Lecture 5 - VTE 1 Flashcards
1
Q
DVT occurs in the….
A
legs
when valves don’t work properly, increased risk
2
Q
Pulmonary embolism occurs in the…
A
lungs
3
Q
Fatal VTE info
A
10-30% within 1 month of diagnosis
sudden death in 25% of those with PE = Cant miss diagnosis
4
Q
Recurrent VTE info
A
highest risk is within 180 days of initial event so treatment lasts 6 months
5
Q
VTE risks
A
Men > Women
Black> White> Hispanics> Asians
Risk 7-10X higher in those > 75, even more >85
6
Q
Virchow’s Triad
A
- Stasis of blood
- Endothelial injury
- Hypercoagulability
7
Q
Stasis of blood due to….
A
- acute hospital illness
- surgery
- paralysis
- Immobility
- obesity
8
Q
Endothelial injury due to…
A
- major surgery
- Trauma
- Indwelling venous catheters
9
Q
Hypercoagulability due to….
A
- Malignancy
- Inherited or acquired clotting disorders
- Pregnancy
- Medications (estrogen containing)
10
Q
Where do Factor Xa and Direct Thrombin Inhibitors work?
A
Work to block tissue factor pathway
Stop production of thrombin from coagulation cascade
11
Q
Where do Plasminogen activator inhibitor -1a2 antiplasmin work
A
work to block Fibrinolysis and clot degradation
12
Q
DVT is likely when Wells score is above…?
A
2
13
Q
Homan’s Sign
A
Sign of DVT, pain behind the knee when walking
14
Q
Signs of DVT
A
Unilateral leg pain
Swelling
Warmth
Homan’s Sign
15
Q
Signs of PE
A
Chest pain
SOB
Tachycardia
16
Q
Lab values of DVT/PE
A
D-dimer < 500 ng/ml = rule out DVT or DE
17
Q
PE Rule-out criteria
A
Age > 50 Unilateral leg swelling Prior PE or DVT HR > 100 Hemoptysis Hormone use Sa02 > 95% Recent surgery/trauma in last 4 weeks
will req further testing if any of these are true
18
Q
PE is likely if its Wells score is….?
A
> 4
19
Q
non-pharmacologic DVT treatments
A
- IPC devices (compression things for legs)
- GC stockings (compression stockings)
- IVC filter (not use much anymore, implant can cause issues)
20
Q
What factors does UFH act on?
A
12/11/10/9/2
21
Q
What factors does LMWH act on?
A
10 & 2
22
Q
What factors do VKA (Vitamin K antagonists) act on?
AKA Warfarin
A
2,7,9,10
23
Q
What factors do Direct Thrombin Inhibitors (DTI) act on?
A
Factor 2
24
Q
Example of DTI
A
Dabigatran
25
What factors do Factor Xa Inhibitors (FXal) act on?
Factor X
26
Examples of FxaI?
Rivaroxaban
Apixaban
Edoxaban
27
How do Injectable options work? (UFH, LMWH, Fondaparinux)
```
UFH = blocks Xa and Thrombin
LMWH = blocks Xa only
Fondaparinux = reversible and reusable in blocking Xa
```
28
UFH info
from Bovine lung or porcupine intestinal mucosa = incase someone is religious
ADR: bleeding, HIT, hyperkalemia, osteoporosis
29
UFH Dosing adjustments
can be used in pregnancy, ESRD and renal impairment with no changes
30
UFH Antidote
Protamine
| 1mg/100 units of UFH, Max 50 mg
31
LMWH Antidote
Protamine
1mg/1mg enoxaparin
1mg/ 100 unit anti-Xa units dalteparin
32
Black Box warning of LMWH
Epidural or spinal hematomas may occur in patient who are on LMWH or heparin and are receiving neuraxial anesthesia or undergoing a spinal procedure and could result in paralysis
33
ADR LMWH
Bleeding
HIT (1/3 compared to UFH)
Hyperkalemia
34
aPTT
Activated partial thromboplastin time
use for monitoring UFH
Elevates function of cofactors in intrinsic and common pathway
includes Factors 12,11,10,8,5,2 (prothrombin) & 1 (fibrinogen)
35
Anti Xa
used for monitoring UFH, LMWH and maybe oral factor Xa inhibitors
36
Prothrombin Time
used for monitoring warfarin with INR
37
Heparin-induced Thrombocytopenia (HIT)
