From the Guidelines
The patient's recurrent thrombosis despite rivaroxaban therapy necessitates a comprehensive evaluation and potential switch to a different anticoagulant, with a strong consideration for lifelong anticoagulation to mitigate the high risk of future events.
Evaluation Strategy
My evaluation strategy would include:
- A comprehensive history focusing on medication adherence, drug interactions, and risk factors for thrombosis
- A physical examination looking for signs of underlying disorders
- Laboratory tests including complete blood count, comprehensive metabolic panel, coagulation studies, and thrombophilia testing (factor V Leiden, prothrombin gene mutation, protein C/S deficiency, antithrombin deficiency, antiphospholipid antibodies) 1
- Imaging would include a CT chest with contrast to evaluate the current PE and possibly abdominal imaging to rule out occult malignancy
Probable Causes of Anticoagulation Failure
Probable causes of anticoagulation failure include:
- Inadequate drug levels (despite reported adherence)
- Drug-drug interactions reducing rivaroxaban efficacy
- Underlying thrombophilia disorders
- Antiphospholipid syndrome
- Occult malignancy
- Anatomical factors causing venous stasis
- Rivaroxaban resistance Even with perfect adherence, DOACs have a failure rate of 1-4% for recurrent thrombosis 1
Available Anticoagulation Options
Available anticoagulation options include:
- Switching to a different DOAC like apixaban (5mg twice daily) which has slightly different pharmacokinetics and may be more effective in her case
- Switching to warfarin (target INR 2-3) would allow for monitoring of anticoagulation intensity but requires regular blood tests and has more food/drug interactions
- Low molecular weight heparin (e.g., enoxaparin 1mg/kg twice daily) is highly effective, especially if malignancy is suspected, but requires injections
- Dose escalation of rivaroxaban to 15mg twice daily is another option used in some cases of DOAC failure 1
Lifelong Anticoagulation
Lifelong anticoagulation is strongly recommended for patients with recurrent unprovoked VTE, as it reduces the risk of recurrence by approximately 80-90%. Without anticoagulation, her annual risk of recurrence is 10-20%, with each event carrying a 5-10% mortality risk 1. While anticoagulation does increase bleeding risk (2-3% annually), her young age and lack of major bleeding risk factors make her bleeding risk relatively low compared to the high thrombosis risk.
Anticoagulation Stewardship
For anticoagulation stewardship, I would recommend:
- Switching to a different class of anticoagulant (either warfarin with monthly INR monitoring or LMWH if a malignancy workup is positive)
- Scheduling follow-up visits every 3 months initially, then every 6 months once stable
- Assessing for bleeding complications, medication adherence, and any new drug interactions at each visit
- Annual laboratory monitoring would include renal function, liver function, and complete blood count
- Providing education about recognizing signs of bleeding or recurrent thrombosis and establishing clear communication channels for reporting concerns
- Addressing modifiable risk factors like maintaining healthy weight, regular exercise, and avoiding prolonged immobility 1
From the FDA Drug Label
Evaluation Strategy
To evaluate this patient, the following steps should be taken:
- Confirm adherence to rivaroxaban: Ensure the patient has been taking rivaroxaban as prescribed.
- Assess for bleeding: Evaluate the patient for any signs of bleeding, as this could be a complication of anticoagulation therapy.
- Review medical history: Consider the patient's history of hypertension, hyperlipidemia, and lack of autoimmune disease.
- Consider alternative diagnoses: Rule out other potential causes of shortness of breath, such as heart failure or pneumonia.
Probable Causes of Anticoagulation Failure
The probable causes of anticoagulation failure in this patient include:
- Inadequate anticoagulation: The patient may not be receiving an adequate dose of rivaroxaban.
- Resistance to anticoagulation: The patient may have developed resistance to the effects of rivaroxaban.
- Non-adherence: The patient may not be taking rivaroxaban as prescribed.
- Other medical conditions: The patient's hypertension or hyperlipidemia may be contributing to the anticoagulation failure.
Available Anticoagulation Options
The available anticoagulation options for this patient include:
- Warfarin: A vitamin K antagonist that requires regular monitoring of INR levels.
- Apixaban: A direct oral anticoagulant (DOAC) that does not require regular monitoring.
- Dabigatran: A DOAC that does not require regular monitoring.
