General Principles of Hemostasis - Krafts Flashcards
What is hemostasis a balance between?
Pro-Clotting (plugs up holes in blood vessels) and Anti-Clotting (keeps clotting under control)
What are the 3 factors in pro-clotting?
1) Vascular Constriction
2) Platelets to plug up the hole
3) Fibrin from Fibrinogen cascade
What happens when the blood vessel constricts?
Blood loss decreases
Platelets and factors meet (brings them closer together
What is primary hemostasis?
Platelets form a plug in the hole
What is secondary hemostasis?
Fibrinogen cascade
What happens when the platelets form a plug?
Proteins are exposed Platelets adhese Granules release contents Platelets aggregate Phospholipids are exposed
What happens when the fibrin seals up the plug?
Tissue factor is exposed
Cascade begins and makes fibrin
Fibrin solidifies plug
Where is Tissue Factor NOT normally found?
In the blood
When the first platelet finds a site of injury, what does it do?
Adhesion to the hole and release of granules
When the subsequent platelets find the initial platelet, what do they do?
Aggregation of platelets
How is the inhibition of the coagulation cascade in order to stop a clot from forming?
TFPI (Tissue Factor Pathway Inhibition)
ATIII (Anti-Thrombin III)
Proteins C and S (Cascade Brakes!)
How are clots broken down?
t-PA
Plasmin
What is seen in the vicinity of a clot being remodeled?
Chunks of fibrin from busting down the clot
In the membrane of a platelet, what are the glycoproteins associated with disease?
Phospholipids (active coag factors)
GP Ia (binds collagen)
GP Ib (binds vWF)
GP IIb-IIIa (binds fibrinogen)
What is the whole point of the cascade to a clot?
Make Fibrin
Fibrinogen is converted to fibrin by what?
Thrombin
Prothrombin is converted to thrombin by what?
Factor Xa
When the extrinsic pathway is exposed to tissue factor, what factor does it bind to?
VIIa
Where does tissue factor come from?
Hidden cells exposed during injury
Microparticles floating in blood
Endothelial cells and monocytes (during inflammation)
What activates X –> Xa?
TF-VIIa complex
When Xa is made by using tissue factor, it immediately shuts off what?
Extrinsic Pathway
What activates factor XI –> XIa?
Thrombin
What does XIa activate?
IX –> IXa
What cofactor is used to further activate and speed up the intrinsic pathway?
VIIIa binds to IXa
What converts VIII –> VIIIa, V —> Va, and VII –> VIIa?
Thrombin
What are the key factors in the extrinsic pathway?
Tissue Factor and VIIa
*SEXtrinsic Pathway (simple)
What are the key factors in the intrinsic pathway?
Factors IXa and VIIIa
*SINtrinsic Pathway (busy)
What are the two things that you can do to prevent clotting?
1) Remodel the clot
2) Stop the fibrin cascade
What are FDPs and where do they come from?
Fibrin Degradation Products come from busting up a fibrin clot
Where does t-PA work?
Plasminogen —> Plasmin to bust up the clot into Fibrin Degradation Products
How is a clot formed?
Fibrinogen –> Fibrin –> CLOT
Protein C cleaves what?
Va and VIIIa
Anti-thrombin III effects what?
VIIa, IXa, XIa, Xa, and thrombin
Tissue Factor Pathway Inhibitor (TFPI) mediates what interaction?
Xa turning off the extrinsic pathway
What are we looking for in the morphology of platelets?
Size and Granulation
What is a normal platelet count?
150,000-450,000 x 10^6/L
What is a Template Bleeding Time?
Used to evaluate platelet response to vascular injury
How do you perform a Template Bleeding Time test?
Inflate a blood pressure cuff
Make measured incisions
Time how long it takes to stop bleeding with blotting paper
What is wrong with the Template Bleeding Time test?
Does not measure the coagulation factor, just measures platelet plug formation
What does the Closure Time test measure?
How quickly platelets occlude small holes in a membrane
What is the Closure Time test used for?
Aspirin-Related Bleeding
von Willebrand disease
What is the Platelet Aggregation test?
Used to find platelet function abnormalities
How do you perform a Platelet Aggregation test?
Add aggregating agents to patient’s sample to see if platelets aggregate
Measure the DECREASE in sample turbidity
How does a coagulation lab test work?
Draw blood into citrate tube
Spin tube, decant plasma
Add reagents to plasma
Watch for formation of fibrin
What does the Prothrombin Time (PT) test measure?
Extrinsic Pathway - how long it takes to make fibrin
Plasma + Thromboplastin
What do we measure in the Extrinsic Pathway?
Factor VII
- Made by liver
- Needs Vitamin K to work
- Decreased by Coumadin
- Short half-life
What coagulation factors need Vitamin K to work?
Factor II, VII, IX, and X
What kinds of things would increase the Prothrombin time (or prolong the clotting time)?
- Decreased VII, X, V, II, I
- Coumadin
- Heparin
- Disseminated Intravascular Coagulation (DIC)
When should you order a Prothrombin Time (PT) test?
NEVER!
Order INR instead
What is an INR?
A corrected Prothrombin Time (PT) test
When should you order an INR?
- Assess Liver Function
- Monitor Coumadin Therapy
- Diagnose DIC
- Assess Pre-OP Status
What does the Partial Thromboplastin Time (PTT) test measure?
Intrinsic Pathway
Plasma + Phospholipid
What is another name for Partial Thromboplastin Time (PTT)?
Activated Partial Thromboplastin Time (APTT)
What kinds of things would increase the Partial Thromboplastin Time (or prolong the clotting time)?
Hemophilia A (Missing Factor VIII) Hemophilia B (Missing Factor IX) DIC Heparin Inhibitors
When should you order a PTT?
- Investigate a history of abnormal bleeding
- Monitor heparin therapy
- Diagnose DIC
- Diagnose an anti-phospholipid antibody
- Assess Pre-OP Status
What does the Thrombin Time test measure?
Conversion of Fibrinogen to Fibrin
Plasma + Thrombin
(Ignores the Intrinsic and Extrinsic Pathways)
What kinds of thinks would increase Thrombin Time?
Decreased Fibrinogen
Increased Fibrin Degradation Products
When should you order a Thrombin Time?
When the PTT is prolonged and you want to rule out a fibrinogen problem (VERY rare!)
If you have a prolonged PTT, but the TT is normal, what test would you order to figure out if it is an intrinsic or extrinsic problem?
PTT Mixing Study
What are the factors in the PTT Mixing Study?
Pooled Plasma + Patient Plasma + Phropholipid
What are the outcomes of the PTT Mixing Study?
If PTT corrects: some factor is missing
If PTT doesn’t correct: an inhibitor is present
What does a Fibrin Degradation Product Assay measure?
Fibrin Degradation Products (including D-dimers)
VERY VERY Sensitive
When Fibrin is forming a clot, what factor cross-links the fibrin?
Factor XIII
How is Fibrinogen broken down to FDPs?
Plasmin
How is Cross-Linked Fibrin broken down and what is it broken down to?
Plasmin
D-dimers
When are FDPs increased?
Thrombi
Minor Clotting
When should you order an FDP assay?
To rule OUT a clot
What does a Fibrinogen Assay measure?
Fibrinogen
When is Fibrinogen decreased?
DIC (using up all coag factors)
Massive bleeding
When should you order a Fibrinogen level?
- Diagnose DIC
- Follow patients with massive bleed