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Veli-PekkaHarjola

Deep Vein Thrombosis

Essentials

  • A normal D-dimer test result is enough to rule out deep vein thrombosis (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.
  • Ultrasonography diagnostics may be carried out in primary care usually during office hours. It is good to draw up care pathways locally.
  • 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 Evaluation of Thrombophilia).
  • 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.
  • The treatment of DVT that is below the level of the groin may usually be begun in primary care if the patient's general condition or associated diseases do not require hospital care.

Risk factors Testing for Cancer in Patients with Unprovoked Venous Thromboembolism

  • 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 Evaluation of Thrombophilia.
  • 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

Clinical picture

  • Common signs and symptoms associated with lower limb DVT are:
    • oedema Leg Oedema, pain
    • dilatation of superficial veins.
  • 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

Assessment of pretest probability

  • The scoring of pretest probability of DVT is presented in table T1.

Assessment of pretest probability of deep vein thrombosis on the basis of history and the patient's condition (Sources: Finnish Current Care Guideline Venous thromboembolism (VTE): deep venous thrombosis and pulmonary embolism 2016 http://www.kaypahoito.fi/web/english/guidelineabstracts/guideline?id=ccs00004, and 1,2 ).

Clinical conditionScore
Active cancer (treatment ongoing, within last 6 months or palliative)1
Paralysis, paresis or recent plaster immobilisation of a lower limb1
Recently bedridden for longer than 3 days or major surgery within last month1
Localised tenderness along the distribution of the deep venous system1
Swelling of entire lower limb1
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 veins1
Previously diagnosed deep vein thrombosis1
Alternative diagnosis more likely than that of deep vein thrombosis- 2
  • 3 points or more = high probability, about 75% risk
  • 1-2 points = moderate probability, about 17% risk
  • 0 points = low probability, about 3% risk
Sources:
1 Wells PS, Anderson DR, Bormanis J, et al. Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet 1997;350(9094):1795-8. [PubMed]
2 Wells PS, Anderson DR, Rodger M, et al. Evaluation of D-dimer in the diagnosis of suspected deep-vein thrombosis. N Engl J Med 2003;349(13):1227-35. [PubMed]
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

  • It is not always necessary to request imaging studies as an emergency procedure, and they can be carried out during normal work hours.
  • If the suspicion of venous thrombosis is at least moderate, it is recommended to start to administer before the investigations.

D-dimer Wells Score and D-Dimer in the Diagnosis of Deep Vein Thrombosis

  • 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 concentrations 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. Therefore, untargeted D-dimer determination should be avoided.
  • A D-dimer test result that is below the cut-off value is enough to rule out DVT when, based on clinical presentation, the probability of DVT is no more than moderate:
    • in patients HASH(0x2fd8d10) 50 years of age, D-dimer < 0.5 mg/l and
    • in patients > 50 years of age, D-dimer < (age/100) mg/l (e.g. in a 60-year-old patient < 0.6 mg/l).

Ultrasonography Clinical Value of Simple Proximal Vein Ultrasonography Plus D-Dimer Vs Whole-Leg Colour Doppler Ultrasonography for the Diagnosis of Deep Vein Thrombosis

  • Ultrasonography diagnostics may be carried out in primary care usually during office hours.
  • 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 Deep Venous Thrombosis (Compression Ultrasonography)).
  • If the pretest probability of an occlusion is low, one 2-point investigation is enough.
  • In other cases the investigation should be repeated 5-7 days 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.

Other laboratory tests

  • Basic blood count with platelet count, plasma creatinine (GFR Gfr Calculator), ALT, INR (also APTT, as far as possible, is recommended for coagulation disorder screening)
  • 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 Evaluation of Thrombophilia)
    • 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 HASH(0x2fd8c80) 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).

Other investigations

  • Examination of a patient who has had idiopathic DVT/PE (pulmonary embolism) for the detection of latent malignancy; see article on Evaluation of thrombophilia Evaluation of Thrombophilia

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)
    • Pregnant patients.

Management in primary care Home Versus in-Patient Treatment for Deep Vein Thrombosis

  • 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.
    • The treatment of DVT that is below the level of the groin may usually be begun in primary care.
    • 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:
    • instructions on the anticoagulant therapy
    • 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 Oral Direct Thrombin Inhibitors or Oral Factor Xa Inhibitors for the Treatment of Deep Vein Thrombosis, Duration of Anticoagulant Therapy in Venous Thromboembolism, Low-Molecular-Weight Heparins (Lmwh) Versus Unfractionated Heparin for Venous Thromboembolism, Vitamin K Antagonists or Low-Molecular Weight Heparin for Venous Thromboembolism, Once Versus Twice Daily Low Molecular Weight Heparin for the Initial Treatment of Venous Thromboembolism, Anticoagulation for the Intial Treatment of Venous Thromboembolism in Patients with Cancer, Optimal Loading Dose of Warfarin for the Initiation of Oral Anticoagulation, Anticoagulation for the Long Term Treatment of Venous Thromboembolism in Patients with Cancer, Subcutaneous Unfractionated Heparin for the Initial Treatment of Venous Thromboembolism, , Treatment of Distal Deep Vein Thrombosis

  • Dalteparin by subcutaneous injection 100 international units/kg twice daily or 200 international units/kg once daily (maximum dose 18 000 IU × 1)
  • 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.
  • 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 treatments are initiated directly without heparin treatment.
    • Dabigatran and edoxaban treatments are preceded by treatment with an LMWH (for a minimum of 5 days), after which dabigatran or edoxaban can be started with standard dosage.
    • Consult the appropriate local or national sources for information about drug dosages.
    • Article on Direct oral anticoagulants > Beginning treatment Direct Oral Anticoagulants
  • Warfarin is the preferred anticoagulant in antiphospholipid antibody syndrome Evaluation of Thrombophilia Systemic Lupus Erythematosus (Sle).
  • Pregnant women are treated with low molecular weight heparin (LMWH). Breast feeding is not a contraindication to warfarin.
  • Patients in active treatment for cancer
    • LMWH is used for the first 3-6 months (and usually for as long as the cancer is active)
    • LMWH or warfarin can be used for further treatment.
    • Concerning the therapeutic effect of direct oral anticoagulants, edoxaban and rivaroxaban appear to be equal to LMWH (gastrointestinal cancer is an exception where LMWH entails lower risk of bleeding). These are also alternatives as further treatment if LMWH was initially used.
  • Duration of anticoagulant therapy: see table T2. When considering the duration of therapy, take into account also the extent of the thrombosis, bleeding risk factors, probability of successful implementation, and compliance.

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)

IndicationsDuration
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 thrombosisAt 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
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.
Thrombolytic therapy Thrombolysis for Acute Deep Vein Thrombosis (fibrinolytic therapy)
  • Local thrombolytic therapy 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.

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 Compression Therapy for Prevention of Post-Thrombotic Syndrome

  • If the limb is significantly swollen, during the initial phase elastic spiral bandage is used to reduce the swelling.
    • Using an elastic bandage, the leg is bandaged from the foot to the knee gradually decreasing the pressure as the dressing advances proximally.
    • 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 not useful for the prevention of post-thrombotic syndrome. Instead, compression stockings may be used for the symptomatic treatment of swelling.
  • Patient education. Find out about locally available materials and services.