General Principles of Hemostasis - Krafts Flashcards
1
Q
How is hemostasis a balancing act?
A
- Balance between:
- Pro-clotting
- plugs up holes in blood vessels
- Anti-clotting
- keeps clotting under control
- Pro-clotting
2
Q
What are the three (simplistic) steps of clotting?
A
- Vascular constriction
- Form platelet plug (primary hemostasis)
- Make fibrinogen (secondary hemostasis)
3
Q
Why is vessel constriction important in clotting?
A
- Blood loss decreases
- Platelets and factors meet
- help components come in contact with each other
4
Q
What are the basic steps of platelets forming a plug?
A
- Proteins are exposed in endothelium
- collagen
- Platelets adhesion to proteins
- via collagen
- Platelets change shape and release granules
- attract more platelets
- Platelets aggregate
- Phospholipids are exposed
5
Q
What is fibrin important for?
A
- Fibrin seals up plug
- Tissue factor is exposed
- Cascade begins (fibrinogen → fibrin)
- Cascade makes fibrin
- Fibrin solidifies plug
6
Q
How do you keep clotting from getting out of control?
A
- Breakdown formed clot
- fibrin chunks (remodeling)
- t-PA
- plasmin
- Inhibit formation of clots
- cascade inhibition
- TFPI
- ATIII
- Proteins C, S
- cascade inhibition
7
Q
What are the four membrane glycoproteins that are important in platelet adhesion and aggregation in clot formation?
A
- Phospholipids
- activate coag factors
- GP Ia
- binds collagen
- GP Ib
- binds vWF
- GP IIb-IIIa
- binds fibrinogen
- mediates interactions between platelets
8
Q
What do each of the roman numerals stand for in the coagulation cascade?
A
- Proenzymes that become activated
- activate more enzymes
- Activated enzymes have “a”
9
Q
What are the three parts of the Coagulation Cascade? Why are they named accordingly?
A
- Intrinsic
- components are sitting in the blood
- Extrinsic
- have to add tissue factor
- Final Common Pathway
- two arms meet
- form one pathway
- “meet me at 10”
10
Q
What is the whole point of the Coagulation Cascade?
A
MAKE FIBRIN!
11
Q
What molecule activates fibrinogen → fibrin?
A
Thrombin
12
Q
What molecule activates prothrombin → thrombin?
A
Xa
13
Q
How does the coagulation cascade start?
A
Tissue Factor becomes exposed.
14
Q
Where does tissue factor come from?
A
- “Hidden” cells exposed during injury
- Microparticles floating around in blood
- Endothelial cells and monocytes
- during inflammation
15
Q
What does tissue factor bind to in the coagulation cascade?
A
VIIa
16
Q
What molecule activates X → Xa?
A
TF + VIIa complex
17
Q
What happens immediately after X → Xa in the extrinsic pathway?
A
- Xa inhibits the TF-VIIa complex
- Shuts down extrinsic pathway after it “kickstarts” Xa
18
Q
What most likely converts the co-factors VIII→VIIIa and V→Va?
A
Thrombin
19
Q
How are clots broken down?
A
-
Plasmin breaks down clot into FDPs
- fibrin degradation products
- Plasminogen → Plasmin
- via t-PA
20
Q
What are the three ways you can stop the coagulation cascade?
A
- Protein C (w/ Protein S)
- cleaves VIIIa
- cleaves Va
- Antithrombin III
- affects factors on both sides (mostly intrinsic)
- give co-factors “bear hug” and prevents them from working properly
- TFPI
- acts on TF+VIIa complex
21
Q
What are the two platelet lab tests?
A
- Count
- Done by particle counter
- Normal = 150-450 x 10^9
- Morphology
- Size
- Granulation
22
Q
What are the two zones of a normal platelet?
A
- Granulomere (center)
- Hyalomere (surrounding)
23
Q
What is the Template Bleeding Time test?
