Coagulation Flashcards
Test 4
1
Q
What is normal hemostasis a balance between?
A
Balance between:
-clot generation
-thrombus formation
-regulatory mechanisms
All of these should inhibit uncontrolled thrombosis
2
Q
What are the goals of hemostasis? (3)
A
- Limit blood flow from vascular injury.
- Maintain intravascular blood flow.
- Promote revascularization after thrombosis.
3
Q
What are the two different stages of hemostasis? Describe them.
A
Primary: initial platelet plug formation at the endovascular injury site
-only adequate for minor injuries
Seconday: clotting factors activated
-clot form, stabilized and secured with cross-linked fibrin
4
Q
Vascular endothelium cells have _________ (3) affects. What do these effects do? What are the mechanisms of the endothelial cells to achieve these effects? (6)
A
Anti platelet, anticoagulant, fibrolytic effects –> inhibit clot formation
- Negatively charged –> repel platelet.
- Produce prostacyclin & Nitric Oxide = platelet inhibitors
- Excrete adenosine diphosphatase –> degrades ADP (platelet activator)
- Increases protein C (anticoagulant)
- Produces tissue factor pathway inhibitor (TFPI) –> inhibits factor Xa & TF-VIIa complex
- Synthesizes. tPA
5
Q
Platelets are derived from bone marrow ________
A
megakaryocytes
6
Q
Inactivated platelet circulate as ____-shaped _______ cells. What is their lifespan?
A
disc-shaped
anuclear cells
8-12 days
7
Q
___% a platelets are consumed to support vascular integrity
A
10%
8
Q
_______billion new platelets are formed daily
A
120-150 billion
9
Q
T/F: the surface area membrane of a platelet can increase
A
T
10
Q
What does a platelet have on its surface?
A
Receptors and a canalicular system (channel & ducts)
11
Q
Damage to endothelium exposes the underlying __________ which contains what? (3)
A
Extracellular matrix (ECM)
- Collagen.
- Von Willebrand’s factor (vWBF).
- Glycoprotein.
12
Q
When platelets are exposed to contents in the extracellular matrix (ECM) what three phases do they undergo?
A
- Adhesion.
- Activation.
- Aggregation.
13
Q
Adhesion of platelets occurs when exposed to _______
A
ECM proteins
14
Q
Activation of platelets occurs when platelets interact with _____ & _______. What does this cause?
A
collagen
tissue factor (TF)
release of granular contents
15
Q
What are the two types of platelet storage granules? What do they contain?
A
Alpha granules: fibrinogen
Factors V & VIII (5 & 8)
vWF
Platelet derived growth factors
Dense bodies: ADP
ATP
Calcium
Serotonin
Histamine
Epinephrine
16
Q
When does aggregation of platelets occurs?
A
Granular contents are released –> additional platelets are activated
17
Q
Each stage of the clotting cascade requires assembly of membrane bound activated ___________. What does this consist of?(4)
A
Tenase-complexes:
-A substrate (inactivated precursor)
-an enzyme (activated coagulation factor)
-a cofactor (accelerator/catalyst)
-calcium
18
Q
Clotting factors: Factor I (1)
A
Fibrinogen
19
Q
Clotting factors: Factor II (2)
A
Prothrombin
20
Q
Clotting factors: Factor III (3)
A
Tissue thromboplastin
21
Q
Clotting factors: Factor IV (4)
A
Calcium ions
22
Q
Clotting factors: Factor V (5)
A
Labile factor
23
Q
Clotting factors: Factor VII (7)
A
Stable factor
24
Q
Clotting factors: Factor VIII (8)
A
Anti-hemophilic factor
25
Clotting factors: Factor IX (9)
Christmas factor
Plasma thromboplastin component (PTC)
26
Clotting factors: Factor X (10)
Stuart-Prower Factor
27
Clotting factors: Factor XI (11)
Plasma thromboplastin antecedent (PTA)
28
Clotting factors: Factor XII (12)
Hageman factor
29
Clotting factors: Factor XIII (13)
Fibrin stabilizing factor
30
Describe the extrinsic pathway of the clotting cascade
1. Trauma activates factor VII (7)
2. factor VII (7)--> factor VIIa --> bind to Tissue Factor
3. factor VIIa/TF --> factor X (10) --> factor Xa (common pathway)
4. Prothrombin (F II) --> Thrombin --> activates plates & converts fibrinogen of fibrin
31
The extrinsic pathway is the initiation phase of __________ homeostasis
Plasma mediated
32
Factor ______ begins the final common pathway
Xa (10a)
33
What initiates the intrinsic pathway of the clotting cascade?
