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Veli-PekkaHarjola

Deep Vein Thrombosis

Essentials

  • Assessment of pretest probability forms the cornerstone of diagnosis, defining the ranges for interpreting D-dimer values, for instance.
  • A D-dimer test result below the cut-off limit 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.
  • Diagnostics ultrasonography can in most cases be carried out in primary care during office hours.
  • The aim of treatment is to prevent pulmonary embolism (PE) and post-thrombotic syndrome.
  • All risk factors for thrombosis, 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

  • There are numerous risk factors of various levels predisposing to DVT and PE and their recurrence.
  • The assessment of thrombosisrisk factors is based on patient history and clinical findings as well as laboratory tests, as necessary.
  • The risk factors for DVT and PE may be either permanent or transient, and the classification of their significance influences the planning of the treatment duration and the assessment of the risk of recurrence.
  • The need for further investigations should be considered individually based on patient history, clinical findings, and probabilities based on age and sex.
  • Routine imaging or untargeted cancer screening is not recommended.
  • All risk factors for thrombosis, or their absence, must be recorded.

Risk factors for venous thrombosis and their effects on the risk. Source: Finnish Current Care Guideline [Deep vein thrombosis and pulmonary embolism] 2023 (modified) 1.

Significant thrombosis risk factors (odds ratio, OR > 10)
Extensive trauma or invasive treatment, such as
  • fracture of the hip, lower limb or pelvis
  • hip or knee arthroplasty
  • spinal cord injury
  • significant open surgery (such as abdominal or thoracic surgery with duration of anaesthesia HASH(0x2fd7118) 30 min)
Recent (< 3 months) hospital treatment for acute cardiac event (heart failure, myocardial infarction, significant arrhythmia)
History of venous thrombosis (DVT or PE) without significant transient thrombosis risk factor
Moderately severe thrombosis risk factors (OR 2-9)
Arthroscopic knee surgery
Central venous catheters, other venous access and pacemaker leads, venous injuries and venous surgery
Congestive heart failure or respiratory insufficiency
Paralytic stroke
Significant thrombophilia
Blood transfusion
Erythropoiesis stimulating agents
Active cancer (depending on type and stage of cancer; highest risk in metastatic disease) or cytostatic treatment
Myeloproliferative diseases, such as polycythaemia vera and essential thrombocythaemia
Pregnancy, particularly puerperium (6 weeks)
Oral contraceptives containing oestrogen (depending on product and dosage strength)
Hormone replacement therapy (depending on product and dosage strength)
In vitro fertilization
Antiphospholipid antibody syndrome
Severe disease requiring prolonged bed rest (e.g. intensive care, severe infection)
Significant inflammatory or autoimmune diseases
Superficial venous thrombosis (< 3 cm from the saphenofemoral or saphenopopliteal junction and > 5 cm in length)
Mild thrombosis risk factors (OR < 2)
Bed rest exceeding 3 days or disease requiring acute bed rest; heart failure, lung disease, severe infection and dehydration, in particular
Prolonged sitting/immobility (such as a long drive or flight), with the risk increased by dehydration or acute disease
Age (the risk of thrombosis increases 2-3-fold every 10 years after the age of 40)
General risk factors for arterial diseases
Varicose veins or chronic venous insufficiency (risk of thrombosis decreases with increasing age)
Laparoscopic surgery (such as cholecystectomy)

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 deep veins of the lower limbs, venous thrombosis may also develop occasionally
    • in an upper limb
    • in the pelvic veins
    • in association with a central venous catheter
    • in the right heart chambers
    • in the portal vein and cerebral venous sinuses.

Differential diagnosis

  • Alternate diagnoses to be considered in the differential diagnosis of lower limb venous thrombosis include

Assessment of pretest probability

  • The scoring of pretest probability of DVT is presented in table T2.

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] 2023 1, and 1,2 ).