immune mediated adverse reaction due to production of IgG antibodies that recognize complexes of platelet factor 4 (PF4) and heparin on the platelet leading to platelet activation
more common in pt who receives UFH than LMWH
Thrombosis occurs in 30-50% of pt, mortality 5-10%
38
Steps in diagnosis HIT
1. 4Ts score (if intermediate or high risk continue)
2. ELISA (immunoassay, if positive continue)
3. SRA (Gold standard, can take days)
If low probability or other 2 tests negative then can use heparin
39
Management of HIT
1. Discontinue all heparin-containing products
2. Add heparin to allergy with description of HIT
3. initiate non-heparin anticoagulant
40
Dabigatran (Pradaxa) Adverse effects
** Bleeding and Dyspepsia (indigestion) **
Same BW as LMWH
increased risk of thrombosis if non-adherent
41
Dabigatran (Pradaxa) PK info
prod drug to overcome poor bioavailability
renal elim = req dose adjustment
metabolized via p-gp
has to stay in original packaging
42
How often is Dabigatran (Pradaxa) dosed
twice daily
43
Dabigatran (Pradaxa) antidote
Idarucizumab 5g IV
44
Antidote to Factor Xa inhibitors
Andexaneta alfa (Andexxa)
45
How often is apixaban (Eliquis) dosed?
Twice daily
46
Factor Xa inhibitor adverse effects
increased risk for thrombosis if non-adherent
bleeding and use caution in renal impairment
Same BW as LMWH
47
Warfarin (Coumadin & Jantoven) Mechanism
- Factors 2,7,9,10 need enzyme for which vitamin K is a co factor.
- Warfarin reduces vitamin K reductase = reduced factors = less clotting
****Warfarin blocks enzyme that turns vitamin K from Oxidized - reduced, also inhibits protein C/S****
48
Which isomer is more active for Warfarin?
S - isomer
49
What metabolizes S-isomer warfarin
CYP2C9
50
What metabolizes R-isomer warfarin
CYPs 1A1, 1A2, 3A4
51
Need for warfarin dose adjustments if have polymorphism in...
CYP2C9 and VKORC1
52
How long for anticoagulants effect of warfarin?
within 24hrs, but 2-5 days for peak effect
53
Adverse effects of warfarin?
Bleeding
Purple toe syndrome
Skin necrosis = rare, 1st 10 days (due to protein C/S)
Harmful fetal effects so don't use in pregnancy
54
INR
Also known as PT, but INR is just normalized/standardized so that we can discuss around the world
55
Typical INR warfarin goal
2-3
56
AT9 guidelines for no evidence of bleeding
INR 4.5-10 = no need for vitamin K
| INR >10 = give oral vitamin K
57
AT9 guidelines for evidence of bleeding at any INR
Rapid reversal with 4-factor PCC
| Vitamin K 5-10mg via slow IV injection
58
Signs & Symptoms of bleeding
Nose bleeds that won't stop
bleeding from gums, GI, in urine/stool
Bad bruising
59
higher INR =
Bleeding risk
60
Lower INR =
Clotting risk
61
Issue with Vitamin K
pt can become warfarin resistant, which can take about a week for warfarin to become therapeutic again
62
Increase INR Warfarin Interactions
1. Dec intake of Vitamin K (leafy greens
2. CYP450 inhib (Metronidazole, Bactrim, Azole antifungals, amiodarone, fluoroquinolones, acute alcohol use)
** FAB = Flagy, Amiodarone, Bactrim ****
63
Decrease INR Warfarin Interactions
1. Inc intake of Vitamin K
2. CYP450 inducers ( cig smoke, Rifampin, Carbamazepine, Nafcillin/Dicloxacillin)
3. Hypothyroidism
64
How do anti0infectives impact INR?
reduce gut flora that produce Vitamin K
65
HAS-BLED score
> 3
66
UFH & LMWH antidote
Protamine
67
Dabigatran antidote
Idarucizumab
68
Warfarin antidote
Vitamin K (Phytonadione)
69
Rivaroxaban & Apixaban Antidote
Andexxa (FDA approved)
70
Edoxaban, Fondaparinux, Enoxaparin antidote
Andexxa (Not FDA approved)
