Coags Flashcards
(150 cards)
1
Q
what is normal hemostasis
A
a balance between clot generation, thrombus formation, and counter-regulatory mechanisms that inhibit uncontrolled thrombogenesis or premature thrombus degradation
2
Q
what are the 3 goals of hemostasis
A
- to limit blood loss from vascular injury
- maintain intravascular blood flow
- promtoe revascularization after thrombosis
3
Q
what are the 2 stages of hemostasis
A
primary hemostasis and secondary hemostasis
4
Q
what is primary hemostasis
A
immediate platelet deposition at hte endovascualr injury site
* leads to the intial platelet plug
only adequate for minor injury
5
Q
what is secondary hemostasis
A
clotting actors activated
stabilized clot formed and secured with crosslinked fibrin
6
Q
what is a characteristic of vascular endothelial cells
A
they have antiplatelet, anticoagulant, and profibrinolytic effects that inhibit clot formation
7
Q
anti-clotting mechanisms of the endothelial cell
is the enothelial cell negative or positively charged
A
negatively charged to repel platelets
8
Q
anti-clotting mechanisms of the endothelial cell
what is produced by the endothelial cell
A
prodcue platelet inhibtors such as prostacylin and nitric oxide
9
Q
what is released by vascular endothelial cells and what does it do
A
excrete adenosine diposphotase, which degreades adenosine diphosphate (ADP) a platelet activator
10
Q
what anticoagulant is increased through the endothelial cells
A
increase protein C, an anticoagulant,
11
Q
the endothelial cell produces tissue factor pathway inhibitor (TFPI) which inhibits what
A
factor Xa and TF-VIIa complex
12
Q
what is synthesized by the endothelial cells
A
tissue plasminogen activator (t-PA)
13
Q
platelets play a critical role in hemostasis, where are they derived from
A
bone- marrow megakarocytes
14
Q
what is the lifespan of non-activated platelets
A
nonactivated platelets circulate as discoid anuclear cells with a lifespan of 8 to 12 years
15
Q
approximately 10% of platelets are consumeed to support vascular integrity how many platelets are formed daily
A
1.2-1.5 x 10^11 formed daily
16
Q
damage to the endothelium exposed the underlying
A
extracellular matrix (ECM)
17
Q
the extracellular matrix contains
A
collagen, vWF, and other platelet adhesive glycoproteins
18
Q
upon exposure to ECM platelets undergo what 3 phases of alteration
bonus: what stage of hemostasis is this
A
adhesion, activation, aggregation
19
Q
when does adhesion occur
A
when exposed to ECM proteins
20
Q
activation of platelets happens when the platelets are stimulated and interacts with
A
collagen and tissue factor (TF) causing the release of granular contents
21
Q
platelets contain 2 type of storage granules what are they
A
alpha granules and dense bodies
22
Q
alpha granules contain what
A
fibrinogen, factors V and VIII, vWF, plt-derived growth factor and more
23
Q
what do the dense bodies contain
A
ADP, ATP, calcium, serotonin, histmaine, and epinphrine
24
Q
aggregation occurs when
A
the granular contents are released, which recruits and activates additional platelets, propagating plasma-mediated coagulation
25
activated glycoprotein 2B/3A on the platelet surface bind what
fibrinogen, promoting fibrin crosslinking
26
each stage of the cascade requires assembly of the membrane activation tenase complexes
what is each complex composed of
a substrate (inactive precursor)
an ezyme (activated coagulation factor)
a cofactor (accelerator or catalyst)
calcium
27
# Clotting Factors
Factor I is also called
fibrinogen
28
29
Factor II is also called
prothrombin
30
Factor III is also called
tissue thomboplastin
31
Factor IV is also called
calcium ions
32
Factor V is also called