Clinical conditionScore
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]
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 diameter > 3 cm compared with the asymptomatic leg (measured 10 cm below the tibial tuberosity)1
Pitting oedema (greater in the symptomatic leg)1
Prominent superficial veins1
Previously diagnosed deep vein thrombosis1
Alternative diagnosis more likely than that of deep vein thrombosis-2
Clinical pretest probability of deep vein thrombosisSum
  • Low (approx. 3%)
HASH(0x2fcf4d8) 0
  • Moderate (approx. 17%)
1-2
  • High (approx. 75%)
HASH(0x2fd7118) 3
  • 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

  • Imaging studies can in most cases be carried out during office hours unless the case appears clinically severe.
  • If the suspicion of venous thrombosis is at least moderate, low molecular weight heparin (LMWH) or a direct oral anticoagulant should be started at therapeutic doses 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 (table T3).

Clinical pretest probability of DVT and PE and use of D-dimer cut-off values for diagnosis. Source: Finnish Current Care Guideline [Deep venous thrombosis and pulmonary embolism] 2023 1.

Clinical pretest probability of DVT/PED-dimer interpretationConclusion/imaging
Low<1.0 mg/lDVT/PE excluded / no need for imaging
ModerateBelow 50 years of age: < 0.5 mg/l
Over 50 years of age: < age/100 mg/l		DVT/PE excluded / no need for imaging
HighDon't do a D-dimer testProceed to imaging directly

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

  • Diagnostic ultrasonography can in most cases be carried out in primary care usually during office hours.
  • The investigation is reliable in the diagnosis of proximal DVT (femoral and popliteal veins) but less so in distal DVT.
  • In practice, ultrasonography involving only the popliteal and groin 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 about a week 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, creatinine, ALT should be checked before starting anticoagulants and, in addition, prothrombin time (INR) before starting warfarin.
  • A special thrombophilia test package (check with local laboratory) can be used to detect highly abnormal thrombophilia.
  • Testing for thrombophilia may be justified if venous thrombosis occurred at a young age (before the age of 50), idiopathically or without any significant thrombosis risk factor, particularly if there is a clear tendency for venous thrombosis in the family.

Other investigations

  • Examination of a patient who has had idiopathic DVT/PE for detection of latent malignancy
  • Routine extensive cancer screening is not considered cost-effective, but a thorough clinical examination should always be performed on a patient with venous thrombosis and, as necessary, further investigations are initiated based on the findings.
    • In patients with idiopathic proximal SLT or KE, there is no additional benefit of routine abdominal imaging (CT) compared to limited cancer screening (basic laboratory tests, mammography, gynaecological examination, PSA, lung X-ray).

Treatment

  • The aim of treatment in lower limb DVT is to prevent
  • The decision on whether DVT can be treated in primary health care depends on the clinical picture and the feasibility of providing appropriate care.
  • 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.
  • The treatment choices for upper limb DVT and the duration of treatment, etc., are similar to those for lower limb DVT, although there is a considerable paucity of research evidence.

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 home nursing 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 provided 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).
  • Appointments should in most cases be made for follow-up after 3 months and then annually for the duration of anticoagulant treatment.
    • The patient should be 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, Low-Molecular Weight Heparins in Pregnancy, Treatment of Distal Deep Vein Thrombosis

  • Direct oral anticoagulants are recommended primarily.
  • Warfarin can be used alternatively (INR target 2-3).
    • Warfarin should be started concomitantly with LMWH at 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 should be continued
      • until the 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).
    • In special cases and in association with the use of certain anticoagulants, s.c. LMWH should be used for early treatment.
  • Dalteparin by subcutaneous injection 100 international units/kg twice daily or 200 international units/kg once daily (maximum dose 18 000 IU once daily)
  • Enoxaparin by subcutaneous injection 1 mg/kg twice daily or 1.5 mg/kg once daily
  • Tinzaparine by subcutaneous injection 175 IU/kg once daily
    • The effect of tinzaparine can be reversed with protamine more completely than when using the other drugs mentioned above.
  • Fondaparinux is an alternative to LMWH. It is suitable for patients with heparin allergy or heparin-induced thrombocytopenia (HIT).
  • Warfarin is the preferred anticoagulant in antiphospholipid antibody syndrome Evaluation of Thrombophilia Systemic Lupus Erythematosus (Sle).
  • Pregnant women should be treated with LMWH. Breast feeding is not a contraindication to warfarin.
  • Patients in active treatment for cancer
    • LMWH should be 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, apixaban, edoxaban and rivaroxaban appear to be equal to LMWH (gastrointestinal cancer is an exception where LMWH carries a lower risk of bleeding). These are also alternatives as further treatment if LMWH was initially used.
  • Duration of anticoagulant therapy: see table T4.
  • The individual duration of anticoagulant therapy in patients with a history of thrombosis depends on
    • history of thrombosis (first or recurring)
    • risk of thrombosis (see risk factors for thrombosis, table T1) and differences between non-significant and significant risk factors for thrombosis
    • risk of bleeding
    • how dangerous the thrombosis was
    • chances of successful treatment, and compliance
    • patient's own view.

