Study methods
To provide denominator data for the study, records have been kept of all patients that were referred to the Thrombosis Clinic service, UHBristol for ultrasound assessment for lower limb DVT during the recruitment period, including those with a negative diagnosis. Details have been kept of the recruitment process including the reasons for exclusion and where provided, reasons for patients’ refusal to participate.
On ultrasound diagnosis of a lower limb DVT, each potential participant was assessed for eligibility and, if appropriate, offered an invitation letter and patient information leaflet. If interested in principle, the patient was asked to provide a contact telephone number and convenient contact time. The chief investigator would then contact the potential participant by telephone after 24–48 h to ask them if they wished to participate in the study and to answer any questions they may have. If they agreed, a first follow-up appointment was scheduled for 7 days post diagnosis. Written consent to participate in the study was obtained from each participant at the first follow up visit by the chief investigator in accordance with Good Clinical Practice. Each participant will remain in the study for 2 years post diagnosis.
Complete diagnostic ultrasound assessment of the proximal and distal lower limb veins using a combination of colour and spectral Doppler and compression ultrasound is undertaken on initial presentation. The diagnostic ultrasound is undertaken by Clinical Vascular Scientists from the Vascular Studies Unit, UHBristol who are trained locally under the standards of the National School of Healthcare Science NHS Scientist Training Program. The unit performs between 2000 and 2400 diagnostic ultrasound assessments for DVT annually and has a detection rate of 20–24 %. The following details are recorded: thrombosis location and extent, if the thrombosis is occlusive or partially occlusive and if adherence to the vessel wall is complete or partial. Any relevant clinical history is recorded at initial presentation including the nature and duration of any clinical symptoms.
The presence of any pre-existing medical conditions is recorded at each participant’s first follow-up visit, as well as the baseline details for gender, age and body mass index. Details are recorded of all prescription medications currently being taken by each participant and of any non-prescription medications/vitamins/supplements being taken regularly. Any changes in medical history, prescription medicines and body mass index are recorded at each study visit.
The follow-up schedule comprises six visits for those participants with a first episode of DVT in the limb concerned at the following intervals: 1 week, 1 month, 3 months, 6 months, 1 year and 2 years. Participants with a history of previous ipsilateral DVT will undergo three follow up visits at 1 week, 6 months and 2 years.
At each visit participants undergo full compression ultrasound assessment of the complete lower limb venous tree from the level of the inguinal ligament to the ankle (common femoral vein, popliteal vein, peroneal veins, posterior tibial veins, anterior tibial veins, soleal veins, gastrocnemius veins, greater saphenous vein and short saphenous vein) to identify the presence or absence of residual or new DVT or superficial thrombophlebitis in each venous segment. The ultrasound assessment is undertaken by the chief investigator who is a Health and Care Professions Council (HCPC) registered Clinical Vascular Scientist and is professionally accredited by the Society for Vascular Technology of Great Britain and Ireland (SVTGBI). The presence of thrombus is recorded as occlusive or non-occlusive and details of recanalization patterns are recorded in each segment. If the original diagnostic scan identifies the presence of thrombus in the iliac veins then the abdominal venous system is also scanned in full at each follow-up visit. In all cases, if flow in the common femoral vein on spectral Doppler ultrasound is not phasic with respiration, a full assessment of the external iliac vein, common iliac vein and inferior vena cava is undertaken using colour and spectral Doppler ultrasound.
Fifteen venous segments are assigned a thrombus score at each visit: inferior vena cava, common iliac vein, external iliac vein, common femoral vein, profunda femoris vein, proximal femoral vein, distal femoral vein, popliteal vein, peroneal veins, posterior tibial veins, anterior tibial veins, soleal veins, gastrocnemius veins, greater saphenous vein and short saphenous vein.
The thrombus load score is adapted from the updated reporting standards in venous disease from the Ad Hoc Committee on Reporting Standards of the Joint Council of the Society for Vascular Surgery and the North American Chapter of the International Society for Cardiovascular Surgery [
8] and a modified version of Haenan’s clot score as used by van Rij et al. [
9].
Each venous segment is scored as follows:
-
0 = patent
-
1 = subsegmental, non-occlusive thrombus
-
2 = subsegmental, occlusive thrombus
-
3 = occlusive thrombus throughout segment
A duplex ultrasound assessment for the competency of the deep and superficial veins is undertaken by the chief investigator at each visit. Pulsed and colour Doppler is utilised to assess flow characteristics within the veins including phasicity, spontaneity and direction of flow. Flow characteristics are assessed in a longitudinal scan plane. The patient are examined standing or at a minimum of 30° degree angle on a tilting table in order to assess the competency of the venous valves against gravity. Manual distal compression is applied to the calf to augment the flow and to assess for reflux. Venous incompetence is defined as a reflux time >0.5 s [
10].
At each visit, a detailed clinical assessment is made of the leg in which the thrombosis is/was present and the patients’ symptoms, including pain, aching, heaviness, itching, cramp and paraesthesia are recorded using an interviewer-administered questionnaire. The Villalta Scale [
11] will be used to quantify the symptoms of the burden of venous disease. The presence of oedema, teleangiectasias, reticular veins, varicose veins, hyperpigmentation, eczema, lipodermatosclerosis and ulceration are recorded according to the Clinical, Etiological, Anatomical and Pathophysiological (CEAP) classification system for classifying venous disease severity.
Details of the anti-coagulation treatment received by each patient in the study are collected as it is recognised that there are several different anti-coagulation therapies available and that variation in anti-coagulation regimes can occur depending on patient pathway, patient profile, patient choice and primary care follow-up. Adequacy of anticoagulation therapy is monitored through access to the participants’ medical records where relevant (vitamin K antagonists where international normalized ratio (INR) is monitored) and compliance with taking new oral anticoagulants (NOACs) is assessed by direct questioning at each visit. Participants’ compliance with compression stocking use is also recorded at each visit as ‘no use’, ‘occasional use’ or ‘routine use all day, every day’.
Any participant identified as having a recurrent DVT or an existing DVT that has extended at any point during follow-up is immediately reviewed by the rapid access thrombosis clinic. A recurrent DVT is diagnosed as the presence of a new thrombus either in the ipsilateral or contralateral leg or the presence of new thrombus on old thrombus in the same venous section as the original thrombosis, all of which are confirmed on Duplex ultrasound.