VTE in cancer patients (3) Flashcards
Virchow’s Triad of Thrombosis
- Hypercoagulability
-cancer can cause this
-can be due to release of inflammatory cytokines - Stasis of blood flow
-immobility (which is common in cancer patients)
-compression of vessel by tumor (physical stasis) - Endothelial Injury
-caused by surgery (which can be cancer related)
-or irritation to endothelium by chemo, catheter, or the tumor itself
Incidence of VTE in cancer patients
VTE is 4-7 times more likely in cancer patients
2-6 fold increased mortality
2nd most common cause of outpatient cancer death
Increased risk of bleeding which makes it more challenging to treat
Higher risk of recurrence
Which pre-chemo factors increase risk of VTE? (4)
- Pre-chemo platelets high (> 350 x 10^9/L)
- Pre-chemo leukocyte high (> 11 x 10^9/L)
- Pre-chemo hemoglobin low (< 10 g/dL)
- Obesity (BMI 35 or above)
Which cancer related factors increase risk of VTE? (5)
- Recent diagnosis (last 3-6 months)
- Cancer site/type
-highest risk: pancreatic and stomach
-high risk: gynecological, lung, brain, and hematologic - Surgery
- Catheter placement
- Active chemotherapy
Which patient specific factors increase risk for VTE? (5)
- Genetics
- Older age (> 65 years)
- Immobility
- Hospitalization
- General performance status (lower performance status, they will be less mobile, higher risk)
When is VTE prophylaxis done for ambulatory cancer patients? (3)
-multiple myeloma (the therapy for this increases risk)
-On asparaginase therapy
-Khorana score > 2 (note - this scoring tool is not applicable for brain tumors or myeloma, and it is not for diagnosing, just to assess risk)
VTE prophylaxis for hospitalized cancer patients
Pretty much all hospitalized patients will get VTE prophylaxis
This is typically LMWH, UFH, or fondaparinux
Second line option is mechanically prophylaxis (compression devices) - this can be done if needed but is not the preferred method
What is the preferred LMWH drug and its dose for VTE prophylaxis
Enoxaparin - 40 mg SQ daily
(for obese patients it is often done q12 instead of daily)
What is the dose of UFH for VTE prophylaxis
5000 units SQ q8h
When is fondaparinux considered DOC for VTE prophylaxis?
In patients that have history of HIT
When is warfarin useful for VTE prophylaxis?
In patients with multiple myeloma
What is the dose of apixaban for VTE prophylaxis
2.5 mg PO BID
What is the dose of rivaroxaban for VTE prophylaxis
10 mg PO once daily
What should be considered when deciding on if to treat of not to treat a patient and considering treatment options? In which situation do we always treat?
Can consider no treatment if…
-high bleed risk
-limited life expectancy
Consider treatment if…
-higher clot risk
-complications post clot
Consider patient goals - more aggressive treatment, or are they just receiving palliative care at this point - case by case discussion and individual patient decision
When deciding on which treatment to pick if treating consider - bleed risk, renal function, thrombocytopenia
Note - if it is an emergent situation - then we always treat
Which instances require emergent thrombolytic treatment? (4)
If a patient is in an emergent situation - then we always treat.
This is if…
-symptomatic extremity DVT (at risk for limb gangrene)
-massive or submassive PE (at risk for hypooxygenation)
-spersistent bradycardia (<40 bmp)
-sustained hypotension
How do we treat emergent situations?
If a patient is in an emergent situation - then we always treat
We treat with parenteral anticoagulation - heparin IV continuous infusion
How long do we treat for?
There is some controversy in this
Ideally at least 6 months
-if they are not tolerating it or are a high bleed risk - 3 months
-in some cases we may treat for longer than 6 months
What is the drug of choice for treatment of VTE for patients that are a high bleed risk?
LMWH (enoxaparin)
Which patients are considered high bleed risk?
Luminal GI cancers
Those with increased risk of bleeding from genitourinary tract, bladder, or nephrostomy tubes
Those with active GI mucosal abnormalities - duodenal ulcers, gastritis, esophagitis, colitis
What is the dosing of enoxaparin for treatment of VTE
1 mg/kg BID SQ
(use actual body weight)
Or another option (but with less data) - 1.5 mg/kg once daily SQ
What should we monitor for with enoxaparin treatment?
Renal function
Risk of bleeding
Thrombosis symptom (cessation/improvement)
Anti Xa monitoring is controversial (can be done to make sure effective/appropriate dosing)
What are the 3 DOACs, how do they work?
