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Cancer and its treatment raise the chance of a blood clot in a leg or lung. Most people having treatment as outpatients do not need a blood thinner, but some do: your team can work out your risk with a simple score from your blood count, weight and type of cancer. Everyone should know the signs of a clot: a swollen, painful leg or sudden breathlessness or chest pain.
Routine thromboprophylaxis is not recommended for all outpatients with cancer (ITAC 2022; ASCO 2020; NICE NG89 for mobile people on anticancer treatment). Risk is assessed at the start of systemic treatment and periodically, with a validated model: the Khorana score gives 2 points for a very high-risk cancer site and 1 point each for a high-risk site, platelets of 350 × 10⁹/L or more, haemoglobin below 100 g/L or use of an erythropoiesis-stimulating agent, white cells above 11 × 10⁹/L and a body mass index of 35 or more.
The guidelines differ on who should be offered prophylaxis. ITAC (2022) recommends rivaroxaban or apixaban for ambulatory patients on systemic anticancer therapy with a Khorana score of 2 or more who are not bleeding or at high bleeding risk (grade 1B); ASCO (2020) says clinicians may offer apixaban, rivaroxaban or low-molecular-weight heparin to selected high-risk outpatients. NICE NG89 (2018) does not use a score: it advises against prophylaxis for mobile people on cancer treatment except for myeloma on thalidomide, pomalidomide or lenalidomide with steroids (aspirin or low-molecular-weight heparin) and pancreatic cancer on chemotherapy (low-molecular-weight heparin), continued for as long as chemotherapy lasts. ITAC also recommends prophylaxis in locally advanced or metastatic pancreatic cancer with low bleeding risk (low-molecular-weight heparin grade 1A, rivaroxaban or apixaban grade 1B) and in myeloma on immunomodulatory drugs (grade 1A), and does not recommend low-molecular-weight heparin prophylaxis outside a trial in advanced lung cancer.
Why: For most people the chance of a clot is lower than the chance of a bleed from the blood thinner.
“Thromboprophylaxis is not routinely recommended for all outpatients with cancer.”
Why: Risk changes with the cancer, the treatment and the blood count, and a score picks out the minority at high risk.
“Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE.”
Why: These five items were the ones that predicted clots in a large group of outpatients on chemotherapy; a score of 3 or more marked a risk of about 7 per cent over the first few months.
“Five predictive variables were identified in a multivariate model: site of cancer (2 points for very high-risk site, 1 point for high-risk site), platelet count of 350 x 10(9)/L or more, hemoglobin less than 100 g/L (10 g/dL) and/or use of erythropoiesis-stimulating agents, leukocyte count more than 11 x 10(9)/L, and body mass index of 35 kg/m(2) or more (1 point each).”
Why: Prophylaxis is only for people who are not bleeding and not at high risk of bleeding; some anticancer drugs interact with the newer oral anticoagulants.
“and not actively bleeding or not at a high risk for bleeding (grade 1B).”
International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022
Why: In a meta-analysis ITAC cites, preventive anticoagulation cut clots by about two fifths at a score of 2 or more, and by more at 3 or more, without a rise in major bleeding.
“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 (grade 1B).”
International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 · 1B
Why: Pancreatic cancer carries one of the highest clot risks, and two randomised trials support prophylaxis.
“Primary pharmacological prophylaxis of VTE with LMWH (grade 1A) or with direct oral anticoagulants (rivaroxaban or apixaban; grade 1B) 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.”
International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 · 1A (LMWH); 1B (rivaroxaban or apixaban)
Why: These drugs combined with steroids raise the risk of clots substantially.
“In patients with myeloma treated with immunomodulatory drugs combined with steroids or other systemic anticancer therapies, VTE primary pharmacological prophylaxis is recommended (grade 1A)”
International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 · 1A
Why: The trials in lung cancer did not show a net benefit large enough to recommend it.
“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 (guidance).”
International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 · guidance
Why: The raised risk lasts as long as the treatment that causes it.
“If giving VTE prophylaxis to people with cancer (see recommendations 1.6.2 and 1.6.3), continue for as long as they are receiving chemotherapy.”
Why: A swollen painful leg, or new breathlessness or chest pain, can be a clot that needs treatment straight away.
“Patients with cancer should be periodically assessed for VTE risk, and oncology professionals should provide patient education about the signs and symptoms of VTE.”
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.