labile factor
33
Factor VII is also called
stable factor
34
Factor VIII is also called
antihemophilic factor
35
Factor IX is also called
christmas factor, plasma thomboplastic component (PTC)
36
Factor X is also called
stuart-prower factor
37
Factor XI is also called
plasma thromboplastin antecedent (PTA)
38
Factor XII is also called
hageman factor
39
Factor XIII is also called
fibrin stabilizing factor
40
extrinisc pathway is the intiation of
plasma mediated hemostasis
41
what begins the extrinsic pathway
endothelial injury, exposing TF to plasma
42
what is the extrinisc pathway
TF forms an active complex VIIa (TF/VIIa complex)
TF/VIIa complex binds to and activates factor X converting it to Xa
TF/VIIa complex also activates IX to IXa in the the intrinsic pathway
43
what is needed to convert Factor X to Xa
IXa and calcium
44
what begins the final common pathway
factor Xa
45
what begins the intrinsic pathway
XIIa
46
most thrombotic events follow ______ pathway; however lab-coag studies rely on ____ pathway to activate the cascade
extrinsic ; intrinsic
47
the intrinsic pathway plays a ____ role in the initiation of hemostasis, and is more an ______ _______ system to progoate thombin generation intiated by the extrinisic pathway
minor; amplification system
48
49
upon contact with a ______ charged surface, factor ______ is activated
negatively charged ; factor XII
50
factor XIIa converts
XI to XIa
51
what converts factor X to Xa
XIa + VIIIa + platelet membrane phospholipid + Calcium
52
activated thrombin IIa activates which factors to amplify extrinisc thombin generation
V, VIII, XII
| this process activates platelets leading to the propogation of the FCP
53
Factor X becomes Xa and binds with what to form prothrombinase complex
Va
54
# p
prothrombinase complex rapidly converts
prothrombin (II) into thrombin (IIa)
55
thrombin attaches to platelets and converts
fibrinogen (I) to fibrin (Ia)
56
fibrin molecules _____ to form a mesh that stabilizes the clot
crosslink
57
whats happening
Vascular injury exposes TF, initiating extrinsic pathway. Intrinsic pathway further amplifies thrombin & fibrin generation. Platelets adhere to collagen, become activated, and recruit additional platelets.
58
thrombin cleaves fibrinopeptides A & B from fibringogen to generate fibrin monomers, which does what
polymerize into fibrin strands to form basic clot
59
what factor cross links the fibrin strands to stabilize and make the clot insoluble, resitant to fibrinolytic degradation
XIIIa
60
T/F only the intrinsic tenase complex factilitates the fromation of prothrominase complexes
false both intrinsic and extrinsic tenase complexes factilitate the formation of prothrombinase complexes
61
fibrinolysis
endocvascular TPA and urokinase
**convert plasminogen to plasmin**
62
what does plasmin break down clots ____, and degrades which factors
ezymatically; degrading Factors V and VIII
63
TFPI forms complex with which factor and inhibits what
forms complex with Xa that inhibits TF/7a complex, along with Xa
| downregulating the extrinisic pathway
64
protein C system inhibits which factors
Factor II, Va, VIIIa
65
serine protease inhibitors (SERPINs)
AT3- inhibits thrombin, Factors 9a, 10a, 11a, 12a
heparin - binds to AT causing a conformational change that accelerates AT
Heparin Co-factor II - inhibits thombin alone
66
if you suspect bleeding disorder preop what are the first line lab
PT, aPTT
67
what Rx meds/ herbal supplements increase bleeding risk
ASA, NSAIDs, Vitamin E, Ginko, Ginger, Garlic supplements
68
what coexisting disease are at risk for bleeding
renal, liver, thryoid, and bone marrow disorders
69
list the common bleeding disorders (7)
