Deep Vein Thrombosis

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 ≤ 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 ≥ 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

• The aim of treatment in lower limb DVT is to prevent
  • PE Pulmonary Embolism
  • the development of lower limb vein insufficiency.
• 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, Warfarin Initiation Nomograms for Venous Thromboembolism, 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.