Cancer Associated VTE (bsh 2015)

CLOT Trial 2003

Hokusai VTE Cancer Trial 2017

 

Pathophysiology & Risk Factors

 

Expression of tissue factor on tumour cells

Pro-thrombotic properties of mucin

 

Surgery, CVC lines, infection, chemotherapy, radiotherapy

Risk remains elevated longterm even after remission - ?smoking ?increased weight

 

Thromboprophylaxis

 

Inpatients

  • All routinely assessed since 2007 DoH guidelines

  • Consider extended prophylaxis following abdomino-pelvic surgery

Outpatients

  • Myeloma at increased risk --> aspirin if low risk, LMWH if non-low risk

  • Risk scores for other cancers include factors such as:

    • Site of cancer, pre-chemo plt count >350, pre-chemo WBC >11, Hb <100 or use of Erythropoeitin, BMI >35

    • A high score = 7% VTE per 2.5 months

Not indicated in:

  • Prevention of CVC thrombosis

  • Adjuvant hormonal therapies

  • Solely as a measure to increase life expectancy

 

Treatment of VTE

 

Initial Six Months

  • CLOT trial 2003 = recurrence rates of 8% LMWH > 15% Warfarin

  • DOAC or warfarin acceptable if LMWH not tolerated

  • Hokusai trial 2017 = non-inferiority of edoxaban vs dalteparin

Recurrence during treatment

  • If on warfarin, switch to LMWH

  • If on LMWH, increase dose by 25%

  • If further VTE on increased dose, increase dose to aim anti-Xa 1.6 – 2.0 if OD (0.8 – 1.0 if BD)

  • IVC filters not indicated

Long Term AC?

  • Consider quality of life

  • Stop if cancer eradicated, or offer long term if ongoing cancer

Thrombocytopenia

  • In first 3 months, transfuse to allow ongoing anticoagulation

  • Consider IVC filter if unable to maintain plt count >50

 

Incidental finding of VTE

 

3-4% of CT Chest performed of reasons other than ?PE find a PE in cancer patients

6-month mortality is increased in cancer patients with VTE whether incidental or symptomatic

Indicative of a general pro-thrombotic state

 

Therefore, treat fully as for symptomatic VTE

 

Screening for Cancer in seemingly unprovoked VTE

 

6% undiagnosed cancer in unprovoked VTE patients

 

SOMIT study 2004

  • Screening reduced time to diagnosis but no survival benefit, which may be due to VTE being associated with advanced stage cancer.

  • Extensive screening (CT AP + mammogram + sputum cytology) causes anxiety

 

NEJM 2015 Screening for Occult Cancer in unprovoked VTE

  • 4% cancer diagnosis within 1 year of VTE

  • Missed cancers: 29% limited screening vs 26% extensive screening

  • Time to cancer diagnosis: 4.2 months limited screening vs 4 months extensive screening

 

Annals of Internal Medicine 2017 Systematic Review and Meta-analysis

  • 5.2% cancer diagnosis within 1 year of VTE

  • 7-fold higher prevalence if >50 y.o.

  • Unclear that screening translates into survival benefit

  • Limited screening plus age/sex related Ix as good as extensive screening

  • (Limited = Hx, Ex, FBC, U&E, LFT, CXR. Extensive = limited + CT AP)

 

Consider screening in >40 y.o. with unprovoked VTE

 

Hokusai Trial 2017

 

Open label, non-inferiority study of edoxaban vs dalteparin

1050 patients

Edoxaban 60mg OD (30mg if CrCl 30-50, body weight <60kg or taking P-glycoprotein inhib)

Dalteparin 200 U/Kg for 30 days, thereafter 150 U/Kg. Dose reduced if plt count <100!

 

Primary outcome = composite of recurrent VTE or major bleeding = Edox 12.8%, Dal 13.5%

 

Edoxaban = 7.9% recurrent VTE, 6.9% major bleeding

Dalteparin = 11.3% recurrent VTE, 4.0% dalteparin