Von Willebrand's
Hemophilia
Drug-induced bleeding
Liver disease
Chronic renal disease
Disseminated Intravascular Coagulation
Trauma-induced coagulopathy
70
# 1.
von Willebrand's Disease
deficiency in vWF, causing defective platelet adhesion/aggregation
71
vWF plats a critical role in
platelet adhesion and prevents degradation of factor VIII (8)
72
why might routine coagulation labs not be helpful with von willebrand's disease? what would be a better test to order
platelets and PT will be normal
aPTT may be prolonged depending on level of factor 8
**better test: vWF level, vWF platelet bidning activity, Factor 8 level, platelet function assay**
73
mild vWD often responsive to
DDAVP which increases vWF
| intraop bleeding may require administration of Factor 8/vWF concentrates
74
difference between Hemophilia A and Hemophilia B
A- factor 8 deficiency
B- factor 9 deficiency
| 2/3 genetically inherited; 1/3 new mutation without family hx
75
when does hemophilia present itself
in childhood as spontanoeus hemorrahe involving joints and muscles
76
labs of hemophiliac
normal PT, plts, bleeding time
PTT normally prolonged
77
Preop considerations in hemophilia
hematologist preop
**DDAVP, Factor 8 and/or 9 may be indicated before surgey**
78
drug induced bleeding
Heparin
Warfarin
Direct Oral Anticoags (DOACs)
Beta-Lactam Abx
Nitroprusside
NTG
NO
SSRIs
79
the liver is the primary source of which factors
5,7,9,10,11,12 as well as protein C & S, and antithombin
80
liver disease leads to complex, multifactorial hemostatic issues such as
impaired synthesis of coagulation factors
quantitiative and qualitivat platelet dysfunction
impaired clearance of clotting and fibrinolytic proteins
81
coags of pt with liver disease
prolonged PT and possible prolonged PTT
| TEG & ROTEM are valuable guides
82
CKD have a baseline anemia due to
lack of erythopoietin
platelet dysfunction due to uremic environment
83
what can shorten bleeding times in CKD patietns
dialysis and correction of anemia
84
treatment of platelet dysfunction in CKD includes
cryo
DDAVP
conjugated estrogen (give preop x 5days)
85
what is Disseminated Intravascular Coagulation
pathological hemostatic response to TF/7a complex causing **excessive activation of the extrinisc pathway** which overwhelms the anticoagulant mechanism and generates intravasculat thrombin
86
T/F in DIC: Coagulation factors & platelets become depleted during widespread microvascular thrombotic activity, causing multi-organ dysfunction
true!
87
what can precipitate DIC
trauma, amniotic fluid emobolus, malignancy, sepsis, or incompatible blood transfusion
88
labs of DIC
decreased platelets, prolonged PT/PTT/ thrombin time, increased soluble fibirn and fibrin degradation products
89
management of DIC
treat cause, give appropriate blood products
90
what is trauma-induced coagulopathy
independent acute coagulopathy seen in trauma patietns; thought to be related to **activated protein C** decreasing thombin generation
91
coagulopathies occur to what 3 things
acidosis, hypothermia, and/or hemodilution
92
whats the common cause of trauma related death
uncontrolled hemorrhage
93
in trauma induced coagulopathies what is the driving factor for protein C activation
hypoperfusion
94
endothelial glycocalyx, which contains proteoglycans degrades resulting in
auto-heparinization
95
most common prothrombotic states are caused by a mutation where
factor V or Prothrombin
96
Factor V Leiden Mutation leads to
activated protein C resistance
97
prothrombin mutation causes
increased PT concentration, leading to hypercoagulation
98
thrombophilia
inherited or aquired prediposition for thrombotic events
| generally manifests as venous thrombosis
## Footnote
highly susceptible to virchows triad
99
antiphospholipid syndrome
autoimmune disorder with antibodies against the phospholipid binding proteins in the coag system
**characterized by recurrent thrombosis and pregnancy loss
often require life long anticoags**
100
in patients with thrombotic state disorders what can increase the risk of thrombosis in these patients
oral contraceptives, pregnancy, immobility, infection, surgery, trauma
101
what is HIT (heparin-induced thrombocytopenia) and when does it occur after initiating heparin therapy
mild-moderate thrombocytopenia associated with heparin
occurs 5-14 days after heparin therapy
102
HIT results in
platelet count reduction as well as activation of the remaining platelets and potential thrombosis
103
risk factors for HIT
women, patietnt receiving high heparin doses such as with cardiopulmonary bypass
| UFH greater risk than LMWH
104
if HIT is suspected what should you do
DC heaprin convert to direct anticoagulant
**wafarin CI bc it decreases protein C and protein S synthesis**
105
HIT is diagnosed with what
how long do the antibodies last in circualtion
diagnosed with HIT antibody test
antibodies cleared from circulation in 3 months
106
PT assess integrity of extrinsic and common pathways and can reflect deficiences in what factors
1,2,5,7,10
| used to monitor vitamin K antagonist warfarin (2,7,10 are v.K dependent)
107
aPTT assess the integrity of intrinsic and common pathways and can reflect deficencies in which factors
Factor 8 and 9
may be used to measure effect of heparin
108
which lab am I?