- Edoxaban: A DOAC that does not require regular monitoring.
- Low molecular weight heparin: An injectable anticoagulant that requires regular monitoring.
Pros and Cons of Each Option
The pros and cons of each option are:
- Warfarin:
- Pros: Well-established efficacy, inexpensive.
- Cons: Requires regular monitoring, narrow therapeutic window.
- Apixaban:
- Pros: Convenient dosing, no regular monitoring required.
- Cons: More expensive than warfarin, potential for increased bleeding risk.
- Dabigatran:
- Pros: Convenient dosing, no regular monitoring required.
- Cons: More expensive than warfarin, potential for increased bleeding risk.
- Edoxaban:
- Pros: Convenient dosing, no regular monitoring required.
- Cons: More expensive than warfarin, potential for increased bleeding risk.
- Low molecular weight heparin:
- Pros: Well-established efficacy, can be used in patients with renal impairment.
- Cons: Requires regular monitoring, injectable formulation.
Counseling the Patient
When counseling the patient, it is essential to:
- Discuss the risks and benefits of each anticoagulation option.
- Emphasize the importance of adherence to anticoagulation therapy.
- Address concerns about the potential for bleeding or other complications.
- Provide education on the signs and symptoms of bleeding or other complications.
Anticoagulation Stewardship Strategy
The anticoagulation stewardship strategy for this patient should include:
- Regular monitoring of INR levels (if warfarin is prescribed) or renal function (if a DOAC is prescribed).
- Adherence monitoring: Regularly assess the patient's adherence to anticoagulation therapy.
- Bleeding risk assessment: Regularly assess the patient's risk of bleeding.
- Dose adjustment: Adjust the dose of anticoagulation therapy as needed based on the patient's response or bleeding risk.
- Patient education: Provide ongoing education to the patient on the importance of adherence, signs and symptoms of bleeding, and potential complications of anticoagulation therapy 2.
From the Research
Evaluation Strategy
To evaluate the patient's condition, the following steps will be taken:
- Review the patient's medical history, including the previous DVT and current PE
- Assess the patient's adherence to the current anticoagulation therapy (rivaroxaban 20 mg daily)
- Evaluate the patient's risk factors for anticoagulation failure, including hypertension and hyperlipidemia
- Consider the patient's lack of history of autoimmune disease
Probable Causes of Anticoagulation Failure
The probable causes of anticoagulation failure in this patient include:
- Inadequate anticoagulation dose or regimen 3
- Patient non-adherence to anticoagulation therapy (although the patient reports being adherent)
- Presence of underlying conditions that increase the risk of thrombosis, such as hypertension and hyperlipidemia
- Potential resistance to rivaroxaban or other anticoagulants
Available Anticoagulation Options
The available anticoagulation options for this patient include:
- Continuing rivaroxaban with a potential dose increase or change in regimen 3
- Switching to a different direct oral anticoagulant (DOAC), such as apixaban or edoxaban 3
- Using a vitamin K antagonist (VKA), such as warfarin, with regular monitoring of international normalized ratio (INR) 4
- Adding an antiplatelet agent to the current anticoagulation regimen The pros and cons of each option will be discussed with the patient, including the potential benefits and risks of each medication, as well as the need for regular monitoring and potential interactions with other medications.
Counseling and Convincing the Patient
To counsel and convince the patient to continue anticoagulation therapy, the following points will be discussed:
- The risk of recurrent VTE and potential complications, such as post-thrombotic syndrome and chronic thromboembolic pulmonary hypertension 5, 6
- The benefits of anticoagulation therapy in reducing the risk of recurrent VTE and improving outcomes 3, 5
- The potential risks and side effects of anticoagulation therapy, including bleeding and interactions with other medications 4, 3
- The importance of regular monitoring and follow-up to minimize the risks and optimize the benefits of anticoagulation therapy 4, 5
Anticoagulation Stewardship Strategy
The anticoagulation stewardship strategy for this patient will include:
- Regular monitoring of the patient's INR (if using a VKA) or other relevant laboratory tests 4
- Regular follow-up appointments to assess the patient's adherence to anticoagulation therapy and potential side effects 4, 5
- Education on the importance of anticoagulation therapy and the potential risks and benefits 3, 5
- Collaboration with other healthcare providers to ensure comprehensive care and minimize the risks of anticoagulation therapy 4, 5