Venous thromboembolic diseases: guideline

242 Pages·2012·3.08 MB·English

by  Caroline Hatchett

1
Draft for pre-publication check
Venous thromboembolic
diseases: the management of
venous thromboembolic
diseases and the role of
thrombophilia testing
Venous thromboembolic diseases
Clinical Guideline
Methods, evidence and recommendations
March 2012
Draft for Pre-publication check

Commissioned by the National Institute for
Health and Clinical Excellence
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Published by the National Clinical Guideline Centre at
The Royal College of Physicians, 11 St Andrews Place, Regents Park, London, NW1 4BT
First published October 2011 (Draft)
© National Clinical Guideline Centre - October 2011 (Draft)
Apart from any fair dealing for the purposes of research or private study, criticism or review, as
permitted under the Copyright, Designs and Patents Act, 1988, no part of this publication may be
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for general use.
The rights of National Clinical Guideline Centre to be identified as Author of this work have been
asserted by them in accordance with the Copyright, Designs and Patents Act, 1988.

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Contents
Guideline development group members ....................................................................................... 8
Acknowledgments ....................................................................................................................... 9
Abbreviations ............................................................................................................................. 10
1 Introduction ........................................................................................................................ 12
2 Development of the guideline .............................................................................................. 14
2.1 What is a NICE clinical guideline? ....................................................................................... 14
2.2 Remit ................................................................................................................................... 14
2.3 Who developed this guideline? .......................................................................................... 15
2.4 What this guideline covers .................................................................................................. 15
2.5 What this guideline does not cover .................................................................................... 15
2.6 Relationships between the guideline and other NICE guidance ......................................... 16
3 Methods .............................................................................................................................. 17
3.1 Developing the review questions and outcomes ................................................................ 17
3.2 Searching for evidence ........................................................................................................ 20
3.2.1 Clinical literature search ...................................................................................... 20
3.2.2 Health economic literature search ...................................................................... 20
3.3 Evidence of effectiveness .................................................................................................... 21
3.3.1 Inclusion/exclusion .............................................................................................. 21
3.3.2 Methods of combining clinical studies ................................................................ 22
3.3.3 Appraising the quality of evidence by outcomes ................................................ 23
3.3.4 Grading the quality of clinical evidence............................................................... 25
3.3.5 Study limitations .................................................................................................. 25
3.3.6 Inconsistency ....................................................................................................... 26
3.3.7 Indirectness ......................................................................................................... 26
3.3.8 Imprecision .......................................................................................................... 27
3.4 Evidence of cost-effectiveness ............................................................................................ 28
3.4.1 Literature review ................................................................................................. 28
3.4.2 Undertaking new health economic analysis ........................................................ 30
3.4.3 Cost-effectiveness criteria ................................................................................... 31
3.5 Developing recommendations ............................................................................................ 31
3.5.1 Research recommendations ................................................................................ 32
3.5.2 Validation process ............................................................................................... 32
3.5.3 Updating the guideline ........................................................................................ 32
3.5.4 Disclaimer ............................................................................................................ 32
3.5.5 Funding ................................................................................................................ 32
4 Guideline summary .............................................................................................................. 33

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4.1 Algorithms ........................................................................................................................... 33
4.2 Key priorities for implementation ....................................................................................... 35
4.3 Full list of recommendations .............................................................................................. 37
4.4 Key research recommendations ......................................................................................... 41
5 Diagnosis of deep vein thrombosis ....................................................................................... 42
5.1 Introduction ........................................................................................................................ 42
5.2 Clinical probability scores (clinical scores) .......................................................................... 42
5.2.1 In people with suspected DVT, what is the effectiveness of clinical
probability scores in ruling out DVT? .................................................................. 43
5.3 D-dimer ............................................................................................................................... 44
5.3.1 In people with suspected DVT, what is the effectiveness of D-dimer in ruling
out DVT? .............................................................................................................. 45
5.4 Ultrasound........................................................................................................................... 47
5.4.1 In people with suspected DVT, what is the effectiveness of ultrasound in
ruling out DVT? .................................................................................................... 48
5.5 Recommendations and link to evidence ............................................................................. 54
5.6 Summary of research recommendations ............................................................................ 66
6 Diagnosis of pulmonary embolism ........................................................................................ 67
6.1 Introduction ........................................................................................................................ 67
6.2 Clinical probability scores and D-dimers ............................................................................. 67
6.2.1 In people with suspected PE, can we safely rule out further imaging based
on clinical probability score and D-dimer assay? ................................................ 69
6.3 Ventilation perfusion scans ................................................................................................. 71
6.3.1 In people with suspected PE, what is the effectiveness of ventilation
perfusion scans in ruling out PE? ......................................................................... 72
6.4 Computed tomography (CT) scans ...................................................................................... 76
6.4.1 In people with suspected PE, what it is the effectiveness of CT scans in
ruling out PE? ....................................................................................................... 77
6.5 Economic evidence ............................................................................................................. 78
6.6 Recommendations and link to evidence ............................................................................. 80
7 Pharmacological interventions ............................................................................................. 95
7.1 Introduction ........................................................................................................................ 95
7.1.1 What is the effectiveness of pharmacological interventions to manage
patients with suspected or confirmed DVT? ....................................................... 95
7.1.2 What is the effectiveness of pharmacological interventions to manage
patients with suspected or confirmed PE? .......................................................... 95
7.2 Pharmacological interventions for the initial phase of treatment ..................................... 95
7.2.1 Initial phase of treatment: Matrix of treatment comparisons ............................ 96
7.2.2 Fondaparinux vs LMWH ....................................................................................... 96
7.2.3 Fondaparinux vs UFH ........................................................................................... 98

