We covered a lot of issues this week. Here is a link to the case on Storify: https://storify.com/TeamHaem/case-58-teamhaem-does-dvt Our patient was a 37 year old female with left leg swelling. She had no major medical problems and was on no regular medications. She had been on a car journey but we recognised that a 90 minute journey shouldn’t increase the risk of DVT in an otherwise healthy person. Likewise a great aunt had a possible post-operative DVT. Again when talking about family history of VTE it usually only applies to first degree relatives, although a ‘thrombosis-prone family’ has not been defined. When thinking about unilateral leg swelling it is important to think of other causes:
- Deep vein thrombosis
- Muscular injury
- Ruptured Baker’s cyst
- Lymphoedema or other obstruction of the lymph node e.g. lymphoma/cancer
- Infection e.g. cellulitis
- Bleed (often see these in acquired haemophilia)
Risk factors for VTE
DVT is important to think about. It is vital to think of risk factors for thrombosis and the best way is to divide them into three groups according to Virchow’s triad:
The Wells’ score is the most widely used scoring system for diagnosis of DVT. A similar score is used in PE. Different factors are added up to make a score (remember that the last point involved taking points away!)
Essentially if the DVT is unlikely a d-dimer is performed and if negative the alternative causes for symptoms should be investigated. Remember d-dimer can be elevated in inflammatory states, pregnancy, infections, trauma, DIC, cancer, haemorrhage etc. For this reason the Wells’ score should not be used in pregnancy as it is not validated. There are no scoring systems used in pregnancy. A low score results in a <15% risk of DVT and combined with a negative d-dimer the risk of DVT is approximately 0.5% at three months. If the Wells’ score is high then the patient should receive a doppler ultrasound scan and a d-dimer is not required.
Doppler ultrasound scans
There is much debate over scanning in patients with potential DVT. Two options are available:
- Full leg USS
- Proximal USS only
Full leg USS allows evaluation of the whole venous system in the lower limb. Most DVT start in the distal system (deep veins below the knee including the paired peroneal, posterior tibial, and anterior tibial veins) and migrate and have the potential to embolise. However not all will (difficult to say the rate as many patients studied were given anticoagulation but the majority, probably at least 90%, will have self-resolution). There is less risk of embolisation or progression with distal DVT compared with proximal DVT. There is also less risk of recurrence and post-thrombotic syndrome. Examining the distal veins by USS is more user-dependent and technically difficult. However a negative examination is relatively reassuring and unless clinical suspicion is very strong no further investigation is required. There is debate, however whether treatment is needed for distal DVT hence the debate re imaging. The American College of Chest Physicians Guidance suggest only treat distal DVT with severe symptoms or risk factors for progression or if there is progression on serial ultrasonography. Risk factors for extension include:
- (1) D-dimer is positive (particularly when markedly so without an alternative reason)
- (2) thrombosis is extensive (e.g., >5 cm in length, involves multiple veins, >7 mm in maximum diameter)
- (3) thrombosis is close to the proximal veins
- (4) there is no reversible provoking factor for DVT
- (5) active cancer
- (6) history of VTE
- (7) inpatient status
In reality most patients will have one of these risk factors. In reality the patient needs to be involved in the decision making. Most patients will have asked for medical attention because of symptoms and to not offer treatment for those symptoms especially in the face of a blood clot in the leg may not be acceptable for many despite there being debate in the medical community. If a proximal-only approach is taken then the examination must be repeated to look for extension. Health economics may also play a part in this. Because of the uncertainties and inevitable patient choice many hospitals will perform full leg ultrasonography. This avoids repeated examinations and will detect isolated distal DVT. In addition treament of distal DVT may become more acceptable with newer anticoagulants due to their ease of use and acceptable side effect profile. There is reference to NICE guidance, ACCP guidance and a ‘how I treat isolated distal DVT’ article below. Remember the ‘superficial’ femoral vein is a deep vein!
Here is a flow chart from http://www.rcemlearning.co.uk/references/deep-vein-thrombosis/ which outlines the process if a ‘proximal only’ approach is taken:
Treatment of DVT
The following approaches are examples of suitable management plans:
- LMWH and then warfarin
- LMWH and then dabigatran
- LMWH and then Edoxaban
The final choice often depends on what is funded in your area and also the patient’s renal/liver function, ability to take tablets, co-morbidities, potential side effects, other medications, need for dossette box, availability of reversal agent, bleeding risk etc. Guidance suggest that if a scan cannot take place within four hours then treatment should be initiated prior to confirmatory diagnosis. Treatment generally is carried on for three to six months and then a risk assessment as to whether long term anticoagulation is required. Provoked DVT do not usually require long-term anticoagulation and three months anticoagulation is usually sufficient. For those with unprovoked DVT those that are at higher risk of recurrence are males, proximal over distal VTE, obese patients, anti-phospholipid syndrome, active cancer and positive d-dimer post anticoagulation. The risk of recurrence for an unprovoked DVT is 5-10%/year but higher if risk factors. Therefore long-term anti-coagulation is frequently recommended for unprovoked VTE with risk factors for recurrance. Scoring systems have been developed (e.g. DASH score) but are not validated on a population level. Bleeding risk also plays a part in recommending long term anticoagulation. Newer agents are being investigated in clinical trials and most DOAC are licensed for long-term prevention (apxiaban can be used at reduced doses and rivaroxaban is being investigated at lower doses). Aspirin also has a modest effect in preventing VTE after an initial period of anticoagulation but the bleeding risks and efficacy verses newer anticoagulants must be weighed up.
This is what we thought!
Anti-embolic stockings generally do not help prevent post thrombotic syndrome, but some patients may find them useful for symptom control. This is summarised in the SOX trial (reference below).
Investigation into the cause of a DVT
The investigations involve looking for a cause in the above tabel. Careful history and examination is required. A FBC, U&E, LFTs, bone profile, clotting profile (prior to initiation of anticoagulation), CXR, breast examination (females), PSA (males) is a standard set of investigations. The SOME trial looked at first unprovoked VTE and randomised between standard investigation and standard plus CT abdo pelvis and found no benefit in terms of survival or pick up of malignancy by performing CT scans. Therefore further investigation is only required if suggested by history/examination (e.g. if change in bowel habit may want to do colonoscopy etc.). The trial did include PR/pelvic examination as a ‘basic investigation’. Pelvic examinations are not usually performed in busy medical units and the trial picked up no gynaecological malignancy with a pelvic examination.
Our patient had an isolated prolonged APTT. Remember this flow chart from case 37:
Our patient had a pronged APTT which didn’t correct on mixing and the DRVVT was positive indicating the presence of a lupus antiocoagulant. It is not possible to diagnose antiphospholipid syndrome from one positive DRVVT as the antibodies can be transient. Here is the diagnostic criteria taken from the BSCH guideline into antophospholipid syndrome (http://onlinelibrary.wiley.com/doi/10.1111/j.1365-2141.2012.09037.x/pdf):
Our patient would need the result repeated in 12 weeks to confirm. We can perhaps go over the DRVVT test in another case! Currently warfarin is the standard of care for patients with APS and VTE. DOACs are undergoing investigations as alternatives.
Summary – our patient
Our patient had an unprovoked proximal DVT. She was initiated on LMWH and warfarin as she had a positive DRVVT and there was a concern that she may have anti-phospholipid syndrome. She had the DRVVT repeated (whilst on warfarin using a 50:50 mix) and this remained positive. On further questioning she admitted to a facial rash, joint aches and fatigue which she put down to stress. An auto-antibody screen was sent along with a referral to a rheumatologist.