Apixaban (Eliquis)
Rivaroxaban (Xarelto)
Edoxaban (Lixiana)
MOA - inhibit factor Xa
(can also be used in for VTE treatment, but consider bleeding risks with each)
Apixaban VTE treatment dosing
10 mg PO BID x 7 days
then 5 mg PO BID
Rivaroxaban VTE treatment dosing
15 mg PO BID for the first 3 weeks
then 20 mg PO once a day
Edoxaban VTE treatment dosing. And this dose is only if…
Start by overlapping for 5 days with parenteral anticoagulation
60 mg PO daily
Note - this dose is only if CrCl > 95 ml/min
Rivaroxaban and edoxaban should NOT be used if …
CrCl < 30 ml/min
DOACs should not be used for VTE treatment for patients with which type of cancer?
Gastrointestinal cancer - because these patients have a high bleed risk, so DOC is enoxaparin
DOAC bleed risk comparison
Apixaban has the lowest bleed risk of the DOACs
Rivaroxaban is in the middle
Edoxaban has the highest bleed risk of the DOACs
(keep this in mind when choosing a drug)
What is the efficacy of the 3 DOACs compared to LMWH?
Rivaroxaban
-reduces recurrent VTE risk compared to LMWH
-but increased risk of nonmajor bleeding
Edoxaban
-as efficacious as LMWH
-but increased risk of major bleeding
Apixaban
-may reduce recurrent VTE risk compared to LMWH
-no change in major bleeding risk
VTE treatment pathway summary
First - consider if the patient is in critical danger (is emergent treatment needed?) …
-If yes … parenteral anticoagulation (heparin), then thrombolytic treatment
If patient is NOT in critical danger - consider is the patient a high bleed risk? …
-If yes - LMWH (enoxaparin)
If not a high bleed risk consider if the patient has a CrCl > 30 …
-If yes (CrCl>30) - DOAC or LMWH
-If no (CrCl<30) - UFH or warfarin, or potentially apixaban (limited data)
LMWH vs fondaparinux efficacy/use
Similar recurrence of PE or DVT, major bleeding, and mortality
But, fondaparinux is usually not the DOC mainly because of its high cost
LMWH vs DOACs vs VKA
LMWH and DOACs may reduce VTE recurrence compared to VKA (so warfarin may not be as good)
And they have similar risk of bleeding
Long term anticoagulation considerations
There is some controversy in whether anticoagulation should be continued after 6 months
-have to consider the risk of recurrent VTE vs the risk of bleeding
Generally, if patients are still symptomatic after 6 months, they still have active cancer, or are still receiving chemotherapy - we continue treatment beyond 6 months indefinitely
Consider DOACs vs LMWH for long term treatment - DOACs may be better because they are PO (less invasive)
If risk factors have been addressed (no symptoms, no active cancer or chemo) - then there is less benefit to continue treatment, but there is also a risk of VTE recurrence- harder decision to make
Recurrent thrombosis considerations
Consider potential changes in patient condition which may be causing this
-progression of cancer (metastasis may be the cause)
-type of cancer (pancreatic, brain, ovarian, lung)
-immobility
-heparin induced thrombocytopenia
We could increase the dose of enoxaparin - and in this case we would monitor anti Xa levels - 4 hours after dosing, to make sure levels are where we want them to be
Or we could switch the agent
-patient specific decisions
Renal dysfunction is common in cancer patients, and this puts patients at increased risk of ______________
Bleeding
Agents for CrCl 15-30 ml/min (2)
Enoxaparin can be used but requires a dose adjustment –> 1 mg/kg SQ DAILY (instead of BID with normal renal function)
-and anti-Xa levels should be monitored
VKA (warfarin)
-good for renal patients, because we can monitor INR and is easily reversible - but it is less effective
Which agent should be used if CrCl is < 15 ml/min or patient is on dialysis?
Mostly warfarin (since we can monitor and control it better)
DOACs should be avoided for the most part, but apixaban has some limited evidence in ESRD
What if a patient has thrombocytopenia, how do we treat VTE?
Thrombocytopenia is common in cancer patients (low platelets, < 150,000) - increases bleeding risk - so LMWH is preferred for VTE treatment
If platelets are > 50,000 –> full dose enoxaparin (1 mg/kg SQ BID)
If platelets are 25,000 - 50,000 –> half dose enoxaparin (0.5 mg/kg SQ BID)
If platelet are < 25,000 –> temporarily stop VTE therapy, restart when platelets are higher (>50,000) (can increase platelets with platelet transfusion)
