ST CATHERINE’SHOSPICE

Primary thromboprophylaxis in

advanced diseaseMJ Johnson

(The Mail on Sunday, 17/12/2000) 2

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(The Sunday Telegraph, 28/1/2001)4

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Daily Mail3/2/01

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Background

• VTE : important cause of death in cancer patients • Potentially preventable with appropriate risk assessment

and prophylaxis• Therefore a healthcare priority for many countries• Some (e.g. UK) using financial incentives and targets to

drive implementation • International guidelines:

Farge D, Debourdeau P, Beckers M, Baglin C, Bauersachs RM, Brenner B, et al. International clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer. J Thromb Haemost 2013 Jan;11(1):56-70.

What about palliative care?• Clinical relevance and research focus very recent in

palliative care• Moderate to high risk of VTE

– Advanced/active disease– Received ++ therapies (chemo/surgery)– Poorly mobile

• Secondary prevention is much more accepted• Still divided opinion about primary prevention

– Agreement not for those imminently dying

• But – hospice care now not just for the imminently dying

Things have changed• Hospice is no longer “the Death House”• But

– Only 7% SPC units have TP guidelines (Noble 2007)

– Not perceived as “a big problem” by clinicians– Outcome measures in studies not appropriate– Studies don’t include our patients– “A big PE is a nice way to go” (Noble 2008)

• However, difficult to keep being an ostrich…

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Why prevent VTE in palliative care patients?

• High risk – Up to 50% in hospice in patients

• VTE confers a poor prognosis• Cause symptoms

– Attributable and non attributable• Challenging to treat

– Bleeding– Recurrent thrombosis– Six months of LMWH

(Noble et al Lancet Oncology 2008)

Current state of play

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• Majority of palliative care patients admitted through medical take…

• …will be receiving PTP by default

• Some admitted to the hospice……

• ….won’t get PTP when they could benefit

Hospice VTE risk assessment project

• The utility of risk assessment tools in patients with advanced disease, and prediction of symptomatic VTE is unknown.

• Investigation: i)what is the relationship between risk of VTE and development of symptoms and, ii)what is the utility of risk assessment tools for these patients?

Method

• Retrospective consecutive admission case-note data from seven UK hospices

• Data collected during an evaluation of a VTE risk assessment protocol – Pan Birmingham Cancer Network palliative-modified

Thromboembolic Risk Factors (THRIFT) Consensus Group criteria,

– presence/absence of a temporary elevated risk (TER) of VTE.

• Symptoms/signs during admission consistent with possible VTE were documented.

Analysis plan• An exploration of the association of THRIFT, TER with

– prescription of PTP,– development of symptoms

• An estimation of the utility of THRIFT and TER in predicting symptomatic VTE during their hospice admission: – sensitivity, specificity, – predictive value (PPV and NPV), – likelihood ratios (LR(+/-)) – odds ratios

• Tests were 2-sided using a significance level of 5%, odds ratios and accuracy measures such as sensitivity are presented with 95% confidence intervals.

results• Total population: N=1164• 45 (4%) prescription of PTP on admission; (68

came on PTP; 13 of these continued; 32 new prescription)

• “Clinically relevant population” : N = 528 (45%)– The population who would have been eligible to have

PTP with LMWH– Excludes

• Contraindication to anticoagulation (bleeding, dying, thrombocytopenic) N= 496

• Already on therapeutic anticoagulation N = 139

Patient characteristics Total populationAge, years 70.1 (SD 13.1); range 23 to 99 Sex, male 627 (54%)Diagnostic categoryCancer 949 (82%)THRIFT Risk Score Low 48 (4)Moderate 968 (83)High 148 (13)TER Risk ScoreYes 880 (76%)No 279 (24%)missing 5 (0%)

Symptoms (N=528)

Clinically Relevant Population

Total Population

N=528 (%) N=1164 (%)

Symptom

Pleuritic chest pain 12 (2) 21 (2)

Leg swelling 14 (3) 32 (3)Breathlessness 47 (9) 99 (9)

• Overall 12% in clinically relevant group• Those not prescribed PTP had OR 1.74, 95% CI 0.69 to

4.4, p=0.241• Too few with PTP for estimation

Symptoms by riskTHRIFT TER

symptomsN (%)

High Moderate Low Yes No Total

Yes 4 (10) 57 (12) 1 (4) 26 (21) 36 (9) 62 (12)

No 36 (90) 403 (88) 27 (96) 98 (79) 368 (91) 466 (88)

Total 40 (100) 460 (100) 28 (100) 124 (100) 404 (100) 528 (100)

•21% of those with a TER developed symptoms compared to 9% of patients without a TER (Chi-squared, p<0.001).

Prediction of symptomatic VTEVTE risk assessment Clinically important

populationN=528; (95% CI)

THRIFT 1; High+Mod v Low Sensitivity (%) 98.4 (91.3, 100.0)Specificity (%) 5.8 (3.9, 8.3)THRIFT 2; High v Mod+LowSensitivity (%) 6.5 (1.8, 15.7)Specificity (%) 92.3 (89.5, 94.5)TERSensitivity (%) 41.9 (29.5, 55.2)Specificity (%) 79.0 (75.0, 82.6)

Limitations

• Symptoms not routinely investigated with imaging - proxy measure

• Number caused by confirmed VTE events not known• Severity not systematically documented

– But significant enough to the patient and doctor to document in the clinical record.

• Retrospective chart review– symptoms were not systematically sought for, graded or

documented – Therefore likely to be an underestimate.

Conclusions 1: Does risk matter?

• Most patients admitted to these hospices were at moderate to high risk of developing VTE during their stay.

• Does this matter?

• There is a highly significant association between

TER and “proxy” symptoms in those who could have PTP

Conclusions 2: what should we do about it?

• Use TER rather than THRIFT for hospice patients on admission

• But…• Unknown whether PTP improves outcome • Unknown what effect symptoms have on QoL

• Therefore consider PTP in those at risk and discuss with patient