Guideline sources The following summarized guidelines for the evaluation and management of cancer-associated thrombosis are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2023; 2015), the American Society of Clinical Oncology (ASCO 2023; 2013), the American Society of Hematology (ASH 2023; 2021), the International Initiative on Thrombosis and Cancer (ITAC 2022), the American Association for Thoracic Surgery (AATS/ESTS 2022), the European Society for Vascular Surgery (ESVS 2021), the American College of Chest Physicians (ACCP 2021), the British Committee for Standards In Haematology (BCSH 2015), the Canadian Consensus Group on Cancer-Associated Thrombosis (CCG-CAT 2015), the Canadian Consensus Group on Venous Thromboembolism in Cancer (CCG-VTEC 2015), and the International Society on Thrombosis and Haemostasis (ISTH 2014). 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 1/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway Guidelines 1. Screening and diagnosis Screening for occult malignancy: consider obtaining CT (and mammography in females) for screening of cancer in > 40 years old patients with unprovoked VTE. Set a lower threshold for screening patients with bilateral deep vein thrombosis, very high D-dimers, or an early recurrence of VTE. C Landmark trials: SOME In patients who had a first unprovoked VTE, limited occult-cancer screening plus CT was not superior to limited occult-cancer screening with respect to occult cancer diagnosis at 1 year. Carrier M et al. N Engl J Med. 2015 Aug 20. 2. Classification and risk stratification Risk assessment: As per ASCO 2023 guidelines, assess patients with cancer for VTE risk initially and periodically thereafter, particularly when starting systemic antineoplastic therapy or at the time of hospitalization. B Show 2 more As per ESMO 2023 guidelines, obtain a cancer-associated thrombosis risk assessment and offer an opportunity to discuss the particular risk in patients with cancer. B Show 3 more 3. Diagnostic investigations Baseline laboratory tests: obtain a baseline CBC, creatinine, LFTs, and INR or PTT to rule out severe thrombocytopenia, renal or hepatic impairment, and coagulopathy. B Diagnostic imaging: obtain compression ultrasound in case of suspected deep vein thrombosis and CT pulmonary angiography in case of suspected PE for diagnosis without using clinical prediction rules and measuring D-dimer levels in patients with cancer. A 4. Medical management Anticoagulant therapy, initiation/treatment phase: As per ASCO 2023 guidelines, consider administering LMWH, UFH, fondaparinux, rivaroxaban, or apixaban for initial anticoagulation. Prefer LMWH over UFH for the initial 5-10 days of https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 2/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway anticoagulation in patients with newly diagnosed VTE, in the absence of severe renal impairment (CrCl < 30 mL/min). B As per ESMO 2023 guidelines, administer LMWH, UFH, fondaparinux, apixaban, or rivaroxaban for the acute phase in patients with cancer-associated thrombosis. A Prefer LMWH over UFH or fondaparinux. B Consider administering UFH in patients with severe renal impairment, i.e. CrCl < 30 mL/min. B Show 3 more As per ITAC 2022 guidelines, administer LMWH for the initial treatment of established VTE in patients with cancer and a CrCl 30 mL/min. A Administer LMWH once daily unless a twice- per-day regimen is required because of the patient's characteristics, such as the risk of bleeding or moderate renal failure, or the need for technical intervention, such as surgery or changing regimen. Use only enoxaparin 1 mg/kg when a twice-per-day regimen is required. Show 3 more As per ACCP 2021 guidelines: Administer oral Xa inhibitors (apixaban, edoxaban, rivaroxaban) rather than LMWH for the initiation and treatment phases in patients with cancer-associated acute deep vein thrombosis. B Consider preferring apixaban and LMWH in patients with luminal gastrointestinal malignancies due to the lower risk of major gastrointestinal bleeding. As per ASH 2021 guidelines, consider administering direct OACs (apixaban or rivaroxaban) or LMWH for initial treatment of VTE in patients with cancer. C Show 5 more As per ESVS 2021 guidelines: Administer LMWH for the initial and principal treatment in patients with cancer-associated deep vein thrombosis. A Consider administering approved direct OACs for the initial and principal treatment