Damage to the endothelial; contact with negatively charged surface --> factor XII becomes activated
34
Describe the intrinsic pathway of the clotting cascade
1. Factor XII (12) --> factor XIIa
2. Factor XIIa --> FXI (11) --> F XIa
3. F XIa --> F IX (9) --> F IXa
4. F IXa --> F X (10) --> F Xa (common pathway)
5. Prothrombin (F II) --> Thrombin --> activates plates & converts fibrinogen of fibrin
35
What additional factors does Thrombin (F IIa) activate?
V - 5
VII - 7
VIII - 8
XI - 11
36
What forms the prothrombinase complex? What does this do?
Factor Xa & Factor Va
Converts prothrombin --> thrombin
37
Describe the common pathway
1. Factor Xa & Factor Va --> Prothrombin to thrombin
2. Thrombin attaches to platelet --> converts fibrinogen to fibrin
3. Fibrin cross link --> stabilize clot
38
_________ is the key step in regulating hemostasis
Thrombin generation
39
What are the 4 major anticoagulation mechanisms? Describe them
1. Fibrinolysis: TPA & Urokinase
Convert plasminogen to plasmin
Breaks down clots
Degrades factors V & VIII
2. Tissue factor pathway inhibitor (TFPI): forms complex with Xa --> inhibits VIIa/TF complex & Xa
Down regulates the extrinsic pathway
3. Protein C system: inhibits factors II, Va, VIIIa
4. Serine Protease inhibitors (SERPINs):
-antithrombin (AT): inhibits thrombin, factors IXa, Xa, XIa, XIIa,
-Heparin: Bonds to antithrombin --> confirmational change that accelerates antithrombin activity
-heparin cofactor II: inhibits thrombin alone
40
_______ are first line labs if bleeding disorder is suspected
PT, aPTT
41
Pinpoint important things from vWBF disease
**Most common bleeding disorder**
Deficiency in vWBF --> defective platelet adhesion/aggregation
vWBF prevents degradation of Factor 8 --> decreased Factor 8
aPTT prolonged (platelets/PT normal)
Mild cases will respond to DDAVP
Tx: vWBF & Factor 8 concentrates
42
Describe Hemophilia
Hemophilia A: Factor 8 deficiency (1/5000)
Hemophilia B: Factor 9 deficiency (1/30000)
**2/3 genetic**
**1/3 present as a new mutation w/o family hx**
Presents in childhood as spontaneous hemorrhage involving joints & muscles
**Labs: PTT prolonged**
Normal PT & bleeding time
Tx: DDAVP
Factors 8/9 concentrates before Sx
43
What drugs induce bleeding?
Heparin
Warfarin
PO anticoags
Beta-lactam abx
Nitroprusside
Nitroglycerin
NO
SSRIs
44
What herbs induce bleeding?
Cayenne
Garlic
Ginger
Ginkgo Biloba
Grapeseed oil
St. John wort
Turmeric
Vitamin E
45
The liver is the primary source of what factors? How does liver disease affect this?
Factors:
5
7
9
10
11
12
Protein C & S
Antithrombin
Hemostatic issues:
-Impaired synthesis of coagulation factors
-quantitative and qualitative platelet dysfunction
-impaired clearance of clotting in fibrinolytic proteins
**Labs: prolonged PT/PTT**
46
How does Chronic Kidney Disease affect coagulation? How do we Tx this?
