Coags- Exam IV (Mordecai) Flashcards
1
Q
What is hemostasis?
A
A balance between clot generation, thrombus formation, and regulatory mechanisms that inhibit uncontrolled thrombogenesis.
2
Q
What are the goals of hemostasis?
A
- Limit blood loss from vascular injury
- Maintain intravascular blood flow
- Promote revascularization after thrombosis
3
Q
What are the two stages of hemostasis?
A
- Primary Hemostasis
- Secondary Hemostasis
4
Q
What occurs during primary hemostasis?
A
Immediate platelet deposition at the endovascular injury site leading to the initial platelet plug formation.
5
Q
What happens during secondary hemostasis?
A
Clotting factors are activated and a stabilized clot is formed and secured with crosslinked fibrin.
6
Q
What is the role of vascular endothelial cells in hemostasis?
A
They have antiplatelet, anticoagulant, and fibrolytic effects to inhibit clot formation.
7
Q
What are some anti-clotting mechanisms of endothelial cells?
A
- Negatively charged to repel platelets
- Produce platelet inhibitors such as prostacyclin and nitric oxide
- Excrete adenosine diphosphatase
- Increase protein C, an anticoagulant
- Produce Tissue Factor Pathway Inhibitor (TFPI)
- Synthesize tissue plasminogen activator (t-PA)
8
Q
What is the lifespan of platelets?
A
8-12 days.
9
Q
What are the two types of storage granules in platelets?
A
- Alpha granules
- Dense bodies
10
Q
What is the function of alpha granules?
A
Storage of fibrinogen, factors V & VIII, von Willebrand factor, platelet-derived growth factor
11
Q
What is the function of dense bodies?
A
Storage of ADP, ATP, calcium, serotonin, histamine, and epinephrine.
12
Q
Extrinsic Pathway
What is the role of factor Xa in hemostasis?
A
Begins the final common pathway.
13
Q
What is the intrinsic pathway primarily thought to do?
A
Amplifies thrombin generation initiated by the extrinsic pathway.
14
Q
What activates the intrinsic pathway?
A
Trigger: contact with a negatively charged surface (e.g., exposed collagen inside the vessel) activates factor XIIa
It’s a chain reaction that starts when blood touches something it shouldn’t, like the damaged inner wall of a blood vessel. That exposure triggers clotting.
15
Q
What is the prothrombinase complex?
A
- Formed by factor Xa and Va in the common pathway
- Converts prothrombin (II) into thrombin (IIa).
16
Q
It converts Factor __? into Factor ___?
What does thrombin do?
A
Converts fibrinogen (I) to fibrin (Ia), stabilizing the clot.
17
Q
What are the four major coagulation counter-mechanisms?
A
- Fibrinolysis
- Tissue factor pathway inhibitor (TFPI)
- Protein C system
- Serine Protease Inhibitors (SERPINs)
18
Q
What is the most common inherited bleeding disorder?
A
Von Willebrand’s Disease.
19
Q
What is the primary defect in Von Willebrand’s Disease?
A
Deficiency in von Willebrand factor (vWF), causing defective platelet adhesion/aggregation.
20
Q
What are the common laboratory findings in Hemophilia?
A
Normal PT, platelets, and bleeding time; prolonged aPTT.
21
Q
What is disseminated intravascular coagulation (DIC)?
A
A pathological hemostatic response causing excessive activation of the extrinsic pathway, leading to multi-organ dysfunction.
Decreased platelets, prolonged PT/PTT/Thrombin time, HIGH fibrin degradation products
22
Q
Coagulation factors made in the liver:
A
- 5, 7, 9, 10, 11, 12
- Protein C and S
- Antithrombin
23
Q
Decreases the generation of which clotting factor?
What is the role of activated protein C in trauma-induced coagulopathy?
A
Decreases thrombin generation, leading to coagulopathy.
24
Q
What is thrombophilia?
A
Inherited or acquired predisposition for thrombotic events.
25
What does the prothrombin mutation cause?
Increased prothrombin concentration, leading to hypercoagulation.
26
What is the function of the Anti-factor Xa activity assay?
Provides functional assessment of heparin's anticoagulant effect.
27
What does a prolonged PT indicate?
