VTE Introduction Flashcards
Pathophysiology
venous thrombi are formed in areas of slow/disturbed flow; stasis blood promotes thrombus –> decreased clotting factor clearance
venous thrombi composed of RBCs, fibrin, and few platelets
Symptoms result when
flow is obstructed
vascular tissue wall becomes inflamed (i.e. surgical procedure/traumatic injury)
thrombus occurs and affects venous blood flow
emboli occur and enter pulmonary circulation
not all DVTs lead to PEs but all PEs come from DVTs
3 main things contributing to a blood clot in our pts (virchow’s triad)
hypercoagulable state - abnormalities of clotting components (i.e. pregnancy or cancer)
circulatory stasis - abnormalities in blood flow, occurs during long periods of immobility
endothelial injury - abnormality of surfaces in contact with blood flow (i.e. injury of blood vessel)
Postthrombotic syndrome
long-term complications of DVT caused by damage to venous valves - chronic venous obstruction, caused by venous hypertension, chronic pain and swelling, stasis ulcers, development of infection
DVT risk factors
age > 40 yrs
family history of DVT
heart failure
immobilization > 10 days
malignancy
myocardial infarction
obesity
othopedic injury
oral contraceptive/estrogen
paralysis
postoperative state
pregnany
prior DVT
varicose veins
Nonpharmacologic treatment
baseline monitoring
DVT: bed rest (w/ appropriate anticoagulation), elevation of feet, pain management, compression stockings
PE: oxygen, mechanical ventilation, compression stockings
Unfractionated heparin
rapid, parenteral antigoagulant (most often given as continuous infusion)
variable dose response –> need for aPTT monitoring (time that represents how long it takes the bood to form a clot) - goal 1.5-2.5 time control
AEs: bleeding, thrombocytopenia
Weight based dosing for unfractionated heparin
monitor aPTT at baseline 6 hours after dose or with each dosage change (for 1st 24hrs); check daily after first day
lower the aPTT is, necessitates an increase in the dose
more elevated aPTT, need to decrease rate or hold infusion for short period of time
Heparin associated thrombocytopenia (HAT)
non-immune mediated
mild decrease in platelets
occurs around 48-72 hours after administration of heparin
transient, do not need to stop heparin
Heparin induced thrombocytopenia (HIT)
immune mediated
thrombotic complications
occurs between 7-14 days
one of 2 things to recognize HIT: platelets drop >50% from baseline OR <100,000/mm3
HIT management
STOP all heparin products
give alternate anticoagulant
do NOT give platelet infusions
do NOT give warfarin until platelet count > 150,000
evaluate for thrombosis
Low molecular weight heparin
advantages over UFH:
reduced protein binding - good bioavailability, predictable dose response (don’t need to monitor aTTPs)
longer plasma half-life - once or twice daily dosing
smaller molecule - improved SQ absorption
less effect of platelets and endothelium - reduced incidence of HIT and possibly bleeding
Monitoring Anti Xa levels
measures plasma heparin; consider for children, severe kidney failure, obesity, long courses, pregnancy
Fondaparinux
use: prophylaxis following THA, TKA, hip replacement, or abdominal surgery; treatment of DVT or PE (1st med used)
Fondaparinux considerations
do not use if have renal function (CrCl < 30 mL/min)
do not use for prophylaxis with low body weight (<50 kg)
can be used in HIT
no routine monitoring for therapeutic efficacy; can monitor anti-Xa levels
pregnancy category B (safe to use)
IV direct thrombin inhibitors
all three are reserved for pts diagnosed with HIT
lepirudin
bivalirudin
argatroban (adjust dose based on hepatic impairment; elevated INR, overlap with warfarin until INR >/= 4)
NOACs/DOACs
direct thrombin inhibitor: dabigatran etexilate