I measure the seconds until clot forms after mixing plasma w/phospholipid, Ca², and an activator of the intrinsic pathway
Activated Partial Thromboplastin Time (aPTT)
109
What lab am I?
I measure the time until a clot forms after plasma is mixed w/TF
prothrombin time (PT)
110
antifactor Xa activity assay provides assessment of which antiacoagulant effect
heparin's anticoagulant effect
can also be used to assess effect of LMWH, fondaparinux, factor Xa inhbitors
111
normal plt count
greater than 100K/microliter
112
activated clotting time (ACT) measures which pathways?
what is the normal ACT value
addresses the intrinsic and common pathways
normal = 107 +/- 13 seconds
| measures responsiveness to heparin
113
1 mg of protamine will inhibit how much heparin (in mg)
## Footnote
increasing protamine will cause the clot time to decrease until protamine concentration > heparin concentration
1mg
114
TEG :)
## Footnote
on the TXWes Reference Guide for alpha angle < 53 it has give cryo -/+ platelets
115
3 main classes of antiplatelet drugs
Cyclooxygenase Inhibitors
P2Y12 receptor antagonists
Platelet GIIb/IIIa R antagonists
116
moa of Cyclooxygenase Inhibitors
Block COX 1 from forming TxA₂, which is important in plt aggregation
ASA: anti-plt effects x 7-10 days after d/c
NSAIDS: anti-plt effect x 3 days
117
P2Y12 receptor antagonists MOA
Inhibit P2Y12-R→preventing GIIb/IIIa expression
Clopidogrel: anti-plt effects x 7 days after d/c
Ticlopidine: anti-plt effects x 14-21 days after d/c
Ticagrelor & Cangrelor: Short-acting, <24h activity
118
Platelet GIIb/IIIa receptor antagonists MOA
prevent vWF & fibrinogen from binding to GIIb/IIIa-R
Abciximab, Eptifibatide, Tirofiban
119
# anticoagulant drug
Vitamin K antagonist (wafarin)
* inhibit synthesis of factors 2,7,9,10, protein C & S
* DOC for valvular Afib & valve-replacements
* Long half life (40h), can take 3-4 days to reach therapeutic INR (2-3)
* Usually requires heparin until therapeutic effect achieved
* Frequent lab monitoring required (PT/INR)
