Venous Thromboembolism Flashcards
What two conditions are encompassed by venous thromboembolism?
Deep vein thrombosis (DVT)
Pulmonary embolism (PE)
What are signs and symptoms of a DVT?
Swelling and pain in the affected extremity
What are signs and symptoms of PE?
Shortness of breath
Pleuritic chest pain
If PE or DVT is suspected, what’s a helpful test we can perform?
D-dimer
VTE can be excluded without imaging if patient has pre-test probabilities of low, moderate or unlikely in combo with negative d-dimer test
If patient is diagnosed with distal DVT (calf veins) and symptoms are not severe, how do we manage?
No treatment needed.
Repeat imaging at 1 week
- No change, no treatment
- Significant clot extension, treat
When should we screen for thrombophilia? What is thrombophilia?
Patient age <40 year with recurrent VTE or family history
Blood that clots more easily
Which VTE patients can be treated outpatient?
Majority of DVT patients
PE patients without compromised cardiopulmonary function
What’s the ideal analgesic for patients with VTE?
Acetaminophen
Opioids may be required for a few days
NSAIDs are effective but increases risk of bleeding, especially if using with anticoagulants
What are non-pharms for DVT?
Rest if needed(reduces pain and swelling)
Evidence suggests early ambulation is preferred (resolves pain and swelling faster)
Elevate swollen limb
What are non-pharms for PE?
Oxygen if hypoxic
IV fluids if hypotensive
Vasopressor if hypotensive or organ hypoperfusion (shock)
What is a frequent complication of DVT?
Post-thrombotic syndrome (PTS)
What are signs and symptoms of PTS?
Chronic swelling and pain
Discomfort when walking
Skin discolouration
Does the compression stockings prevent development of PTS following DVT?
No
What can graduated compression stockings help with in DVT?
Improve edema and pain for DVT.
Relieve symptoms in those who do develop PTS
What patient population should not use graduated compression stockings?
Patients with pre-existing peripheral vascular disease (PAD)
What is the difference between PAD and DVT?
PAD= narrowed arteries in the legs
DVT= blood clot in the legs
What are the drug classes used in the treatment of VTE?
- Direct oral anticoagulants (DOACs)
- Warfarin
- Low molecular weight heparin (LMWH)
- Fondaparinux
- Unfractionated heparin (UFH)
What are drugs under the DOAC class?
Apixaban
Rivaroxaban
Dabigatran
Edoxaban
What are the two types of DOACs?
Direct thrombin inhibitor
Direct Xa inhibitor
What DOACs are in which class?
Direct thrombin inhibitor
- Dabigatran
Direct Xa inhibitor
- Edoxaban
- Rivaroxaban
- Apixaban
What makes apixaban and rivaroxaban different from dabigatran and edoxaban?
Dabigatran and edoxaban can only be used following a 5-10 days of parenteral anticoagulant
Apixaban and rivaroxaban can be used alone
If warfarin is used, do you need parenteral anticoagulation?
Yes, use together for a minimum of 5 days or until INR ≥2 for 24–48 hours
When is parenteral anticoagulation preferred over oral?
Patients with significant comorbidities that need to be stabilized
When oral agents are contraindicated or ineffective
When parenteral anticoagulation is selected, what are the three options?
Is there a preference out of the three?
LMWH
Fondaparinux
UFH
LMWH is recommended
What is the recommended duration of oral anticoagulation for the treatment of DVT/PE?
If patient’s first episode and transient risk factors= 3 months
Unprovoked VTE or irreversible risk factors= indefinite treatment
What is the mechanism of action of direct oral anticoagulants (DOAC)?
Dabigatran= directly inhibit the active site of thrombin
Apixaban, edoxaban, rivaroxaban= directly inhibit factor Xa
Is inhibiting factor Xa better than inhibiting thrombin?
Inhibiting factor Xa is considered a more targeted approach than targeting thrombin
DOACs have a ______ onset of action. Drug levels peak in __-__ hrs. They also have ______ half lives of __-__ hrs.
Rapid
3-4
short
7-14
Do DOACs have a lot of drug interactions?
Very few and no significant food interactions
What’s the benefit of giving DOACs?
They can be given in fixed dose and no monitoring of anticoagulant effect is needed.
Non-inferior for prevention of recurrent VTE compared to LMWH
Do DOACs have to be renally adjusted?
Yes so may not be appropriate for renal insufficiency.
Avoid dabigatran, edoxaban, and rivaroxaban if CrCl<30 ml/min.
Avoid apixaban if CrCl<15 mL/min
What’s the antidote for dabigatran?
Idarucizumab
What’s the antidote for direct Xa inhibitors?
Andexanet alpha
Does LMWH have to renally adjusted?
Yes
Is UFH or LMWH more predictable?
LMWH is more predictable and is an effective initial treatment of DVT in outpatients
If unfractionated heparin is used for treatment of VTE, what is the common route?
IV
What’s a relatively rare but serious complication of UFH?
Heparin-indued thrombocytopenia (HIT)
How do we manage HIT?
Stop immediately. Use a non-heparin alternative.
Start non-vitamin K antagonist anticoagulation should be initiated.
UFH (usually IV), and LMWH (usually SC), is available in SC injection form. When should SC route be avoided?
Anasarca (severe swelling all over body) and patients on vasopressors.
Warfarin (vitamin K antagonist) therapy should be titrated to maintain INR at what levels?
INR 2-3
How often is INR measured when initiating warfarin therapy?
