Coagulation Pharmacology Flashcards
1
Q
hemostasis
A
prevents blood loss, keeps blood within the vessels
2
Q
4 steps of clot formation
A
- initiation
- amplification
- propagation
- stabilization
3
Q
3 key players of hemostasis
A
vascular endothelium, platelets, plasma coagulation proteins
4
Q
primary hemostasis vs secondary
A
1: when PLTs arrive to site of injury and form the initial plug
2: requires crosslinking of fibrin
5
Q
4 events of hemostasis
A
- vasoconstriction
- formation of a temporary loose plt plug (primary…adhesion, activation, aggregation)
- stable fibrin clot formation (secondary)
- clot retraction and dissolution
6
Q
how is plt plug formed
A
vonWillebrand factor is released and binds plts to the damaged endothelium
7
Q
what protein binds platelets to vWF
A
glycoprotein 1B
8
Q
how is the plt plug activated
A
Thrombin (factor 2a) binds to the plt, which causes it to change shape and release ADP & TXA2 (thromboxane A2). ADP & TX2 promote aggregation
thrombin+PLT = ADP/TXA2 release
9
Q
4 factors that activate platelets
A
collagen, ADP, TXA2, activated neutrophils secrete plt-activating factor
10
Q
plt aggregation…what is main factor involved
A
Fibrinogen (TXA2 and ADP uncover fibrinogen receptors on plts so fibrinogen (factor 1) can bind to plt, causing plts to link together)
11
Q
what binds plt and fibrinogen
A
glycoprotein 2B/3A
12
Q
what is released after endothelial injury
A
thromboplastin or tissue factor (TF or factor 3)
13
Q
what is the first event of the extrinsic pathway of clotting cascade
A
endothelial release of thromboplastin or TF/factor 3
14
Q
4 steps of secondary hemostasis
A
- generate thrombin
- thrombin breaks down to fibribogen (factor 1)
- fibrin is released
- fibrin stands solidify the clot (acts like a glue)
(TFFC: thrombin, fibrinogen, fibrin, clot)
15
Q
3 pathways of the clotting cascade and associated factors
A
intrinsic (12, 11, 9, 10)
extrinsic (3, 7, 10)
common (1, 2, 5, 10, 13)
16
Q
steps of the extrinsic pathway (4)
A
injury to vessel releases thromboplastin (factor 3/TF) –> factor 3 forms complex w/ factor 7 on plt surface –> factor 10 –> Factor 10 is activated by Calcium to 10a
17
Q
steps of intrinsic pathway (7)
A
exposure of blood to collagen activates factor 12 –> 12a –>11–> 11a –> 9 –> 9a complexes with factor 8a & Cal on plt surface –> this activates factor 10
18
Q
steps of the common pathways (4)
A
factor 10a complexes w factor 5 and cal –> this converts factor 2 (prothrombin) to 2a (thrombin) –> thrombin converts fibrinogen(1) to fibrin(1a).
Factor 13 –> 13a by thrombin and calcium
19
Q
what factor causes fibrin to crosslink and stabilize the clot
A
Factor 13a
20
Q
all clotting factors are made in the liver except…(3)
A
vWF
TF (factor 3)
calcium (factor 4)
21
Q
what factors are vit k dependent and require calcium for activity (board Q*)
A
2, 7, 9, 10
(2+7 is 9 not 10)
22
Q
name for factor 1
A
fibrinogen
23
Q
name for factor 2
A
prothrombin
24
Q
name for factor 3
A
tissue factor (TF) or thromboplastin
25
name for factor 4
calcium
26
name for factor 5
proaccelerin or labile factor
27
name for factor 7
proconvertin or stable factor
28
vWF =
von Willebrand (doen't have a #)
29
name for factor 13
fibrin stabilizing
30
5 steps to stop clotting
1. liver clears activated factors
2. AT and thrombomodulin inactivate proteases
3. protein C inactivates fac 5 & 8
4. thrombin inhibited (by development of fibrin)
5. fibrinolysis via plasmin
31
what converts plasminogen to plasmin
tPA (tissue plasminogen activator)
32
what activates protein C and what does this do
-thrombomodulin activates protein C
-protein C inactivates factor 5 and 8
-this inactivates thrombin
33
whats the inactive form of plasmin
plasminogen
34
2 substances that are incorporated in the the clot as its developing
plasminogen and tPA
35
what does tPA do
converts plasminogen to plasmin
36
what does plasmin do
breaks down fibrin
37
what does antithrombin (AT) do
1. inhibits thrombin (2a) and 10a
2. partially inhibits factor 9a, 11a, 12a
3. results in anticoagulation
38
AT is a cofactor for...?
heparin
39
where is AT made? what happens if pt has AT deficiency?
