Procedures for the outpatient management of patients with deep venous thrombosis1
The Haemostasis and Thrombosis Task Force meet every 6 months and will review these guidelines if any major developments occur, or by September 2008 at the latest. Members of the working party: Dr Mark Winter (Chairman, Consultant Haematologist, Canterbury), Dr David Keeling (Consultant Haematologist, Oxford), Dr Hannah Cohen, Consultant Haematologist, UCH, London, Freda Sharpen (Anticoagulant Specialist Nurse, Manchester), Prof. Patrick Vallance (Clinical Pharmacologist, UCH, London).
Mark Winter, Haemophilia Centre, Kent and Canterbury Hospital, Canterbury, UK. Tel.: +44 01227 783157; Fax: +44 01227 783167; E-mail: email@example.com
Although deep venous thrombosis (DVT) is now widely managed on an outpatient basis, at a practical level there remains a potential for uncertainty as to which patient might prove suitable and in particular in regard to the lines of responsibility of each department involved in the delivery of clinical care. This guideline sets out recommendations for the standardization of the outpatient management of patients with DVT.
Deep venous thrombosis (DVT) has an incidence which most studies place at around 1 : 1000 patients per year; the incidence increases with age (Carter, 1996). Prior to the development of low molecular weight heparins (LMWH) the traditional management of venous thrombosis involved the treatment of the patient with unfractionated heparin (UFH) on an inpatient basis for a period of several days (Hull et al., 1986). UFH has most commonly been administered via an intravenous infusion device, with regular laboratory control using an activated partial thromboplastin time (APTT) ratio of patient when compared with control plasma. There is consensus that the significant inter-patient and intra-patient variability in heparin dosage requirement results in the APTT being in the therapeutic range in 50% of patients at best at any one time.
The advent over the past few years of LMWH has resulted in a sea-change in the management of venous thrombo-embolism. LMWH have been demonstrated to be at least as effective, and probably safer, than UFH for the initial management of DVT (Siragusa et al., 1996).
The introduction of an anticoagulant agent, given once daily with predictable pharmacokinetics – associated with the lack of any requirement for regular blood monitoring – has resulted in a number of local initiatives to develop outpatient therapy for patients presenting with DVT (Koopman et al., 1996; Wells et al., 1998). Given that the previous management of these patients inevitably involved a significant period of hospital admission, these developments have generally been supported by hospital trusts at a time when pressure on hospital beds has been intense. These initiatives also serve to reduce the length of time that these patients need to spend in a doubtless overcrowded accident department (A/E) or medical assessment unit (MAU).
Whilst ambulatory care for DVT will quite clearly be of benefit for a substantial percentage of patients there will be a number of medical conditions and social situations which preclude outpatient therapy in some cases. Furthermore, the advent of ambulatory therapy for DVT will necessarily involve collaboration between a number of health care agencies, including A/E and MAU, haematologists, haemostasis nurses, radiology departments, general practitioners and district nurses. Under such circumstances there is potential for confusion unless there are clearly defined lines of responsibility in the management of patients as they progress from diagnosis to outpatient treatment and follow-up.
These guidelines therefore set out to recommend unifying standards for the outpatient management of patients with venous thromboembolism; they should be read in conjunction with task force guidelines on the diagnosis of venous thromboembolism (Haemostasis and Thrombosis Task Force, 2003) and the management of oral anticoagulation (BCSH Haemostasis and Thrombosis Task Force, 1998).
Target patient group
Patients with clinically suspected DVT who would be suitable for outpatient management.
Wherever possible, recommendations in this document are related to formal levels of published evidence (Appendix 1).
Criteria for outpatient therapy
Where local arrangements exist, in uncomplicated DVT, LMWH is safe to administer on an outpatient basis. The following are unlikely to be suitable for outpatient treatment.
- •Patients with co-existent serious medical pathology.
- •Severe acute venous obstruction (phlegmasia cerulea dolens).
- •Patients in significant pain.
- •Significant renal impairment (creatinine in excess of 200 μmol/l).
- •Known heparin allergy or heparin-associated thrombocytopenia.
- •Suspected problems with adherence to treatment.
- •Communication problems (deafness, language difficulties, lack of home telephone).
- •Poor social circumstances.
- •Patients with limited mobility.
- •Patients with active bleeding.
- •Patients at significant risk of bleeding.
- –active peptic ulceration;
- –liver disease (PT > 2 s beyond normal range);
- –uncontrolled hypertension (diastolic >110 mmHg, systolic >200 mmHg);
- –recent eye or CNS surgery (within 1 month);
- –recent haemorrhagic stroke (within 1 month);
- –thrombocytopenia (platelet count below 100 × 10/l).
It should be noted that pregnant women were excluded from the published trials demonstrating the efficacy of ambulatory care. Furthermore, appropriate LMWH dosing schedules have not been definitively established in pregnancy and there is also continuing debate about the need for monitoring of LMWH by an anti-Xa assay during pregnancy.
Nevertheless, despite the lack of published evidence, it is reasonable to treat pregnant patients with DVT with LMWH on an outpatient basis.
