1
Q
What is hemostasis of Clotting?
A
The balance b/w clot formation and mechanisms that inhibit uncontrolled clotting
2
Q
What are the goals of hemostasis of clotting?
A
-limit blood loss from vascular injury
-maintain blood flow
-promote revascularization after thrombosis
3
Q
What are the 2 stages of Hemostasis of Clotting?
A
Primary and Secondary Hemostasis
4
Q
What is primary hemostasis of clotting?
A
For minor injury, immediate platelet plug formation
5
Q
What is Secondary Hemostasis?
A
Clotting cascade resulting in cross-linking of fibrin to stabilize the clot
6
Q
What is the role of vascular endothelium in clot hemostasis?
A
-Antiplatelet, Anticoagulant, Fibrinolytic
(Healthy endothelium prevents clot formation)
7
Q
What anti-clotting mechanisms do endothelial cells use?
A
Produces:
-Wall has negative charge to inhibit platelets
-Prostacyclin (PGI₂) + Nitric oxide (NO) → inhibit platelets
-ADPase → degrades ADP (platelet activator)
-Protein C activation → anticoagulant
-TFPI → inhibits factor Xa & TF–VIIa
-TPA + urokinase → fibrinolysis
8
Q
Damage to endothelium exposes what to the extracellular matrix (ECM)?
A
Collagen, vWF, and glycoproteins
9
Q
What are the 3 phases of platelet function in primary hemostasis?
A
Adhesion
Activation
Aggregation
10
Q
When does platelet adhesion occur?
A
Occurs after endothelial injury → ECM exposure
11
Q
What triggers platelet activation?
A
Triggered when platelets interacts with exposed collagen and Tissue Factor (TF) → Releasing granules
12
Q
What are the 2 types of storage granules involved in platelet Activation?
A
Alpha granules + Dense bodies
13
Q
What doe Alpha granules contain?
A
Factors I, V, VIII, Plt-derived growth factor
14
Q
What doe Dense bodies contain?
A
ADP, ATP, Ca++, Serotonin, Histamine, Epinephrine
15
Q
What is platelet aggregation?
A
When granular contents released activate: → Additional Platelets + propagating clotting cascades
16
Q
What does each stage of the clotting cascade require assembly of?
A
Tenase-complexes
17
Q
What is the INTRINSIC Pathway Tenase complex?
A
(Plt membrane) phospholipid + 9a + 8a + Ca++
18
Q
What is the EXTRINSIC Pathway Tenase-complex?
A
(Plt membrane) Phospholipid + TF + 7a+ Ca++
19
Q
What doe the Intrinsic and extrinsic complexes facilitate the formation of what complex?
A
Prothrombinase Complex (10a/5a + Ca++)
20
Q
What are the structural components of a tenase complex in the clotting cascade?
A
Substrate (inactive precursor)
Enzyme (activated clotting factor)
Cofactor (accelerator)
Calcium (Ca²⁺)
21
Q
What are the 2 major Pathways of clot formation?
A
Intrinisic and Extrinisc Pathways
22
Q
how does the Intrinsic pathway activate and what does current research suggest of its role?
A
Activated by damage INSIDE the vessel
Plays a minor role in initiation of hemostasis, and more of an amplication system for the extrinsic pathway
23
Q
What pathway is the workhorse of coagulation and which pathway is the spark?
A
Intrinsic = most of work
Extrinsic = spark
24
Q
What doe the Extrinsic pathway mediate and how is it activated?
A
Its plasma-mediate hemostasis and due to tissue injury OUTSIDE the vessel
25
Where does the intrinsic and extrinsic pathways ultimately meet?
Intrinsic and extrinsic activate → common pathway forms the clot.
26
What is considered a negatively charged surface?
Dextran or Glass
27
What factors are in the intrinsic pathway (with names)?
XII – Hageman factor
XI – Plasma thromboplastin antecedent (PTA)
IX – Christmas factor
VIII – Antihemophilic factor
💡 “12 → 11 → 9 → 8”
28
What is the 2 pathways of Intrinsic pathway initiation?
Hemostasis intiation and Propagation
29
How is the intrinsic homeostasis pathway initiated?
