Prevention of Venous Thromboembolism

Permanent risk factors

Transient risk factors

• Acute disease requiring bed rest (e.g. cardiac failure, pulmonary disease, severe infection or dehydration)
• Prolonged immobility (e.g. a flight)
• Other cause of immobility (e.g. paralysis, spinal cord injury, [femoral or tibial] fracture or postsurgical condition, extensive tissue trauma, other injuries) for a period of about 3 months
• Surgical procedures (particularly those of the hips or knees, other invasive procedures of bone tissue, cancer surgery in the abdominal or pelvic area, fractures, particularly pathological ones, neurosurgery, laparoscopy, extensive or complicated surgical procedures taking more than 2 h, or repeat operation)
  • The increased risk of thrombosis associated with the aforementioned operations usually continues for about one month and in the most susceptible patients for at least 3 months.
• Temporary mechanical hindrance to venous return (tumour, urinary retention, pregnancy, plaster casts of the limbs, splints, tight bandage of the limbs)
• Cancer treated curatively, radiotherapy, certain cytotoxic drugs and cytolysis caused by them
• Pregnancy, childbirth and puerperium (6 weeks)
• Hormonal contraception, hormonal replacement therapy, treatment of cancer with tamoxifen or other adjuvant therapies, androgens taken to improve performance or to increase muscle mass
• Central venous catheter, venous injuries or venous surgery
• Repeated minor trauma (contact sports), particularly in patients with thrombophilia
• Clozapine or olanzapine medication
• High-dose glucocorticoid therapy, haematological growth factors, erythropoietin and interferon

Implementation Combined Intermittent Pneumatic Compression and Pharmacological Prophylaxis for Prevention of Venous Thromboembolism, Thrombus Prophylaxis in Colorectal Surgery, Extended DVT Prophylaxis after Hospital Discharge in Patients with Elective Hip Arthroplasty, Graduated Compression Stockings in the Prevention of Postoperative Venous Thromboembolism, Prolonged Thromboprophylaxis with Low Molecular Weight Heparin for Abdominal or Pelvic Surgery, Dabigatran Versus Lmwhs for Thromboprophylaxis after Total Hip or Knee Replacement, Fondaparinux in the Prevention of Venous Thromboembolism after Surgery

• The planning of thromboprophylaxis must consider the risk of both thrombosis and bleeding, related not only to the patient but also to the planned procedure and the patient's clinical condition.
• Check local guidance on thromboprophylaxis in hospital patients.
• Factors predisposing the patient to bleeding include:
  • uncontrolled hypertension
  • renal failure (slows down the elimination of medicines but this does not apply to unfractionated heparin)
  • liver failure
  • anaemia (haematocrit < 30% or Hb < 100 g/l)
  • thrombocytopenia (platelet count < 50 × 10⁹ /l)
  • medication (particularly antithrombotic therapy, NSAIDs, SSRIs, SNRIs, omega-3)
  • injuries.
• If the risk of bleeding is high, pharmaceutical prophylaxis should be avoided, but mechanical methods of prophylaxis must not be forgotten.
• Compression bandages or anti-embolism stockings are the most common and easiest mechanical methods of thromboprophylaxis, and are sometimes sufficient as the sole method of prophylaxis in patients with a low thrombosis but a high bleeding risk. Evidence of their benefit exists in surgical and obstetric patients but not in haematological patients. Venous foot pumps and intermittent pneumatic compression devices offer similar benefit.
• Immobilization (long, over 6-hour flights, for example) should be avoided before and after the surgery or after a severe infection for about 1-4 weeks.
• The surgery-associated increased risk of thrombosis continues for 1-3 months even if the patient were ambulatory.
• Warfarin is also suitable for long-term prophylaxis as it is inexpensive and effective (e.g. pelvis fracture followed by a long period of immobility). Warfarin is associated with a risk of bleeding, drug interactions and the need for regular monitoring.
• Low molecular weight heparins (LMWH) are administered subcutaneously once daily and routinely used in thromboprophylaxis.
  • The chosen LMWH preparation should not be unnecessarily changed to another preparation during the treatment period, and it is advisable to stay with the same preparation during future treatment in order to avoid immunological activation.
  • Usual prophylactic doses: 40 mg enoxaparin, 5 000 IU dalteparin or 3 500-4 500 IU tinzaparin subcutaneously once daily; for more detailed information see the respective summaries of product characteristics.
  • The individual risk factors, weight and renal function should be considered in dosage.
  • In renal failure, tinzaparin is best suitable for prophylactic use, but it may accumulate in therapeutic doses and, as necessary, its effect can best be reversed by protamine (effect neutralized by 65-80%, whereas the effect of other drugs is neutralized by 40-60%). It is not recommended for patients with liver failure.
  • Prophylactic treatment with LMWH is safe, and the treatment can often be self-administered or administered by a home nurse.
  • The duration of prophylactic treatment is 10 days in knee arthroplasty (longer if there are other factors increasing the risk of thrombosis), 4 weeks in hip arthroplasty and cancer surgery. During pregnancy according to a specific consultation and 6 weeks during the puerperium.
• Fondaparinux can be used in high-risk patients, particularly if heparin is contraindicated.
• Direct oral anticoagulants (apixaban, dabigatran, rivaroxaban) are only suitable for postoperative prophylaxis after elective hip or knee arthroplasty.
• Adverse effects
  • Postoperative and post-traumatic bleeding (see contraindications and warnings in the summaries of product characteristics).
  • LMWH products are not indicated if the patient has a history of heparin-induced thrombocytopenia (HIT), which is associated with a paradoxical risk of thrombosis triggered by heparin due to immunological platelet activation.
  • Caution should be exercised in renal failure and minimal dosage used.