CKD --> anemia at base dt:
-lack of erythopoietin
-platelet dysfunction dt uremic environment
Tx: Dialysis
Correction of anemia
(Both shorten bleeding time)
Cryo
DDAVP
Conjugated estrogen preop x5days
(these are for platelet dysfunction only)
47
Describe DIC
Disseminated intravascular coagulation
Pathologic hemostatic response to TF/7a complex --> excessive activation of extrinsic pathway
Coagulation factors & platelets become depleted --> widespread microvascular thrombosis --> multiorgan dysfunction
causes: trauma, amniotic fluid in embolus, malignancy, sepsis, incompatible blood transfusion
labs: decreased platelets,
Prolonged PT/PTT/TT/Soluble fibrin/fibrin degration products
Tx: correct underlying condition
Administer appropriate blood products
48
Coagulopathies occur dt ______ (3)
Acidosis
Hypothermia
Hemodilution
49
What is trauma induced coagulopathy?
Acute coagulopathy scene and trauma patient thought to be related to **activated protein C decreasing thrombin generation**
Hypoperfusion is thought to be the driving factor for protein C activation
50
Decribe the Prothrombotic disorders (4). Which are most common?
**Inherited/genetic**
Factor V Leiden mutation: activated, protein C resistance
-present 5% Caucasian population
Prothrombin mutation: increase prothrombin concentration --> hypercoagulation
Thrombophilia: can be inherited or acquired
-highly susceptible to Virchow's triad (blood stasis, endothelial injury, hypercoagulability)
Antiphospholipid syndrome: autoimmune disorder with antibodies against phospholipid binding proteins in the coagulation system
-recurrent thrombosis and pregnancy loss
Requires lifelong anticoagulant
**PO contraceptives, pregnancy, and mobility, infection, surgery and trauma, greatly increased the risk of thrombosis**
51
Describe HIT
Heparin induced thrombocytopenia
Occurs 5 to 14 days after heparin treatment
Platelet count reduction --> potential thrombosis
Auto immune response in 5% patient receiving heparin
**Response can occur within 1 day if previously had heparin before**
Infraction heparin >> LMWH risk
Cannot bridge to warfarin
Dx confirmed with HIT antibody testing
Antibodies cleared within 3 months
52
Labs: PT
Second until clot forms
**extrinsic/common**
Deficiencies in factors: 1, 2, 5, 7, 10
**Used for Warfarin**
53
Labs: aPTT
Second until clot forms after mixing plasma with phospholipid, Ca++, and an activator of the intrinsic pathway
**intrinsic/ common**
Deficiencies in factors: 8, 9
**Used for Heparin**
54
Labs: Anti-factor Xa
Functional assessment of heparins anticoagulant effects
55
Labs: platelet count
Normal: >100,000plts/microliter
56
Labs: activated clotting time (ACT)
Normal: 107 +/- 13seconds
Addition of clotting activator to accelerate clotting time
**intrinsic/common**
Measure responsiveness to heparin
57
Labs: heparin concentration measurements
Determines preoperative heparin concentration
58
1mg protamine will inhibit ____ heparin
1mg
59
What are my Viscoelastic coagulation test?
TEG
ROTEM
60
TEG values/Tx: R time
Time to start forming clot
Normal: 5-10minutes
>10min --> FFP
61
TEG values/Tx: K time
Time until clot reaches a fixed strength
Normal: 1-3 mins
>3min --> cryo
62
TEG values/Tx: Alpha angle
Speed of fibrin accumulation
Normal: 53 - 72 degrees
Tx: cryo
63
TEG values/Tx: maximum amplitude (MA)
Highest vertical amplitude of the TEG
Normal: 50 - 70 mm
Tx: Platelets
DDAVP
64
TEG values/Tx: LY30
Percentage of amplitude reduction 30 minutes after maximum amplitude (percentage of clot dissolved after 30 minutes)
Normal: 0-8%
>8% --> TXA or Aminocaproic acid
65
What are the three classes of anti-platelets? How do they work? How long do their anti-platelet effects last after stopping the drug?
