Cancer Associated VTE (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 include factors such as

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

o   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 increase 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

-       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 relared 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