Bridging therapy for patients on warfarin

• Bridging therapy for patients on warfarin must be planned in advance, as necessary Warfarin Therapy.
• Check local guidance on pausing antithrombotic therapy in the context of surgical procedures.
• Minor procedures can be carried out if the INR is at the lower end of the therapeutic range, but in major surgery requiring accurate haemostasis, or if potential bleeding may cause permanent organ damage, or if uncontrolled bleeding is a potential complication, warfarin should be paused (INR < 1.5). In patients with high risk of thrombosis, LMWH is started, as necessary, preoperatively as an alternative anticoagulant according to the operative policy.
• The dose of LMWH should be chosen according to the patient's risk of thrombosis as well as the bleeding risk associated with the surgical operation; prophylactic doses are usually sufficient until the target INR has been achieved by warfarin therapy.
• In high-risk patients (mechanical mitral valve, history of stroke, atrial fibrillation [CHA₂DS₂VASc score ≥ 2] and heart disease or other high risk of thrombosis, PE or any VTE during the preceding 3 months), bridging therapy should be planned individually and near therapeutic doses of LMWH are used as long as haemostasis is confirmed.
  • A prophylactic dose of LMWH can be administered on the day of surgery and the day after but the dose should then be increased, the patient's condition allowing.
  • A therapeutic dose of LMWH can usually be introduced about 48(-72) hours after surgery in patients with adequate postprocedural haemostasis.
  • Highly detailed individual planning and monitoring is needed for patients undergoing neurosurgery or surgery involving the liver or thoracic cavity, repeat surgery in particular, all of which entail a high risk of bleeding, and in renal failure.
  • During bridging therapy it is important to ensure that in association with a high bleeding risk the INR value is normal (1.0), otherwise below 1.5.
  • Anaemia in association with anticoagulant therapy (regardless of the strategy applied) predisposes the patient to bleeding; its cause should therefore be defined and it should be treated preoperatively. Iron deficiency is the most common cause.
• Warfarin therapy should not be reintroduced until it is ascertained that no complications have arisen, that there is no need for repeat surgery and that no drug interactions are likely to complicate the re-establishment of warfarin therapy.

Special groups

• Patients with high risk of thrombosis
  • Thromboprophylaxis should be started at the very beginning of pregnancy.
• Patients with a prior episode of VTE associated with a transient risk factor
  • Follow-up and imaging during pregnancy as required by the symptoms
  • Thromboprophylaxis for 6 weeks after delivery
• A history of a single thrombosis in a patient with thrombophilia or of idiopathic VTE in a patient not on continuous anticoagulant therapy.
  • Thromboprophylaxis throughout the pregnancy and for 6 weeks after delivery
• Thrombophilia alone without a history of VTE
  • LMWH prophylaxis should be started towards the end of the pregnancy or right after delivery, at the latest, and continued for no less than 6 weeks after delivery.
• Antithrombin deficiency
  • The risk is so high that LMWH prophylaxis must always be given (even if the patient has no history of thrombosis). Dosage is individual and usually higher than ordinary prophylactic doses.
  • Antithrombin replacement therapy is given with LMWH prophylaxis in association with operations and delivery (consult a specialist in coagulation disorders). LMWH prophylaxis both during pregnancy and for at least 6 weeks following it, depending on laboratory response to antithrombin and LMWH.
  • If the case of thrombosis, in a patient with severe antithrombin deficiency, warfarin may be used during second trimester.
• Acquired coagulation disorders with a high risk of VTE include antiphospholipid syndrome and myeloproliferative diseases.
  • A haematologist should always be consulted in the case of haematological diseases.