Venous thromboembolism in the palliative care setting: what are the challenges?

Dr Simon NobleDr Simon NobleCardiff University and Royal Gwent HospitalCardiff University and Royal Gwent Hospital

Evidence

base

d medici

ne

Where the evidence is lacking

Where the evidence is lacking

To cover

• Is cancer associated VTE different?

• Can the evidence be applied to the palliative population?

• Heterogeneity of palliative population

• Attitudinal challenges

• Outcome measures

• How it fits into health policy

• Finding the answers

How does the thrombogenicity of cancer patients differ to from non cancer patients?

Virchow’s triad Circulatory

stasis

Endothelial Hypercoagulable injury state

Mechanism of tumour mediated hypercoaguable state

MalignantMalignant tumourtumour

Tumour cell surface tissue factor

MacrophageTissue factor

Other tumour-derived procoagulants

Tumour mediatedplatelet activationand accumulation

Tumour inducedendothelial cell

activationExpression of cell surface

phospholipids that supportcoagulation activation

Relative risk for VTE by Cancer Type

Type of Cancer

VTE (n) Cancer (n) Relative Risk (95% CI)

Breast 469 186 273 0.44 (0.40-0.48)

Oesophagus 64 14 472 0.76 (0.58-0.97)

Prostate 1230 218 743 0.98(0.93-1.04)

Hospitalised non-cancer patient

1.00

Lung 1504 232 764 1.13 (1.07-1.19)

Colon 1320 168 832 1.36 (1.29-1.44)

Pancreas 488 41 551 2.05 (1.87-2.24)

Ovary 327 26 406 2.16 (1.93-2.41)

Brain 184 13 529 2.37 (2.04-2.74)

Prothrombotic state

• Therapeutic interventions

-Chemotherapy

-Surgery

-Central venous access

-Brachytherapy

Chemotherapy

• Pyrimidine analogues– Reduced protein C– Increased fibrinopeptide A– Endothelial damage

• Platinum based regimes– Increased TF expression on monocytes– Increased platelet activation– Endothelial damage

How does cancer associated thrombosis differ?

DVT/PE onlyDVT/PE only

Number of daysNumber of days

Probability of readmissionProbability of readmission

0.050.05

0.000.00

0.100.10

0.150.15

0.200.20

0.250.25

4040 8080 120120 16016000

Nonmalignant Nonmalignant diseasedisease

Malignant diseaseMalignant disease

DVT/PE and DVT/PE and malignant diseasemalignant disease

Levitan et al (1999)Levitan et al (1999)

The risk of recurrence of VTE is increased in cancer patients

Probability of hospital readmission with DVT/PE within 183 days of initial hospital admission

DVT/PE onlyDVT/PE only

Nonmalignant Nonmalignant diseasedisease

Malignant Malignant diseasedisease

DVT/PE and DVT/PE and malignant diseasemalignant disease

Probability of deathProbability of death

0.200.20

0.000.00

0.400.40

0.600.60

0.800.80

1.001.00

Number of daysNumber of days4040 8080 120120 16016000 Levitan et al (1999)Levitan et al (1999)

Concurrent VTE and cancer increases the risk of death

Probability of death within 183 days of initial hospital admission

Long term anticoagulation

• Cancer patients at high risk of recurrent thromboses

• Higher risk of bleeding (28% vs 8%)1

• Bleeding risk increases with disease progression2

• Poorer control of INR despite increased INR monitoring3

1. Hutten et al (1997)

2. Noble et al (2008)

3. Bona et al (1997)

Incidence increases with advancing disease

• Incidence of symptomatic VTE in cancer patients VTE is 15 %

• VTE evident in 30-50% of cancer post mortems

• Asymptomatic DVT present in 50% of hospice inpatients.

What the evidence covers

• Metastatic disease

• Performance status 0-2

• Estimated prognosis > 3 months

• Platelet count >75,000 mm3

• Weight > 40kg

• No active bleeding

THROMBOGENICITYPERFORMANCE

STATUS

BLEEDING RISKPROGNOSIS

METASTATIC SPREAD

THERAPEUTIC

INTERVENTION

CO-MORBIDITIES

QUALITY OF

LIFE

Attitudinal issues…

We don’t see many DVTs or PEs!

Hmmm.. A large PE is a nice way to go…

Attitudinal issues…

We don’t see many DVTs or PEs!

