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