Negatively charged surface →12 (Hageman factor) → 12a → 11 (Plasma Thromboplastin Antecedent) → 11a → 9 → (9a + 8a (Antihemophilic factor) + phospholipid + Ca²⁺) → 10 (Stuart-Prower factor) → 10a
30
What happens during intrinsic pathway propagation (with names)?
Common Pathway's Thrombin (2a) feeds back and re-activates:
-5 (Labile factor) of FCP
-7 (Stable factor) of FCP
-11 (Plasma Thromboplastin Antecedent) **INTRINSIC**
-13 (Fibrin stabilizing factor) of FCP
💡 Positive feedback → amplifies clotting
31
What factors are in the extrinsic pathway (with names)?
Activated by either:
3 – Tissue factor (thromboplastin)
7 – Stable factor
3/7a complex activates 10 and 9 on intrinisc pathway
💡 3 →3/7a complex → 10
32
Extrinsic Pathway: Upon injury what is exposed to plasma?
Tissue Factor
33
Extrinsic Pathway: What does the TF/VIIa (3/7a) complex activate?
Factor X (10)
and
IX (9) in intrinsic pathway
34
What factors are in the common pathway (with names)?
X – Stuart-Prower factor
V – Labile factor
II – Prothrombin
I – Fibrinogen
XIII – Fibrin stabilizing factor
💡 “10 → 5 → 2 → 1 → 13”
35
What Factor begins the final common pathway?
Xa
36
Intrinsic or extrinsic pathway ends at Factor X, When activated what does (Xa + Va + Ca++ ) form?
Prothombinase complex
37
What is the Purpose of the Prothominase complex (Xa/Va + Ca++)?
Rapidly converts prothombin (II) into thrombin (IIa)
38
How does thrombin (IIa) work?
Attaches to platelets and converts Fibrinogen (I) to Fibrin (Ia)
39
What does Factor XIIIa (13a) do after Fibrinogen is converted to fibrin?
Crosslinks fibrin strands to stabilize clot (makes stronger)
40
Why is Thrombin (2a) the master factor?
Key regulator of hemostasis
Thrombin drives clotting, but also prevents excessive clotting (anticoagulant property)
41
What are the 4 major coagulation counter-mechanisms?
-Fibrinolysis
-Tissue Factor Pathway inhibitior (TFPI)
-Protein C system
-Serine Protease inhibitiors (SERPINs)
42
What is fibrinolysis and how does it work?
Clot breakdown system: tPA & urokinase → plasminogen → plasmin.
-Plasmin breaks down fibrin (clots) and degrades factor V (5) and VIII (8)
43
What does Tissue Factor Pathway Inhibitor (TFPI) do?
Blocks Extrinsic pathway: Inhibits 3/7a complex and inhibits factor Xa (10a)
44
What does the Protein C system inhibit?
Turns off amplification factors: Protein C + S complex inhibits II (prothombin), Va (5a), and VIIIa (8a)
45
What does antithrombin (AT) inhibit?
What can the endogenous and exogenous heparin do?
-Inhibits Thrombin (IIa),
IXa (9a), Xa (10a), XIa (11a), XIIa (12a)
-Endogenous Heparin cofactor II → inhibits thrombin (2a) alone
-Exogenous Heparin → accelerates AT
46
What preOp question should be asked about Coagulation History?
History of excessive bleeding, Trauma, Bloodtransfusions?
47
What blood thinners should be assessed prior to surgery? What other drugs that induce bleeding?
-ASA, NSAIDS, Vitamin E, Tumeric, St. John Wort.
-Cayenne pepper, Ginko, Ginger, Garlic, and Grape seed
-Beta-Lactam ABX and SSRIs
Nitroprusside, NO, and NTG
48
What comorbities effect coagulation?
Renal, Liver, Thyroid, and Bone marrow disorders
49
What are First line labs for suspected bleeding disorders?
PT and aPTT
50
Which lab test the extrinsic and common pathway?
PT
51
PT reflects what factors?
I, II (2), V(5), VII (7), X (10)
52
What drugs do PT labs monitor?
