Thromboembolic events
A thromboembolic event is the term used to describe the formation of a blood clot (thrombus) within a blood vessel, usually a vein. They can affect anyone and occur for no apparent reason but several individual risk factors can increase the risk of a thromboembolic event.
Compared to the general population, cancer patients in general are at a four-fold increased risk of a thromboembolic event but for myeloma patients this risk increases further. This is due to the cumulative combination of the myeloma itself, side effects of anti-myeloma treatment particularly IMiDs and especially when used in combination with high-dose dexamethasone (Table 9) and individual risk factors (Table 10).
Table 9: Treatment-related risk factors for thromboembolic events
| Therapy | Higher risk | Lower risk |
|---|---|---|
| Lenalidomide | In combination with ixazomib and/or high-dose dexamethasone; dexamethasone plus erythropoietin; erythropoietin, cyclophosphamide, or combinations containing doxorubicin (including liposomal doxorubicin) | In combination with bortezomib or low-dose dexamethasone |
| Thalidomide | In combination with high-dose dexamethasone; erythropoietin; melphalan, melphalan plus prednisone; doxorubicin (including liposomal doxorubicin) with or without dexamethasone, or in combination with two or more chemotherapy agents with or without steroid | In combination with low-dose dexamethasone |
Table 10: General risk factors for thromboembolic events
| Patient characteristics | – Increasing age Obesity Immobilised or low activity level (e.g. during air travel, inpatient admissions) – Smoker – Varicose veins – Pregnancy |
| Genetic factors | – Family history of thromboembolic events – Blood-clotting disorders |
| Disease or medical condition | – Sickle cell disease – Cardiovascular diseases – Chronic renal disease – Diabetes – Stage of myeloma disease |
| Procedure-related factors | – Current or previous central venous catheter, IV catheter, or pacemaker – Recent general, orthopaedic, neurologic, or gynaecologic surgery – Anaesthesia |
| Medications | – Chemotherapy – Steroids – Contraceptive pill particularly those containing oestrogen, such as the pill, patch or ring. – Oral hormone therapy (HRT) containing oestrogen – Hormone formulations used for transgender patients – Vitamin K – Lenalidomide, thalidomide, bortezomib |
The most common location for a thromboembolic event is in the veins of the legs i.e. deep vein thrombosis (DVT). It is a serious condition that is potentially life-threatening and should be treated as a medical emergency. The clinical consequences of a DVT are varied and may include:
- Post-thrombotic chronic venous insufficiency
- Skin changes and ulcerations
- Pulmonary embolism
- Ischaemic stroke
- Death
A thromboembolic event can, cause life-changing complications. It can also interfere with the course of treatment, complicate decisions regarding future treatment options and possible drug combinations.
Therefore, primary prevention, thorough assessment and optimum management of thromboembolic events are key to the overall treatment and care of myeloma patients.
Assessment of thromboembolic events
Nursing assessment is vital to help ensure thromboembolic events are prevented or managed appropriately. Patients should therefore be assessed for their risk for a thromboembolic event at:
- Diagnosis
- Before the start of treatment, especially thalidomide or lenalidomide
- Relapse
- On admission electively or for emergency care
Formal documentation of this process is recommended, for example, using a risk assessment proforma that takes into account individual patient and treatment factors. Completion of the assessment will identify those patients who are at low risk of a thromboembolic event and do not require intervention in the form of thromboprophylaxis from those with additional risk factors who do.
However, it is essential to assess bleeding risk prior to the start of prophylactic treatment, particularly if patients are, or are likely to become, thrombocytopenic. Measurement of baseline platelet count is crucial before deciding on thromboprophylaxis.
The most appropriate thromboprophylactic treatment plan will be given based on the risk assessment carried out and tailored to each individual. These include pharmacological (aspirin, low molecular weight heparin, warfarin, apixaban), mechanical (compression devices, antithrombotic stockings, exercise) and myeloma treatment-related (dose and/or schedule modification) prophylactic measures.