Attitudinal issues…

We don’t see many DVTs or PEs!

At least not in all our breathless patients with swollen legs…

Post mortem study

• 92 patients where PE identified as cause of death

• 27 (30%) died within 10 minutes of symptoms

• 9 (10%) had no symptoms

Havig (1977)

60% of patients:“gradual deterioration dominated by dyspnoea, tachycardia and fever”

• Correct diagnosis of PE in 10% of cases

• Approximately 2 hours to die

• Treated with diuretics, digoxin, antibiotics

Evidence not appropriate in our patient group

• Does the efficacy of LMWH in general medical/ healthier cancer patients transfer to palliative patients?

• Evidence base of– Analgesic ladder– EAPC constipation guidelines– APM BcP recommendations

Outcome measures not applicable

• Radiologically apparent VTE

• Major bleeding– Death– Critical site– Requiring transfusion– Requiring

hospitalisation

• Minor bleeding– All other bleeds

Outcome measures not applicable

• Radiological apparent VTE

• Major bleeding– Death– Critical site– Requiring transfusion– Requiring

hospitalisation

• Minor bleeding– All other bleeds

• Symptomatic VTE• Quality of life• Clinically relevant

bleeding events– Haemoptysis– Epistaxis– Bruising

DoH. Letter from the CMO, 24 March 2010. Available at: www.dh.gov.ukNICE clinical guideline 92. Venous thromboembolism, 2010. Available at: www.nice.org.ukDoH. Using the CQUIN payment framework – an addendum to the 2008 policy guidance for 2010/11. Available at: www.dh.gov.uk Patient safety alert 18. Actions that can make anticoagulant therapy safer. 2007

NICE Guidelines 2010Chapter 28: Palliative Care

• Consider thromboprophylaxis for people admitted with potentially reversible pathology

• Do not offer thromboprophylaxis to those admitted for terminal care or on ICP

• Regularly review decisions

Heterogeneity of our hospice population

• 52% discharge rate

• Earlier involvement in patient journey

• Not solely terminal care

• Reversible causes of deterioration

(NICE 2010)

Medical thromboprophylaxis

(Aslett M Pan Birmingham Guidelines 2008)Available www.palliativedrugs.com

• Majority of palliative care patients admitted through medical take

• Will be receiving thromboprophylaxis by default

Research needed

• If we don’t find the answers, the majority of our patient group will receive thromboprophylaxis by default.

• Need to have the answer one way or another

What needs doing

• True prevalence and natural history of VTE in the palliative patient.

• Symptom burden of VTE and impact on quality of life

• A development of outcome measures that may be meaningful to the hospice setting

– VTE measures– Symptoms– Complications

• Consensus of what clinical/ symptomatic outcome difference would be required to change thromboprophylaxis.

What needs doing

• True prevalence and natural history of VTE in the palliative patient.

• Symptom burden of VTE and impact on quality of life

• A development of outcome measures that may be meaningful to the hospice setting

– VTE measures– Symptoms– Complications

• Consensus of what clinical/ symptomatic outcome difference would be required to change thromboprophylaxis.

What needs doing

• True prevalence and natural history of VTE in the hospice patient.

• Symptom burden of VTE and impact on quality of life

• A development of outcome measures that may be meaningful to the hospice setting

– VTE measures– Symptoms– Complications

• Consensus of what clinical/ symptomatic outcome difference would be required to change thromboprophylaxis.

What needs doing

• True prevalence and natural history of VTE in the hospice patient.

• Symptom burden of VTE and impact on quality of life

• A development of outcome measures that may be meaningful to the hospice setting

– VTE measures– Symptoms– Complications

• Consensus of what clinical/ symptomatic outcome difference would be required to change thromboprophylaxis.

Prophylactic anti-coagulation in cancer palliative care: a prospective randomised

study

• 20 patients 1:1 randomisation

• Nandroparin vs nil

• Insufficient recruitment to conclude

Weber C (2008)

That’s where you come in…

www.tradalliance.org

What is needed

• Network of palliative care teams willing to recruit to studies

• 1-2 patients per year

• Increase knowledge base

• Experience of research

• Improve patient care

What are we asking of you?

• Be part of the alliance

• Europe wide strategy

• Register an interest so you can share your experiences and contribute to the work

TRAD ALLIANCE

www.tradalliance.org

Thank you