The guidelines agree that routine prophylaxis for all outpatients is not recommended and that pancreatic cancer and myeloma on immunomodulatory drugs are exceptions; they disagree on whether a risk score should decide it for everyone else. ITAC (2022, GRADE) recommends rivaroxaban or apixaban at a Khorana score of 2 or more with low bleeding risk (grade 1B); ASCO (2020) allows apixaban, rivaroxaban or low-molecular-weight heparin for selected high-risk outpatients, and its 2023 update did not change this; NICE NG89 (2018) does not use a score and limits prophylaxis in mobile people on cancer treatment to myeloma on thalidomide, pomalidomide or lenalidomide with steroids and to pancreatic cancer on chemotherapy. The ESMO 2023 guideline could not be read.
International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 · ASCO, Journal of Clinical Oncology 2020 · ASCO, Journal of Clinical Oncology 2023 · NICE 2018 · ESMO, Annals of Oncology 2023
Where it differs: Advises against prophylaxis for mobile people on chemotherapy, radiotherapy or immunotherapy unless they have another reason for raised risk, and considers it only for myeloma on thalidomide, pomalidomide or lenalidomide with steroids (aspirin 75 mg or 150 mg, or low-molecular-weight heparin) and pancreatic cancer on chemotherapy (low-molecular-weight heparin).
Evidence: NICE does not grade recommendations; NG89's cancer recommendations date from 2018, before the direct oral anticoagulant trials in outpatients were reflected in ITAC 2022.
Where it differs: Includes low-molecular-weight heparin, as well as apixaban and rivaroxaban, for selected high-risk outpatients, where ITAC's Khorana recommendation names the two oral drugs only.
Evidence: Read as an abstract; the abstract does not give the score threshold or the grade.
Where it differs: Lists low-dose aspirin 100 mg daily, prophylactic low-molecular-weight heparin, low or therapeutic-dose vitamin K antagonists and prophylactic apixaban as options in myeloma on immunomodulatory drugs, where NICE names aspirin 75 or 150 mg or low-molecular-weight heparin.
Evidence: ITAC grades the choice among these 2B, saying they have shown similar effects in preventing clots.
International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 · NICE 2018
People with cancer get blood clots more often than others. A score built from the cancer type and routine blood tests picks out those at higher risk, and in two placebo-controlled trials a low-dose blood-thinning tablet reduced clots but caused more bleeding. United States guidance says it may be offered; surveys in the Netherlands and China found most specialists do not use the score.
| Recommendation | Grade, as printed | Source |
|---|---|---|
| Rivaroxaban or apixaban for ambulatory patients on systemic anticancer therapy with a Khorana score of 2 or more and low bleeding risk | 1B (GRADE) | International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 |
| Low-molecular-weight heparin in locally advanced or metastatic pancreatic cancer on systemic treatment, low bleeding risk | 1A (GRADE) | International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 |
| Rivaroxaban or apixaban in the same pancreatic cancer setting | 1B (GRADE) | International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 |
| Prophylaxis in myeloma on immunomodulatory drugs with steroids or other systemic therapy | 1A (GRADE) | International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 |
| Choice among anticoagulants and low-dose aspirin in myeloma “or low-dose aspirin (100 mg daily) can be used, and have shown similar effects with regard to preventing VTE (grade 2B).” | 2B (GRADE) | International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 |
| No low-molecular-weight heparin prophylaxis outside a trial in advanced lung cancer | guidance (no GRADE rating) | International Initiative on Thrombosis and Cancer (ITAC), Lancet Oncology 2022 |
Shares National Institute for Health and Care Excellence, American Society of Clinical Oncology (ASCO) and the tags protocol, supportive-care.
Shares National Institute for Health and Care Excellence, American Society of Clinical Oncology (ASCO), Multiple myeloma and the tags protocol, supportive-care.
Shares National Institute for Health and Care Excellence, American Society of Clinical Oncology (ASCO) and the tags protocol, supportive-care.
Shares National Institute for Health and Care Excellence, American Society of Clinical Oncology (ASCO) and the tags protocol, supportive-care.
Shares National Institute for Health and Care Excellence, American Society of Clinical Oncology (ASCO) and the tags protocol, supportive-care.
Shares European Society for Medical Oncology (ESMO), American Society of Clinical Oncology (ASCO) and the tags protocol, supportive-care.
Shares National Institute for Health and Care Excellence and the tags protocol, supportive-care.
Shares European Society for Medical Oncology (ESMO) and the tags protocol, supportive-care.