Despite best efforts, thromboprophylaxis cannot completely prevent a thromboembolic event and proper diagnosis and management should one occur is crucial. Nurses and patients should be aware of the following signs and symptoms of thromboembolic events:
Deep vein thrombosis
- Slight fever
- Tachycardia
- Unilateral swollen, red, warm extremity
- Cyanosis and cool skin (if venous obstruction is present)
- Dull ache, pain, or tight feeling over area and with palpation
- Positive Homan’s sign (calf pain when knee is flexed and foot is dorsi-flexed); present in approximately 35% of patients – note however, there is a high false-positive rate
- Obvious swelling (may not be present early)
- Distension of superficial venous collateral vessels
Pulmonary Embolism*
- Anxiety
- Sudden dyspnoea
- Chest pain that can be sharp or stabbing and may get worse with deep breaths
- Tachycardia
- Unexplained breathlessness
- Low-grade fever
- Pleural friction rub, crackles followed by diminished breath sounds; wheezing also may be present
- Sudden collapse
- Electrocardiogram right axis deviation or new right bundle branch block
*Pulmonary embolism is a medical emergency and patients should call 999 if they notice any of the symptoms above.
For myeloma patients with any of the above symptoms, investigations to consider in diagnosing thromboembolic events include:
- Imaging techniques:
Doppler ultrasonography, contrast venography, radionuclide scintigraphy (for DVT), ventilation perfusion lung (V/Q) scan, spiral (helical) computed tomography (CT) angiography, pulmonary angiography (for PE) - Laboratory tests:
Serum D-dimer, antithrombin level, renal function, platelet counts & clotting screen
If DVT or PE is diagnosed, further investigations should be considered including: prothrombin time, adjusted partial thromboplastin time, and baseline international normalized ratio.
The NCI CTCAE (5.0) is used to grade thromboembolic events to determine the need for intervention (Table 11).
Table 11: Grading of thromboembolic events, NCI CTCAE (5.0)
| Grade 1 | Grade 2 | Grade 3 | Grade 4 | Grade 5 | |
|---|---|---|---|---|---|
| Thromboembolic event | Venous thrombosis (e.g. superficial thrombosis) | Venous thrombosis (e.g. uncomplicated deep vein thrombosis), medical intervention indicated | Thrombosis (e.g. uncomplicated pulmonary embolism [venous], non-embolic cardiac mural [arterial] thrombus), medical intervention indicated | Life-threatening (e.g. pulmonary embolism, cerebrovascular event, arterial insufficiency); hemodynamic or neurologic instability; urgent intervention indicated | Death |
Prevention and treatment of thromboembolic events
Nurses play a pivotal role in the overall management of myeloma patients at risk of or who require treatment for a thromboembolic event. They are at the forefront of coordinating measures to prevent a thromboembolic event and/or its complication. To that end, they should educate patients and their families about thromboembolic events; what the risk factors are, how they can be prevented signs and symptoms to look out for and the importance of reporting them as soon as possible. Patients should be provided with a 24 hour contact number and encouraged to seek help at any time if they develop symptoms of a thromboembolic event. Read more about how to assess and manage this complication and educate your patients in the our Myeloma Nurse Guide: Venous Thromboembolism.
Once a thromboembolic event has been diagnosed, treatment and/or future preventative measures include:
- Oral anticoagulants such as aspirin or warfarin
- Direct oral anticoagulants (DOACs) such as apixaban or rivaroxaban
- LMWH injections or unfractionated heparin for patients with significant renal impairment
- Mechanical means (e.g. stockings, gentle exercise)
- Myeloma treatment modification (dose reduction of medications which increase risk)
Note: platelet count should be monitored carefully and in some cases (counts < 50 x109/L) treatment may need to be paused while platelets recover. Length of anticoagulation will depend on whether the thromboembolic event was provoked (i.e clot at site of central line) or unprovoked.
Further reading
MD+CALC IMPEDE-VTE online risk assessment tool: mdcalc.com/calc/10498/impede-vte