Integrated care pathway
There must be an integrated care pathway, with clearly defined lines of responsibility, for the management of such patients (Appendices 2 and 3). This will usually involve two separate processes.
Whilst this traditionally falls under the responsibility of A/E departments or MAU an as yet relatively small number of Haematology departments have taken on this function. Where this latter situation applies, this must be clearly articulated in local clinical care pathways and must be accompanied by appropriate staffing and financial resource.
This will usually fall under the auspices of the Haematology department.
Whatever the local arrangements, the patient must at all times know who to contact in the event of problems arising.
The care pathway should be approved by all relevant stakeholders and the local clinical policy board.
The diagnostic process
Updated guidelines on the diagnosis of venous thrombosis have recently been produced by the BCSH (BCSH Haemostasis and Thrombosis Task Force, 2004). The diagnosis of venous thromboembolism has lately been facilitated by the advent of validated clinical probability scores and second generation d-dimer assays. (Wells, Anderson & Ginsberg, 2000). This may allow the discharge of a subgroup of patients without further radiological investigation.
For an outpatient therapy programme to be effective it is important that there should be no undue delay (which might therefore necessitate admission) in the diagnosis of the patient. It is therefore essential that a number of dedicated diagnostic imaging slots should be reserved each day for the diagnosis of patients with DVT who might then be suitable for outpatient care. This will need to be discussed and agreed with local radiologists and appropriately resourced by local management.
Those patients who are considered on clinical grounds as being at high risk of DVT should be treated with therapeutic doses of LMWH pending confirmation of the diagnosis. Appropriate local arrangements will need to be established for out of hours care.
It is not considered good medical practice for the patient to be treated on this presumptive basis for more than 24 h, as for many patients this would involve unnecessary treatment and an unacceptable degree of risk.
The diagnosis of DVT, and possible suitability for outpatient care, is usually the responsibility of the on-call medical team/A/E, depending on local arrangements. Where by local agreement the haematology department does take responsibility for diagnosis this must be clearly articulated in local clinical care pathways and resourced appropriately.
The role of the haematology department in the management of these patients usually begins when a patient with objectively confirmed DVT is in the opinion of the assessing doctor suitable for outpatient care.
These critical lines of responsibility must be clearly articulated in local clinical care pathways.
Local arrangements need to ensure that appropriate arrangements are in place for the patient to receive a comprehensive medical review at diagnosis, particularly in regard to the following.
- •Would the patient be suitable for outpatient therapy?
- •Is there any evidence of limb ischaemia?
- •Are there any associated pathologies – cancer, polycythaemia, etc.?
- •Will medical follow-up as an outpatient be required?
The attending medical team should issue the patient with appropriate analgesia. Non–steroidal anti-inflammatory agents and aspirin-containing medications should be avoided.
The post-thrombotic syndrome will affect at least 30% of patients after 8 years (Prandoni et al., 1999). Arrangements should be made for the patient to receive appropriately fitting grade II compression stockings which significantly reduce the incidence of the post-thrombotic syndrome (grade A recommendation, level 1B; Brandjes et al., 1997). This may best be carried out a few days after the thrombotic event, once the swelling in the affected leg has begun to reduce.
The patient should then be educated in the importance of wearing the stockings for at least 2 years and given advice about appropriate exercise and limb elevation.
Possible models of ambulant care
In practice, there are several potential models of care for the patient with DVT receiving outpatient treatment.
- •Daily attendance at Haematology department/MAU/A/E.
- •Domiciliary care, administered by outreach haemostasis nurses.
- •Domiciliary care, administered by district nurses and general practitioners.
- •Domiciliary care, with injection of LMWH by patient or relative.
Each of these systems has been shown to be a practical way of delivering effective care. Appropriate training programmes and competency assessments must be established for patients administering their own treatment.
The role of the haemostasis nurse specialist
Outpatient management care programmes for DVT are greatly facilitated by the appointment of a haemostasis nurse specialist who will act as a critical co-ordinator, liaising with the various departments involved in the care of the patient and carrying out the following functions:
- •administration of outpatient care programme;
- •commencement and control of anticoagulant therapy;
- •monitoring for signs of thrombus extension or PE;
- •liaison with community agencies and general practitioners;
- •patient information and education.
Starting anticoagulant treatment
Anticoagulation is the standard treatment for venous thromboembolism. Subcutaneous daily LMWH should be used for DVT. At this time it is agreed that no significant differences in clinical effectiveness have been established between the different preparations of LMWH. Whatever LMWH is chosen for local use it must carry a full product licence. Monitoring the APTT is unnecessary. Baseline bloods for platelet count, PT, APTT, renal and liver function should be taken.
Warfarin is started as soon as the diagnosis is made and should be given after the first injection of LMWH. Patients with previous allergy or resistance to warfarin should be treated with acenocoumarol or phenindione. Warfarin is teratogenic and must be avoided during the first trimester of pregnancy. There may be rare occasions where a pregnant patient may require warfarin during the second trimester but this should only be given in close collaboration with a consultant haematologist.