Vitamin K anatgonist/ Warfarin
53
What Factors are K dependent?
II(2), VII (7), and X (10)
54
What lab test the intrinsic and common pathway?
aPTT
55
The aPTT reflects what factors?
VIII (8) and IX (9)
56
What drug does aPTT test?
Heparin
57
What is demographic of vWF disease?
Most common inherited blood disorder effecting 1% of population
58
↓ vWF causes what?
↓ vWF → impaired platelet to collagen adhesion and ↓ factor VIII (8) stability (increase degredation)
59
What are typical lab findings of vWD?
Platelets: normal
PT: normal
aPTT: normal or ↑ (due to low factor VIII (8))
LABS ARE NOT HELPFUL
60
What tests are used to diagnose vWD?
vWF level
vWF activity (platelet binding)
Factor VIII level
Platelet function assay
61
How is von Willebrand disease treated (2)?
-DDAVP → ↑ vWF release (mild cases)
-vWF + Factor VIII concentrate (severe or intraOp-surgery)
62
What are Hemophilia A vs B?
Hemophilia A → Factor VIII (8) deficiency
Hemophilia B → Factor IX (9) deficiency
63
Which hemophilia is more common?
Hemophilia A
A 1:5K > B 1:30K
64
How does hemophilia typically present?
Presents in childhood:
Spontaneous bleeding Joints and Muscles
65
What are lab findings in hemophilia?
Platelets: normal
PT: normal
Bleeding time: normal
PTT: ↑ prolonged
💡 Intrinsic pathway problem
66
How is hemophilia managed perioperatively?
Factor VIII or IX replacement
DDAVP (mild Hemophilia A)
Hematology consult
67
What coagulation-related factors are produced by the liver?
Clotting factors: V (5), VII (7), IX (9), X (10), XI (11), XII (12)
Anticoagulants: Protein C, Protein S, Antithrombin
68
What are typical coagulation labs in liver disease?
PT: ↑ prolonged (earliest change)
PTT: normal or ↑
69
Why are coagulation labs misleading in liver disease? What is this called?
Rebalanced Hemostasis = Labs show ↓ procoagulant factors
BUT also ↓ anticoagulants
(So higher risk of both bleeding and thrombosis)
70
What tests are most useful to assess coagulation in liver disease?
TEG / ROTEM
71
Why do CKD patients develop anemia?
↓ Erythropoietin (EPO) production =
Leads to ↓ RBC production
72
Why do CKD patients have platelet dysfunction?
Uremic environment → platelet dysfunction = Impaired platelet adhesion & aggregation
73
How is platelet dysfunction treated in CKD?
-DDAVP → ↑ vWF release
-Cryoprecipitate → provides vWF
-Conjugated estrogens given 5 DAY PRIOR
74
What is disseminated intravascular coagulation (DIC)?
Pathologic activation of coagulation (via TF/VIIa) causing:
-Widespread microthrombi
-Consumption of clotting factors
75
What conditions can trigger DIC?
Trauma
Sepsis ⭐
Malignancy
Amniotic fluid embolism
Incompatible transfusion
76
What are lab findings in DIC?
↓ Platelets
↑ PT, PTT, thrombin time
↑ fibrin degradation products (D-dimer)
💡 Everything prolonged + platelets low
77
How is DIC treated?
FIRST: Correct the underlying condition.
SECOND: Replace appropriate blood components
78
What causes trauma-induced coagulopathy(2)?
* Overactivation of Protein C system via hypoperfusion (Mass protein C causes → inhibits clotting → bleeding)
* Autoheparization
79
What is “auto-heparinization” in trauma?
Proteoglycan in the endothelial glycocalyx degrade which
causes releases in heparin-like substances
→ ↑ anticoagulation
💡 Body acts like it gave itself heparin
80
What worsen to trauma-induced coagulopathy?
Platelet dysfunction
81
What are the Prothrombotic states (4)?
-Factor V Leiden mutation
-Prothrombin mutation
-Thrombophilia
-Antiphospholipid syndrome
82
What is Factor V Leiden mutation?
