In the last few days we have established that the 74 year old man with a confirmed DEEP vein thrombosis (in the superficial femoral vein – see this link for discussion of this misnomer: http://jama.jamanetwork.com/article.aspx?articleid=389874).

He has had significant indigestion for some time and has been taking his wife’s lansoprazole as he didn’t want to ‘make a fuss’. Despite this his symptoms persist and have now been present for six months. He denies any weight loss or melaena. However his FBC shows he is slightly anaemic with a low MCV.

We have summarised the debate and key learning points below. The next questions we are posing for debate are:

Does your hospital screen all new VTE patients for cancer? Or do you select certain patients for further tests? If you investigate further what investigations do you use? Is there a protocol or is it a case-by-case decision? 

Please reply on twitter using the hashtag #teamhaem in your reply.

VTE patients and cancer

Several of you felt concerned about his anaemia/symptoms and felt that this should be investigated. For some of you this was because you were concerned about anticoagulating a patient who may have a chronic GI bleed; for others you were concerned about cancer as an underlying cause of the DVT. You were all correct – he needs further investigation at this point. Endoscopy was suggested as a next step by many, requiring a periprocedure heparin bridging policy (that is perhaps a discussion for another time).

Discussion at this point moved on to the association between malignancy and thrombosis. Pancreatic malignancy was correctly identified as being most closely associated with thrombosis, but ovarian/gynaecological and stomach cancers were also mooted.

Sorenson (2000) calculated the standardised incidence ratio for malignancy identified in new VTE patients. This adjusts for the prevalence of cancers and showed that pancreatic, ovarian and prostate cancer had the highest standardised incidence, i.e appear to be the most prothrombotic cancers. However VTE associated with lung cancer was much more prevalent, as lung cancer is much more common. Sorenson also established that bilateral DVT (but not PE) was more likely to be associated with an underlying cancer.

We went back to physiology basics to highlight the cause of thrombosis in cancer patients:

Stasis                due to compression of the vessel by tumour, the presence of central lines, decreased patient mobility or increased plasma viscosity.

Endothelial Injury      direct invasion of the endothelium, endothelial injury from chemo, angiogenic stimulus by tumour.

Hypercoagulability     Decreased fibrinolysis, increased platelet activation, drug effects (for example asparaginase and thalidomide), use of hormonal therapy

How should cancer associated DVTs be managed?

Most favoured the use of low molecular weight heparin (LMWH) for these patients because:

• This is what the evidence favours: the CLOT trial showed that dalteparin was superior to warfarin for preventing recurrence of thrombosis without any increased bleeding rates. See this summary from the excellent 2 Minute Medicine Team: http://www.2minutemedicine.com/the-clot-trial-dalteparin-better-than-warfarin-in-preventing-recurrent-venous-thromboembolism-in-patients-with-malignancy-classics-series/
• Warfarin is difficult to manage in chemo patients due to:
  • interaction with chemotherapy
  • interaction with antibiotics
  • poor/variable patient diet during chemotherapy
  • a reluctance to commit patients to extra clinic visits for INR monitoring
  • Vomiting with chemotherapy.

The DOACs (Direct oral anticoagulants, e.g rivaroxaban, dabigatran and apixaban) were mentioned by a few participants but there was a general lack in confidence in their use in this setting for a number of reasons:

• As yet the site/mechanism of their absorption is not fully understood and thus the impact of surgery on the GI tract or the altered GI absorption of medication during chemotherapy (due to diarrhoea or mucositis) is not understood.
• Interaction with chemotherapy is a concern – some interaction with vinblastine, doxorubicin and tyrosine kinase inhibitors are reported, but other interactions are likely to exist.
• There is no evidence base for DOACs as cancer patients were excluded from some of the initial DOAC trials, and any analysis of these patients is post hoc. In the UK this area of ‘ignorance’ is currently being addressed by the SELECT-D trial:   http://www2.warwick.ac.uk/fac/med/research/hscience/ctu/trials/cancer/select-d/

Whether to screen for cancer in patients presenting with thrombosis can be controversial and is the next area we will examine.

What is your hospital’s practice? Do you investigate every new VTE patient for cancer, some patients, no patients? What tests do you do?

Please reply on twitter using #teamhaem. Join in the debate on this topic – there is no right answer but very variable practice out there. What do YOU think is the right approach? Any patient experiences that have challenged your position ?(anonymise any patient case narratives carefully please).

References:

The Superficial Femoral Vein:  A Potentially Lethal Misnomer