Deficiencies in factors I, II, V, VII, and X.
28
What is the effect of heparin on antithrombin?
Heparin binds to antithrombin, causing a conformational change that accelerates its activity.
29
What is the significance of DDAVP in Von Willebrand's Disease?
It increases von Willebrand factor levels.
30
What are the laboratory tests used for bleeding disorders?
* PT
* aPTT
* vWF level
* vWF-platelet binding activity
* Factor VIII level
* Platelet function assay
31
What is the typical presentation of Hemophilia?
Spontaneous hemorrhage involving joints and muscles.
32
What does the term 'auto-heparinization' refer to?
* The degradation of the endothelial glycocalyx leading to platelet dysfunction and increased bleeding.
* Seen in trauma-induced coagulopathy
33
# Antibodies clear when? What drug is c/i?
What defines Heparin-Induced Thrombocytopenia (HIT)?
Mild-moderate thrombocytopenia associated with heparin causing decreased platelet count, activation of remaining platelets, and potential thrombosis.
Antibodies can clear from circulation w/in 3 months
Warfarin contraindicated
34
What is aPTT measuring?
* Intrinsic and common pathway
* Deficiencies in factor 8 & 9 (VIII, IX)
-Factor VIII and IX are crucial for activating Factor X — the final step of the intrinsic side.
35
What does the anti-factor Xa activity assay measure?
Functional assessment of heparin's anticoagulant effect
## Footnote
It uses plasma combined with Xa and an artificial substrate.
36
What is the normal platelet count?
>100,000 plts/microliter
## Footnote
This is a standard component of coagulation testing.
37
# What is a normal ACT?
What does Activated Clotting Time (ACT) measure?
* Assesses intrinsic and common pathways
* Responsiveness to Heparin
## Footnote
Normal ACT is 107 +/- 13 seconds.
38
What does Heparin Concentration Measurement determine?
Perioperative heparin concentration
## Footnote
1mg protamine reverses 100 units of heparin.
39
What are the main classes of antiplatelet agents?
* Cyclooxygenase Inhibitors
* P2Y12 receptor antagonists
* Platelet GIIb/IIIa R antagonists
## Footnote
These agents inhibit platelet aggregation and/or adhesion.
40
What is the mechanism of action of Cyclooxygenase Inhibitors?
Block Cox 1 from forming TxA₂
## Footnote
Important for platelet aggregation.
41
What is the common anticoagulant that is a Vitamin K antagonist?
Warfarin
## Footnote
DOC for valvular Afib & valve replacements.
42
What is the half-life of Warfarin?
40 hours
## Footnote
It can take 3-4 days to reach therapeutic INR (2-3).
43
What is the reversal agent for Warfarin?
Vitamin K
## Footnote
It is necessary for restoring the synthesis of vitamin K dependent factors.
44
What is the dosing schedule for LMWH?
BID SQ
## Footnote
It has a longer half-life than unfractionated heparin.
45
What are Direct Thrombin Inhibitors?
Agents that bind/block thrombin in both soluble & fibrin-bound states
## Footnote
Examples include Hirudin, Argatroban, and Bivalirudin.
46
# Can be reversed with?
What is the first DOAC approved for CVA prevention?
Dabigatran (Pradaxa)
Can be reversed by Idarucizumab
## Footnote
It is a Direct Thrombin Inhibitor.
47
What are the two categories of thrombolytics?
* Fibrin-Specific: tPA, Reteplase, Tenecteplase
* Non-Fibrin-Specific: Streptokinase; not used d/t allergic reactions
48
What is the role of antifibrinolytics?
Mitigate blood loss
## Footnote
They include lysine analogues and SERPIN.
49
What are lysine analogues used for?
Inhibit plasminogen from binding to fibrin
## Footnote
Examples include Epsilon-amino-caproic acid (EACA) and Tranexamic Acid (TXA).
50
What are the preoperative guidelines for stopping Warfarin?
Low rx pts: d/c 5 days prior;
high rx pts: stop 5 days prior & bridge with UFH or LMWH
## Footnote
Restart 12-24h postop.
51
# Bare metal vs drug-eluting stents
What is the management for patients post coronary stent placement?
* Bare-metal stents: delay elective surgery 6 weeks
* Drug-eluting stents: delay elective surgery 6 months
## Footnote
This is to prevent complications.