A
- Inflate blood pressure cuff
- Make incision
- Measure time it takes to stop bleeding
24
Q
Why would one perform a Template Bleeding Time?
A
- Evaluate platelet response to vascular injury
- Some platelet disorders have a long bleeding time
- Only test that looks at how platelets work inside the patient’s arm as they are stopping the blood flow
- ***test does not measure coagulation
25
What test is an alternative to the template bleeding time that uses a platelet function analyzer to measure how quickly platelets occlude small holes in a membrane?
Closure Time (CT)
| ("in-vitro bleeding time)
26
What is the Platelet Aggregation test?
* Add aggregating agents to patient's sample (plasma with platelets)
* e.g. ADP
* See if platelets aggregate
* Measure **decrease** in sample turbidity
* get clear solution
* Helps find platelet function abnormalities
27
What are the general steps in Coagulation Lab Tests?
* Measure how well patient can make fibrin by:
* draw blood into citrate tube
* Spin tube, decant plasma
* Add reagents to plasma
* Watch for formation of fibrin
* normal time of formation OR
* prolonged time
28
What is a Prothrombin Time (PT) test?
* Plasma + thromboplastin
* thromboplastin acts as Tissue Factor
* measure how fast fibrin is formed
* Measure extrinsic pathway
* and final common pathway
29
What is special about the Extrinsic pathway? What is unique about it?
* Factor VII
* made by liver
* needs Vitamin K to work
* decreased by Coumadin
* shortest half-life
30
What would make the PT increased?
* decreased VII, X, V, II, I
* Coumadin
* affects vitamin K-dependent factors
* Heparin
* works with antithrombin III (potentiates it)
* DIC
* disseminated intravascular coagulation
* use up all coag factors
31
When should you order a PT?
* Never!
* Order INR instead.
32
What is an INR?
* Just a **corrected** PT
* Stands for international normalized ratio
33
When should you order an INR?
* To assess liver function
* To monitor Coumadin therapy
* To diagnose DIC
* To assess pre-op status
34
What is a Partial Thromboplastin Time (PTT) test?
* Plasma + phospholipid
* phospholipid is part of thromboplastin molecule
* Measures intrinsic pathway
* APTT = same thing
* activated partial thromboplastin time
* don't worry about differences
35
What things would make the PTT increased (prolonged)?
* Hemophilia A
* missin VIII
* Hemophilia B
* missing IX
* DIC
* missing all the factors everywhere
* Heparin
* Inhibitors
* antibodies that influence intrinsic pathway
36
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
* To assess pre-op status
37
What is a Thrombin Time test?
* Plasma + thrombin
* Measures conversion of fibrinogen ⇒ fibrin
* Bypasses intrinsic and extrinsic pathways
38
What would increase TT?
* decreased fibrinogen
* increased FDPs
39
When should you order a Thrombin Time test?
* When the PTT is prolonged, and you want to rule out a fibrinogen problem
* rare
40
What is a PTT Mixing Study?
* Pooled plasma + patient plasma + phospholipid
* If PTT corects: something missing
* something was added in the pooled plasma that pt was missing
* If PTT doesn't correct: inhibitor
* antibody that messes up test
41
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
42
What is a Fibrin Degradation Product Assay?
* Measures FDPs (fibrin degradation products)
* including D-dimers
* VERY sensitive
43
What happens to fibrin in a clot? What perfoms this?
* Cross-links to form sturdy clot
* Done via XIII
44
What does the D-dimer test measure?
* Cross-linked fibrin broken down by plasmin
* products = d-dimers
45
When should you order an FDP assay?
* To **_rule out_** a clot
* Not to rule in a clot
* SUPER SENSITIVE
46
What causes increased FDPs?
* Thrombi
* Minor clotting
47
What is a Fibrinogen Assay?
* Measure fibrinogen
48
What causes decreased fibrinogen?
* DIC
* Massive bleeding
49
When should you order a fibrinogen level?
* To diagnose DIC
* \*\*To follow patients with massive bleed