-liver
-pt is unresponsive to heparin if deficient
40
prothrombin time (PT) looks at which pathways
extrinsic and common
41
PT is sensitive to deficiencies in...(5)
fibrinogen
factor 2, 5, 7, 10
42
what drugs can PT be used to monitor AC with
vitamin K antagonists/warfarin
43
what is INR
-international normalized ratio...standardized system to report PT (bc of different lab reagents)
-ratio of a pt's PT to a normal (control) sample
44
what pathways does aptt look at
intrinsic and common
45
aptt is sensitive to deficiencies in factors...(2)
8 & 9
46
whats ACT and what pathways
activated clotting time
intrinsic and common
47
what prolongs ACT? what does it assess?
heparin
-assess adequacy of heparinization (most accurate at high conc of heparin)
48
what affects ACT results (4)
plt dysfunction, thrombocytopenia, hemodilution, hypothermia
49
normal PT
12-14s
50
normal aptt
25-32s
51
normal ACT
80-150s
52
normal thrombin time (common pathway)
8-12s
53
3 classes of coag drugs
1. procoagulant
2. antithrombotics (reduce clot formation)
3. thrombolytics (dissolve clots)
54
what are procoagulants used for
used during sx to control bleeding and help clot formation
55
examples of procoagulants (6)
aminocaproic acid (amicar), DDAVP, protamine, fibrinogen, activated factor 7a, topical thrombin
56
2 classes of procoagulants
antifibrinolytics (EACA, TXA, aprotinin) and factor replacements
57
Epsilon aminocaproic acid (EACA) MOA
competitively inhibits the binding site on plasminogen. blocking conversion to plasmin and impairing fibrinolysis
58
tranexamic acid (TXA) MOA
-competitively inhibits the binding site on plasminogen. blocking conversion to plasmin and impairing fibrinolysis (same as EACA, but more data and better outcomes w TXA)
-TXA also directly inhibits plasmin at high doses
59
What types of cases is TXA used in
-cardiac, ortho, trauma sx
-can also be used for neuro, hepatic, OB/gyn sx
60
SE of TXA
seizure
61
Aprotinin MOA
directly inhibits plasmin
(currently off market for renal/CV toxicity)
62
Protamine MOA
-inactivates heparin via acid-base interaction
-protamine is + and hep is -...electrostatic complex is formed and inactivates hep (does NOT work on lovenox)
63
protamine dosing
must be dosed based on how much heparin is in circulation, if too much is given you can induce coagulopathy
-1mg/100u of heparin
64
protamine SE (4)
anaphylaxis
pulm vasoconst
R heart failure
hypotension (admin slowly to avoid)
65
3 causes of protamine sensitization
increased risk of SE
1. NPH insulin (diabetics)
2. vasectomy (protamine made from fish sperm)
3. prior protamine exposure
66
DDAVP MOA
stimulate release of vFW from endothelial cells and shorten bleeding time
67
DDAVP dose
0.3mg/kg over 15-30m to avoid hypotension
68
what is Fibrinogen (factor 1) affected by (3)
thrombin, factor 13a, plasmin
69
what reduces fibrinogen levels
1. hemorrhage
2, hemodilution
70
normal fibrinogen level
200-400mg/dl
71
what level to transfuse fibrinogen? why cant you use FFP?
-100mg/dL
-FFP may not correct the underlying issue
72
what can you use instead of fibrinogen
cryoprecipitate
73
recombinant activated factor 7a MOA/use
-used off label for pro-hemostatic effects for lifethreatening hemorrhage
-increases thrombin, complexes w TF at injury site, amplifies hemostatic activation
74
FDA MedWatch for recomb factor 7a
risk of thromboembolic events PE/DVT if use off label
75
major downside to recomb factor 7a
can normalize elevated INR and PT lab values without actually correcting the coag defect internally
76
Prothrombin Complex Concentrates (PCCs)
ex: KCENTRA has what factors
2, 7, 9, 10
77
Prothrombin Complex Concentrates (PCCs) use/MOA
vitamin K antagonist/warfarin reversal (PCC used more worldwide, FFP in the US)
78
when to use PCC
lifethreatening bleeding, increased INR requiring urgent reversal
--acts quickly and readily available (no cross-matching)
79
2 classes of antithrombotic drugs and purpose
Purpose: reduce formation of clots
Classes: anticoagulants (AC) and antiplatelets
80
AC uses (3)
CV procedures, thromboprophylaxis, CV diease/afib
81
heparin MOA
bind to AT and inhibit factor 2a, 10a, 9a, 11a, 12a
82
when AT and heparin bind, it forms a complex that...
increases the rate of the thrombin-antithrombin reaction by 1000-10,000 times
83
heparin use (3)
1. VTE prophylaxis
2. ACS
3. periop AC (ecmo, HD circuits)
84
heparin onset IV and SQ
IV: immediate
SQ: 1-2h
85
heparin dose for cardiac surgery
300-400 u/kg IV bolus
86
aptt goal with heparin
1.5-2.5x normal...typically 30-35sec
87
ACT monitoring for heparin
-use for high heparin doses
-looks at intrinsic pathway (factor 12a initiates clot cascade)
-detects onset of clot formation
88
what influences ACT during CT surgery (4)
hypothermia, low plt, presence of aprotinin, preexisting coag deficiencies (fibrinogen, factor 12, 7)
89
how often to monitor ACT/heparin during CT surgery and goal ACT
before IV heparin given, 3-5 min after hep, 30min intervals
-goal >350/400 (site specific goal)
90
what is HIT
heparin induced thrombocytopenia
-begins w/in hours of exposure
-drop in plt count (50% in severe cases)
-caused by heparin-dependent antibodies
91
heparin reversal agent?
and consideration?
