Deep vein thrombosis

EBM Guidelines
20.3.2017 • Latest change 20.3.2017
Veli-Pekka Harjola

Essentials

  • As many as half of all cases of deep vein thrombosis (DVT) develop without clinical symptoms.
  • A normal D-dimer test result is enough to rule out DVT when, based on clinical presentation, the probability of DVT is no more than moderate. However, if the likelihood of DVT is clinically high, diagnostic imaging studies are indicated.
  • Before treatment is started (or 1 month after discontinuation of anticoagulant therapy), a blood sample should be collected for the selective analysis of blood clotting factors (see article Laboratory evaluation of thrombophilia «Laboratory evaluation of thrombophilia»1).
  • Treatment aims to prevent PE and post-thrombotic syndrome.
  • All risk factors, or their absence, must be recorded. They determine the duration of the anticoagulant therapy.

Risk factors evd

  • DVT is rare if no risk factors are present.
  • The most important risk factors are
    • previous venous thrombosis or pulmonary embolism
    • severe infection, heart failure
    • obesity
    • oral contraceptives
    • oestrogen therapy or pregnancy
    • immobility (bed rest, flight travel, fractures)
    • surgery
    • cancer
    • inherited thrombophilia «Laboratory evaluation of thrombophilia»1.
  • Additional investigations are only performed if they are warranted by the patient history or clinical presentation.
  • All risk factors, or their absence, must be recorded. They determine the duration of the anticoagulant therapy (3 months – indefinite).

Clinical assessment evd

Clinical picture

  • Common signs and symptoms associated with lower limb DVT are:
    • oedema «Leg oedema»2, pain
    • dilatation of superficial veins
    • Positive Homan’s sign (flexion of the ankle causes calf pain).
  • As many as half of all cases of DVT develop without clinical symptoms. However, the specificity of the above signs and symptoms is small, particularly when they occur alone.
  • Distal muscle vein thrombosis also belongs to deep vein thromboses.
  • In addition to the lower limbs, venous thrombosis may also develop occasionally in
    • an upper limb
    • the pelvic veins
    • association with a central venous catheter
    • the right heart chambers
    • the portal vein and cerebral venous sinuses.

Differential diagnosis

  • Alternate diagnoses to be considered in the differential diagnosis include
    • trauma
    • compartment syndrome
    • Baker’s cyst or its rupture
    • post-thrombotic syndrome.

Assessment of pretest probability

Table 1. Assessment of pretest probability of deep vein thrombosis
Clinical parameterScore
Wells PS, Anderson DR, Bormanis J et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350:1795-8
Active cancer (treatment ongoing, within 6 months or palliative) 1
Paralysis, paresis or recent plaster immobilisation of a lower limb 1
Recently bedridden for longer than 3 days or major surgery within 4 weeks 1
Localised tenderness along the distribution of the deep venous system 1
Entire leg swollen 1
Calf swelling >3 cm compared with the asymptomatic leg (measured 10 cm below the tibial tuberosity)1
Pitting oedema (greater in the symptomatic leg) 1
Collateral superficial veins (non-varicose)1
Alternative diagnosis as likely or greater than that of DVT – 2
  • 3 points or more = high probability, about 75% risk of DVT
  • 1–2 points = moderate probability, about 17% risk of DVT
  • 0 points = low probability, about 3% risk of DVT
  • If the D-dimer test is negative and the score < 3, no other investigations are needed.
  • If the D-dimer test is positive or the score 3 or higher, compression ultrasonography is indicated.

Investigations evd

  • It is not always necessary to request imaging studies as an emergency procedure, and they can be carried out during normal work hours.
  • If there is a high suspicion of venous thrombosis, low molecular weight heparin (LMWH) can be started before the investigations.