in selected patients with cancer-associated deep vein thrombosis, with the malignancy not located in the gastrointestinal or genitourinary systems. B Anticoagulant therapy, extended phase: As per ASCO 2023 guidelines, prefer LMWH, edoxaban, rivaroxaban, or apixaban for at least 6 months over vitamin K antagonists for long-term anticoagulation because of improved efficacy. A Show 3 more Landmark trials: Hokusai VTE Cancer In patients with cancer who had acute symptomatic or incidental VTE, edoxaban was noninferior to dalteparin with respect to recurrent VTE or major bleeding. Raskob GE et al. N Engl J Med. 2018 Feb 15. https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 3/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway As per ESMO 2023 guidelines, consider extending anticoagulation beyond the initial 6 months with LMWH, apixaban, edoxaban, rivaroxaban, or vitamin K antagonists in patients with active cancer when the risk of recurrent thrombosis is higher and may outweigh that of bleeding. C Assess the risk-benefit profile of anticoagulant therapy regularly to ensure a favorable balance. C As per ITAC 2022 guidelines, prefer LMWH over vitamin K antagonists for the treatment of VTE in patients with cancer and a CrCl 30 mL/min. A Show 3 more Landmark trials: SELECT-D In cancer patients with VTE, oral factor Xa inhibition with rivaroxaban, as compared with low- molecular weight heparin (dalteparin), significantly reduced the 6-month cumulative VTE recurrence rate (4%, 95% CI 2%-9% vs. 11%, 95% CI 7%-16%; HR 0.43, 95% CI 0.19-0.99). However, there was an increase in the 6-month cumulative rate of major bleeding (6%, 95% CI 3%-11% vs. 4%, 95% CI 2%-8%; HR 1.83 95% CI 0.68-4.96). In the corresponding groups, there was significantly increased rates of CRNMB (13%, 95% CI 9%-19% vs. 4%, 95% CI 2%-9%: HR 3.76, 95% CI 1.63-8.69). Young AM et al. J Clin Oncol. 2018 Jul 10. As per ASH 2021 guidelines, consider initiating long-term anticoagulation for > 6 months with direct OACs or LMWH C for secondary prophylaxis in patients with active cancer and VTE, and consider continuing anticoagulation indefinitely. C As per ESVS 2021 guidelines: Consider continuing anticoagulation beyond 3 months in patients with symptomatic calf deep vein thrombosis and active cancer. C Switch from LMWH to an OAC after 3-6 months of treatment for extended treatment in patients with active cancer-associated deep vein thrombosis. B Consider administering approved direct OACs for the extended treatment in selected patients with cancer-associated deep vein thrombosis, with the malignancy not located in the gastrointestinal or genitourinary systems. B As per BCSH 2015 guidelines: Administer LMWH for 6 months, if tolerated, as initial treatment in patients with cancer- associated thrombosis. Administer warfarin or other OACs as alternatives if LMWH is impractical. A Continue anticoagulation in the presence of active malignancy taking patient status and wishes and bleeding risk into consideration. B Anticoagulant therapy (monitoring): do not obtain routine monitoring of anti-factor Xa levels in most patients receiving therapeutic anticoagulation. D https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 4/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway Thrombolytic therapy: consider administering thrombolysis in patients with cancer with established VTE only on a case-by-case basis, with specific attention paid to contraindications, especially bleeding risk (such as brain metastasis). C 5. Therapeutic procedures Inferior vena cava filter placement: As per ASCO 2023 guidelines, do not place vena cava filters in patients with established or chronic thrombosis (VTE diagnosis > 4 weeks ago), nor in patients with temporary contraindications to anticoagulant therapy (for example, surgery). D Show 2 more As per ESMO 2023 guidelines, consider placing vena cava filters in patients with acute and life- threatening VTE having absolute contraindications to anticoagulant therapy, C or as an adjunct to anticoagulation in patients with recurrent VTE or extension of thrombosis despite optimal anticoagulant therapy. C As per ITAC 2022 guidelines, consider placing an IVC filter in the initial treatment of VTE when anticoagulant treatment is contraindicated or, in the case of PE, when recurrence occurs under optimal anticoagulation. Obtain periodic reassessment of contraindications for anticoagulation and resume