factor Xa inhibitors: rivaroxaban, apixaban, edoxaban, betrixaban
Labeled use - postoperative prophylaxis
knee or hip replacment surgery
Labeled use - non-valvular atrial fibrillation
prevention of stroke and systemic embolism in pts with non-valvular atrial fibrillation
Labeled use - DVT treatment
treatment of a DVT
need to put on an anticoagulant very quickly
Labeled use - PE treatment
treatment of pulmonary embolism
need to put on an anticoagulant very quickly
Labeled use - Indefinite anticoagulation (secondary prevention of recurrent DVT and/or PE)
reduction in risk of recurrence of DVT and PE following initial 6 months of treatment for them
Labeled use - VTE prophylaxis
prophylaxis of VTE in adults hospitalized for an acute medical illness
NOAC approved indications - postoperative prophylaxis
dabigatran, rivaroxaban, apixaban
NOAC approved indications - non-valvular atrial fibrillation
dabigatran, rivaroxaban, apixaban, edoxaban
NOAC approved indications - DVT/PE treatment
dabigatran, rivaroxaban, apixaban, edoxaban
NOAC approved indications - secondary prevention of recurrent DVT/PE
rivaroxaban, apixaban
NOAC approved indications - VTE prophylaxis
rivaroxaban, betrixaban
Warfarin available doses
1, 2, 2.5, 3, 4, 5, 6, 7.5, 10
all tabs scored, meant to split in half as needed
Challenges of warfarin
narrow therapeutic window (range considered to be safe is very close to the range considered to be unsafe)
considerable inter-subject variability (have to individualize warfarin dosing)
drug and diet interactions
labs difficult to standardize (INR monitoring is standardized)
good PK/PD understanding by both patient/provider
Warfarin MOA
does not effect circulating factors or previously formed thrombi (stops body from making new ones)
inhibits enzymes responsible for cyclic conversion of vit K
inhibit synthesis of vit K dependent clotting factors - factors II, VII, IX, X, protein C and S
PK/PD and half-lives of warfarin
anticoagulant effect within 24hrs, peak effect 72-96 hours, duration of action from single dose 2-5 days
hepatically metabolized by CYP450; enantiomer S metabolized by CYP2C9, 2C19, 2C18 and R metabolized by CYP1A2 and CYP3A4 - lots of drug interactions
Genetic variances - VKORC1
VKORC1 is the reductase enzyme that forms the active form of vit K that then converts vit K into vit K dependent clotting factors
1639A and 1173T: decreased VKOR production
1639A: increased warfarin sensitivity (lower dose needed)
1639G: increased warfarin resistance (higher dose needed)
more 2/3 - more sensitive
more 1/2 - more resistant
Who should be tested for warfarin?
3 requirements need to be met:
1. patient is warfarin naive
2. genetic test results are available before teh 6th dose
3. pt is at a high risk of bleeding if INR is elevated
if a single one is not met, do NOT offer warfarin genetic testing
Warfarin drug interactions
increase INR: erythromycin, metronidazole, amiodarone, alcohol, anabolic steroids, fluconazole, isoniazid, ciprofloxacin, bactrim, propafenone, liver disease
decrease INR: rifampin, cholestyramine, carbamazepine
Food drug interactions
vit K reverses warfarin activity
consistency is key
Alcohol and warfarin
acute EtOH: increase anticoagulant effect of warfarin by inhibiting its metabolism (increase INR)
chronic EtOH w/o liver damage: enhances warfarin metabolism by inducing hepatic enzymes –> decreases the effect of warfarin (decrease INR)
chronic EtOH w/ liver damage: due to lack of hepatic enzymes, increased anticoagulant effect (increase INR)
Antiplatelet use in VTE
limited role in VTE
ASA: consideration for CHA2-DS-VASc score 1
dipyridamole: consider concomitant use with warfarin with prosthetic heart valves
concomitant use with anticoagulants and increased risk of bleeding
