Pre VTE Flashcards
Virchow’s Triad
- ___ state - abnormalities of clotting componnets
- ___ injury - abnormality of surfaces in contact with blood flow
- circulatory ___ - abnormalities in blood flow
1) hypercoaguable
2) endothelial
3) stasis
Activators of Coagulation
- vWF
- tissue factor
- VIIa
- Xa
- XIIa
- thrombin (IIa)
- XIIIa
- tissue plasminogen activator (t-PA)
Inhibitors of Coagulation
- heparin
- thrombomodulin
- antithrombin
- protein C and S
- tissue factor pathway inhibitor
- plasminogen activator inhibitor -1 (PAI-1)
DVT Risk Factors
- age > ___ years
- family history
- heart failure
- immobilization > ___ days
- malignancy
- myocardial nifarction
- obesity
- orthopedic injury
- oral contraceptive/estrogen use
- paralysis
- post operative state within ___ months
- pregnancy
- prior DVT
- varicose veins
- 40
- 10
- 3
Which heparin product has a higher risk of HIT?
LMWH or UFH?
UFH
UFH
- rapid, ___ anticoagulant
- variable dose response = need for ___ monitoring
- aPTT: activated Partial Thromboplastic Time = time it takes to form a ___
- goal: ___ - ___ time control
Adverse Effects:
- bleeding
- thrombocytopenia
- parenteral
- aPPT
- clot
- 1.5-2.5
UFH dosing - weight based
IV bolus: ___ units/kg
infusion: ___ units/kg/hr
Monitoring:
- aPTT at baseline
- ___ hours after dose or with each dosage change (for first ___ hours)
- check daily after first day, unless out of range
- 80
- 18
- 6, 24
HAT
Heparin Associated Thrombocytopenia
- aka HIT ___
- ___ mediated
- mild decrease in platelets, but still greater than ___ mm3
- occurs around ___ - ___ hours after administration of heparin
- transient
- do not need to d/c heparin
- type I
- non-immune
- 100,000
- 48-72
HIT
Heparin Induced Thrombocytopenia
- ___ mediated
- ___ complications
- occur between: ___- ___ days
- can occur up to ___ days after stopping therapy
- platelets drop > ___% from baseline OR < _____ mm3
- immune
- thrombotic
- 7-14
- 9
- 50, 100,000
HIT Management
- stop all ___ products
- give alternate anticoagulant ( ___ , ___ , ___ , or ____ )
- do not give ___ infusions
- do not give ___ until platelet count is > ___
- evaluate for thrombosis
- heparin
- lepirudin, argatroban, bivalirudin, fondaparinux
- platelet
- warfarin, 150, 000
LMWH advantages vs UFH
- ___ protein binding
- ___ dose response: fixed or ___ based dosing possible, ___ not required
- ___ plasma t1/2
- smaller molecule: improved ___ absorption
- less effect of ___ and endothelium: reduced incidence of ___
- reduced
- predictable, weight, monitoring
- longer
- SQ
- platelets, HIT
LMWH dosing - enoxaparin (Lovenox)
Prophylaxis
- ___ mg SQ q12h (surgery)
- ___ mg SQ daily (medical)
Treatment:
- ___ mg/kg SQ q12h
- ___ mg/kg SQ daily
Renal Dysfunction
- ___ mg SQ daily (prophylaxis)
- ___ mg/kg SQ daily (treatment)
- 30
- 40
- 1
- 1.5
- 30
- 1
LMWH dosing - dalteparin (Fragmin)
Prophylaxis
- ___ - ___ units SQ daily
Treatment
- ___ units/kg SQ daily for ___ days, then ___ units SQ daily
treatment is also used for VTE patients with cancer
- 2500-5000
- 200, 30, 150
Monitoring Anti Xa Levels
consider for children, severe kindey failure, obesity, long courses, pregnancy
- Twice daily dosing: ___ - ___ units/mL, obtained ___ hours post dose
- once daily dosing: ___ - ___ units/mL, obtained as ___
- can. consider peak of ___ - ___ units/mL obtained ___ hours post dose
Routine monitoring not ___
- 0.6-1.0, 4
- 0.1-0.3, trough
- 1-2, 4
- recommended
Injectable Factor Xa Inhibitor
Fondaparinux
- uses: prophylaxis following ___ , ___ , ___ replacement, or ___ surgery
- treatment of ___ or ___
prophylaxis dosing: ___ mg SQ once daily (following ___ , ___ , or ___ surgery)
treatment:
- < 50 kg: ___ mg SQ once daily
- 50-100 kg: ___ mg SQ once daily
- > 100 kg: ___ mg SQ once daily
- THA, TKA, hip, abdominal
- DVTT, PE
- 2.5 mg, hip, knee, abdominal
- 5
- 7.5
- 10
Fondaparinux Considerations
- do not use if there is ___ dysfunction (CrCl < ___ mL/min)
- do not use for prophylaxis with body weight less than ___ kg