anticoagulation when safe. C As per BCSH 2015 guidelines, place an IVC filter only when there is a strong contraindication to anticoagulation and remove it as soon as anticoagulation is possible. B As per CCG-VTEC 2015 guidelines, do not use IVC filters in addition to anticoagulation therapy. D 6. Specific circumstances Elderly patients: Recognize that elderly patients (> 70 years of age) with reduced CrCl could be at greater risk of LMWH-induced complications such as bleeding. B Insufficient evidence to recommend one LMWH or UFH over another in elderly patients with active malignancy. Consider preferring tinzaparin for a favorable biologic profile using therapeutic dosing in the setting of renal insufficiency. I Pregnant patients: consider administering LMWH for the treatment of established VTE and for VTE prophylaxis in pregnant patients with cancer. Avoid using vitamin K antagonists and direct OACs. C Pediatric patients: administer LMWH for thromboprophylaxis in pediatric patients with acute lymphoblastic leukemia undergoing induction chemotherapy. B Show 2 more Patients with obesity: https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 5/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway As per ITAC 2022 guidelines, consider administering a higher dose of LMWH in patients with obesity undergoing cancer surgery. C As per CCG-VTEC 2015 guidelines, administer low molecular weight in patients with obesity based on actual body weight rather than ideal body weight. Avoid dose-capping. B Patients with COVID-19 infection: do not prescribe routine primary thromboprophylaxis in ambulatory patients with cancer and COVID-19. D Show 5 more Patients with impaired renal function: As per ITAC 2022 guidelines: Consider administering UFH followed by early vitamin K antagonists (possible from day 1) or LMWH adjusted to anti-factor Xa level for the treatment of established VTE in patients with severe renal failure (CrCl < 30 mL/min). C Consider applying an external compression device and administering pharmacological prophylaxis with UFH on a case-by-case basis in patients with severe renal failure (CrCl < 30 mL/min). C As per CCG-VTEC 2015 guidelines, insufficient evidence to recommend one LMWH or UFH over another in patients with impaired renal function. Recognize that enoxaparin may have a less favorable biologic profile than tinzaparin and dalteparin in patients with impaired renal function. I Show 3 more Patients with thrombocytopenia, thromboprophylaxis: As per ITAC 2022 guidelines, consider administering pharmacological prophylaxis in patients with mild thrombocytopenia with a platelet count > 80, 000/ L. Consider administering pharmacological prophylaxis in patients with a platelet count < 80, 000/ L only on a case-by- case basis and with careful monitoring. C As per BCSH 2015 guidelines, reassess thromboprophylaxis in patients with thrombocytopenia, recognizing that a platelet count of < 50, 000/ L is a relative contraindication to pharmacological prophylaxis. B As per CCG-VTEC 2015 guidelines: Refer patients with persistent or severe thrombocytopenia to a hematologist or thrombosis expert, if possible. B Prefer LMWH or UFH over vitamin K agonists, if anticoagulation is required, in patients with significant thrombocytopenia. B Patients with thrombocytopenia, anticoagulant therapy: As per ITAC 2022 guidelines, consider administering anticoagulation at full doses for the treatment of established VTE in patients with thrombocytopenia with a platelet count > 50, 000/ L and in the absence of bleeding. Decide on the treatment and dosages in patients with a platelet count < 50, 000/ L on a case-by-case basis with the utmost caution. C As per BCSH 2015 guidelines, administer platelet support in patients with a platelet count < 50, 000/ L to elevate the count to > 50, 000/ L to allow full-dose anticoagulation, especially in the https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 6/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway immediate period following thrombosis development. B Show 2 more As per CCG-VTEC 2015 guidelines, hold anticoagulation in patients with acute (< 1 month) thromboembolism with platelet counts < 20, 000/ L unless platelet transfusion support is available to maintain a platelet count of at least 50, 000/ L. B Show 4 more Patients with heparin-induced thrombocytopenia: obtain platelet monitoring at baseline and in 5-14 days in patients receiving LMWH