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Clots in a leg vein or the lungs are common in cancer. They are treated with blood thinners, either daily injections (low-molecular-weight heparin) or tablets (such as apixaban, rivaroxaban or edoxaban), usually for at least six months and often while the cancer is active. Tablets suit most people, but injections may be safer with some stomach, bowel or bladder cancers and some cancer drugs.
ITAC (2022) recommends LMWH for initial treatment when creatinine clearance is at least 30 mL/min (1A), or rivaroxaban or apixaban from the start, or edoxaban after at least 5 days of parenteral anticoagulation, in patients not at high risk of gastrointestinal or genitourinary bleeding (1A). For maintenance, LMWH is preferred over vitamin K antagonists (1A) and DOACs are recommended in the absence of strong drug interactions or impaired gastrointestinal absorption (1A), with caution in gastrointestinal, especially upper gastrointestinal, cancers. Treat for at least 6 months (1A); after 6 months, continue or stop by individual assessment of benefit and risk and cancer activity (guidance). ASCO (2023) is concordant: LMWH, edoxaban, rivaroxaban or apixaban for at least 6 months, preferred over VKAs (strong, high-quality evidence), noting less recurrence but more clinically relevant non-major bleeding with factor Xa inhibitors and checking drug interactions first.
NICE NG158 (2020) differs on emphasis and duration: it suggests considering a DOAC first and, if unsuitable, LMWH alone or with a VKA, and gives 3 to 6 months then review, saying evidence on duration in active cancer is very limited. ASH (2021, abstract) makes conditional recommendations for LMWH or DOAC initially, a DOAC for short-term treatment and LMWH or DOAC long term. ITAC treats incidental clots like symptomatic ones. For special situations ITAC gives guidance, not graded evidence: full-dose anticoagulation if platelets are above 50 x 10^9/L without bleeding, case-by-case below that; unfractionated heparin then early VKA, or anti-Xa-adjusted LMWH, when creatinine clearance is below 30 mL/min; LMWH or DOAC with a brain tumour (2A); LMWH in pregnancy. For recurrence on treatment, increase LMWH by 20 to 25% or switch class (guidance). Vena cava filters only when anticoagulation is contraindicated or a PE recurs despite optimal treatment (guidance).
Why: Both injections and tablets prevent the clot growing or coming back; the choice depends on the person's bleeding risk, cancer and other medicines.
“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 (grade 1A).”
Why: In trials, the tablets caused more bleeding from tumours of the stomach, bowel and urinary tract.
“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 (grade 1A).”
Why: Some cancer drugs change blood levels of the tablets, and some tumours bleed easily.
“When choosing anticoagulation treatment for people with active cancer and confirmed proximal DVT or PE, take into account the tumour site, interactions with other drugs including those used to treat cancer, and the person's bleeding risk.”
NICE 2020 · [2020]
Why: Interactions with cancer treatments can make the tablet too strong (bleeding) or too weak (new clots).
“Drug-drug interaction should be checked before using a direct factor Xa inhibitor (Type: Evidence based; Evidence quality: High; Strength of recommendation: Strong).”
ASCO (Journal of Clinical Oncology, Key et al.) 2023 · Evidence based; Evidence quality: High; Strength of recommendation: Strong
Why: Clots often come back in people with active cancer; six months was the length tested in the trials.
“LMWH or direct oral anticoagulants should be used for a minimum of 6 months to treat established VTE in patients with cancer (grade 1A).”
Why: The risk of another clot stays high while the cancer is active, but so does the risk of bleeding.
“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 (guidance, in the absence of data).”
Why: Clots found by chance carried the same risks as symptomatic ones in the trials.
“These findings further support managing patients with incidental cancer-associated thrombosis in a similar manner as symptomatic cancer-associated thrombosis.”
Why: Chemotherapy can lower platelets, and anticoagulation with very low platelets risks serious bleeding.
“decisions on treatment and dose should be made on a case-by-case basis with the utmost caution (guidance, in the absence of data and a balance between desirable and undesirable effects depending on the bleeding risk vs VTE risk).”
Why: LMWH and the tablets build up when the kidneys are failing.
“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 (guidance, in the absence of data and an unknown balance between desirable and undesirable effects).”
Why: A clot that recurs on treatment may need a stronger dose or a different drug.
“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 (guidance, based on evidence of very low quality and an unknown balance between desirable and undesirable effects).”
Why: A filter can stop clots reaching the lungs but does not treat the clot and can cause its own problems.
