Principles of Hemostasis Flashcards
2 pathways of clotting
Extrinsic
Intrinsic
Pro clotting
plugs up holes in vessels
anti clotting
keeps clotting under control
primary hemostasis
formation of platelet plug
secondary hemostasis
forming of fibrin meshwork
First step in pro clotting cascade
blood vessels constrict - blood loss decreases and platelets and factors meet
What happens when platelets form a plug
proteins are exposed platelets adhese Granules release contents platelets aggregate phospholipids are exposed
Why is phospholipid exposure so important?
Coag factors need phospholipids to adhere to surface of endothelium
Fibrin
Seals up plug
What happens when TF is exposed?
Cascade begins, makes fibrin
General mechanism?
- Platelets see subendothelium and stick
- Layer of platelets adhese, flatten out and release granules
- Granules attract other platelets
- phospholipids exposed on newly activated surface
- Coag factors come and sit down
- fibrin made
What busts up fibrin
FDPs
Clotting cascade inhibition mediated by?
TFPI
ATIII
Proteins C and S
Clot lysis mediated by?
t-PA
Plasmin
Granules in platelets
a (firbrinogen, vWF)
d (serotonin, ADP, Ca)
Membrane of platelets contain
phospholipids (bind coag factors)
GP Ia (collagen)
GP Ib (vWF)
GP IIb-IIIa (fibrinogen)
GP Ia
Binds collagen
GP Ib
Binds vWF
GP IIb-IIIa
binds fibrinogen
vWF
helps platelets stick together
fibrinogen to fibrin mediated by what enzyme?
Thrombin (IIa)
Prothrombin to thrombin mediated by?
Xa
What activates X to Xa in extrinsic pathway?
TF and VIIa
What activates VII in Extrinsic pathway?
exposed TF
Where does tissue factor come from?
- Hidden cells exposed during injury
- Microparticles floating in blood
- Endothelial cells and monocytes (during inflammation)
Factor XII
Always hanging out. TF binds and turns to VIIa which then binds to X and makes Xa
What happens to the extrinsic pathway once Xa is made?
It is turned off - anything further goes through the intrinsic pathway
Once a small amount of thrombin is made via extrinisic…
goes up to the intrinsic pathway, activates XI to turn into XIa
XIa activates
IX to IXa
IXa activates
X to Xa
VIIIa
cofactor, helps with conversion IXa to Xa
Va
helps Xa turn protrombin into thrombin
What breaks up clots to FDPs
plasmin
plasminogen to plasma enzyme
via t-PA
Can give t-PA if
recent clot, speed process along (needs to be right kind of clot)
Protein C
Acts on cofactors VIIIa and Va.
If cofactors are working then…
process moves along well. If you turn off process -want cofactors to stop.
ATIII
Acts on both sides of cascade.
Bear hugs the activated factor and prevents from doing what supposed to do.
TFPI
Tissue factor pathway inhibitor - turns of extrinsic side
For a platelet count to account for bleeding…
would need to be extremely low (like 20,000)
agranular
no granules
Template bleeding time - why?
Evaluate platelet response to vascular injury
Some platelet disorders have a long bleeding time
Template bleeding time - how?
Inflate BP cuff
Make incision
Time how long it takes to stop bleeding
Template bleeding time - is it reliable?
Not really, lots of factors affect the test.
Closure time (CT)
Measures how quickly platelets get into and occlude small holes in a membrane.
Platelet aggregation tests - why?
Find platelet abnormalities
Platelet aggregation tests - how?
Add aggregating agents to patient’s sample
See if aggregate
Measure DECREASE in turbidity
Coag lab tests
Draw blood into citrate tube
Spin and decant plasma
Add reagents to plasma
Watch for formation of fibirn
Prothrombin time
plasma + thromboplastin
measures extrinsic pathway
Factor VII
Made by liver
Need K
Decreased by coumadin
Short half life
PT increased when
Decrease in VII, X, V, II or I
Coumadin
Heparin
DIC
Is PT ever decreased?
NO
Coumadin affects
all vitamin k dependent factors (II, VII, IX, X)
When should you order a PT?
Never, always an INR
INR
a corrected PT
When should you order an INR?
To assess liver function
To monitor coumadin therapy
Diagnose DIC
assess pre-op status
Partial Thromboplastin Time (PTT)
plasma + phospholipid
Measures intrinsic pathway
APTT = same thing
PTT increased with
Hemophilia A Hemophilia B DIC Heparin Inhibitors
When should you order PTT?
Investigate abnormal bleeding Monitor heparin therapy Diagnose DIC Diagnose antiphospholipid antibody Assess pre-op status
thrombin time
plasma + thrombin
Measures conversion of fibrinogen to fibrin
Bypasses the intrinsic and extrinsic pathway
TT increaess
decreased fibrinogen
increased FDPs
When should you order a thrombin time?
When the PTT is prolonged and you want to rule out a fibrinogen problem
PTT mixing study
pooled plasma + patient plasma + phospholipid
PTT corrects
something is missing (VIII or IX usually - hemophilia)
PTT doesn’t correct
inhibitor (anti phospholipid ab)
When order a mixing study?
PTT is prolonged, but TT is normal
Fibrin Degradation Product assay
measures FDP (including d dimers) VERY SENSITIVE (almost too much)
FDPS increase in
Thrombi
minor clotting
Factor XIII
Cross links once in clots - makes lattice shape and strengthens
Should order an FDP to…
Rule OUT a clot