in an outpatient setting. B Show 2 more Patients with brain tumor, thromboprophylaxis: As per ITAC 2022 guidelines: Do not administer primary pharmacological prophylaxis of VTE in medically-treated patients with a brain tumor not planned to undergo neurosurgery. D Administer postoperative LMWH or UFH for the prevention of VTE in patients with cancer after neurosurgery. A As per CCG-VTEC 2015 guidelines, consider administering prophylactic anticoagulant therapy in patients with CNS malignancy. C Patients with brain tumor, anticoagulant therapy: As per ASCO 2023 guidelines, administer anticoagulation in patients with primary or metastatic CNS malignancies and established VTE as described for other patients with cancer. B As per ITAC 2022 guidelines, consider administering LMWH or direct OAC for the treatment of established VTE in patients with a brain tumor. C Patients with incidental thrombosis: As per ASCO 2023 guidelines: Treat patients with incidental PE or deep vein thrombosis in the same manner as symptomatic VTE, given their similar clinical outcomes compared with patients with cancer with symptomatic events. B Treat isolated subsegmental PE or splanchnic or visceral vein thrombi diagnosed incidentally on a case-by-case basis, taking into account potential benefits and risks of anticoagulation. B As per ESMO 2023 guidelines, treat patients with incidentally detected VTE similar to patients with symptomatic VTE. B Show 2 more As per ASH 2021 guidelines: Consider administering short-term anticoagulation treatment rather than offering observation in patients with cancer and incidental (unsuspected) PE. C Consider administering short-term anticoagulation treatment rather than offering observation in patients with cancer and subsegmental PE. C As per BCSH 2015 guidelines, initiate anticoagulation in patients with incidental pulmonary embolus or deep vein thrombosis as for symptomatic disease. B https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 7/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway As per CCG-VTEC 2015 guidelines, treat patients with incidental VTE generally in the same manner as patients with symptomatic VTE. B Patients with catheter-related thrombosis, thromboprophylaxis: As per ESMO 2023 guidelines, do not administer routine pharmacological prophylaxis for catheter-related thrombosis. D As per ITAC 2022 guidelines, do not administer anticoagulation for routine prophylaxis of catheter-related thrombosis in patients with cancer. D Landmark trials: AVERT (subgroup analysis) In patients with cancer-initiating chemotherapy who were at intermediate-to-high risk of VTE, apixaban was superior to placebo with respect to VTE at 180 days. Willem Brandt et al. Thromb Res. 2022 May 29. As per ASH 2021 guidelines, avoid administering parenteral or oral thromboprophylaxis in patients with cancer and a central venous catheter. D As per CCG-CAT 2015 guidelines, do not administer primary thromboprophylaxis in patients with an indwelling catheter and cancer. D As per CCG-VTEC 2015 guidelines, do not administer prophylactic anticoagulation therapy in outpatients with active malignancy solely based on the presence of an inserted central venous catheter presence. D As per ESMO 2015 guidelines, do not administer extensive routine prophylactic anticoagulation for the prevention of central venous catheter thrombosis in patients with cancer. D Show 2 more As per ISTH 2014 guidelines, do not administer routine pharmacologic prophylaxis for the prevention of catheter-related DVT in patients with cancer. D As per ASCO 2013 guidelines: Do not administer routine prophylaxis with anticoagulants for the prevention of central venous catheter thrombosis in patients with cancer. Insufficient evidence to suggest the routine use of urokinase and/or other thrombolytics for the prevention of central venous catheter thrombosis in patients with cancer. I Patients with catheter-related thrombosis (catheter insertion techniques): Insert catheters on the right side, in the jugular vein, and locate the distal extremity of the central catheter at the junction of the superior vena cava and the right atrium. B Consider using implanted ports over peripherally inserted central catheter lines in patients requiring central venous catheters. C Patients with catheter-related thrombosis, catheter flushing: As per ESMO 2015 guidelines, perform flushing with 0.9% normal saline. B