Activated Protein C resistance = ↑ clotting (hypercoagulable state)
83
What is the prothrombin mutation?
↑ Prothrombin (Factor II) levels = ↑ thrombin formation and Hypercoagulability
84
What is thrombophilia?
Inherited or acquired hypercoagulable state that presents as venous thrombosis
85
What is the triad associated with Thrombophilia?
Virchow’s Triad:
Stasis
Endothelial injury
Hypercoagulability
86
What is antiphospholipid syndrome?
Autoimmune antibodies activate phospholipid-binding proteins in platelets= hypercoagulability
87
What is associated with Antiphosopholipid Syndrome?
Recurrent thrombosis
Pregnancy loss
Need for life long anticoagulation
88
What is heparin-induced thrombocytopenia (HIT)?
Immune-mediated reaction to heparin.
89
When does HIT occur?
Typical: 5–14 days after heparin
If prior exposure: can occur within 1 day
90
What does HIT cause?
Causes:
Increase consumption of clotting factors
↓ platelets and
↑ clotting activation of remaining platelets
91
What are risk factors for HIT?
-Unfractionated heparin > LMWH
-High Heparin doses (e.g., Cardiopulmonary bypass)
-Female
92
How is HIT managed?
STOP heparin immediately
Start alternative anticoagulant (e.g., argatroban, bivalirudin)
❌ Avoid Warfarin
93
How is HIT diagnosed?
HIT antibody testing
94
What happens to HIT antibodies over time?
Typically clear in ~3 months
95
What does the Anti-Xa labs measure? and what drugs does it assess?
Measures factor Xa inhibition
Assess:
-Heparin
-LMWH
-Fondaparinux
-Xa inhibitors
96
What is a normal platelet count?
>100,000 platelets/µL
97
What does ACT measure and when is it used?
Measures whole blood clotting time and responsiveness to heparin
98
What is normal ACT?
94-120
99
What pathways does ACT measure?
Intrinsic and common pathways
100
1mg of Protamine will inhibit how much of Heparin?
1mg
1:1 ratio
101
How is heparin concentration assessed and reversed?
Assessment based on plasma heparin levels
Used to titrate protamine to neurtalize heparin (Protamine > Heparin amount)
102
103
What do viscoelastic coagulation tests (TEG/ROTEM) measure?
Measure entire clot formation process
104
What does R time represent and normal value?
Time to initial clot formation
Normal: 5–10 min
105
What does ↑ R time mean and how do we treat?
Delayed clot initiation
FFP
106
What does K time represent and normal value?
Time to clot strength formation
Normal: 1-3 mins
107
What does ↑ K time mean and how do we treat?
Fibrinogen problem
Cryo
108
What does alpha angle represent and normal value?
Rate of fibrin buildup
Normal: 53–72°
109
What does ↓ alpha angle mean and how do we treat?
Low fibrinogen
Cyro
110
What does MA represent and normal value?
Clot strength
Normal: 50–70 mm
111
What does ↓ MA mean and how do we treat?
Platelet dysfunction or low platelets
Platelets ± DDAVP
112
What does LY30 represent and normal value?
Clot breakdown (fibrinolysis)
Normal: 0–8%
113
what is ↑ LY30 mean and how do we treat it?
Hyperfribrinolysis/Clot breakdown
TXA ± aminocaproic acid
114
How do COX inhibitors affect platelets?
Block COX-1 → ↓ TxA₂ → ↓ platelet aggregation
115
What are the COX inhibitors?
ASA and NSAIDs
116
What are the Anti-platelet effects of ASA and NSAIDs?
ASA= 7-10 days
NSAIDs = 3 days
117
How do P2Y12 inhibitors work?
Block P2Y12 (ADP receptor)
→ ↓ GIIb/IIIa expression = ↓ platelet aggregation
118
What are P2Y12 inhibitors?
Clopidogrel:
Ticlopidine:
Ticagrelor, Cangrelor:
119
How long are the antiplatelet effects of P2Y12 inhibitors?
Clopidogrel: ~7 days
Ticlopidine: 14–21 days
Ticagrelor, Cangrelor: short-acting (<24 hr)
120
How do GIIb/IIIa inhibitors work?
