Last updated July 19, 2022

Treatment and Prophylaxis of Venous Thromboembolism in Patients with Cancer Including Patients with COVID-19

Treatment of incidental or symptomatic established VTE in patients with cancer

Initial treatment of established VTE (up to 10 days of anticoagulation)

Low-molecular-weight heparin (LMWH) is recommended for the initial treatment of established VTE in patients with cancer when creatinine clearance is ≥30 mL/min. (A, 1)
Values and preferences: LMWH is easier to use than unfractionated heparin. A regimen of LMWH, taken once per day, is recommended, unless a twice-per-day regimen is required because of patients’ characteristics (eg, risk of bleeding or moderate renal failure) or the need for technical intervention (eg, surgery or changing regimen). When a twice-per-day regimen is required, only enoxaparin (1 mg/kg, twice-daily) can be used.
1971233
For patients who do not have a high risk of gastrointestinal or genitourinary bleeding, rivaroxaban or apixaban (in the first 10 days), or edoxaban (started after at least 5 days of parenteral anticoagulation) can also be used for the initial treatment of established VTE in patients with cancer when creatinine clearance is ≥30 mL/min. (A, 1)
1971233
Unfractionated heparin can be also used for the initial treatment of established VTE for patients with cancer when LMWH or direct oral anticoagulants are contraindicated, or not available. (C, 2)
1971233
Fondaparinux can be also used for the initial treatment of established VTE in patients with cancer. (D, 2)
Values and preferences: fondaparinux is easier to use than unfractionated heparin.
1971233
Thrombolysis in patients with cancer and with established VTE can only be considered on a case-by-case basis, with specific attention paid to contraindications, especially bleeding risk—eg, brain metastasis. (U, G)
Values and preferences: an expert opinion is recommended before using thrombolytics, and the procedure should be done in centres with health-care practitioners who have appropriate expertise.
1971233
In the initial treatment of VTE, inferior vena cava filters might be considered when anticoagulant treatment is contraindicated or, in the case of pulmonary embolism, when recurrence occurs under optimal anticoagulation. Periodic reassessment of contraindications for anticoagulation is recommended, and anticoagulation should be resumed when safe. (U, G)
1971233

Early (up to 6 months) and long-term (beyond 6 months) maintenance

LMWHs are preferred over vitamin K antagonists for the treatment of VTE in patients with cancer when creatinine clearance is ≥30 mL/min. (A, 1)
Values and preferences: daily subcutaneous injection can represent a burden for patients.
1971233
Direct oral anticoagulants (edoxaban, rivaroxaban, or apixaban) are recommended for patients with cancer when creatinine clearance is ≥30 mL/min in the absence of strong drug–drug interactions or gastrointestinal absorption impairment. (A, 1)
Use caution in patients with gastrointestinal tract malignancies, especially upper gastrointestinal tract malignancies, as the available data show increased risk of gastrointestinal tract bleeding with edoxaban and rivaroxaban.
1971233
LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer. (A, 1)
1971233
After 6 months, termination or continuation of anticoagulation (LMWH, direct oral anticoagulants, or vitamin K antagonists) should be based on individual evaluation of the benefit–risk ratio, tolerability, drug availability, patient preference, and cancer activity. (U, G)
1971233

Treatment of VTE recurrence in patients with cancer under anticoagulation

In the event of VTE recurrence, three options can be considered: (1) increase LMWH by 20–25% or switch to direct oral anticoagulants; (2) for direct oral anticoagulants, switch to LMWH; and (3) for vitamin K antagonist, switch to LMWH or direct oral anticoagulants. (U, G)
Values and preferences: individual decision. Effect of therapy should be monitored by improvement of symptoms.
1971233

Treatment of established catheter-related thrombosis

For the treatment of symptomatic catheter-related thrombosis in patients with cancer, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place; in this setting, LMWHs are suggested and direct comparisons between LMWHs, direct oral anticoagulants, and vitamin K antagonists have not been made. (U, G)
1971233
In patients with cancer and with catheter-related thrombosis, the central venous catheter can be kept in place if it is functional, well positioned, and not infected, with good resolution of symptoms under close surveillance while anticoagulation therapy is administered. No standard approach in terms of duration of anticoagulation is established. (U, G)
1971233

