General Principles of Hemostasis Flashcards

1
Q

What are the three steps involved in making a clot?

A
  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)

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2
Q

What are the two types of granules in a platelet?

A

alpha and delta

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3
Q

What doe the alpha granules contain?

A

fibrinogen and vWF

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4
Q

What do the delta granules contain?

A

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

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5
Q

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

A

a phospholipid surface

provided by the platelets

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6
Q

What does GP1a bind to?

A

exposed collagen on the subendothelial layer

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7
Q

What does GP1b bind to?

A

vWF

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8
Q

What does GP2a-Gp3b bind to?

A

fibrinogen

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9
Q

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

A

you have to expose tissue factor

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10
Q

Where can tissue factor come from?

A
  1. hidden cells that are exposed during injury
  2. microparticles floating in the blood
  3. endothelial cell and monocytes (during inflammation)
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11
Q

What does tissue factor activate?

A

factor VII to VIIa

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12
Q

What does VIIa do?

A

Activates factor X to Xa - starting the common final pathway

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13
Q

What does Xa do?

A

It (along with Va) will convert prothrombin to thrombin

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14
Q

What does thrombin do?

A

converts fibrinogen to fibrin, which solidifies the clot

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15
Q

Which pathway uses tissue factor and factor VII?

A

the extrinsic (sextrinic pathway)

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16
Q

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

A

because once you make Xa, it inhibits the extrinsic pathway

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17
Q

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

A

thrombin activates the intrinsic pathway

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18
Q

Specifically, what factor is activated by thrombin?

A

factor XI to XIa

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19
Q

What does XIa do?

A

activates factor IX to IXa

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20
Q

What does IXa do?

A

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

21
Q

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

A
  1. bust it up into FDPs

2. turn off coagulation cascade

22
Q

What molecles isresponsible for breaking down clots to FDPs?

A

plasmin

23
Q

How do you get plasmin?

A

tPA catalyzes the conversion of plasinogen to plasmin

24
Q

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

A
  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
25
Q

How do you do a Template Bleeding Time test?

A

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

26
Q

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

A

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

27
Q

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

A

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

28
Q

What is a platelet aggregation test?

A

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

29
Q

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

A
  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
30
Q

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

A

the extrinsic pathway

31
Q

What’s the reagent in a PT?

A

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

32
Q

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

A

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

33
Q

What would be some reasons to see a prolonged PT?

A
  1. decreased factor 7, 10, 5, 2, and 1
  2. coumadin
  3. heparin
  4. DIC
34
Q

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

A

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

35
Q

When should you order an INR?

A
  1. to assess liver function
  2. to monitor coumadin therapy
  3. to diagnose DIC
  4. To assess pre-op status
36
Q

What does the partial thromboplastin time (PTT) measure?

A

the intrinsic pathway

37
Q

What is the reagent with a PTT?

A

you do plasma + phospholipid

38
Q

Why would a PTT be prolonged?

A
  1. hemophilia A or B
  2. DIC
  3. Heparin
  4. Inhibitors - antibodies that bind to phospholipids
39
Q

When should you order a PTT?

A
  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
40
Q

What does a Thrombin Time (TT) measure?

A

ony measure the time to convert fibrinogen to fibrin

41
Q

What are the reagenets in a TT?

A

plasma and thrombin

42
Q

When would the TT be prolonged?

A

low fibinogen

high FDPs

43
Q

When should you order a TT?

A

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

44
Q

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

A

A PTT Mixing Study

45
Q

What are the steps for a mixing study?

A

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

46
Q

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

A

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.

47
Q

What test do we use instead of an FDP?

A

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

48
Q

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

A

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

49
Q

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

A
  1. DIC

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