D-dimer evd

  • The body’s fibrinolytic system is activated in the presence of thrombosis, which results in an increased concentration of D-dimer in the plasma.
  • Elevated D-dimer levels are also present in many conditions other than thrombosis (e.g. severe infection/inflammation, cancer, trauma, surgery, pregnancy). Up to 90% of elderly hospitalised patients have elevated D-dimer concentrations as a consequence of infections and tissue damage.
  • A normal D-dimer test result is enough to rule out DVT when, based on clinical presentation, the probability of DVT is no more than moderate.

Ultrasonography evd

  • The investigation is reliable in the diagnosis of proximal DVT (groin and popliteal veins) but less so in distal DVT.
  • In practice, ultrasonography involving only the groin and popliteal area is sufficient (2-point compression ultrasonography, videos «Compression ultrasonography of veins»1 «Deep venous thrombosis (compression ultrasonography)»2).
  • If the pretest probability of an occlusion is low, one 2-point investigation is enough.
  • In other cases the investigation should be repeated 1–2 weeks after the initial negative result, if the D-dimer test is positive.
  • Ultrasonography of the entire lower extremity is more accurate, and a single investigation is enough to exclude thrombosis.
  • Venography is nowadays very rarely performed.

Other laboratory tests

  • Before treatment is started (or 1 month after discontinuation of anticoagulant therapy), a blood sample should be collected for the analysis of blood clotting factors (thrombophilia screening «Laboratory evaluation of thrombophilia»1)
    • from a patient < 50 years of age in association with the first thrombosis already, at least if the thrombosis is idiopathic or occurs during pregnancy or use of contraceptive pills
    • from a patient ≥ 50 years of age, if the thrombosis is associated with the following features:
      • recurrent idiopathic thrombosis
      • thrombosis in close relatives
      • history also includes arterial thromboses, repeated miscarriages or foetal deaths
      • thrombosis at an atypical location (cerebral, hepatic, splenic, portal, mesenterial or renal vein).

Treatment

  • The aim of treatment in lower limb DVT is to prevent
  • The decision on whether DVT can be treated in the primary health care depends on the clinical picture and the patient’s home situation.
  • Most cases are treated primarily at the patient’s home.
  • Hospital treatment is required for
    • DVT with severe symptoms
    • patients with other diseases that complicate the treatment or diseases that predispose to bleedings (e.g. severe renal failure).

Management in primary care evd

  • The treatment of both DVT with only a few symptoms and mild, low-risk PE can be carried out at a health centre, by a district nurse or self administered by the patient. Based on the individual situation, the treating physician will decide where the treatment should be carried out.
    • Patients with several comorbidities or severe renal failure are usually not suitable for home treatment.
    • The patient must be supplied with written instructions concerning monitoring and duration of the treatment.
  • If treatment is carried out at home, the following must be ensured:
    • correct injection technique
    • monitoring of possible warfarin therapy
    • drug dosage
    • instructions regarding compression bandages and stockings
    • monitoring the patient for possible complications (bleeding, emboli).
  • A follow-up appointment should be made at the latest when the anticoagulant therapy is about to finish.
    • The patient is asked about his/her health and checked for signs of a possible predisposing factor that has not been previously diagnosed and of recurrence and post-thrombotic syndrome.