Prophylaxis of VTE in patients with cancer

Prophylaxis of VTE in surgically-treated patients with cancer

Use of low-molecular-weight-heparin (LMWH) once per day (when creatinine clearance is ≥30 mL/min) or low-dose unfractionated heparin three times per day is recommended to prevent postoperative VTE in patients with cancer; pharmacological prophylaxis should be started 2–12 h preoperatively and continued for at least 7–10 days; there are no data allowing conclusions regarding the superiority of one type of LMWH over another. (A, 1)
Values and preferences: LMWH once per day is more convenient.
1971233
There is insufficient evidence to support
fondaparinux (C, 2)
1971233
or direct oral anticoagulants (B, 2)
1971233
as an alternative to LMWH for the prophylaxis of postoperative VTE in patients with cancer. Values and preferences: as per the first recommendation.
Use of the highest prophylactic dose of LMWH to prevent postoperative VTE in patients with cancer is recommended. (A, 1)
1971233
Extended prophylaxis (4 weeks) with LMWH to prevent postoperative VTE after major abdominal or pelvic surgery (either laparotomy or laparoscopy) is recommended in patients with cancer who do not have a high risk of bleeding. (A, 1)
Values and preferences: longer duration of injections.
1971233
Mechanical methods are not recommended as monotherapy except when pharmacological methods are contraindicated. (A, 2)
Values and preferences: no injection.
1971233
Inferior vena cava filters are not recommended for routine prophylaxis. (A, 1)
1971233

Prophylaxis of VTE in medically-treated patients with cancer

We recommend prophylaxis with LMWH or fondaparinux when creatinine clearance is ≥30 mL/min, or with unfractionated heparin in medically-treated patients with cancer and reduced mobility who are admitted to hospital. (B, 1)
In this setting, direct oral anticoagulants are not recommended routinely (guidance). Values and preferences: subcutaneous injections. Costs: in some countries, price differences between LMWH, unfractionated heparin, or fondaparinux might affect the choice.
1971233
Primary pharmacological prophylaxis of VTE
with LMWH (A, 1)
1971233
or with direct oral anticoagulants (B, 1)
1971233
is indicated in ambulatory patients with locally advanced or metastatic pancreatic cancer treated with systemic anticancer therapy and who have a low risk of bleeding. Values and preferences: subcutaneous injections.
Primary pharmacological prophylaxis of VTE with LMWH is not recommended outside of a clinical trial for patients with locally advanced or metastatic lung cancer treated with systemic anticancer therapy, including patients who have a low risk of bleeding. (U, G)
1971233
Primary prophylaxis with direct oral anticoagulant (rivaroxaban or apixaban) is recommended in ambulatory patients who are receiving systemic anticancer therapy and are at intermediate-to-high-risk of VTE, identified by a validated risk assessment model (ie, a Khorana score ≥2), and not actively bleeding or not at a high risk for bleeding. (B, 1)
1971233
In patients with myeloma treated with immunomodulatory drugs combined with steroids or other systemic anticancer therapies, VTE primary pharmacological prophylaxis is recommended. (A, 1)
in this setting, oral anticoagulants (vitamin K antagonists at low or therapeutic doses and apixaban at prophylactic doses), LMWH at prophylactic doses, or low-dose aspirin (100 mg daily) can be used, and have shown similar effects with regard to preventing VTE (grade 2B). Values and preferences: subcutaneous injections.
1971233

Prophylaxis of catheter-related thrombosis

Use of anticoagulation for routine prophylaxis of catheter-related thrombosis is not recommended. (A, 1)
Values and preferences: bleeding risk with anticoagulants.
1971233
Catheters should be inserted on the right side, in the jugular vein, and the distal extremity of the central catheter should be located at the junction of the superior vena cava and the right atrium. (B, 1)
1971233
In patients requiring central venous catheters, we suggest the use of implanted ports over peripherally inserted central catheter lines. (U, G)
1971233

Treatment of VTE in unique situations

For the treatment of established VTE in patients with a brain tumour, low-molecular-weight heparin (LMWH) or direct oral anticoagulants can be used. (A, 2)
1971233

We recommend the use of LMWH or unfractionated heparin commenced postoperatively for the prevention of VTE in patients with cancer undergoing neurosurgery. (A, 1)
1971233

Primary pharmacological prophylaxis of VTE in medically-treated patients with a brain tumour who are not undergoing neurosurgery is not recommended. (B, 1)
1971233

In the presence of severe renal failure (creatinine clearance <30 mL/min), we suggest using unfractionated heparin followed by early vitamin K antagonists (possible from day 1) or LMWH adjusted to anti-Xa concentration for the treatment of established VTE. (U, G)
1971233

In patients with severe renal failure (creatinine clearance <30 mL/min), an external compression device can be applied, and pharmacological prophylaxis could be considered on a case-by-case basis; in patients with severe renal failure (creatinine clearance <30 mL/min), unfractionated heparin can be used on a case-by-case basis. (U, G)
1971233