Block GIIb/IIIa receptor
→ Prevent fibrinogen & vWF binding = No platelet aggregation
121
What are the GIIb/IIIa inhibitors?
Abciximab
Eptifibatide
Tirofiban
122
How do vitamin K antagonists work?
Inhibit vitamin K–dependent factor synthesis:
↓ Factors: II (2), VII (7), IX (9), X (10) and Protein C & S
123
Warfarin is the drug of choice for?
Valve-replacement
NOT AFIB anymore
124
Key characteristics of warfarin?
-Long half-life (~40 hr) that takes 3–4 days to reach effect
-Target INR: 2–3
125
How is warfarin reversed?
Vit K
126
How does heparin work?
Upregulates ↑ AT activity and inhibits Thrombin (IIa) and Factor Xa (10a)
127
Key features of unfractionated heparin?
-IV, short half-life
-Requires monitoring (PTT or ACT)
-Fully reversible with protamine
128
Key features of LMWH?
-Longer half-life andn SQ dosing
-NO routine monitoring
-Protamine only **partially** reverses
129
Key features of fondaparinux?
-Very long half-life (17–21 hr)
-Once daily dosing
-NO reversal with protamine
130
What are the direct thrombin inhibitiors?
Hirudin, Argatroban, Bivalirudin, and Dabigatran (pradaxa)
131
What is the mechanism of direct thrombin inhibitors?
Directly inhibit thrombin (Factor IIa)
132
Where is Hirudin synethsized from?
Leeches
133
Key features of argatroban?
Reversibly binds thrombin and Short half-life (~45 min)
Monitored by PTT or ACT
134
Key features of bivalirudin?
Shortest Half-life
Drug of choice with renal or liver impairment
135
What is dabigatran (Pradaxa)?
Drug of choice for Afib and CVA prevention
136
What are the Oral Anticoagulants?
DTI's: Dabigatran (pradaxa)
Direct Xa inhibitors: Rivaroxabn (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa)
137
What is the benefits of Direct oral anticoagulants?
-Predictable Pharmcokinetics
-Fexwer drug interactions
-PO w/o lab monitoring
-Similar to Warfarin but shorter half-life
138
DOACs vs Warfarin?
DOACs have lower mortality than warfarin
139
How do thrombolytics work?
Convert plasminogen → plasmin = plasmin breaks down fibrin → clot dissolution
140
What are fibrin-specific thrombolytics?
Alteplase (tPA)
Reteplase
Tenecteplase
141
What are nonfibrin-specific thrombolytics?
Streptokinase but
Less used due to allergic reactions
142
How long is surgery contraindicated for after thrombolytic treatment?
<10 days
143
What are absolute contraindications to thrombolytics?
-Vascular lesions, Brain tumors
-Recent trauma, Cranial surgery, Active bleeding
-Severe uncontrolled HTN (SBP >185 or DBP >110)
-Ischemic stroke <3 months
144
What are relative contraindications to thrombolytics?
-Ischemic stroke >3 months after
-Major surgery <3 weeks prior
-Active peptic ulcer and anticoagulant use
-Pregnancy
-Prolonged/traumatic CPR (<3 weeks)
145
How do antifibrinolytics work?
Inhibit plasminogen binding to fibrin → ↓ plasmin formation = ↓ clot breakdown
146
What are the catagories of Procoagulants?
Antifribrinolytics + Factor replacements
147
What are the 2 subclasses of Antifibrinolytics?
Lysine analogues
SERPINs
148
What are lysine analogue antifibrinolytics and their MOA?
Tranexamic Acid (TXA)
Epsilon-aminocaproic acid (EACA)
MOA: Block plasminogen → fibrin binding
149
What is the SERPIN antifibrinolytic and their MOA?
Aprotinin
MOA= Inhibits proteases (plasmin, kallikrein)
150
Why was Aproptin removed from the Market?
Due to cardiac and renal toxicity
151
What are the Factor Replacements(4)?
-Recombinant VIIa
-Prothombin complex concentrate
-Fibrinogen Concentrate
-Cyroprecipitate + FFP
152
What does recombinant Factor VIIa (7a) do?