https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 8/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway As per ISTH 2014 guidelines, do not perform routine heparin flushes for the prevention of catheter-related DVT in patients with cancer. D As per ASCO 2013 guidelines: Insufficient evidence to suggest either for or against the routine use of antibiotic- flush/antibiotic-lock therapy for the prevention of central venous catheter thrombosis in patients with cancer. Perform routine flushing of the central venous catheter with saline to prevent fibrin buildup. Patients with catheter-related thrombosis, catheter removal: As per ESMO 2023 guidelines, remove the catheter if it is not needed or is infected, anticoagulant treatment is contraindicated, or there is clinical deterioration due to thrombus extension despite treatment. B As per ITAC 2022 guidelines, consider keeping the central venous catheter in place if it is functional, well positioned, and not infected, under close surveillance while administering anticoagulation therapy. Insufficient evidence to recommend a specific duration of anticoagulation. C As per ASH 2021 guidelines, consider keeping the central venous catheter in place in patients with cancer with central venous catheter-related VTE receiving anticoagulant treatment. C As per ESVS 2021 guidelines, consider removing the catheter in patients with catheter-related thrombosis when: it is not needed it is not functional anticoagulation is contraindicated symptoms are not resolving with anticoagulation the thrombosis is limb- or life-threatening. C As per CCG-CAT 2015 guidelines, keep the catheter stay in place in patients with catheter- related thrombosis started on anticoagulation as long as symptoms improve and the catheter is needed, working, and not infected. B As per ISTH 2014 guidelines: Remove the non-functional, infected or incorrectly positioned catheter and consider initiating anticoagulation with LMWH for catheter-related thrombosis in patients with cancer. E Consider removing the central venous catheter without anticoagulation if therapeutic anticoagulation cannot be safely administered due to the active risk of hemorrhage. E As per ASCO 2013 guidelines, remove the central venous catheter in patients with radiologically confirmed thrombosis not responding to fibrinolytic therapy, or if fibrinolytic or anticoagulation therapy is contraindicated. Patients with catheter-related thrombosis, anticoagulation: As per ESMO 2023 guidelines: Initiate anticoagulant therapy with LMWH, or alternatively vitamin K antagonists or direct OACs, B for a minimum of 3 months for the treatment of symptomatic catheter-related https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 9/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway thromboses in patients with cancer. B Consider extending anticoagulation until catheter removal if the bleeding risk is low in patients with catheter-related thrombosis received 3 months of anticoagulant treatment. C As per ITAC 2022 guidelines, initiate anticoagulation with LMWH for a minimum of 3 months and as long as the central venous catheter is in place for the treatment of symptomatic catheter- related thrombosis in patients with cancer. B As per ESVS 2021 guidelines, consider initiating LMWH or LMWH followed by vitamin K antagonists for a minimum of 3 months in patients with catheter-related thrombosis. C As per CCG-CAT 2015 guidelines, treat catheter-related cancer-associated deep vein thrombosis if the thrombus involves the deep veins, such as the axillary and subclavian, or more proximal veins. Consider obtaining close clinical surveillance (symptom resolution, serial ultrasound) alternative to treatment for thrombosis involving the brachial deep vein or the basilic and cephalic superficial veins. B Show 2 more As per CCG-VTEC 2015 guidelines: Administer anticoagulation therapy for the duration of the central venous catheter in patients with cancer and upper extremity deep vein thrombosis. A Continue anticoagulation therapy for at least 3 months after catheter removal in patients with cancer and upper extremity deep vein thrombosis. B As per ESMO 2015 guidelines, initiate anticoagulation therapy with LMWH as the preferred treatment, as it is more effective in preventing thrombosis and carries a lesser risk of bleeding compared with vitamin K antagonists. B Show 3 more As per ISTH 2014 guidelines, consider initiating anticoagulation with