* Reversable w/Vitamin K
120
UFH
Short 1/2 life, given IV
Fully reversable w/Protamine
Close monitoring required
121
# 1.
LMWH
Longer 1/2 life, dosed BID SQ
No coag testing needed
Protamine only partially effective
122
Fondaparinux
Much longer HL (17-21h), dosed once/day
Protamine not effective
123
direct thrombin inhibtors MOA
bind/block thrombin in both soluble and fibrin bound states
124
direct thrombin inhibitors
**Hirudin**: naturally found in leeches
**Argatroban**: synthetic, reversibly binds to thrombin. HL 45 min.
Monitored intraop w/PTT or ACT
**Bivalirudin**: synthetic, shortest HL of DTI’s
DOC for renal or liver impairment
**Dabigatran** (**Pradaxa**): 1st DOAC
DTI approved for CVA prevention and non-valvular A-fib
125
direct oral anticoagulants
**Direct Thrombin Inhibitor**-Dabigatran (Pradaxa)
**Direct Xa Inhibitors: **Rivaroxaban (Xarelto), Apixaban (Eliquis), Edoxaban (Savaysa)
## Footnote
Predictable PK/PD
Fewer drug interactions
Dosed daily w/o lab monitoring
Efficacy similar to Warfarin, but much shorter HL
Fewer embolic events, intracranial hemorrhages, and lower mortality than warfarin
126
thrombolytics
**used to dissolve blood clots**
Most are Serine Proteases that convert plasminogen to plasmin, which breaks down fibrinogen to fibrin
127
how long is surgery CI with use of thrombolytic therapy
10 days
128
the 2 categories of thrombolytics are
Fibrin-Specific: Altepase (tPA), Reteplase, Tenecteplase
Non-Fibrin-Specific: Streptokinase * not widely used d/t allergic reactions
129
absolute contraindications to thrombolytics (6)
vascular lesions
uncontrolled HTN (>185/>110)
recent cranial surgery or trauma
brain tumor
ischemic stroke <3 months prior
active bleeding
130
relative contraindications to thrombolytics
ischemic stroke > 3 months
active peptic ulcer
current use of anticoagulant
pregnacy
prolonged/traumatic CPR < 3 weeks prior
major surgery < 3 weeks prior
131
procoagulants are used to mitigate blood loss; which 2 classes are there
**Antifibrinolytics**:
Lysine analogues: Epsilon-amino-caproic acid (EACA) & Tranexamic Acid (TXA)
SERPIN: Aprotinin (removed from market d/t renal & cardio toxicity)
**Factor Replacements**
Recombinant VIIa (RfVIIa): ↑’s thrombin generation via intrinsic & extrinsic paths
Prothrombin Complex Concentrate (PCC): contain vitamin-K factors
Fibrinogen Concentrate: derived from pooled plasma.
Cryoprecipitate & FFP
132
lysine analogues MOA
bind and inhibit plasminogen from binding to fibrin impairing fibrinolysis
133
post coronary stent placement guidelines:
**Bare-metal stents**→ delay elective surgery 6 weeks after placement
**Drug-eluding stents**→ delay elective surgery 6 months after placement
134
preop ASA guidelines
**mod/high rx pts**- current recommendation is to continue ASA
**low rx pts**- stop 7-10 days prior to surgery
135
preop heparin guidelines
**UFH** should be d/c’d 4-6h prior to surgery & resumed (no bolus) ≥12h postop
**LWMH** should be d/c’d 24h prior to surgery & resumed 24h postop
136
wafarin preop guidelines
**low rx pts **should d/c 5 days prior to surgery & restart 12-24h postop
**high rx pts** should stop 5 days prior & bridge w/UFH or LMWH
137
neuraxial anesthesia and anticaogs
## Footnote
top 6 rows most common
138
emergent reversal for wafarin
Prothrombin complex concntrates: DOC for emergent coumadin reversal (short 1/2 life)
concurrent Vitamin K required to restore carboxylation of Vitamin K dependent factors by the liver for more sustained correction
139
emergent reversal of direct thrombin inhibitors
no reversal, however most direct thrombin inhibitors have a relativelt short half life
| The DOAC Dabigatran (Pradaxa) does have an antidote –Idarucizumab
140
Factor Xa inhibitors emergent reversal
Andexanet, a derivative of factor Xa
141
anotha one..
## Footnote
know this one!
142
how long should garlic be DC'd before surgery
7-10 days
143
T/F st.johns wort will increase bleeding times
false, increased clotting risk
144
what herbal supplements increased bleeding time (7)
cayenne
garlic
ginger
ginkgo bibloa
grapseed oil
tumeric
vitamin E
145
heparin MOA
binds to antithrombin and directly inhibits soluble thrombin and Xa
146
direct thrombin inhibitors
bind/block thrombin in both soluble and fibrin bound states
147
NSAIDs/ASA neuraxial guidelines
no restrictions for catheter placement or removal
148
BID Heparin SQ and neuraxial considerations
no restrictions for catheter placement or removal
149
TID SQ Heparin and neuraxial anesthesia
at least 4 hours between last dose and catheter placement and removal
at least 2 hours after catheter placement and resuming drug, and removal of catheter and next dose
150
Lovenox QD and neuraxial
