4.2 CHESNEY Platelets Flashcards
1
Q
Platelet Production
A
- Endomitotic replication: DNA rep in the absense of nuclear or cytoplasm division
- one meg makes 2,00-5,000 plts taks about 5 days
- platelets last for about 10 days
2
Q
Storage of Platelets
A
~1/3 of plts are sequestered in the Spleen
- Losing spleen will cause an increase in plts b/c they have no where to go
- Over time the plt count will normalize
3
Q
Platelet structure
A
- Dense granules: nucleotides (ADP), Ca and serotonin
- Alpha granule: PDGF, fibrinogen, vWF, fibronectin, beta-thromboglobulin (heparin agonist) and thrmobospondin
- Contents of the granules is released from the platelet, not used w/n the platelet
- Dense tubular system: Ca storage, responsible for Ca release w/n the platelet during activation
- Open-canalicular system: invagination of surface area into cell
- Submembranous filaments: made of actin and myosin, responsible for contraction of platelets
4
Q
Primary Hemostatic Plug
A
- ADP: released from dense granule, happens rather fast, pro-aggregation
- Thromboxane A2 also induces more platelet act and aggregation, syn by platelets, takes more time for release
5
Q
Platelet Aggregation
A
-Platelets use IIb/IIIa to bind to fibrinogen which links platelets to each other and responsible for aggregation of platelets
6
Q
Activation of Platelets
A
2 things lead to platelet activation:
- Mobilization of Ca from the dense tubular system
- Increase in ADP levels (high cAMP levels turn the cell off)
7
Q
Clotting System
A
- Platelet is surface area where a lot of the clotting system will happen
- cofactor VIII is located on the surface and binds, XI and together they activate X
8
Q
Platelet Receptors
A
- Platelets have several surface receptors
- Thrombin is the most potent activator of platelets
9
Q
Metabolic cascades: Endothelial cells vs Platelets
A
- Platelets make TXA2 which inhibits cAMP production and activates the platelet
- Endothelial cells make Prostacyclin, inhibits platelet, vasodilator and favors cAMP production in platelets
10
Q
Testing if Platelets work
A
- Platelet aggregometry, measures the fall in light absorbance in platelet rich-plasma as platelets aggregate
- Initial aggregation is caused by an external agen, the secondary response by aggregating agents released from the platelets themselves.
- External agents: ADP, collagen, ristocetin, arachidonic acid and adrenaline
- Patients on aspirin: will see initial clotting b/c of external factors, but will not continue b/c platelets are inactivated
11
Q
Causes of Thrombocytopenia
A
- Failure of production
- increased consumption: bleeding, DIC
- sequestration: spleen, alcoholics, portal hypertension
- dilution
12
Q
Selective megakaryocyte depression
A
- drug tox
- viral infection
- congenital mutation of c-MPL receptor
- congenital absent radii
- May-Hegglin anomaly
- Wiscott-Aldrich syndrome
13
Q
Increased destruction-Immune
A
- Autoimmune-idiopathic, SLE, CLL/lymphoma (most common ones)
- Infection-H pylori, HIV, other viral malaria
- Post transfusion
- Feto-maternal alloimmune thrombocytopenia
14
Q
Drug induced destruction
A
15
Q
TPO
A
- Binds receptors on Megs and platelets
- If platelets are high in circulation, they will bind up TPO and will prevent them from binding Megs and activating them
- If low platelets TPO will bind Megs and lead to platelet production
