VIII , XI and XIII
* 5, 8, 11, 13
Factor _ is carried by vWF until it gets cleaved/ activated by thrombin
Factor VIII is carried by vWF until it gets cleaved/ activated by thrombin
The vitamin K dependent coagulation factors are _
The vitamin K dependent coagulation factors are 10, 9, 7, 2
* “Kids Summer Camp- since 1972”
Factor Xa is created by joining _ and _ or _ and _
Factor Xa is created by joining VIIa and TF or by joining VIIIa and IXa
* 7a + tissue factor or 8a + 9a
Factor IIa is created by joining _ and _
Factor IIa is created by joining Va and Xa
* 5a + 10a = thrombin
Steps of fibrin cross-linking
- Fibrinogen
- Thrombin comes in and makes a fibrin monomer
- The fibrin monomers come together to make fibrin polymers
- Factor XIIIa stabilizes the fibrin polymer
Antithrombin inhibits which 5 coagulation factors?
- IIa (2)
- Xa (10)
- VIIa (7)
- IXa (9)
- XIa (11)
Protein S and Protein C are anticoagulant factors that inhibit _ and _
Protein S and Protein C are anticoagulant factors that inhibit VIIIa and Va
To get from fibrinogen to a fibrin clot we need _
To get from fibrinogen to a fibrin clot we need thrombin
To break up fibrin clots into fibrin split products we need _
To break up fibrin clots into fibrin split products we need plasmin
Plasmin can be blocked by _
Plasmin can be blocked by alpha2- antiplasmin
Plasminogen –> plasmin requires _
Plasminogen –> plasmin requires tPA
tPA can be blocked by _
tPA can be blocked by PAI-1 (plasminogen activator inhibitor 1)
When plasma breaks down fibrin we get _ as byproduct; when plasma breaks down cross-linked fibrin we get _
When plasma breaks down fibrin we get FDPs as byproduct; when plasma breaks down cross-linked fibrin we get D-dimers
_ are the product of cross-linked fibrin breakdown via plasmin
D-dimers are the product of cross-linked fibrin breakdown via plasmin
_ assess primary hemostasis; they include platelet count, bleeding time, platelet aggregation studies
Platelet assays assess primary hemostasis; they include platelet count, bleeding time, platelet aggregation studies
_ access secondary hemostasis
Coagulation assays access secondary hemostasis
* PT
* INR
* aPTT/PTT
* TT
* APTT mixing studies
To do a coagulation assay on a patient’s blood we need to draw blood into a _ tube
To do a coagulation assay on a patient’s blood we need to draw blood into a blue-top tube containing citrate
* The citrate prevents the blood from clotting by removing calcium
Why use INR?
INR is used to standardize patient values
* Normal is 0.8-1.2
What is the difference between aPTT and PTT?
aPTT stands for activated partial thromboplastin time
* Instead of having tissue factor to kick things off we use activator silica, phospholipid, and calcium
If PTT is corrected following a mixing study it indicates _
If PTT is corrected following a mixing study it indicates that clotting factor was missing
Normal platelets should aggregate in response to agonists like _ in an assay
Normal platelets should aggregate in response to agonists like ristocetin, collagen, ADP, epinephrine in an assay
Von willebrand disease or bernard soulier
Glanzmann
