Anticoagulants Flashcards
1
Q
Define hemostasis.
A
to stop bleeding
2
Q
What does hemostasis involve?
A
involves a complex inflammatory response that prevents exsanguination following injury, trauma, and/or surgery
3
Q
When does hemostasis begin?
A
tissue injury & vascular endothelial disruption
4
Q
What is the function of platelets?
A
work to form a primary plug to stop bleeding
5
Q
Define adhesion.
A
involves GpIb attaching to vWF; makes platelets “sticky”
6
Q
Define activation.
A
-involves tissue factor & platelets undergo conformational transformation; -GpIIb/IIIa receptor complexes on platelet surfaces enable platelets to link together to form a platelet plug
7
Q
Define aggregation.
A
platelets release procoagulant mediators into the blood to form a primary unstable clot
8
Q
Review the coagulation cascade.
A
Intrinsic, extrinsic, & common pathways
9
Q
What is the current blood coagulation modeling involves in cell-based theory involving (2)?
A
Tissue Factor Pathway & Contact Pathway
10
Q
Tissue Factor Pathway is the ______ Pathway)
A
Extrinsic
11
Q
Contact Pathway is ______ Pathway
A
Intrinsic
12
Q
Where does theorizes coagulation occur?
A
Theorizes coagulation occurs on different “cell surfaces” of platelets that bear Tissue Factor and these surfaces play a role in factor expression leading to hemostasis
13
Q
What are the four phases of blood coagulation?
A
Initiation, amplification, propagation, & stabilization
14
Q
Review the Blood Coagulation: Cell-Based Theory.
A
15
Q
What is the initation phase of the Cell-Based Theory triggered by?
A
Triggered by injury to blood vessel endothelial surface
16
Q
After injury, tissue factor recruits _____ & activates ________
A
Cell-Based Theory: Initiation Phase
- recruits platelets & activates factor VII
17
Q
What is the part of the Cell-Based Theory: Amplification?
A
As platelets mobilize to the site of injury, the amplification phase generates thrombin and additional clotting factors are activated
18
Q
What factors does thrombin activates?
A
Cell-Based Theory: Amplification
- Thrombin activates factors V, VIII, and IX
19
Q
What does factor XI generate?
A
Cell-Based Theory: Amplification
- Activated factor XI generates even more factor IX on the platelet surface
20
Q
What does von willebrand factor promote?
A
Cell-Based Theory: Amplification
- Von Willebrand factor promotes platelet aggregation through its adhesive properties w/GpIb and expression of GpIIb/IIIa causing additional platelet aggregation
21
Q
What is the basis of Cell-Based Theory: Propagation?
A
All coagulation factors are actively influencing one another promoting coagulation
22
Q
What does Activation of prothrombin results?
A
Cell-Based Theory: Propagation
- in large burst of thrombin
23
Q
What does thrombin convert?
A
Cell-Based Theory: Propagation
- then converts fibrinogen to fibrin to form a stable secondary hemostatic plug
24
Q
What does stabilization in the Cell based theory?
A
Cell-Based Theory: Stabilization
- Stabilization results in fibrin (insoluble) clot formation
25
Review coagulation cascade.
* Tissue Injury (Extrinsic Pathway)
* Contact Activation (Intrinsic Pathway)
26
What is the physiologic balance of the coagulation system?
Delicate Physiologic Balance
27
Define Antithrombin.
Antithrombin (AT) - (previously known as AT III) is a member of the serine protease inhibitor family
28
What is the one of the most important natural proteins?
one of the most important natural proteins responsible for the prevention of spontaneous intravascular clot formation
29
What is the genetic components of Antithrombin definicency?
AT deficiency can be inherited or acquired
30
What is inherited AT deficiency?
inherited form is usually marked by extremely low levels of this endogenous anticoagulant
31
What does AT inhibit?
thrombin and also effectively inhibits factors XI, X, and IX
32
What are the characterisitics of congenital AT deficiency ?
Patients with congenital AT deficiency present with venous thromboses throughout life; develop many complications because of their hypercoagulable state and are unresponsive to heparin
33
How does heparin exert its effect?
Unfractionated heparin (UFH) exerts anticoagulant effect by binding to antithrombin (AT) in circulation
34
What does heparin binding to AT enhances?
the rate of thrombin-AT complex formation by 1000 to 10,000 times
35
What does heparin inhibit factors?
inhibits factors Xa & IIa
36
What does flood state about heparin?
Flood states other factors inhibited by AT: factors XII, XI, and IX
37
What does heparin inhibit?
factors Xa & IIa (factor IIa = thrombin)
38
What does anticoagulation of heparin depend on?
Anticoagulation depends on presence of adequate amounts of circulating AT
39
What is heparin pk?
