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Flashcards in Platelets Deck (34):
1

Describe how Megs make/releases platelets.

When the meg reaches a certain number of nuclear divisions, it releases 2000-5000 platelets
*stimulated by TPO

2

What is endomitotic synchronous nuclear replication?

replication scheme of megs in which the replicate their nucleus many times but do not divide their cytoplasm

3

What proportion of platelets does the spleen normally sequester?

1/3 or 30%

4

What percentage of total body platelets can be sequestered in the spleen of a pt with an MDS or lymphoproliferative disorder?

60-90%

5

What is the open canalicular system?

invaginations of the platelet plasma membrane
*inc surface area of the platelet

6

The submembranous filaments in a platelet allow ________

the platelet to contract and expand
*actin and myosin filaments

7

What is found in the dense granules?

- nucleosides/ADP (NOT available for metabolism)
-Calcium
-serotonin

8

What is found in the alpha granules?

growth factors (PDGF)
B-thromboglobulin
PF4
fibrinogen
factor V
VWF
fibronectin
heparin agonist
thrombospondin

9

What are the platelet specific proteins?

B-thromboglobulin
PF4

10

What is the dense tubular system

similar to ER

Where calcium is stored

11

What are the 3 types of granules in platelets?

lysosome
dense
alpha

12

Describe the formation of the primary hemostatic clot

1. GpIb binds vWF to adhere platelets endothelium
2. platelets contact collagen become activated
3. degranulation
4. aggregation

13

What mediates plateet adhesion to subendothelium?

GpIb binding vWF

14

What is the role of GpIIb/IIIa?

binds fibrinogen to link the platelets together

15

What is the consequence of nonfunctional GpIIb/IIIa?

Glanzmans --> bleeding
normal platelet count
platelets can do everything but aggregate

16

(High or low) levels of cAMP inhibit platelets

high

17

T or F: GpIIb/IIIa binds fibrin

F: fibrinogen (which is cleaved into fibrin)

18

What is the biochemical effect of an agonist/stimulus binding a platelet surface receptor and activating PLC?

Ca released from dense tubule which activates phospholipase A2 to make TXA2 from arachidonic acid

19

What happens on the surface of the platelet (in terms of coag cascade)? Why does this need to happen on a platelet surface and not just freely in the blood?

8a is embedded in the platelet surface and forms a complex with 9a which together acts to activate 10

*if this reaction had to happen freely in the blood these substrates (8a, 9a, and 10) would rarely ever meet. This ensures they are all brought together in close proximity at the right time

20

What are the 2 most potent activators of platelets?

thrombin and TXA2

21

What effect does inc PGI2 have on platelets?

inhibits platelet aggregation

(activates adenylate cyclase to make cAMP which inactivates platelet)

22

Why must must a LOW dose aspirin be taken for desired therapeutic effects (as opposed to a higher does)?

If the dose is too high the cycloxygenase in the endothelial cell will also be inhibited. if the endo COX is inhibited, then platelets become activated/aggregate (via dec PGI2 --> adenylate cyclase inactivation --> dec cAMP--> inc activ)

With low does aspirin, only the COX in the platelet is inhibited --> dec TXA2 --> activation of adenylate cyclase --> inc cAMP --> dec aggregation

23

What does bleeding or DIC do to the number of platelets?

decreases

24

What are the 2 major causes of splenic sequestration?

alcoholic cirrhosis and portal hypertension
*much more common than lymphoma and leukemia

25

What is the c-MPL receptor?

TPO receptor on Megs

26

What are the 4 causes of thrombocytopenia?

1. failure of production
2. inc consumption (bleeding DIC)
3. sequestration
4. dilution

27

What are immune related causes of thrombocytopenia?

idiopathic
infection (esp HIV)
Drug: Heparin, quinidine
post transfusion
feto-maternal alloimmune thrombocytopenia

28

What do the Abs in ITP often recognize?

GpIIb/IIIa

29

What is HIT?

Heparin-plasma protein complex binds Ab which binds platelet.
Complement is deposited and platelet-drug-Ab complex removed

30

What molecule regulates platelet production?

TPO

31

What is the treatment for chronic ITP?

corticosteroids

32

What are 2 non-immune related causes of platelet destruction?

DIC and TTP

33

What are the 4 major causes of reactive thrombocytosis

trauma
surgery
blood loss
chronic iron deficiency

34

Why does essential thrombocytopenia progress to MF?

platelets release growth factors (from alpha granules...PDGF?) that stimualte fibroblasts