General Principles of Hemostasis Flashcards
Hemostasis is a balancing act between
pro-clotting and anti-clotting
pro-clotting
plugs up holes in blood vessels
anti-clotting
keep clotting under control
3 steps in pro-clotting
blood vessel constricts
Platelets form a plug
Fibrin seals up plug
blood vessel constriction –>
blood loss dec.
Platelets and factors meet
primary hemostasis
Platelets form a plug. Proteins are exposed Platelets adhese Granules release contents Platelets aggregate Phospholipids are exposed
secondary hemostasis
Fibrin seals up plug. Tissue factor is exposed Cascade begins Cascade makes fibrin Fibrin solidifies plug
Platelet adhesion vs. aggregation
cover initial hole vs. cover other prior platelets
anticlotting methods
Cascade inhibition
Clot lysis
Cascade inhibition players
TFPI
ATIII
Proteins C, S
Clot lysis players
t-PA
plasmin
Platelet granules
α (fibrinogen, vWF)
δ (serotonin, ADP, Ca2+)
Membranes of platelets
Phospholipids (activate coag factors) GP = glycoprotein GP Ia (binds collagen) GP Ib (binds vWF) GP IIb-IIIa (binds fibrinogen)
GP1a
binds collagen - mediates first platelet adhesion
GP1b
binds vWF = vonWillebron Factor to help platelets bind to each other
GP IIb-IIIa
binds fibrinogen
a granules
fibrinogen, vWF
d granules
serotonin, ADP, ca2+
Bottom line of cascade pathway
fibrinogen –> fibrin
How to make fibrin
fibrinogen --> fibrin Need thrombin (activated prothrombin)
How to activate prothrombin
–> thrombin
Need Xa
Activated X is important why
X –> Xa
central part of whole process - where extrinsic and intrinsic pathways meet
Necessary for prothrombin –> thrombin
Where does tissue factor come from?
“Hidden” cells exposed during injury
Microparticles floating in blood
Endothelial cells and monocytes (during inflammation)
What does TF do in cascade?
Join up with VII (already activated in blood) –> TF, VIIa –> go to activate X –> Xa
What does Xa do to TF,VIIa complex
Turn it off - then more fibrin needs to be made via intrinsic pathway
How to activate XI
thrombin
XI –> XIa
How to activate IX
XIa
IX –> IXa
What factors/cofactors help speed up process
VIII (complex with IXa)
V (helps Xa do its job)
How to activate X
TF, VIIIa (extrinsic) - once
IXa (intrinsic)
X –> Xa
complex with Va to be more efficient
which pathway works first
Extrinsic, once get Xa then turn off
TF
VII
Extrinsic (sextrinsic)
Complicated side
Intrinsic (sintrinsic)
Clot lysis pathway
Plasminogen activated → Plasmin by t-PA –> break up clot into FDPs
Cascade inhibition
Protein C
TFPI
ATIII
Protein C
inhibit cofactors VIIIa, Va
ATIII
inhibit activated factors (XIa, IXa, Xa, TF/VIIa, Xa, thrombin)
TFPI
inhibit TF/VIIIa
How do platelet count
done by particle counter
normal platelet number
150-450 x10^9/L
morphology of platelet normally have
granulomeres
hyalomeres
template bleeding time evaluates
platelet response to vascular injury
Some platelet disorders have a long bleeding time
How template bleeding time
Inflate blood pressure cuff
Make incision
Time how long it takes to stop bleeding
limitation template bleeding time
Lots of factors affect the test!
Some consider the test unreliable.
closure time (CT)
alternative to bleeding time
how quickly platelets occlude small holes in a membrane
platelet aggregation finds
platelet function abnormalities
How does platelet aggregation work
Add aggregating agents to patient’s sample
See if platelets aggregate
Measure decrease in sample turbidity
limitation/caveat with platelet aggregation test
always repeat abnormal test
Coagulation lab tests
Draw blood into citrate tube
Spin tube, decant plasma
Add reagents to plasma
Watch for formation of fibrin
Factor VII
Made by liver
Needs K
Dec. by Coumadin
Short half-life (so really the one you want to watch, goes down faster)
Prothrombin Time
Plasma + thromboplastin
Measures extrinsic pathway (factor VII)
Things that increase prothrombin time
Dec. VII, X, V, II, I
Coumadin
Heparin
DIC
When should you order a PT
Never - order an INR instead
Coumadin affects what factors
II, VII, IX, X
What is an INR
corrected PT
When shoudl you order an INR
To assess liver function
To monitor Coumadin therapy
To diagnose DIC*
To assess pre-op status
Partial thromboplastin time
Plasma + phospholipid
Measures intrinsic pathway
APTT = same thing
PTT increased when
Hemophilia A, B
DIC
Heparin
Inhibitors
When should you order a PTT
To investigate a history of abnormal bleeding
To monitor heparin therapy
To diagnose DIC
To diagnose an antiphospholipid antibody (ie. SLE, syphilis)
To assess pre-op status
Thrombin time
Plasma + Thrombin
Measures coversion of fibrinogen to fibrin
Bypasses intrinsic and extrinsic pathways
TT increased when
Dec. fibrinogen (ie trauma)
Inc. FDPs
PTT Mixing Study
Pooled plasma + patient plasma + phospholipid
If PTT corrects: something missing
If PTT doesn’t correct: inhibitor
When should you order a mixing study
When PTT is prolonged, but TT is normal
If PTT corrects = factor deficiency
If PTT doesn’t correct = inhibitor present
how to measure extrinsic side
PT, INR
how to measure intrinsic side
PTT
how to measure fibrinogen to fibrin
TT
Fibrin Degradation Product Assay
measures FDPs (including D-dimers) Very sensitive (almost too sensitive to dx a bad clot)
D-dimers
breakdown products of cross-linked fibrin
what cross links fibrin
Factor XIII
When are FDPs increased?
Thrombi
Minor clotting
When to order an FDP assay?
Rule out a clot - not rule in