Heparin is a highly charged acidic molecule administered IV or SC
40
Review anticoagulant pathways.
41
What is the aPTT of Heparin?
approx. 1.5 to 2.5 times normal values (typically 30-35 seconds)
42
What is the activated clotting time (ACT)?
used for high heparin doses (i.e., CPB); normal values 100-150 sec; in cardiac surgery, measured q30min – target 350-400sec
43
What is the anti-Xa assay of Heparin?
low-dose regimen: 0.3-0.5 units/mL, high-dose regimen: 0.5-0.8 units/mL
44
What is the clinical use of heparin?
prevention & tx of venous thrombosis, PE, acute coronary syndromes, perioperative anticoagulation for extracorporeal circulation & hemodialysis
45
What is the main characteristics of Heparin-induced thrombocytopenia (HIT)?
Thrombocytopenia due to heparin injection/infusion can begin within hours of exposure
46
When can severe thromobcytopenia from Heparin-induced thrombocytopenia (HIT) develop?
Severe thrombocytopenia can develop in some patients: 50% drop in platelet count/or \<100,000 cells/µL
47
What is Heparin-induced thrombocytopenia (HIT) caused by?
Caused by heparin-dependent antibodies to platelet factor IV that triggers platelet aggregation & thrombocytopenia
48
What is HIT development?
heparin usually dc’d and patient switched to a different anticoagulant
49
Heparin: _________ molecule
negatively-charged acidic
50
Protamine: ___________ molecule
positively-charged alkaline
51
What does protamine combine with heparin form?
form a stable complex devoid of anticoagulant activity
52
How is the Protamine-heparin complex removed?
by the reticuloendothelial system (within tissues such as spleen, liver, lungs, bone marrow, & lymph nodes)
53
What is the dose of protamine?
1mg for 100units of circulating heparin
54
What are Low-Molecular-Weight Heparin?
Enoxaparin (Lovenox) & dalteparin (Fragmin) – administered via SC inj
55
What are the LMWHs derived from?
from UFH and are depolymerized to yield fragments with a mean molecular weight 4,000 – 5,000 daltons
56
LMWH anti-Xa to anti-IIa activity varies between _____ and \_\_\_\_\_\_\_.
4:1 and 2:1
57
When is LMWH effects prlonged?
LMWH prolonged in patients with renal failure UFH should be used
58
What is the delay of surgey for LMWH?
Surgery delayed 12 hrs after last dose of LMWH in patients w/normal renal function; longer w/renal dysfunction
59
What is a risk with LMWH?
Risk of epidural/spinal hematoma
60
What does protamine not reverse?
LMWH anticoagulation
61
What is the characteristics of Fondaparinux (Arista)?
Synthetic anticoagulant resembles active sites of a heparin molecule that binds AT
62
What does Fondaparinux (Arista) inhibit?
inhibits factor Xa but not thrombin
63
What is Fondaparinux (Arista) used for?
Used for DVT prophylaxis, patients w/PE, & alternative anticoagulant in patients with HIT
64
How are Fondaparinux (Arista) used?
Administered SC inj
65
What is the duration of action/elimination half time of Fondaparinux (Arista)?
Long duration of action/elimination half-time = 15 hours
66
When is Fondaparinux (Arista) not used?
Not used in patients w/renal failure (primarily renally excreted)
67
What is an example of Direct Thrombin Inhibitors?
Bivalirudin & Argatroban
68
What is the MOA Direct Thrombin Inhibitors: Bivalirudin?
Binds directly to factor IIa – thrombin
69
When is Direct Thrombin Inhibitors: Bivalirudin indicated?
Indicated for patients w/ unstable angina undergoing PTCA or patients w/ HIT
70
What is the MOA of Direct Thrombin Inhibitors: Argatroban?
An injectable, synthetic univalent direct thrombin inhibitor
71
What is the indication for Direct Thrombin Inhibitors: Argatroban?
Indicated for prophylaxis or tx of thrombosis in patients with or at risk for HIT and undergoing PCI
72
What is the elimination of Direct Thrombin Inhibitors: Argatroban?
Hepatic elimination
73
What is the dose adjustment Direct Thrombin Inhibitors: Argatroban in renal dysfunction?
no dose adjustment required in patients w/renal dysfunction
74
What is an example of a Vitamin K Antagonist?
Warfarin
75
What is the formularities of Vitamin K Antagonist: Warfarin?
Oral anticoagulant
76
What is the characterisitics of Vitamin K Antagonist: Warfarin?
Most frequently used oral anticoagulant b/c predictable onset & duration of action, excellent bioavailability after oral administration
77
What is the MOA of Vitamin K Antagonist: Warfarin?
inhibits vitamin K synthesis and thereby inhibiting production of vitamin K-dependent clotting factors II, VII, IX, & X
78
What is the bioavailability of Vitamin K Antagonist: Warfarin?