In patients with cancer and with thrombocytopenia, full doses of anticoagulant can be used for the treatment of established VTE if the platelet count is >50 × 109 per L and there is no evidence of bleeding; for patients with a platelet count <50 × 109 per L, decisions on treatment and dose should be made on a case-by-case basis with the utmost caution. (U, G)
1971233

In patients with cancer and with mild thrombocytopenia, platelet count >80 × 109 per L, pharmacological prophylaxis could be used; if the platelet count is <80 × 109 per L, pharmacological prophylaxis can only be considered on a case-by-case basis and careful monitoring is recommended. In the CASSINI64 and AVERT65 trials, patients with a platelet count as low as 50 × 109 per L were allowed to receive thromboprophylaxis. (U, G)
1971233

In patients with cancer who are pregnant, we suggest the use of LMWH for treatment of established VTE and for VTE prophylaxis and avoidance of vitamin K antagonists and direct oral anticoagulants. (U, G)
1971233

In patients with cancer who are obese, consideration for a higher dose of LMWH should be given for cancer surgery. (U, G)
1971233

For the treatment of symptomatic catheter-related thrombosis in children with cancer, anticoagulant treatment is recommended for a minimum of 3 months and as long as the central venous catheter is in place; in this setting, direct comparisons between unfractionated heparin, LMWHs, direct oral anticoagulants, and vitamin K antagonists have not been done. (U, G)
1971233

In children with acute lymphoblastic leukaemia undergoing induction chemotherapy, we recommend LMWH as thromboprophylaxis. (A, 2)
1971233

In children requiring central venous catheters, we suggest the use of implanted ports over peripherally inserted central catheter lines. (U, G)
1971233

Treatment and prophylaxis of VTE for patients with cancer and with COVID-19

Recommendations for the treatment of established VTE for patients with cancer are similar, independent of whether or not they have COVID-19. (U, G)
1971233

Recommendations for the prophylaxis of VTE in patients with cancer are similar in those with and without COVID-19. (U, G)
1971233

Patients with cancer and with COVID-19, whether they are hospitalised, post-discharge, or ambulatory, should be assessed for risk of VTE as any other patient with COVID-19. (U, G)
1971233
Pharmacological prophylaxis during hospitalisation should be given, with the same dose and anticoagulant type as in patients with cancer who do not have COVID-19, based on current institutional practice. (U, G)
1971233
Post-discharge VTE prophylaxis is not advised in patients with cancer and with COVID-19; as with any patient with cancer, individual assessment of benefit–risk ratio should be done. (U, G)
1971233
Primary pharmacological prophylaxis of VTE in ambulatory patients with cancer who have COVID-19 is not recommended routinely. (U, G)
1971233

Recommendation Grading

Overview

Title

Treatment and Prophylaxis of Venous Thromboembolism in Patients with Cancer Including Patients with COVID-19

Authoring Organization

Publication Month/Year

July 1, 2022

Document Type

Guideline

Country of Publication

US

Document Objectives

He International Initiative on Thrombosis and Cancer is an independent academic working group of experts aimed at establishing global consensus for the treatment and prophylaxis of cancer-associated thrombosis. The 2013, 2016, and 2019 International Initiative on Thrombosis and Cancer clinical practice guidelines have been made available through a free, web-based mobile phone application. The 2022 clinical practice guidelines, which are based on a literature review up to Jan 1, 2022, include guidance for patients with cancer and with COVID-19. 

Inclusion Criteria

Male, Female, Adult, Older adult

Health Care Settings

Hospital

Intended Users

Nurse, nurse practitioner, physician, physician assistant

Scope

Treatment, Prevention

Diseases/Conditions (MeSH)

D054556 - Venous Thromboembolism, D000086402 - SARS-CoV-2

Keywords

cancer, VTE, Venous Thromboembolism, VTE Prophylaxis, VTE in Cancer, Coronavirus, covid-19, COVID

Source Citation

Farge D, Frere C, Connors JM, Khorana AA, Kakkar A, Ay C, Muñoz A, Brenner B, Prata PH, Brilhante D, Antic D, Casais P, Guillermo Esposito MC, Ikezoe T, Abutalib SA, Meillon-García LA, Bounameaux H, Pabinger I, Douketis J; International Initiative on Thrombosis and Cancer (ITAC) advisory panel. 2022 international clinical practice guidelines for the treatment and prophylaxis of venous thromboembolism in patients with cancer, including patients with COVID-19. Lancet Oncol. 2022 Jul;23(7):e334-e347. doi: 10.1016/S1470-2045(22)00160-7. PMID: 35772465; PMCID: PMC9236567.