VTE bleeding management
discontinue med, apply manual compression, maintain BP, surgical or radiological intervention, blood products +/- PCC +/- antidotes
consider: activated charcoal </= 2hrs of bleeding; hemodialysis - dabigatran only; tranexamic acid
targeted reversal: UFH, LMWH - protamin sulfate; dabigatran - idacruzimab; factor Xa inhibitors - andexanet alfa
Protamine sulfate: UFH and LMWH antidote
protamine sulfate binds UFH and LMWH to inhibit their further ability to cause anticoagulation
AEs: hypotension, bradycardia
Idacruzimab
MOA: direct binder to dabigatran (higher affinity than dabigatran to thrombin)
ADR: delirium, HA, hypokalemia, constipation, pneumonia, fever
monitoring schedule: baseline aPTT –> repeat in 2 hours –> every 12 hours until normal
Andexanet alfa
MOA: binds and sequesters FXa inhibitors
need to consider when last dose of those meds was given and what the last dose was to determine if we use the low or high dose
ADR: local site indusion rxn, DVT, ischemic stroke, AMI, PE, UTI, pnuemonia
no specific monitoring parameters
Warfarin: bleeding management
dependent on INR and presence/absence of bleeding
vit K, fresh frozen plasma, prothrombin complex concentrate
INR 4.5-10 + NO evidence of bleeding: avoid vit K
INR > 10 + NO evidence of bleeding: PO vit K
major bleeding: PCC preferred over FFP
Warfarin reversal
rapid (complete): PCC
fast (partial): FFP
prompt: IV vit K
slow: PO vit K
very slow: omit warfarin (no vit K)
VTE prophylaxis
without prophylaxis: VTE incidence 5-15% in medical pts
without prophylaxis: VTE incidence 40-80% in surgical pts
VTE prophylaxis options: UFH, LMWH, factor Xa inhibitors, vit K antagonists
Risk stratification - low risk < 10%
minor surgery
fully ambulatory medical pts
no specific pharmacologic therapy recommended
early and aggressive ambulation
Risk stratification - moderate 10-40%
most non-orthopedic surgery pts
acutely ill medical pts
Risk stratification - high 40-80%
major orthopedic surgery
major trauma
spinal cord injury
Moderate VTE risk treatment
general surgery pts: UFH, LMWH, and factor Xa inhibitor recommended; continue prophylaxis up to 28 days after hospital discharge
acutely ill medical pts: UFH, LMWH, fondaparinux, rivaroxaban, betrixaban all apprpriate; UFH, LMWH, and fondaparinux have no specific recommendations for post discharge VTE prophylaxis duration
High VTE risk treatment
orthopedic surgery (hip/knee replacement pts) - LMWH, fondaparinux, rivaroxaban, apixaban, dabigatran (hip), UFH or vit K
continue >/= 10-14 days postop
High bleeding risk
mechanical prophylaxis preferred: intermittent pneumatic compression devices, venous foot pumps, graduated compression stockings
CHA2DS-VAS and HAS-BLED
afib increases risk of stroke or systemic VTE by 5 fold - anticoagulant therapy reduces risk of stroke and all-cause mortality
CHA2DS2-VAC: risk factors for stroke or systemic VTE
HAS-BLED: risk factors for bleeding
Score interpretations
CHA2DS2-VAS: >/=2 - oral anticoagulation; 1 - no antithrombotic therapy OR oral anticoagulant OR antiplatelet
HAS-BLED: >/=3 - high risk of bleeding, caution and regular monitoring of pt are recommended
CHA2DS2-VASc congestive heart failure score
1
CHA2DS2-VASc hypertension score
1
CHA2DS2-VASc age >/= 75 years score
2
CHA2DS2-VASc diabetes score
1
CHA2DS2-VASc stroke/TIA score
2
CHA2DS2-VASc vascular disease score
1
CHA2DS2-VASc age 65-74 years score
1
CHA2DS2-VASc female score
1
HAS-BLED hypertension score
1
HAS-BLED abnormal renal and liver function score
1 point each
HAS-BLED stroke score
1
HAS-BLED bleeding tendency/predisposition score
1
HAS-BLED labile INRs (if on warfarin) score
1
HAS-BLED age > 65 years score
1
HAS-BLED drugs or EtOH score
1 or 2