1. Cyclooxygenase inhibitors: Block COX1 from forming TXA2
-ASA: 7-10 days
-NSAIDS: 3 days
2. P2Y12-Receptor antagonists: Inhibit those receptors & prevent IIb/IIIa granulation/aggregation
-Clopidogrel: 7 days
-Ticopidine: 14-21 days
-Ticagrelor & Cangrelor: 24 hrs
3. Platelet GIIb/IIIa antagonists: prevents vWF & fibrinogen from binding to those receptors
-Abciximab, Eptifibatide, Tirofiban
66
What are the vitamin K dependent factors?
2
7
9
10
Protein C & S
67
Anticoagulants: Warfarin
Long 1/2 life (40h)
3-4 days to reach therapeutic INR (2-3)
Reversible with vitamin K
68
Anticoagulants: Heparin
MOA: binds to ANTITHROMBIN!!!! --> inhibits thrombin & Xa
(indirect thrombin inhibitor)
UFH:
Short 1/2 life
fully reversable w/ protamine
Close monitoring required
LMWH:
Longer HL
Dose BID SQ
Partially reversed w/ protamine
Fondaparinux:
Much longer half life (17-21h)
Dose once a day
Not reversible
69
Anticoagulants: direct thrombin inhibitors
MOA: bind/block thrombin
Hirudin: found in leeches
Argatroban: reversible
Bivalirudin: shortest half life
Dabigatran (Pradaxa): 1st DOAC (PO)
70
DOAC =
Direct Oral anticoagulants
71
What are the benefits of DOAC? What drugs are they?
More predictable pharmacokinetics/ pharmacodynamics
-fewer drug interactions
-does daily without lab monitoring
-shorter half life
-fewer embolic events
-lower mortality
Direct thrombin inhibitors: Dabigatran (Pradaxa)
Direct Xa inhibitors: Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa)
72
What are the 2 categories of thrombolytics?
Fibrin-Specific: tPA, Reteplase, Tenecteplase
Non-Fibrin-Specific: Streptokinase (has allergic reactions sometimes)
73
Surgery is contraindicated within _______ of thrombolytic treatment
10 days
74
What are absolute contraindications for thrombolytic treatment?
Vascular lesions
-severe uncontrolled hypertension (SBP >185; DBP >110)
-recent cranial surgery or trauma
-brain tumor
-ischemic stroke <3 months
-Active bleeding
75
What are relative contraindications for thrombolytic treatment?
Ischemic stroke >3 months
-Active Pepcid ulcer
-current use of anticoagulant drug drugs
-pregnancy
-prolonged or traumatic CPR <3 weeks prior
-major surgery <3 weeks prior
76
What are the 2 Procoagulant classes? Describe them. What is included in them?
Antifibrinolytics:
-Lysine analogues: Epsilon-amino-caproic acid (EACA) & Tranexamic acid (TXA) - inhibits plasminogen from binding to fibrin --> impairs fibrinolysis
-SERPIN: Aprotinin - removed from market dt renal/cardio toxicity
Factor Replacements:
-Recombinant VIIa
-prothrombin complex concentrates (PCC): has vit K factors
-fibrinogen concentrates
-cryoprecipitate & FFP: more coag factors but less specific
77
When should you stop/start taking this med for Sx: Warfarin
low risk:
stop: 5 days prior
start: 12-24 h
high risk:
Stop: 5 days prior & bridge to heparin
78
When should you stop/start taking this med for Sx: Heparin
UFH:
Stop: 4-6h
Start: 12h
LMWH:
Stop: 24h
start: 24h
79
When should you stop/start taking this med for Sx: aspirin
mod/high risk: continue
low risk:
stop: 7-10 days
80
We delay elective Sx for _____ with bare metal stents & ______ for drug eluding stents
6 weeks
6 months
81
What are the reversals for warfarin?
Prothrombin complex concentrates (PCC) = for emergent reversal
vitamin K = more sustained reversal (slower)
82
The reversal for DOAC Dabigatran (Pradaxa) is ________
Idarucizumab
83
The reversal for DOAC factor Xa inhibitors is __________
Andexanet