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7.2.4 LMWH vs UFH .................................................................................................... 100
7.3 Pharmacological interventions for the continuation phase of treatment ........................ 109
7.3.1 Matrix of treatment comparisons ..................................................................... 109
7.3.2 LMWH vs VKA .................................................................................................... 110
7.4 Duration of anticoagulation .............................................................................................. 117
7.4.1 Introduction ....................................................................................................... 117
7.4.2 What is the optimal treatment duration for pharmacological interventions? . 117
7.5 Recommendations and link to evidence ........................................................................... 127
7.6 Summary of research recommendations .......................................................................... 142
8 Thrombolytic therapy for DVT ............................................................................................ 143
8.1 Introduction ...................................................................................................................... 143
8.1.1 What is the effectiveness of thrombolytic therapy and mechanical
thrombectomy to manage acute DVT? ............................................................. 143
8.2 Recommendations and link to evidence ........................................................................... 148
8.3 Summary of research recommendations .......................................................................... 150
9 Thrombolytic therapy for PE .............................................................................................. 151
9.1 Introduction ...................................................................................................................... 151
9.1.1 What is the effectiveness of open surgical thromboectomy, combination of
mechanical and pharmacological thrombolysis, pharmacological
thrombolytic therapy and heparin to manage acute PE? ................................. 152
9.2 Recommendations and link to evidence ........................................................................... 157
9.3 Summary of research recommendations .......................................................................... 160
10 Mechanical Interventions ................................................................................................... 161
10.1 Introduction ...................................................................................................................... 161
10.2 Vena caval filters ............................................................................................................... 161
10.2.1 What is the clinical effectiveness of vena caval filters to manage venous
thromboemobolic diseases in people that are unable to have
pharmacological treatment? ............................................................................. 161
10.3 Graduated compression stockings .................................................................................... 166
10.3.1 What is the effectiveness of graduated compression stockings to prevent
post thrombotic syndrome in people with venous thromboembolic
diseases? ............................................................................................................ 166
10.4 Recommendations and link to evidence ........................................................................... 168
11 Patient information ........................................................................................................... 175
11.1 Introduction ...................................................................................................................... 175
11.2 Patient information ........................................................................................................... 175
11.2.1 Does the provision of information and support about the management of
VTE improve patient outcomes? ....................................................................... 175
11.3 Recommendations and link to evidence ........................................................................... 178
12 Self-management and self-monitoring for patients treated with a vitamin K antagonist ...... 183

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12.1 Introduction ...................................................................................................................... 183
12.1.1 What is the effectiveness of self monitoring or self management compared
to hospital/GP testing for long-term pharmacological treatments? ................. 184
12.2 Recommendations and link to evidence ........................................................................... 189
13 Investigations for cancer in VTE patients ............................................................................ 191
13.1 Introduction ...................................................................................................................... 191
13.1.1 Do investigations for cancer in patients with spontaneous VTE (DVT or PE)
improve patient outcomes (morbidity and mortality)? .................................... 192
13.2 Recommendations and link to evidence ........................................................................... 195
Summary of research recommendations .................................................................................... 200
14 Thrombophilia testing ........................................................................................................ 201
14.1 Introduction ...................................................................................................................... 201
14.1.1 What is the effectiveness of thrombophilia testing in preventing recurrence
of a venous thromboembolic event? ................................................................ 201
14.2 Recommendations and link to evidence ........................................................................... 203
14.3 Thrombophilia testing for first degree relatives of people who had thromboembolic
disease and thrombophilia................................................................................................ 207
14.3.1 Does thrombophilia testing improve the outcomes of first degree relatives
of people who have had thromboembolic disease and thrombophilia? .......... 207
14.4 Recommendations and link to evidence ........................................................................... 210
14.5 Research recommendations ............................................................................................. 211
15 References ........................................................................................................................ 212
16 Glossary ............................................................................................................................ 229