Anticoagulant therapy: dose and duration evd

  • Dalteparin by subcutaneous injection 100 units/kg twice daily or 200 units/kg once daily
  • Enoxaparin by subcutaneous injection 1 mg/kg twice daily or 1.5 mg/kg once daily
  • Tinzaparine 175 IU/kg × 1 s.c.
    • The effect of tinzaparine can be reversed with protamine more completely than when using the other drugs mentioned above.
    • May also be used in patients with renal failure (if eGFR > 20–30 ml/min)
  • Warfarin is started concomitantly at the dose of 5 mg/day. In elderly patients and in patients with heart or liver failure, the recommended initial dose is 3 mg/day.
    • Further dosage is guided by INR readings.
  • Heparin is continued
    • until INR has been within the target range (2.0–3.0) for at least 1 day (24 hours)
    • in any case for at least 5 days (taking the risk of bleeding and the INR readings into account).
  • Fondaparinux is an alternative for LMWH. It is suitable for patients with heparin allergy and for the treatment of heparin-induced thrombocytopenia (HIT).
  • Direct oral anticoagulants that do not require laboratory monitoring for the adjustment of dosage may be used as alternatives to warfarin.
    • Rivaroxaban and apixaban are initiated directly without heparin treatment.
    • Dabigatran treatment is preceded by treatment with an LMWH (for a minimum of 5 days), after which dabigatran can be started with standard dosage.
  • Pregnant women are treated with LMWH. Breast feeding is not a contraindication to warfarin.
  • Patients in active treatment for cancer can be managed with LMWH for the first 3–6 months (and usually for as long as the cancer is active), followed by LMWH or warfarin.
  • Duration of anticoagulant therapy: see table «Duration of anticoagulant therapy (modified from the Finnish Current Care Guideline Venous thromboembolism (VTE): deep venous thrombosis and pulmonary embolism 2016 )»2
Table 2. Duration of anticoagulant therapy (modified from the Finnish Current Care Guideline Venous thromboembolism (VTE): deep venous thrombosis and pulmonary embolism 2016 «http://www.kaypahoito.fi/web/english/guidelineabstracts/guideline?id=ccs00004»1)
Indications Duration
The safety and suitability of antithrombotic treatment are evaluated by regular monitoring. Continuation of the treatment is evaluated on case-by-case basis after e.g. a significant bleeding complication.
First episode of thrombosis with a transient risk factor present (e.g. surgery, trauma, immobility, hormonal contraception or replacement therapy, pregnancy) 3 months
First episode of unprovoked thrombosis At least 3–6 months
First episode of thrombosis in a patient with
  • active cancer
  • antiphospholipid antibodies in repeated tests (with a 3 month interval)
  • Factor V or prothrombin (factor II) homozygous gene mutation
  • established antithrombin or protein C deficiency
  • established protein S deficiency and venous thrombosis in close relatives
  • combination of two or more thrombophilias
  • based on individual assessment, if there are some other risk factor of permanent nature
Permanent
Recurrent unprovoked thrombosis
First life-threatening thrombosis without a predisposing factor
First thrombosis without a predisposing factor at an atypical location (e.g. veins of the abdominal area or venous sinus thrombosis)
Permanent

Thrombolytic therapy evd (fibrinolytic therapy)

  • Thrombolysis may be attempted if the thrombus
    • is recent (symptoms for less than 2 weeks) and
    • extends above the inguinal ligament or proximally in an upper limb thrombosis and
    • causes severe symptoms and significant oedema.
  • Thrombolysis can be considered if all the above criteria are fulfilled and the patient is not at an increased risk of bleeding.
  • Local, catheter-directed thrombolysis is the treatment of choice if a radiologist competent in the procedure is available.

Surgical treatment

  • Surgery is the first-line treatment approach if the viability of the limb is threatened and particularly if both thrombolytic and anticoagulant therapy are contraindicated.

Other treatment evd

  • Immediate bandaging during the acute phase to ensure the competence of the communicating veins
    • Using an elastic bandage, the leg is bandaged from the foot to the knee gradually decreasing the pressure as the dressing advances proximally.
    • The bandage is applied in circular turns; a figure of eight bandage is too tight.
    • Catheter-directed thrombolysis is not a contraindication to bandaging.
    • If the swelling extends to the thigh, the leg should be bandaged up to the groin.
  • The patient should mobilise as soon as clinically possible.
  • The need and duration of follow-up treatment with graduated compression stockings (Class II; usually knee-high) is assessed on an individual basis.
  • Routine use of graduated compression stockings is probably not useful for the prevention of post-thrombotic syndrome, but it may reduce oedema or pain.
  • Patient education