VTE prophylaxis recommendations
In myeloma, the vast majority of VTE cases have been reported within the first 6 months of treatment.rr
Trials utilising the newer IMiDs have included thromboprophylaxis as part of the protocol with either aspirin or low-molecular-weight heparin (LMWH), making assessment of the true VTE incidence difficult to ascertain.
Although VTE risk is greatest in the first 6 months of treatment, it is reasonable to continue VTE prophylaxis in patients at risk for the duration of myeloma treatment.rrr
Specific recommendations on the use of thromboprophylaxis should be given according to the individual risk factors and the type of therapy given.
Reassessment is recommended at relapse or when clinically indicated, eg in the event of occurrence of VTE.
The table below may be used as a guide:
Table 3: VTE risk stratification and recommended VTE prophylaxis
Treatment + risk factors present |
VTE risk |
Recommended VTE prophylaxis |
Single agent thalidomide/lenalidomide/pomalidomide +
Nil patient or myeloma-related risk factors present
Note: new diagnosis of myeloma confers a risk factor
|
No significant additional VTE risk |
No specific recommendation however low-dose aspirin (100 mg - 300 mg) may be prescribed at the discretion of the treating physician.
|
Single agent thalidomide/lenalidomide/pomalidomide +
1 patient or myeloma-related risk factor present
OR
Thalidomide/lenalidomide/pomalidomide in combination with low-dose dexamethasone (< 480 mg per month)
|
Intermediate VTE risk |
Low-dose aspirin (100 mg - 300 mg daily)
OR
Prophylactic dose Low Molecular Weight Heparin
e.g. enoxaparin 40 mg daily (20 mg daily if CrCl < 30 mL/min) is recommended.
|
≥ 2 patient or myeloma-related risk factors present (irrespective of the type of myeloma treatment being given)
OR
Thalidomide/lenalidomide/pomalidomide in combination with:
- High-dose dexamethasone (≥ 480mg per month) or
- Melphalan or
- Anthracycline or
- Multi-agent chemotherapy
|
High VTE risk |
Prophylactic dose Low Molecular Weight Heparin
e.g. enoxaparin 40 mg daily (20 mg daily if CrCl < 30 mL/min) or dalteparin 5000 IU daily
OR
Warfarin (target INR 2 - 3) is recommended.
Use of low-fixed-dose warfarin therapy (e.g. 1 mg daily) is not recommended.
|
Contraindications to prophylactic or therapeutic anticoagulation r
Absolute
- Recent central nervous system (CNS) bleed, haemorrhagic CNS metastases
- Active bleeding (major): more than 2 units transfused in 24 hours
Relative
- Chronic, clinically significant measurable bleeding > 48 hours
- Thrombocytopenia (platelets <50,000/mcL)
- Severe platelet dysfunction (uraemia, medications, dysplastic haematopoiesis)
- Recent major operation at high risk of bleeding
- Underlying haemorrhagic coagulopathy
- High risk for falls (head trauma)
- Neuraxial anaethesia/ lumbar puncture
- Interventional spine and pain procedures
- CNS metastases
- Long-term antiplatelet therapy
Mechanical VTE prophylaxis
Mechanical methods of VTE prophylaxis (e.g. graduated compression stockings, intermittent pneumatic compression devices and venous foot pumps) reduce frequency of VTE, however no data from large studies are available.r Such devices are a reasonable alternative for patients in whom pharmacological VTE prophylaxis is contraindicated.r
Inferior vena cava (IVC) filters do not prevent DVT and have been associated with increased risk for recurrent DVT, hence they are not recommended for VTE prophylaxis in multiple myeloma patients.r
Direct-acting Oral Anticoagulants (DOACs)
There remains limited published data on the safety and efficacy of DOACs in cancer patients and the use of these agents is not currently recommended by Australian and most international guidelines.rrrrrr
While there are guidelines that recommend the use of apixaban,r DOACs are currently not TGA licensed or PBS reimbursed for the prophylaxis of VTE in cancer patients.
The drug interaction between dexamethasone and rivaroxaban/apixaban should be considered if DOACs were used in this patient group. If a patient is already on a DOAC for another pre-existing indication, caution is recommended due to this interaction, and alternatives should be considered. In addition, there may be issues in patients with altered GI absorption (chemotherapy related vomiting and diarrhea), or when drug clearance is reduced in kidney dysfunction.