Deep Vein Thrombosis

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See also: Pulmonary embolism

Deep vein thrombosis (DVT) is a common complication of advanced cancer, which is the context it is seen most commonly in palliative medicine. In addition to the local symptom of a painful, swollen leg, the key worry about DVTs is the high likelihood of the further, and often fatal, complication of pulmonary embolism. As in all palliative medicine, the decision about whether or not to investigate and treat a DVT is based on numerous factors including the likely prognosis of the patient given his or her terminal illness, the patient's functional status and the patient's wishes. There will be times when investigation and treating is not appropriate, for example, in a person who appears to be in the last few days of life, however, given DVTs and pulmonary emboli (PE) can cause very distressing symptoms, treatment is usually appropriate in most other patients.

Pathogenesis and Epidemiology

DVTs are more likely to develop if there are issues with any of the following:

  • Immobility and venous stasis
  • Hypercoagulability of the blood
  • Inflammation of the vascular wall

Cancers are a major risk factor for DVTs, primarily through causing hypercoagulability, but also, as the disease progresses, through causing fatigue with immobility. Cancers especially associated with DVTs include pancreas cancer, prostate cancer, breast cancer and ovarian cancer.[1]

Clinical Features

Patients will often present with a unilaterally swollen leg with calf tenderness that has developed within the last few days.

Less frequently a patient will present with new bilateral leg swelling. In cases of bilateral swelling, consideration of heart failure, hypoalbuminaemia and bilateral inguinal adenopathy as possible causes is appropriate but if there is no good alternative explanation for the peripheral oedema then there is a good chance that bilateral leg DVT are present. An alternative explanation may be that there is thrombus obstructing the inferior vena cava.

Rarely DVTs occur in the upper limb, particularly in association with a peripheral lines.

A history of recent immobility (e.g. associated with an acute illness, long car trip or surgery) should increase the suspicion that a DVT may be causing leg swelling, however, DVTs also frequently occur in a patient with underlying cancer without any additional risk factors.

Investigations

In general, when a DVT is thought to be a possibility in a palliative care patient, an urgent same-day (or next day) ultrasound is required to exclude or rule in a DVT.

In cases where the possibility of DVT is considered very remote then a case can be made to use a d-dimer or point of care ultrasound to exclude DVT.

  • D-dimer is almost always raised in any patient with an inflammatory illness and so a negative result is an extremely unlikely finding in cancer patients regardless of whether or not a DVT is present. This makes the test relatively useless in the palliative care context however in the unlikely event that a negative result was obtained then this could be used as assurance that a DVT was not present.
  • Point of Care Ultrasound can be used by an experienced non-radiologist operator to rule out a DVT at the popliteal and femoral veins in a patient where DVT is thought to be very unlikely.

Management

See also: Management of Pulmonary Embolism

Anti-coagulation

Untreated symptomatic deep vein thrombosis is associated with a 50% chance of pulmonary embolism (and there is a 30% chance of death in an pulmonary embolism). Therefore anti-coagulation with low molecular weight heparin is the usual treatment of choice for DVTs, e.g. enoxaparin 1mg/kg twice daily SC. An alternative and more convenient dosing schedule is 1.5mg/kg daily SC. In patients who have poor renal function, a reduced dose of enoxaparin is required, or alternatively, standard unfractionated heparin via intravenous infusion can be given.

Long-term anticoagulation should usually continue with enoxaparin or another low-molecular weight heparin. Warfarin is a less useful option because maintaining a stable INR is often very difficult in patients with advanced malignancy because of an inconsistent diet, drug-drug interactions and liver metastases. As such, warfarin is usually reserved for patients where low molecular weight heparin is inappropriate (e.g. in patients with significantly impaired renal function).

The duration of treatment for anti-coagulation in palliative care patients is typically indefinitive as DVTs associated with malignancy are not usually due to a temporary reversible fact such as immobility post-surgery or an aeroplane flight. Rather the precipitating factor is usually the malignancy, thus the anti-coagulation is commonly given long-term and only stopped once the benefits of it outweighs the risk.

Significant bleeding complications, such as gastrointestinal haemorrhage, occur relatively frequently with any anticoagulation. If the risk of bleeding is very high then the benefit of anticoagulation may be outweighed by its use and an inferior vena cava filter insertion may be a more appropriate treatment; alternatively no specific DVT treatment may sometimes be the most appropriate option.

IVC Filter

In patients whom treatment to prevent a PE is appropriate but for whom anti-coagulation is very dangerous (e.g. patients with a recently gastric haemorrhage from stomach cancer), an inferior vena cava filter can be inserted by an interventional radiologist. The filter will sit permanently within the inferior vena cava and any clot that travels superiorly towards the right heart will be caught in the filter and unable to pass further, thus preventing pulmonary embolization. The insertion of a filter is a relatively straight-forward procedure and serious complications are uncommon. However filters do not prevent DVT from extending locally and many patients with filters develop severe and intractable swelling of a leg or legs.

VTE prophylaxis

Given the common occurrence of DVTs in palliative care patients, the issue of DVT prophylaxis for inpatients in a hospice is a very relevant concern. On the one hand, prevention with a daily dose of low-molecular weight heparin (LMWH) (e.g. enoxaparin 40mg daily SC) is quite straight-forward. However this is not risk free and significant bleeding complications can occur with even low-doses of anticoagulants. Additionally, subcutaneous injections cause pain and discomfort. Furthermore, the context and situation of an individual patient may make DVT prophylaxis seem inappropriate. Giving DVT prophylaxis to patients who are in their last few days or weeks of life makes little sense. In most hospices, the vast majority of patients do not routeinly receive DVT prophylaxis. In general, prophylactic LMHW should be reserved for palliative care inpatients with an acute illness that is likely to respond to treatment with a subsequent improvement of mobility expected.[2] In these patients who are expected to return home then prevention of a DVT is important.

References

  1. Turner RA. Clinical Management of anaemia, cytopenias, and thrombosis. In: Hanks G, Cherny NI, Christakis NA, Fallon M, Kaasa S and Portenoy RK eds. The Oxford Textbook of Palliative Medicine. 2010. Oxford University Press, p932.
  2. Gillon S1, Noble S, Ward J, Lodge KM, Nunn A, Koon S, Johnson MJ. Primary thromboprophylaxis for hospice inpatients: who needs it? Palliat Med. 2011 Oct;25(7):701-5.

Authors

Graham Llewellyn Grove