General Principles of Hemostasis- Krafts Flashcards
What are the three steps in clotting?
(1) Blood vessel constricts
- Blood loss decreases
- Platelets and factors meet
(2) Platelets form a plug
- Proteins are exposed
- Platelets adhere
- Granules release contents
- Platelets aggregate
- Phospholipids are exposed
(3) Fibrin seals up the plug
- Tissue factor is exposed
- Cascade begins
- Cascade makes fibrin
- Fibrin solidifies plug
What are the two mechanisms of anti-clotting?
(1) Cascade inhibition
- TFPI
- ATIII
- Proteins C, S
(2) Clot lysis
- t-PA
- Plasmin
What are the platelet membrane molecules we need to memorize?
Phospholipids (activate coag factors)
GP Ia (binds collagen)
GP Ib (binds vWF)
GP IIb-IIa (binds fibrinogen)
What is the end goals of the coagulation cascade?
Make fibrin!!!
Why are the two arms of the cascade named intrinsic and extrinsic?
Intrinsic- everything you need for the cascade is in the blood
Extrinsic- Need extrinsic factor for cascade to go
Where does tissue factor (TF) come from?
- “Hidden” cells exposed during injury
- Microparticles floating in blood
- Endothelial cells and monocytes (during inflammation)
What does thrombin do?
Thrombin converts:
VIII –> VIIIa (Intrinsic)
VII –> VIIa (Extrinsic)
V –> Va (Intrinsic)
These are cofactors in the cascade
What happens in the SEXtrinsic pathway?
Simple pathway….
- Exposed TF complexes with VIIa (which was converted from thrombin from VII)
- TF/VIIa complex converts X –> Xa
COMMON PATHWAY
-Xa converts prothrombin to thrombin
-Thrombin converts fibrinogen to fibrin –> CLOT!!!
What happens after a little bit of thrombin is produced via the Extrinsic pathway?
Xa has a negative feedback on the TF/VIIa complex essentially shutting down the extrinsic pathway……
But, you have some thrombin there to start the intrinsic pathway
What are the factors we need to remember on the Extrinsic side?
Exposed TF
TF/VIIa complex
TF, 7
Explain the SINtrinsic pathway…..
- Thrombin converts XI to XIa
- XIa converts IX –> IXa
- IXa complexes with VIIIa (thrombin converts VIII to VIIIa)
- IXa/VIIa complex converts X –> Xa
- V is converted to Va by thrombin
- Va complexes with Xa
COMMON PATHWAY
-Xa/Va converts prothrombin to thrombin
-Thrombin converts fibrinogen to fibrin –> CLOT!!!
What are the factors/cofactors we need to remember for the SINtrinsic pathway?
XI to XIa
VII to VIIa (cofactor)
V to Va (cofactor)
11, 9, 10, 5
What are the little chunks of broken up clot called?
Fibrin Degradation Products (FDP)
What converts clots to FDP’s?
Plasmin
How is plasmin formed?
Plasminogen is converted to plasmin using t-PA
What does Protein C do?
Blocks Va and VIIIa cofactors…..less clotting
What does ATIII do?
Blocks XIa, IXa, Xa, Thrombin, and VIIa….less clotting
What does TFPI do?
Tissue Factor Pathway Inhibitor
Blocks TF……less clotting
What are the two important platelet lab tests?
Count: 150-450 x10^9
Morphology: size and granulation
What is the dark center part of the platelet called? Outer light layer?
Granulomere
Hyalomere
What is the Template Bleeding Time (Bleeding Time)?
This evaluates patients response to vascular injury….this is the one you use a blood pressure cuff and slice the patient and time how long it takes them to clot…..lots of factors that effect this test.
What is an alternative to the Bleeding Time test? How does it work? Are there any advantages of this test?
Closure time:
Machine measures how quickly platelets occlude small holes in a membrane “in vitro” bleeding time
Better at detecting aspirin related bleeding and von Willenbrand disease
How and why do you do a platelet aggregation test?
How: add aggregating agents to patients sample and see if it aggregates, measure the decrease in sample turbidity…..always repeat an abnormal test
Why: To find platelet function abnormalities
How do coagulation tests work?
Draw blood into citrate tube
Spin tube, decant plasma
Add reagents to plasma
Watch for formation of fibrin
This test is either normal or prolonged