52
What is the preferred method for emergent reversal of Warfarin?
Prothrombin Complex Concentrates
## Footnote
Vitamin K is also used for sustained correction.
53
True or False: Protamine is effective against Fondaparinux.
False
## Footnote
Protamine is not effective against Fondaparinux.
54
What is the antidote for Dabigatran?
Idarucizumab
## Footnote
It is specifically for the direct thrombin inhibitor.
55
Fill in the blank: The DOAC Factor Xa Inhibitors may be reversed by _______.
Andexanet
## Footnote
It is a derivative of factor Xa.
56
Step-By-Step; Intrinsic Pathway
* Factor XII (12) gets activated → XIIa
* *Trigger: contact with a negatively charged surface (e.g., exposed collagen inside the vessel)*
* XIIa activates Factor XI (11) → XIa
* XIa activates Factor IX (9) → IXa
* IXa works with Factor VIIIa (8a), calcium, and phospholipids to activate...
* Factor X (10) → Xa
This is the key step that leads into the common pathway, where thrombin and fibrin form the final clot.
57
Pneumonic to remember instrinsic pathway
"12, 11, 9, 8 → 10"
Think:
💥 Something triggers 12 → 11 → 9 (with help from 8) → leads to 10
Everything is happening inside the vessel = intrinsic
58
What activates the extrinsic pathway?
Damage to vascular endothelial cells and blood escapes the vessel --> initiates plasma-mediated hemostasis
59
Step-By-Step; Extrinsic Pathway
* Tissue Factor (TF) (also Factor III) is released from damaged tissue outside the vessel.
* Tissue Factor binds to Factor VII → activates it to VIIa
* The TF–VIIa complex (plus calcium) activates... Factor X → Xa
-You’re now in the common pathway just like the intrinsic side.
“3 + 7 = 10”
Tissue Factor (III) + Factor VII → activates X
60
What initiates the Common Pathway?
Whether the clotting started from inside the vessel (intrinsic) or outside the vessel (extrinsic), both feed into the common pathway at Factor X.
61
Step-By-Step; Common Pathway
* Factor X (10) is activated → Xa
* Xa teams up with:
-Factor V (5a)
-Calcium
-Phospholipids
-**This combo forms the prothrombinase complex**
* Prothrombinase turns Prothrombin (Factor II) → Thrombin (IIa)
* Thrombin (IIa) then converts Fibrinogen (Factor I) → Fibrin (Ia)
* Fibrin strands form a meshwork to create a stable clot
* Finally, Factor XIII (13) cross-links the fibrin → making the clot strong and permanent
62
What is fibrinolysis?
* Endovascular t-PA & urokinase convert plasminogen into plasmin
* Clot lysis
* Degradation of of factor V & VIII
63
What does tissue factor pathway inhibitor do?
TFPI
* Forms complex with Xa --> inhibiting TF and VIIa
* Suppresses Extrinsic pathway
64
Which factors does Protein C inhibit?
* II
* Va
* VIIIa
65
SERPINS; AT, Heparin, Heparin Cofactor II.
What do they do?
**Antithrombin:**
* Inhibits thrombin and factors IXa, Xa, XIa, XIIa
**Heparin**
* Binds antithrombin --> accelerating activity
**Heparin Cofactor II**
* Inhibits thrombin
66
Hemophilia A vs B
**Hemophilia A**
Factor VIII deficiency
**Hemophillia B**
Factor IX deficiency
67
Pre-op Considerations for Hemophilia
* Hematology consult
* DDAVP
* Factors VIII and IX may be indicated
68
What is Factor V Leiden?
Activated protein C resistance --> resistant to the lysis of clots
69
Antiphospholipid Syndrome
Autoimmunie disorder with antibodies against the phospolipid-binding proteins in the coagulation system
70
Coagulation lab that measures the function of extrinsic and common pathway?
PT
Plasma is combined with TF --> seconds until a clot forms is measured
Used to monitor warfarin
71
Coagulation lab that measures the function of intrinsic and common pathway?
aPTT
Plasma is mixed with phospholipids and Ca++ --> seconds until a clot is formed is measure
Used to monitor heparin
72
# What is it?
What is the value for TEG-ACT?