-protamine (1mg for every 100u of circulating heparin)
-protamine clearance is more rapid than heparin --> risk for heparin rebound
92
vit k antagonists use (3)
(warfarin)
prevent VTE, prevent stroke w/ prosthetic valves and afib, tx for thrombophilia
93
warfarin MOA
-inhibit vit k eroxide reductase whih converts vitK dependent facctors to their active forms
-factors 2, 7, 9, 10
94
target INR w warfarin
2-3 (2.5-3.5 w mech valves)
95
5 things that can change INR (not meds)
1. diet
2. undisclosed drug use
3. poor compliance
4. "surreptitious self-medication"
5. alcohol
96
what class is xarelto (rivaroxaban)
direct factor 10a inhibitor
97
xarelto use (7)
1. reduce stroke risk w afib
2. DVT prophylaxis
3. DVT treatment
4. tx of PE
5. reduce risk of recerrent DVT/PE
6. w/ ASA to reduce risk of CV events in CAD/PAD pts
7. can be used w HIT
98
anesthetic concern w/ xarelto
-neuraxial anesthesia
-can remove epidural cath 18h AFTER last dose given
-must wait 6h to give next dose after d/c epidural
99
Direct Thrombin Inhibitor drugs
bivalirudin, argatroban, lepirudin, desirudin
100
Bivalent direct thrombin inhibitors/MOA
-bivalirudin, lepirudin, desirudin
-bond to thrombin in a bivalent manner at the catalytic site and fibrinogen-binding site
101
argatroban use
prophylaxis or treatment of thrombosis in pts with HIT or high risk of HIT needing PCI
102
argatroban aptt goal and elimination
-1.5-3x baseline
-liver (not renal dosing needed)
103
Dabigatran Etexilate (Pradaxa) anesthetic concern
-direct thrombin inhibitor
-neuraxial anesthesia...first dose can be given 2h after catheter removal
-observe for s/s of neuro dysfunction
-adjust dose for renal dysfunction
104
antiplatelet moa
inhibit thrombus formation by inhibiting plt aggregation and inhibiting adhesion to clot (reversibly or irreversibly)
105
altiplt agents
-COX inhibitors, P2Y12 receptor antagonists, Plt GP 2b/3a antagonists
106
cox inhibitors
-2 types
-MOA
NSAIDs/ASA
-acts on arachidonic acid cascade, COX normally converts AA to prostacyclin and thromboxane A2 which gets blocked
107
ASA MOA
-non-selective and irreversible COX inhibitor
-COX1 is more sensitive to ASA
-prevents formation of thromboxane A2 to prevent plt aggregation
108
COX 1
maintain integrity of gastric lining and renal BF
initiate the formation of thromboxane A2*
109
COX 2
synthesized PG mediators in pain and inflammation
110
when to stop ASA before sx?
-7-10 days bc ASA effect on plt is irreversible and lasts for the life of the plt (low risk)
-continue ASA for pts at mod-high risk for CV events getting non-cardiac sx
111
when to resume ASA post-op?
~24h
112
how to reverse ASA
plt transfusion
113
NSAID MOA
reversible, nonsel COX inhibitor
-antipyretic, antiinflamm, antiplt effects
114
P2Y12 antagonists: thienopyridines MOA
irreversibly inactivate ADP-binding site of P2Y12 receptor
115
P2Y12 antagonists: thienopyridines drug examples
ticlopidine, clopiddogrel (Plavix), prasugrel (Effient), ticagrelor
116
when to dc thienopyridines before sx
5-7d before elective sx and avoid regional anes until effects of drug have dissipated
117
what is dual antiplt therapy
Dual antiplatelet therapy = a thienopyridine (ADP
P2Y12 receptor antagonist) coadministered with
aspirin
118
when to stop vit k antagonists before sx? when to resume?
-5 days before if low risk for VTE
-12-24h post op if adequate hemostasis
-if high risk for VTE use hep or lovenox to bridge after dc
119
when to stop heparin drip before sx? resume?
-stop 4-6h preop
-resume >12h post op
-if high risk of bleeding, wait 48-72h post op to resume
120
when to give last dose of lovenox before sx? resume?
-last dose 24h prior to sx
-resume 24h post-op (low risk)
-48-72h post-op if high risk
121
risks w/ ASA in periop setting
MI/CV events > bleeding
122
how long to delay sx after bare metal stent placement
6 weeks
123
how long to delay sx after drug eluding stent
6 months
124
what if pt needs surgery after stent placement before the 6week or 6 month goal is met?
If surgery is required before this time has passed, dual anti-platelet therapy should be continued
unless the risk of bleeding is thought to outweigh the risk of stent thrombosis