Basic duration of anticoagulant therapy modified from sources1,2 . Source: Finnish Current Care Guideline [Deep venous thrombosis and pulmonary embolism] 2023) 1

Clinical conditionDuration of treatment*
The safety and suitability of antithrombotic treatment should be evaluated by regular monitoring. Continuation of the treatment is evaluated on case-by-case basis after e.g. a significant bleeding complication.
Sources:
1 Konstantinides SV, Meyer G, Becattini C et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J 2020;41:543-603. [PubMed]
2 Ortel TL, Neumann I, Ageno W et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020;4:4693-4738. [PubMed]
  • First episode of thrombosis with a transient significant thrombosis risk factor present
  • Recurrent thrombosis and a transient significant thrombosis risk factor present, if the thrombosis recurred after a long time interval and there are no factors favouring permanent treatment
Treatment for 3 months is recommended (provided that the transient significant thombosis risk factor has been eliminated).
  • Complicated thrombosis (with risk of losing the limb or risk to the patient's life)
Consider permanent treatment.
  • Idiopathic thrombosis
  • First episode of thrombosis with a transient non-significant thrombosis risk factor present (see table TT1)
Consider permanent treatment.
  • Recurrent thrombosis (except if both cases were due to transient significant thrombosis risk factors, only, and the time to recurrence was long)
  • Significant permanent thrombosis risk factor
  • Protein S or protein C deficiency, antithrombin deficiency, antiphospholipid antibody syndrome, homozygous FV Leiden mutation and homozygous prothrombin gene mutation or a combination of heterozygous gene mutations
Permanent treatment recommended.
  • Thrombosis and active cancer
For as long as the cancer is active

Intravenous catheter-directed therapy Thrombolysis for Acute Deep Vein Thrombosis

  • Intravenous treatments include mechanical breaking up and aspiration of the venous thrombus and local thrombolysis.
  • Intravenous treatment should be considered for suprainguinal DVT (extending above the inguinal ligament) if
    • there are severe symptoms and significant oedema of the limb
    • there is no increased bleeding risk, and
    • the symptoms have continued no more than 2-3 weeks (older cases of thrombosis can be treated case by case thanks to the development of new methods of treatment).
  • Intravenous treatment can also be considered in equivalent cases of upper limb thrombosis.

Surgical treatment

  • Surgical thrombectomy can be considered for lower limb DVT where the viability of the limb is threatened and intravenous catheter-directed therapy is unsuccessful.
  • Such situations are rare.

Other treatment Compression Therapy for Prevention of Post-Thrombotic Syndrome

  • If the limb is significantly swollen, during the initial phase an elastic spiral bandage should be 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 for and duration of follow-up treatment with graduated compression stockings (class II), usually knee-high, should be 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.

    References

    • [Deep vein thrombosis and pulmonary embolism]. A Current Care Guideline. Working group appointed by the Finnish Medical Society Duodecim, the Finnish Society of Anaesthesiologists, and the Finnish Cardiac Society. Helsinki: Finnish Medical Society Duodecim, 2023 (accessed 17.1.2024). Available in Finnish at http://www.kaypahoito.fi/hoi50022.
    • Ortel TL, Neumann I, Ageno W, et al. American Society of Hematology 2020 guidelines for management of venous thromboembolism: treatment of deep vein thrombosis and pulmonary embolism. Blood Adv 2020;4(19):4693-4738 [PubMed]
    • Carrier M, Lazo-Langner A, Shivakumar S, et al. Screening for Occult Cancer in Unprovoked Venous Thromboembolism. N Engl J Med 2015;373(8):697-704 [PubMed]