General Principles of Hemostasis Flashcards
What are the three steps involved in making a clot?
- constrict the blood vessel to staunch blood flow
- Make platelet plugs
- make fibrin from fibrinogen to seal up the platelet plug and form a clot
(and then break down the clot)
What are the two types of granules in a platelet?
alpha and delta
What doe the alpha granules contain?
fibrinogen and vWF
What do the delta granules contain?
ADP and Ca2+ - and other things necessary for the coag cascade
What sort of surface is needed for the coag cascade to work? What provides it in vivo?
a phospholipid surface
provided by the platelets
What does GP1a bind to?
exposed collagen on the subendothelial layer
What does GP1b bind to?
vWF
What does GP2a-Gp3b bind to?
fibrinogen
What is the very first thing that has to happen in the body in order for the coag cascade to work?
you have to expose tissue factor
Where can tissue factor come from?
- hidden cells that are exposed during injury
- microparticles floating in the blood
- endothelial cell and monocytes (during inflammation)
What does tissue factor activate?
factor VII to VIIa
What does VIIa do?
Activates factor X to Xa - starting the common final pathway
What does Xa do?
It (along with Va) will convert prothrombin to thrombin
What does thrombin do?
converts fibrinogen to fibrin, which solidifies the clot
Which pathway uses tissue factor and factor VII?
the extrinsic (sextrinic pathway)
Why can’t the extrinsic pathway just do the whole thing?
because once you make Xa, it inhibits the extrinsic pathway
If the extrinsic pathway is inhibited right away, how do we clot?
thrombin activates the intrinsic pathway
Specifically, what factor is activated by thrombin?
factor XI to XIa
What does XIa do?
activates factor IX to IXa
What does IXa do?
WIth factor VIIIa as a cofactor, it will convert factor X to Xa, thus meeting at the commn pathway
What are the two general ways you can break up a clot?
- bust it up into FDPs
2. turn off coagulation cascade
What molecles isresponsible for breaking down clots to FDPs?
plasmin
How do you get plasmin?
tPA catalyzes the conversion of plasinogen to plasmin
What are three things that will turn off the coaglaiton cascade?
- Tisue factor pathway inhibitor (TFPI) - does what it says
- 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
- Antithrombin 3, which works on all three pathways - gives a big bear hug to the factors sot hey can’t work
How do you do a Template Bleeding Time test?
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
WHy isn’t a template bleeding time done much anymore?
becacause lots of different factors will affect the test - not just the platelets and many consider it to be unreliabie
What’s a more standardized alterative to the template bleeding time?
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
What is a platelet aggregation test?
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
In general what are the steps to any coaglation lab test?
- draw blood into citrate tube which will prevent clotting of the blood bc it removes Ca2+
- spin tube, take off plasma
- add reagents of interest
- watch for formation of fibrin - either normal or prolonged
What are you measuring with a prothrombin time (PT)?
the extrinsic pathway
What’s the reagent in a PT?
you do plasma + thromboplastin, which basically just acts like tissue factor
the PT is often used to monitor someone on Coumadin. why?
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
What would be some reasons to see a prolonged PT?
- decreased factor 7, 10, 5, 2, and 1
- coumadin
- heparin
- DIC
We don’t actually order PTs though - what test do we use?
INR - it’s basically the PT corrected for the non-standardized reagents used
When should you order an INR?
- to assess liver function
- to monitor coumadin therapy
- to diagnose DIC
- To assess pre-op status
What does the partial thromboplastin time (PTT) measure?
the intrinsic pathway
What is the reagent with a PTT?
you do plasma + phospholipid
Why would a PTT be prolonged?
- hemophilia A or B
- DIC
- Heparin
- Inhibitors - antibodies that bind to phospholipids
When should you order a PTT?
- investigate hx of abnormal bleding
- monitor heparin (INR would work, but PTT is better)
- dignoase DIC
- diagnose antiphospholipid antibody
- assess pre-op status
What does a Thrombin Time (TT) measure?
ony measure the time to convert fibrinogen to fibrin
What are the reagenets in a TT?
plasma and thrombin
When would the TT be prolonged?
low fibinogen
high FDPs
When should you order a TT?
If the PTT is prolonged, you do it to rule out a fibinogen problem (which is super rare)
If a TT is normal, what other study can you do after an abnormal PTT?
A PTT Mixing Study
What are the steps for a mixing study?
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
A fibrin degradation product assay does what the name says, but what is the issue with it?
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.
What test do we use instead of an FDP?
D-dimer - it measures only fibrin break down that occurred after the fibrin was already cross-linked.
Can a D-dimer be used to rule in a clot?
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
Fibrinogen assays can be used to measure fibinogen. WHat would cause it to be low?
- DIC
2. Massive bleed (we do this test to see if we need to give them blood product with fibrinogen)