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Guideline development group members
1
Name Role
Gerard Stansby (Chair) Professor of Vascular Surgery, Freeman Hospital and Newcastle University
Roshan Agarwal Senior Lecturer/Honorary Consultant Medical Oncologist, Imperial College
London
Susan Ballard Patient/carer representative
David Berridge Consultant Vascular Surgeon, Leeds General Infirmary
Christian Clark Patient/carer representative. Member of the Atrial Fibrillation Task Force
Richard Day Consultant Physician (Geriatrics), Poole Hospital NHS Foundation Trust
Hayley Flavell Anticoagulant and Thrombosis Consultant Nurse, Royal Bournemouth and
Christchurch Hospitals NHS Foundation Trust
Scott Harrison Lead Pharmacist, Oxford Radcliffe Hospital NHS Trust
Beverley Hunt Professor of Thrombosis and Haemostasis, King’s College, London
Medical Director of Lifeblood
David Keeling Consultant Haematologist, Oxford University Hospitals NHS Trust
Nigel Langford Acute Medical Physician, Sandwell and West Birmingham NHS Trust, City
Hospital, Birmingham
Steven Moser Consultant Radiologist, St Mary’s and Charing Cross Hospitals, London
Kat Noble General Practitioner with a specialist interest in Emergency Care, NHS County
Durham
Karen Sheares Respiratory Consultant with an interest in pulmonary vascular diseases,
Papworth Hospital NHS Foundation Trust
Expert adviser
2
Name Role
Richard Graham Consultant Radiologist, Royal United Hospital Bath
NCGC staff on the guideline development group
3
Name Role
Joanna Ashe Senior Information Scientist
Liz Avital Associate Director
Caroline Blaine Research Fellow (from January 2011)
Sara Buckner Research Fellow (from January 2011)
Lee-Yee Chong Senior Research Fellow
Elisabetta Fenu Senior Health Economist
Caroline Hatchett Research Fellow/Project Manager (from March 2011)
Jennifer Hill Operations Director
Clare Jones Senior Research Fellow/Project Manager (until March 2011)
Zahra Naqvi Research Fellow (from January 2011)
Sarah Riley Senior Research Fellow/Project Manager (until January 2011 and from
February 2012)
Julie Neilson Senior Research Fellow (until January 2011)
4

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Acknowledgments
1
2 The development of this guideline was greatly assisted by the following people:
3  Serena Carville (Senior Research Fellow/Project Manager, NCGC)
4  Saoussen Ftouh (Senior Research Fellow/Project Manager, NCGC)
5  Ralph Hughes (Health Economist, NCGC)
6  Kate Kelley (Associate Director, NCGC)
7  Susan Latchem (Operations Director, NCGC)
8  Kate Lovibond (Senior Health Economist, NCGC)
9  Grammati Sarri (Senior Research Fellow, NCGC)
10  Carlos Sharpin (Head of Information Science/Research Fellow, NCGC)
11  Ebenezer Tetteh (Senior Health Economist, NCGC)
12  Maggie Westby (Clinical Effectiveness Lead, NCGC)
13  David Wonderling (Head of Health Economics, NCGC)
14  Hati Zorba (Project Coordinator, NCGC)
15

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Abbreviations
1
Acronym Abbreviation
AF Atrial fibrillation
BMI Body mass index
BNF British National Formulary
CCA Cost-consequences analysis
CCT Controlled clinical trial
CEA Cost-effectiveness analysis
CI(s) Confidence interval(s)
COCP Combined oral contraceptive pill
CT Computerised tomography (scan)
CTEPH Chronic thromboembolic pulmonary hypertension
CTPA CT pulmonary angiogram
CUA Cost-utility analysis
DH Department of Health
DVT Deep vein thrombosis
ECG Echocardiogram
ELISA Enzyme linked immunosorbent assay
FP Forest plot
GCS Graduated compression stocking
GDG Guideline Development Group
GP General Practitioner
GRADE Guidelines Recommendations Assessment Development Evaluation
GRP Guideline Review Panel
HES Hospital episode statistics
HIT Heparin induced thrombocytopenia
HRQoL Health related quality of life
HRT Hormone replacement therapy
HTA Health technology assessment
ICER Incremental cost-effectiveness ratio
ICU Intensive care unit
IM/im Intramuscular
INB Incremental net benefit
INR International normalised ratio
ITT Intention to treat
IV/iv Intravenous
LMWH Low molecular weight heparin
LOS Length of stay
LY Life-year
MHRA Medicines and Healthcare Products Regulatory Agency
MID Minimal important difference
NCC-AC National Collaborating Centre for Acute Care
NCGC National Clinical Guideline Centre for Acute and Chronic Conditions (Formerly known as the

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Acronym Abbreviation
National Collaborating Centre for Acute Care)
NHS National Health Service
NICE National Institute for Health and Clinical Excellence
NMA Network meta-analysis
NNT Number needed to treat
NPV Negative predictive value
OR Odds ratio
PASA NHS Purchasing and Supply Agency
PE Pulmonary embolism
PICO Framework incorporating patients, interventions, comparisons, outcomes
POCT Point of care test
PPIP Patient and Public Involvement Programme
PPV Positive predictive value
PSA Probabilistic sensitivity analysis
PT Prothrombin time
PTS Post-thrombotic syndrome
QALY Quality-adjusted life year
RCT Randomised controlled trial
RR Relative risk
SC/sc Subcutaneous
SP Synthetic pentasaccharide
SR Systematic review
UFH Unfractionated heparin
US Ultrasound scan
VKA Vitamin K antagonist
V/Q Ventilation perfusion scan
V/Q (SPECT) Ventilation perfusion scan (single photon emission computerised tomography)
vs Versus
VTE Venous thromboembolism

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