General Principles of Hemostasis

Question 1

What are the three steps involved in making a clot?

Answer 1

1. constrict the blood vessel to staunch blood flow
2. Make platelet plugs
3. make fibrin from fibrinogen to seal up the platelet plug and form a clot

(and then break down the clot)

Question 2

What are the two types of granules in a platelet?

Answer 2

alpha and delta

Question 3

What doe the alpha granules contain?

Answer 3

fibrinogen and vWF

Question 4

What do the delta granules contain?

Answer 4

ADP and Ca2+ - and other things necessary for the coag cascade

Question 5

What sort of surface is needed for the coag cascade to work? What provides it in vivo?

Answer 5

a phospholipid surface

provided by the platelets

Question 6

What does GP1a bind to?

Answer 6

exposed collagen on the subendothelial layer

Question 7

What does GP1b bind to?

Answer 7

vWF

Question 8

What does GP2a-Gp3b bind to?

Answer 8

fibrinogen

Question 9

What is the very first thing that has to happen in the body in order for the coag cascade to work?

Answer 9

you have to expose tissue factor

Question 10

Where can tissue factor come from?

Answer 10

1. hidden cells that are exposed during injury
2. microparticles floating in the blood
3. endothelial cell and monocytes (during inflammation)

Question 11

What does tissue factor activate?

Answer 11

factor VII to VIIa

Question 12

What does VIIa do?

Answer 12

Activates factor X to Xa - starting the common final pathway

Question 13

What does Xa do?

Answer 13

It (along with Va) will convert prothrombin to thrombin

Question 14

What does thrombin do?

Answer 14

converts fibrinogen to fibrin, which solidifies the clot

Question 15

Which pathway uses tissue factor and factor VII?

Answer 15

the extrinsic (sextrinic pathway)

Question 16

Why can’t the extrinsic pathway just do the whole thing?

Answer 16

because once you make Xa, it inhibits the extrinsic pathway

Question 17

If the extrinsic pathway is inhibited right away, how do we clot?

Answer 17

thrombin activates the intrinsic pathway

Question 18

Specifically, what factor is activated by thrombin?

Answer 18

factor XI to XIa

Question 19

What does XIa do?

Answer 19

activates factor IX to IXa

Question 20

What does IXa do?

Answer 20

WIth factor VIIIa as a cofactor, it will convert factor X to Xa, thus meeting at the commn pathway

Question 21

What are the two general ways you can break up a clot?

Answer 21

1. bust it up into FDPs

2. turn off coagulation cascade

Question 22

What molecles isresponsible for breaking down clots to FDPs?

Answer 22

plasmin

Question 23

How do you get plasmin?

Answer 23

tPA catalyzes the conversion of plasinogen to plasmin

Question 24

What are three things that will turn off the coaglaiton cascade?

Answer 24

1. Tisue factor pathway inhibitor (TFPI) - does what it says
2. Protein C (and S) - breaks down factor VIIIa, so you don’t have cofactor for the conversion of X to Xa in the intrinsic pathway
3. Antithrombin 3, which works on all three pathways - gives a big bear hug to the factors sot hey can’t work

Question 25

How do you do a Template Bleeding Time test?

Answer 25

you put a blood pressure cuff on the patient, make an incision on their arm and then measure how lon it takes to stop the bleeding

Question 26

WHy isn't a template bleeding time done much anymore?

Answer 26

becacause lots of different factors will affect the test - not just the platelets and many consider it to be unreliabie

Question 27

What's a more standardized alterative to the template bleeding time?

Answer 27

the Closure Time - it uses a platelet function analyzer to measure how quickly plateets can occlude small holes in a membrane - in vitro bleeding time

Question 28

What is a platelet aggregation test?

Answer 28

You take patient samples, add aggregating agents to it and see if the platelets aggregate - measure as a decrease of sample turbidity - takes a TON of time to do

Question 29

In general what are the steps to any coaglation lab test?

Answer 29

1. draw blood into citrate tube which will prevent clotting of the blood bc it removes Ca2+ 2. spin tube, take off plasma 3. add reagents of interest 4. watch for formation of fibrin - either normal or prolonged

Question 30

What are you measuring with a prothrombin time (PT)?

Answer 30

the extrinsic pathway

Question 31

What's the reagent in a PT?

Answer 31

you do plasma + thromboplastin, which basically just acts like tissue factor

Question 32

the PT is often used to monitor someone on Coumadin. why?

Answer 32

Because factor VII (which is really all you're measuring with a PT) has the shortest half life of all the factors, which means it will be affected before an of the others - ost sensitive to loss of therapeutic value

Question 33

What would be some reasons to see a prolonged PT?

Answer 33

1. decreased factor 7, 10, 5, 2, and 1 2. coumadin 3. heparin 4. DIC

Question 34

We don't actually order PTs though - what test do we use?

Answer 34

INR - it's basically the PT corrected for the non-standardized reagents used

Question 35

When should you order an INR?

Answer 35

1. to assess liver function 2. to monitor coumadin therapy 3. to diagnose DIC 4. To assess pre-op status

Question 36

What does the partial thromboplastin time (PTT) measure?

Answer 36

the intrinsic pathway

Question 37

What is the reagent with a PTT?

Answer 37

you do plasma + phospholipid

Question 38

Why would a PTT be prolonged?

Answer 38

1. hemophilia A or B 2. DIC 3. Heparin 4. Inhibitors - antibodies that bind to phospholipids

Question 39

When should you order a PTT?

Answer 39

1. investigate hx of abnormal bleding 2. monitor heparin (INR would work, but PTT is better) 3. dignoase DIC 4. diagnose antiphospholipid antibody 5. assess pre-op status

Question 40

What does a Thrombin Time (TT) measure?

Answer 40

ony measure the time to convert fibrinogen to fibrin

Question 41

What are the reagenets in a TT?

Answer 41

plasma and thrombin

Question 42

When would the TT be prolonged?

Answer 42

low fibinogen | high FDPs

Question 43

When should you order a TT?

Answer 43

If the PTT is prolonged, you do it to rule out a fibinogen problem (which is super rare)

Question 44

If a TT is normal, what other study can you do after an abnormal PTT?

Answer 44

A PTT Mixing Study

Question 45

What are the steps for a mixing study?

Answer 45

You add the patient's plasma in with pooled plasma (which is presumed to be normal) Add phospholipid If the PTT corrects, then there's a factor missing If the PTT doesn't correct, then there's an inhibitor present

Question 46

A fibrin degradation product assay does what the name says, but what is the issue with it?

Answer 46

It's VERY sensitive and NOT specific. It will pick up any FDPs from any clots - even normal ones, so it's not very good at ruling IN a clot. Can only rule out if negative.

Question 47

What test do we use instead of an FDP?

Answer 47

D-dimer - it measures only fibrin break down that occurred after the fibrin was already cross-linked.

Question 48

Can a D-dimer be used to rule in a clot?

Answer 48

Unfortunately not. Like the FDP assay, it's still super sensitive (but more specific), so you can only use it to rule out a clot if it's normal

Question 49

Fibrinogen assays can be used to measure fibinogen. WHat would cause it to be low?

Answer 49

1. DIC | 2. Massive bleed (we do this test to see if we need to give them blood product with fibrinogen)