“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.”
How care is usually carried out, read from the guidelines and standards cited. Your own team's protocol and their judgement come first; this page is for understanding it, not for doing it yourself.
For most people with active cancer: LMWH or a DOAC (apixaban, rivaroxaban, or edoxaban after 5 days of parenteral treatment), for at least 6 months, rather than a vitamin K antagonist (ITAC 2022, 1A; ASCO 2023, strong, high-quality evidence), with LMWH favoured where gastrointestinal or genitourinary bleeding risk is high or strong drug interactions exist, and a decision at 6 months on continuing. The guidelines differ on duration and order of preference: ITAC and ASCO set a minimum of 6 months; NICE NG158 (2020) treats for 3 to 6 months then reviews, and suggests considering a DOAC first; ASH 2021 (read as abstract) conditionally favours a DOAC for short-term treatment. ESMO 2023 could not be read.
International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.) 2022 · ASCO (Journal of Clinical Oncology, Key et al.) 2023 · NICE 2020 · American Society of Hematology (Blood Advances, Lyman et al.) 2021
Where it differs: Considers a DOAC as the first choice and LMWH (alone or with a VKA) only if a DOAC is unsuitable, for 3 to 6 months and then review.
Evidence: NICE NG158 [2020]. Its committee found evidence on duration in active cancer very limited and judged apixaban the most cost-effective option on a small number of people with cancer in the trials. Most anticoagulants were off label for cancer-associated VTE in the UK in March 2020.
Where it differs: Uses daily LMWH injections throughout, the standard before DOACs.
Evidence: ITAC: LMWH for 6 months was more effective than VKAs in five randomised trials without more bleeding; DOACs reduce recurrence compared with LMWH (pooled RR 0.62, 95% CI 0.43 to 0.91) without a significant increase in major bleeding, but with more clinically relevant non-major bleeding, and one meta-analysis in gastrointestinal cancers found more major bleeding with DOACs (RR 2.3).
| Recommendation | Grade, as printed | Source |
|---|---|---|
| LMWH for initial treatment (creatinine clearance 30 mL/min or more) | 1A | International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.) 2022 |
| Rivaroxaban, apixaban or edoxaban for initial treatment, without high gastrointestinal or genitourinary bleeding risk | 1A | International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.) 2022 |
| DOACs for maintenance in the absence of strong drug interactions or impaired gastrointestinal absorption “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 (grade 1A).” | 1A | International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.) 2022 |
| Minimum 6 months of LMWH or DOAC | 1A | International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.) 2022 |
| LMWH, edoxaban, rivaroxaban or apixaban for at least 6 months, preferred over VKAs “For long-term anticoagulation, LMWH, edoxaban, rivaroxaban, or apixaban for at least 6 months are preferred over vitamin K antagonists (VKAs) because of improved efficacy.” | Evidence based; Evidence quality: High; Strength of recommendation: Strong | ASCO (Journal of Clinical Oncology, Key et al.) 2023 |
| Brain tumour: LMWH or DOAC “For the treatment of established VTE in patients with a brain tumour, low-molecular-weight heparin (LMWH) or direct oral anticoagulants can be used (grade 2A).” | 2A | International Initiative on Thrombosis and Cancer (ITAC), endorsed by the ISTH (Lancet Oncology, Farge et al.) 2022 |
| Active cancer: 3 to 6 months, then review “Offer people with active cancer and confirmed proximal DVT or PE anticoagulation treatment for 3 to 6 months.” | [2020] (NICE does not grade recommendations) | NICE 2020 |
| Consider a DOAC for active cancer with proximal DVT or PE “Consider a direct-acting oral anticoagulant (DOAC) for people with active cancer and confirmed proximal DVT or PE.” | [2020] (NICE does not grade recommendations) | NICE 2020 |
Shares Venous thromboembolism (VTE), Cancer-associated thrombosis prevention and treatment.
Shares Venous thromboembolism (VTE), Cancer-associated thrombosis prevention and treatment.
Shares Venous thromboembolism (VTE), Cancer-associated thrombosis prevention and treatment.
Shares Venous thromboembolism (VTE), Cancer-associated thrombosis prevention and treatment.
Shares Venous thromboembolism (VTE), Cancer-associated thrombosis prevention and treatment.
Shares Venous thromboembolism (VTE), Cancer-associated thrombosis prevention and treatment.
Shares Venous thromboembolism (VTE).