Every other day for the first week
Every 3 days for a week
1-2 times weekly
Every 2-4 weeks once stable.
What is the drug interaction between warfarin and ASA or NSAIDs?
Does not affect INR control but may contribute to bleeding by causing gastric irritation (NSAIDs) and inhibiting platelet function (INR)
What are some common OTC interactions with warfarin?
Ginkgo
Ginseng
St. John’s wort
Is ASA used in the treatment of VTE?
Can be considered, but was the least effective agent in a network meta-analysis
Are thrombolytics often used in patients with VTE?
No, less than 10% are potential candidates
When do we avoid the use of thrombolytics?
Short life expectancy
Poor functional status
High risk of bleeding (Ex: intracranial hemorrhage)
If using a thrombolytic, when are the best results obtained?
If symptoms have existed for <14 days
Thrombolytics are rarely required for DVT, but when are they usually recommended?
- Hypotensive and not a high risk of bleeding
- Deteriorating clinically with low bleeding risk
- Life or limb threating thrombosis without bleeding contraindication
Recommendation for thrombosis prophylaxis is based on surgery type. What surgeries have strong recommendation for post-op prophylaxis?
- Elective total hip replacement
- Elective total knee replacement
- Hip fracture surgery
- High-risk general and abdominal surgery
Besides surgical patients, what other types of patients may also be a candidate for thrombosis prophylaxis?
Acute infection
Heart failure
Respiratory failure
Cancer (strongly consider)
ICU admission
Central line
History of prior VTE
What’s the typical duration of prophylaxis?
At least 10-14 days
in high risk situations such as hip-knee arthroplasty, may need to continue post-discharge
VTE is more common in patients with COVID 19. True or false?
True when they are hospitalized
What is a non-pharm prophylaxis choice? When is this used instead of pharmacological choices?
Graduated compression stocking or intermittent pneumatic compression devices.
Reserved for when risk of bleeding is high (Ex: neurosurgery)
If anticoagulants have failed or are contraindicated, what can we use to prevent lung clots?
Inferior vena cava filters
What pharmacological choices are approved for prevention of VTE?
LMWH
- Dalteparin
- Enoxaparin
- Nadroparin
- Tinzaparin
Unfractionated heparin
Warfarin (target to INR 2-3)
ASA (equal efficacy and safety)
if combined with an initial 5 days of LMWH or DOAC
DOAC (not edoxaban)
- Apixaban
- Dabigatran
- Rivaroxaban
What role does fondaparinux play in VTE? What is it’s mechanism of action?
Fondaparinux is only used in prevention of VTE. More so indicated in high-risk orthopedic patients.
It’s an indirect factor Xa inhibitor
Is there a preference for prophylaxis agents for cancer patients?
LMWH injections or apixaban
How do we manage acute VTE in pregnancy? (agent of choice? alternative?)
LMWH is the anticoagulant of choice.
UFH when LMWH not available
Both do not cross the placental barrier
Why is LMWH preferred over UFH?
LMWH does not induce as much bone loss and can be used daily
What’s the treatment duration for acute VTE in pregnancy?
A minimum of 3 months (including at least 6 weeks postpartum)
Which agents should be avoided in pregnancy?
Warfarin, DOACs
If fondaparinux ok to use in pregnancy?
Only if all other agents cannot be used
What agents can we use for secondary prevention following delivery or during breastfeeding?
Warfarin, UFH, LMWH for 6 weeks after delivery.
Avoid DOACS
Summary: If patient has isolated distal DVT/subsegmental PE, how do we manage?
Clinical surveillance or 3 months of anticoagulant therapy
If patient has transient risk factors, how long do we treat for?
3 months of anticoagulant therapy
If patient has unprovoked VTE, how long do we treat for?
3-6 months of anticoagulant therapy
Women with low recurrence risk= stop
Women with high recurrence and high bleeding= stop
Women with high recurrence but low/moderate bleeding = indefinite
Men with high bleeding= stop
Men with low to moderate bleeding risk= indefinite
If VTE is cancer associated, how long is treatment?
6 months or as long as cancer is active
Which DOAC has a unique dose adjustment depending on age and weight?
Apixaban 5mg BID usually
Change to 2.5mg BID if patient has two of the following:
≥ 80 years
Weight ≤ 60 kg
Serum creatinine ≥ 133 mcmol/L
What is the typica dosing for apixaban?
10mg BID for 7 days, then 5 mg BID for 3-6 months
What is the dosing for edoxaban?
60 mg daily after treating with parenteral anticoagulant for 5-10 days
What is the dosing for rivaroxaban?
15mg BID PO x 3 weeks, then 20 mg PO daily
What is the dosing for dabigatran?
<80y: 150 mg BID
≥80y = 110 mg BID
Following a treatment of parenteral anticoagulant for 5-10 days
What are the treatment of choice for HIT?
Argatroban (does not need to be renally adjusted but is IV infusion)
Danaparoid
Other alternatives include
Fondaparinux (DoC between the alternatives)
Rivaroxaban
Bivalirudin
If patient has HIT and does not want to have an IV infusion, what is the best choice?
Fondaparinux
If patient has HIT and is renally impaired, what is the best choice?
Argatroban (no renal adjustment needed)
What is the minimum duration of therapy for HIT?
At least 4 weeks
What is the antidote for unfractionated heparin?
Protamine sulfate
When does rivaroxaban have to be taken with food?
≥15 mg/day
Which of the DOACs has dyspepsia as a side effect?
Dabigatran