- can be used in ___
- no routine monitoring; can monitor ___ levels (similar to LMWH)
- pregnancy category ___ (Safe)
- renal, 30
- 50
- HIT
- anti-Xa
- B
IV Direct Thrombin Inhibitors
Lepirudin
- Use: ___
- Goal aPTT: 1.5-2.5 normal
- reduce dose CrCl < ___ mL/min
Bivalirudin (Angiomax)
- Use: ___ , UFH alternative during ___
Argatroban
- Use: ___
- elevates ___, overlap with warfarin until INR >/= 4
- caution in ___ dysfunction
- HIT, 60
- HIT, PCI
- HIT, INR, hepatic
NOACs/DOACs
Direct Thrombin Inhibitor (1)
Factor Xa Inhibitors (4)
Direct Thrombin Inhibitor
- dabigatran (Pradaxa)
Factor Xa Inhibitors
- rivaroxaban (Xarelto)
- apixaban (Eliquis)
- edoxaban (Savaysa)
- betrixaban (Bevyxxa)
NOAC approved indications
Dabigatran (3)
- postoperative prophylaxis ( ___ )
- non-valvular ___
- ___ / ___ Treatment
- hip
- A-fib
- DVT/PE
NOAC approved indications
Rivaroxaban (5)
- ___ prophylaxis
- non-valvular ___
- ___ / ___ treatment
- secondary prevention of recurrent ___ / ___
- ___ prophylaxis
everything
- postoperative
- A-fib
- DVT/PE
- DVT/PE
- VTE
NOAC approved indications
Apixaban (4)
- ___ prophylaxis
- non-valvular ___
- ___ / ___ treatment
- secondary prevention of recurrent ___ / ___
- postoperative
- A-fib
- DVT/PE
- DVT/PE
NOAC approved indications
Edoxaban (2)
- non-valvular ___
- ___ / ___ treatment
- A-fib
- DVT/PE
NOAC approved indications
Betrixaban
- ___ prophylaxis
VTE
Which enantiomer of warfarin is more potent? R or S?
S
Warfarin Drug Interactions
Increase INR
erythromycin
metronidazole
fluconazole
amiodarone
ciprofloxacin
bactrim
anabolic steroids
isoniazid
propafenone
Warfarin Drug Interactions
Decrease INR
Rifampin
cholestyramine
carbamazepine
Alcohol and Warfarin
Acute ingestion of alcohol will ___ INR
increase
increase anticoagulant effect of warfarin by inhibiting its metabolism
Alcohol and Warfarin
Chronic alcohol use without liver damage will ___ INR
decrease
enhances metabolism by inducing hepatic enzymes, decreases effect of war
Alcohol and Warfarin
Chronic alcohol use with liver damage will ___ INR
increase
due to lack of hepatic enzymes, increased anticoagulant effect
Warfarin Strengths
available in 9 strengths
- 1
- 2
- 2.5
- 3
- 4
- 5
- 6
- 7.5
- 10
MOA of warfarin
- does not effect ___ factors or previously formed ___
- inhibits enzymes responsible for cyclic conversion of vitamin ___
- inhibit synthesis of vitamin K dependent clotting factors: ___ , ___ , ___ , and ___
- protein __ and ___
- circulating, thrombi
- K
- II, VII, IX, X
- C, S
Warfarin PK/PD and half-lives
- anticoagulant effect within ___ hours
- peak effects ___ - ___
- duration of action from a single dose: ___ - ___ days
___ metabolized
S: CYP ___ , ___ , ___
R: CYP ___ and ___
- 24
- 72-96
- 2-5
Hepatically
- 2C9, 2C19, 2C18
- 1A2, 3A4
Warfarin Genetic Variances
CYP ___
___* and ___* decrease S-warfarin clearance
- occurs in 1/3 ___ pts
- need to ___ the dose
- potential ___ bleeding risk and ___ time to reach goal
- 9, 5, 8, and 11 are ore common in ___ and ___
2C9
2* and 3*
- white
- lower
- increased, longer
- asians, AA
Warfarin Genetic Variances
VKORC1
- ___ A and ___ T - decreases VKOR production
- ___ A increases warfarin ___ ; requires lower dose ( ___ )
- 1639 ___ - increased warfarin ___ ; requires higher dose ( ___ )
1639, 1173
1639, sensitivity; asians
- G, resistance, AA
Antiplatelets - medication classes
1) COX- ___ inhibitors; Example: ___
2) ___ receptor inhibitors
3) GP ___ / ___ receptor blockers
4) ___ - 3 inhibitors; Example: ___
5) ___ acivated receptor inhibitors
- 1, aspirin
- ADP
- IIb/IIIa
- phosphodiesterase, dipyridamole
- protease
Antiplatelet use in VTE
limited role in VTE
- ___ : consideration for CHA2DS2-VASc score 1
- ___ : consider concomitant use with warfarin with prosthetic heart valve
- concomitant use with ___ and increased risk of bleeding
- adjunct role to ___
- significant role in ACS and other atrial ischemic vascular disorders like ___ and CVA