Oral bioavailability of 100%
79
What is the protein binding of Vitamin K Antagonist: Warfarin?
97% protein-bound to albumin (this means is easily displaced by other highly protein-bound drugs)
80
What is the onset of action of Vitamin K Antagonist: Warfarin?
delayed onset of action (8-12 hours)
81
What is the peak effect of peak effect of Vitamin K Antagonist: Warfarin?
peak effects do not occur for 36-72 hours
82
What is the metabolism of Vitamin K Antagonist: Warfarin?
hepatic metabolism
83
What is the clinical use of Vitamin K Antagonist: Warfarin?
VTE prophylaxis, prevention of systemic embolization/stroke in patients w/Afib or prosthetic heart valves, patients w/hypercoagulable states
84
What is the lab evaluation of Vitamin K Antagonist: Warfarin?
tx guided by measurement of PT
85
What is the standardized system of measurement of Vitamin K Antagonist: Warfarin?
INR measurement overcomes variability of PT measurement among various labs – is a standardized system of measurement
86
What is the target INR for Vitamin K Antagonist: Warfarin?
target INR 2.0-3.0 for patients requiring moderate anticoagulation (prosthetic heart valves)
87
What does unexpected fluctuations in dose response to warfarin may reflect?
changes in diet, undisclosed drug use, poor patient compliance, patient self-medication, alcohol consumption
88
What can affect warfarin?
Concomitant OTC & prescription drugs can augment or inhibit the anticoagulant effect of warfarin
89
What can potentiate warfarin's anticoagulation effects?
can be potentiated in patients w/inadequate vitamin K intake, preexisting liver disease, & advanced age
90
Patients receiving warfarin should have ______ checked preop
INR
91
What is the recommendation of minor surgery procedures with anticoagulants?
can be safely performed in pts receiving oral anticoagulation
92
What is the recommendation of major surgery procedures with anticoagulants?
recommended to DC 1-3 days preop to enable PT to return to within 20% of normal range
93
When should anticoagulation be reinstituted?
reinstitution of oral anticoagulation 1-7 days postop
94
High-risk patients (pts w/prosthetic heart valves) may require bridging with \_\_\_
UFH
95
\_\_\_\_\_\_\_ is the main complication of anticoagulation
Bleeding (esp. w/concomitant use of aspirin)
96
What can anticoagulation drugs increase the incidence of?
Anticoagulation drugs may increase incidence of intracranial hemorrhage after CVA
97
What is the Warfarin reversal?
Vitamin K IV or PO can be used; will not immediately reverse anticoagulant effect
98
What can be given for immediate Warfarin reversal?
(i.e., performance of high-risk surg procedures such as craniotomy): prothrombin complex concentrates (PCCs) or FFP
99
What is the components of Rivaroxaban (Xarelto) ?
Oral, direct factor Xa inhibitor
100
What does Rivaroxaban (Xarelto) not require?
Doesn’t require AT as a cofactor
101
What molecule is Rivaroxaban (Xarelto)? What could it potentially treat?
Is a non-heparin like molecule; may be suitable for mgmt. of patients w/HIT
102
When is Rivaroxaban (Xarelto) used?
Used in HIT patients, DVT prophylaxis, patients w/Afib, treatment of DVT/PE, in combo w/ASA to reduce risk of major CV events in patients w/chronic CAD or peripheral artery dz
103
What is the relationship of Rivaroxaban (Xarelto) and neuraxial anesthesia?
risk of epidural hematoma; follow ASRA guidelines in patients taking rivaroxaban & epidural catheter management
104
What is the formulary for Apixaban (Eliquis)?
Oral, direct factor Xa inhibitor
105
What is the use for Apixaban (Eliquis)?
* Approved to reduce risk of stroke & systemic embolism in patients w/Afib
* DVT prophylaxis; patients having hip or knee replacement surgery
* tx of DVT/PE & reduce risk of recurrent DVT/PE
106
What is the relationship of Apixaban (Eliquis) and neuraxial anesthesia?
risk of epidural hematoma; follow ASRA guidelines in patients taking rivaroxaban for epidural catheter management
107
What is the MOA of Dabigatran (Pradaxa)?
Oral, direct thrombin inhibitor
108
What is the Dabigatran (Pradaxa) used for?
* approved to reduce risk of stroke & systemic embolism in patients w/Afib
* tx of DVT/PE & reduce recurrence of DVT/PE
109
What labs are important with Dabigatran (Pradaxa)?
Anticoagulant effects measured by thrombin time, clotting time; can use activated PTT for screening