* 80-140 sec
* Activated clotting time to initial fibrin formation
73
# What is R-Time? What does it measure? Short/prolonged values?
What is the normal value for R time?
* 5.0 - 10.0 min
* Reaction time, initial clot formation (time for first fibrin strand to appear)
* Measures coagulation factor activity, specifically intrinsic pathway clotting factors
* Prolonged R-time: Hypocoagulable
* Short R-time: Hypercoagulable
74
# What is K time? What does it measure? Short/long values mean?
What is the normal value for K time?
* 1-3 minutes
* "Kinetic" time; the speed at which the clot reaches a 20mm amplitude on the TEG tracing
* Measures the speed at which fibrin builds and cross-links--> directly reflects fibrinogen function
* Short K time --> hypercoagulable state (high fibrinogen, pregnancy). Corresponds w/ a large a-angle
* Long K time --> prolonged clot formation (anticoags, low fibrinogen). Corresponds w/ a short a-angle
75
# What is it/what does it measure? Small or large A-angle?
What is the normal value for α angle?
| Inversely related to what?
* 53 - 72°
* The α-angle represents the rate of clot formation and reflects fibrin cross-linking and fibrinogen function
* Determined from the slope between R (reaction time) and K (kinetics time) on the TEG tracing.
* Small a-angle values indicate hypofibrinogenemia or the affects of anticoags
* Large a-angle values indicate hypercoagulable state
Inversely related to K-time
76
# What is it? What does it measure? High or low values mean what?
What is the normal value for MA?
* 50-70mm
* Maximum amplitude of teg tracing; peak of clot firmness
* Measures platelet number and function
* High MA suggests increased clot strength
* Low MA indicates low fibrinogen or abnormal platelet function
77
# What is it? What does it measure? High or low values?
What is the normal value for G value?
* 5.3-12.4 dynes/cm2
* Measures overall clot strength and function of the entire coagulation cascade
* Directly reflects platelet function and fibrin crosslinking
* High value indicates very strong clot, possible hypercoagulapathy. Increased risk of thrombosis
* Low value indicates weak clot, hypocoagulable states. Increased risk of bleeding
78
# What is it? What does it measure? High or low values?
What is the normal value for LY 30?
* 0-3%
* Represents the proportion of the clot lost due to fibrinolysis at 30 minutes
* High LY30 indicates excessive fibrinolysis. The body is lysing the clots too quickly-> bleeding risk
* Low LY30 indicates hypercoagulopathic state. Body is failing to break clots down-> thrombosis risk
79
If TEG-ACT is > 140 what do we transfuse?
* FFP
80
If R time is > 10 what do we transfuse?
* FFP or prothrombin complex concentrate
81
If K time is > 3 what do we transfuse?
* Cryo because K time directly measures fibrinogen
82
If α angle < 53° what do we transfuse
* Cryo and platelets
83
If MA < 50 what do we transfuse?
Check fibrinogen and platelet mapping
FF low—> give cryo
Platelet mapping abnormal —> give platelets
84
If LY30 is >3% what do we transfuse?
TXA (Tranexamic Acid)
85
1. R-Time
2. K-time
3. A-angle
4. Maximum amplitude
5. LY-30
6. Shows time in minutes
7. This side of the graph indicates coagulation
8. This side indicates fibrinolysis
86
When do Cox-Inhibitors need to be stopped prior to surgery?
ASA: 7-10 days
NSAIDS: 3 days
87
P2Y12 Receptor MOA
Inhibit the P2Y12-r from activating GIIb/IIIa, inhibiting fibrinogen from binding to GIIb/GIIIa-R
88
When do P2Y12 Antagonists need to be stopped prior to surgery?
* Clopidogrel: 7 days
* Ticlopidine: 14-21 days
* Ticagrelor & Cangrelor: < 24hr
89
Platelet GIIb/GIIIa Receptor Antagonist MOA
* Prevent vWF and fibrinogen from binding to receptor
* Abciximab, Eptifibatide, Tirofiban
90
Which factors are Vitamin-K dependent?
2, 7, 9, 10
Protein C and S
91
Direct Xa Inhibitors
Rivaroxaban
Apixaban
Edoxaban