LMWH should be administered for at least 5 days or until the INR has been in the therapeutic range for two successive days, whichever is the longer (grade C recommendation, level IV). This is because the INR is raised as a result of low levels of factor VII in the early stages of warfarinization, but full anticoagulation is not achieved until the other vitamin K dependent clotting factors (II, IX and X) become depressed. This usually takes 3–5 days. A full blood count should be arranged after 5 days on LMWH – and throughout the period of LMWH treatment – to exclude the possibility of heparin-related thrombocytopenia. Patients with previous exposure to heparin within the past 100 days should also have a platelet count performed before the second dose of heparin.
Oral anticoagulant treatment should be given according to thrombosis task force guidelines (BCSH Haemostasis and Thrombosis Task Force, 1998). A baseline INR should be carried out. The initiation of oral anticoagulant treatment may be carried out according to a nomogram (grade B recommendation, level IIB), an example of which is given as Appendix 4. In most circumstances, the INR will need to be checked daily until the therapeutic range (usually 2–3) is achieved. Beware of potential interactions (particularly amiodarone, tamoxifen, macrolide antibiotics and NSAID). A lower initial dose will usually be required in the following circumstances:
- •elderly (over 70);
- •liver disease;
- •alcohol abuse;
- •body weight <50 kg;
- •congestive heart failure.
Duration and intensity of anticoagulant therapy
The duration and intensity of oral anticoagulant treatment are determined by the clinical aspects of the individual case. General principles are set out in the relevant Haemostasis and Thrombosis Task Force guidelines.
- •Guidelines on anticoagulant treatment (1998).
- •Guidelines on investigation and management of heritable thrombophilia (2001).
- •Guidelines for the investigation and management of the antiphospholipid syndrome (2000).
Outpatient therapy of pulmonary embolism
Pulmonary embolism carries a higher mortality than DVT. Whilst many patients will require hospital admission there is a subgroup of patients who present with peripheral PE (pleuritic chest pain and/or haemopytsis) who can safely be treated on an outpatient basis (Wells et al., 1998).
The patient and family should be fully informed and educated prior to being discharged on an ambulatory care progamme; verbal information should be supplemented by appropriate patient leaflets.
- •Investigation of possible venous thromboembolism.
- •Provision of appropriate analgesia.
- •Assessment of patients with confirmed DVT for outpatient care.
- •Assessment of requirement for medical outpatient follow-up.
- •Investigation of possible DVT recurrence.
- •Formal medical assessment for associated pathology.
- •Liaison with general practitioners.
- •Administration of outpatient care programme.
- •Liaison with community agencies and general practitioners.
- •Provision of appropriate support stockings.
- •Patient information and education.
- •Thrombophilia testing where appropriate.
- •Commencement and control of anticoagulant therapy.
- •Daily assessment for signs of thrombus extension or PE.
Clinical governance – Audit
Ambulatory care programmes should be administered in accordance with clinical governance frameworks and should be monitored by regular clinical audit with the results being made available to relevant stakeholders.
Areas of relevant audit activity would include:
- •percentage of DVT patients on outpatient therapy;
- •resource – bed days, finance, etc. – saved by use of outpatient DVT care;
- •time from clinical presentation to diagnosis of DVT;
- •use of support stockings.
Both the diagnostic and treatment processes must be clearly recorded in the patient's formal hospital record and be readily accessible.
Date of issue: January 2005
Recommended review date: January 2007
Although the advice and information contained in these guidelines is believed to be true and accurate at the time of going to press, neither the authors nor the publishers can accept any legal responsibility for any errors or omissions that may have been made.
Levels of published evidence.
|Grade A (evidence levels Ia, Ib)||Requires at least one randomized controlled trial as part of the body of literature of overall good quality and consistency addressing the specific recommendation|
|Grade B (evidence levels IIa, IIb)||Requires availability of well conducted clinical studies but no randomized controlled trials on the topic if recommendation|
|Grade C (evidence level IV)||Requires evidence from expert committee reports or opinions and/or clinical experience of respected authorities; indicates absence of directly applicable studies of good quality|
|Ia||Meta analysis of randomized controlled trials|
|IIb||At least one randomized controlled trial|
|IIa||At least one well-designed study without randomization|
|IIb||At least one well-designed quasi-experimental study|
|III||Well-designed non-experimental descriptive studies|
|IV||Expert committee reports or opinions and/or clinical experience of respected authorities|
[ Clinical care pathway for DVT outpatient management. ]
Lines of accountability in the ambulatory care of DVT.
|Investigation of initial DVT/PE||Administration of ambulatory care|
|Investigation of recurrent DVT/PE||Support stockings|
|Patient analgesia||Patient education|
|Assessment for ambulatory care||Thrombophilia testing|
|Formal medical assessment||Anticoagulant therapy|
|Medical follow-up as indicated||Liaison with GP|
|Liaison with GP|| |
Warfarin loading schedule.
|2||<1.8||10 (or 5 as above)|
| 1.5||7 & 8 alt. days|
| 1.8||6 & 7 alt. days|
| 2.0–2.1||5 & 7 alt. days|
| 2.4–2.6||4 & 5 alt. days|
| 3.1–3.5||3 & 4 alt. days|
| 4.1–4.5||Miss 1 day then 2 mg|
|5 Onwards|| ||As per day 4|