↑ thrombin generation = promotes clot generation
153
What is Prothrombin Complex Concentrate (PCC)?
Contains vitamin K–dependent factors:
II, VII, IX, X
154
What are fibrinogen replacement options?
Fibrinogen concentrate
Cryoprecipitate + FFP
155
How is warfarin managed preoperatively? What about high clot-risk pts?
Stop 5 days before surgery and Restart 12–24 hr postop
High-risk pts → bridge with UFH or LMWH
156
When do you stop and restart Unfractionated Heparin?
Stop 4–6 hours before surgery
Restart ≥12 hr postop (no bolus)
157
When do you stop and restart LMWH (Lovenox)?
Stop 24 hours before surgery
Restart 24 hours postop
158
How is aspirin managed preoperatively?
-Low risk → stop 7–10 days prior
-Moderate/high risk → continue ASA
159
When do we stop DTI's prior to surgery?
Normally 4-6 hrs prior
W/ Renal impairment 2-4 days prior
160
When do we stop Factor Xa inhibitiors prior to surgery?
2-3 days prior
161
When should elective surgery be delayed after Metal or Drug stent placement?
-Bare-metal stent → wait 6 weeks
-Drug-eluting stent → wait 6 months
162
Neuraxial anesthesia timing for ASA/NSAIDs?
No restrictions
Safe for:
Placement and Removal
163
Neuraxial timing for UFH SQ heparin (BID)?
No restrictions
Safe for:
Placement
Removal
164
Neuraxial timing for UFH SQ heparin (TID)?
-STOP 4 hours before placement
-Wait 2 hours after placement to restart drug
-STOP 4 hours before catheter removal
-Wait 2 hours after removal → next dose
165
Neuraxial timing for LMWH (lovenox) (daily dosing)?
-STOP 12 hours before placement
-Wait 6 hours after placement to restart drug
-STOP 12 hours before removal
Wait 4 hours after removal → next dose
166
Neuraxial considerations for warfarin?
Stop 5 days prior + INR < 1.5
❌ Contraindicated with catheter in place
Wait 2 hours after removal → next dose
167
What is the Emergent Reversal for Warfarin?
Prothrombin complex then FFP + Vit K
168
What is the emergent reversal for DTI's?
NO reversal but HL are short.
-Pradaxa antidote is: Idarucizumab
169
What are the DOAC Factor Xa Inhibitor reversals?
Andexanent
170
Kahoot: What is the lifespan of a non-activated platelet?
8-12 days
171
Kahoot: The platelet activation occurs during?
interaction w/collagen and tissure factor (TF)
172
Kahoot: Which element is an essential part of the coagulation tenase-complex?
Ca++
173
Kahoot: Which Factors activate factor XI (9)?
TF/VIIa Complex and XIa (11a)
174
Kahoot: Phase II hemostasis is primarily initiatied by?
Extrinsic pathway
175
Kahoot: Which system mainly amplifies thrombin generation?
Intrinsic pathway
176
Kahoot: Which lab value may be abnormal in Hemophilia?
PTT
177
Anemia in chronic Renal disease is due to?
EPO deficiency and Platelet dysfunction
178
Kahoot: What lab findings are associated with DIC?
-Thrombocytopenia
-Increased Fibrin degredation yet increase fibrin
-Prolonged PT/PTT
Health Ass
flashcards
Decks in class (15)
# Cards
-
Self Assessment Questions for Exam 2 (Dr. Erickson)20
-
Exam 2 Musculoskeletal Disease61
-
Exam 2 Airway Assessment71
-
Ischemic Heart Disease (Exam IV)89
-
Valvular Disease (Exam IV)80
-
Blood Disorders (Exam III) Marcus's Cards39
-
Blood Products and Transfusion (Exam II)110
-
Acute pain75
-
Renal Assessment Final Edit137
-
Vascular Diseases (Final Draft)104
-
Hepatic and Biliary126
-
Neurologic Diseases115
-
Coagulation Test 4178
-
Gastrointestinal Test 4128
-
Endocrine Test 4151