- ASA
- dipyridamole
- anticoagulants
- thrombolytics
- PAD
Bleeding Management/Antidotes
Consider:
- activated ___ </= 2 hours of bleeding
- hemodialysis: ___ only
- ___ acid
Targeted Reversal:
- UFH, LMWH: ___ sulfate
- Dabigatran: ___ (Praxbind)
- Factor Xa inhibitors: ___ alfa
- charcoal
- dabigatran
- tranexamic
- protamine
- idarucizumab
- andexanet
idarucizumab (Praxbind)
MOA: direct binder to ___ (higher affinity than ___ to ___)
- Dose: ___ g IV (2 separate ___ g doses no more than 15 min apart)
- ADR: delirium, headache, hypokalemia, constipation, pneumonia fever
Monitoring Schedule:
- baseline ___ , repeat in 2 hours, every ___ hours until normal
dabigatran
dabigatran, thrombin
- 5 g, 2.5 g
- aPTT, 12
Andexanet Alfa (Andexxa)
MOA: binds and sequesters ___ inhibitors ( ___ and ___ )
- ADR: local site infusion reaction, DVT, schemix stroke, AMI, PE, UTI, or pneumonia
- no specific monitoring parameters
FXa
rivaroxaban and apixaban
Warfarin Bleeding Management
dependent on __ and presence of bleeding
Vit K
- PO: ___ mg tabs
- Parenteral: do not exceed ___ mg/min ( anaphylaxis)
Fresh Frozen Plasma (FFP)
- ___ - ___ mL/kg
Prothrombin Complex Concentrate (PCC)
- ___ IU/kg (check INR before, 30-60 min after)
INR
5 mg, 1mg/min
10-15 mL/kg
30 IU/kg
Warfarin: Bleeding Management
- if INR 4.5-10 + no bleeding: avoid ___
- if INR > 10 + no evidence of bleeding: PO ___
- major bleeding while on warfarin: ___ preferred over ___ . May add ___ 5-10 mg as well
- vit K
- vit K
- PCC, FFP, vit K
Warfarin Reversal
- rapid reversal (10-15 min, complete) - ___
- fast (partial) - ___
- prompt (4-6 hours) - IV ___
- slow (within 24 hours) - PO ___
- very slow (3-5 days) - omit ___
- PCC
- FFP
- vit K
- vit K
- warfarin
VTE Prophylaxis
- without prophylaxis: VTE incidence ___ - ___ % in medical patients
- without prophylaxis: VTE incidense ___ - ___ % in surgical patients
- 5-15%
- 40-80%
VTE Prophylaxis
VTE Prophylaxis Options (4)
- UFH
- LMWH
- Factor Xa inhibitors
- Vit K antagonists
VTE Risk Stratification - Moderate risk
General Surgery : ___ , ___ , and ___ ( ___ ) recommended, continue prophylaxis up to 28 days after hospital discharge
Acutely ill medical patients: ___ , ___ , ____ , ___ , and ___ , all appropriate
- ___ : 31-39 days total treatment
- ___ : 35-42 days total treatment
- UFH, LMWH, Factor Xa inhibitors (fondaparinux)
- UFH, LMWH, fondaparinux, rivaroxaban, betrixaban
- rivaroxaban
- betrixaban
VTE Risk Stratification - High risk
Orthopedic Surgery (TKA, THA) (7)
- continue longer than ___ - ___ days postop (consider up to ___ days)
- LMWH
- UFH
- Fondaparinux
- rivaroxaban
- apixaban
- dabigatran (hip)
- vitamin K antagonist
10-14 days, 35 days
High Bleeding risk
___ prophylaxis preferred
- intermittent pneumatic compression devices
- venous foot ___
- ___ compression stockings
mechanical
- pumps
- graduated
What does CHA2DS2-VASc stand for?
- Congestive HF (1)
- HTN (1)
- Age >/= 75 YO (2)
- diabetes (1)
- Stroke/TIA (2)
- Vascular Disease (1)
- Age 65-74 years (1)
- Female (1)
vascular disease = prior MI, peripheral artery disease, or aortic plaque
CHA2DS2- VASc and HAS-BLED
- anticoagulant therapy reduces risk of stroke and all cause mortality
- used to guide the use of anticoagulants in patients with ___
- CHA2DS2-VASc: risk factors for ___ or systemic ___
- HAS-BLED: risk factors for ___
- A-fib
- stroke, VTE
- bleeding
A-fib increases risk of stroke/systemic VTE by 5x
What does HAS-BLED stand for?
- Hypertension (SBP > ___ mmHg) (1)
- abnormal ___ and ___ function (1 or 2)
- ___
- bleeding tendency/predisposition (1)
- labile ___ (if on warfarin) (1)
- Age > ___ YO
- drugs or EtOH (1 or 2)
- 160
- renal, liver
- stroke
- INRs
- 65
Score Interpretations
CHA2DS2-VASc; start anticoagulant is score greater or equal to ___
HAS-BLED; patient has high risk of bleeding if score greater than or equal to ___
- if any medication is used, oral ___ is preferred over ___
- 2
- 3
- anticoagulation, antiplatelet