LMWH without removal of the catheter if the central venous catheter is functional and required for ongoing therapy. E Show 7 more As per ASCO 2013 guidelines, initiate a 3-6-month anticoagulant therapy with LMWH or LMWH followed by warfarin for the treatment of symptomatic central venous catheter thrombosis, with duration depending on clinical issues in individual patients. Patients with catheter-related thrombosis, thrombolysis: As per CCG-CAT 2015 guidelines, consider offering thrombolysis for the treatment of refractory or extensive cases of catheter-associated deep vein thrombosis in patients with cancer, if catheter removal does not result in symptomatic improvement. C As per ESMO 2015 guidelines, do not use thrombolytic agents (urokinase, streptokinase and alteplase) as first-line therapy, due to a greater risk of thrombosis. D As per ISTH 2014 guidelines, reserve clot-directed thrombolysis for cases of massive clot burden and/or refractory thrombosis. E As per ASCO 2013 guidelines, administer low-dose tPA (2 mg IV) to restore patency and preserve catheter function in patients with central venous catheter thrombosis not having https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 10/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway contraindications to tPA. Patients with visceral thrombosis: consider administering short-term anticoagulation or offering observation in patients with cancer and visceral/splanchnic vein thrombosis. C 7. Patient education General counseling: As per ASCO 2023 guidelines, educate patients regarding VTE, particularly in settings increasing the risk, such as major surgery, hospitalization, and while receiving systemic antineoplastic therapy. B As per ESMO 2023 guidelines, provide patient education materials on cancer-associated thrombosis including risk factors, signs, and symptoms and information on positive lifestyle factors in all ambulatory patients scheduled to receive systemic cancer treatment. B As per CCG-VTEC 2015 guidelines, provide patients with verbal and written education about their condition, including their personal risk for developing recurrent VTE. B Show 2 more 8. Preventative measures Thromboprophylaxis, general indications: As per ASCO 2023 guidelines, initiate pharmacologic thromboprophylaxis in hospitalized patients with active malignancy and acute medical illness or reduced mobility in the absence of bleeding or other contraindications. B Show 2 more As per ASH 2021 guidelines, consider initiating thromboprophylaxis in hospitalized medical patients with cancer without VTE and discontinue thromboprophylaxis at the time of hospital discharge. C As per BCSH 2015 guidelines, do not use anticoagulants at prophylactic or therapeutic dose routinely to prevent catheter-related thrombosis in patients with cancer. D Show 2 more As per CCG-VTEC 2015 guidelines, do not administer prophylactic anticoagulant therapy in all outpatients with active malignancy. D Show 3 more Thromboprophylaxis, improving survival: As per ASCO 2023 guidelines, do not use anticoagulants to improve survival in patients with cancer without VTE. D As per BCSH 2015 guidelines, do not use antithrombotics with the sole purpose of increasing the life expectancy in patients with cancer without a history of VTE. D https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 11/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway As per CCG-VTEC 2015 guidelines, do not use adjuvant anticoagulant therapy to prolong survival in patients without established VTE or unselected (low-risk) patients. D Thromboprophylaxis, choice of anticoagulation: As per ASH 2021 guidelines: Consider preferring pharmacological thromboprophylaxis over mechanical thromboprophylaxis or a combination of pharmacological and mechanical thromboprophylaxis in hospitalized medical patients with cancer without VTE. C Consider preferring LMWH over UFH for pharmacological thromboprophylaxis in hospitalized medical patients with cancer without VTE. C As per CCG-VTEC 2015 guidelines, administer LMWH as the treatment of choice in hospitalized patients with cancer. B Show 2 more Thromboprophylaxis, patients receiving anticancer therapy: As per ASCO 2023 guidelines: Consider administering thromboprophylaxis with apixaban, rivaroxaban, or LMWH in high-risk outpatients with cancer (Khorana score of 2 before starting a new systemic chemotherapy regimen) provided there are no significant risk factors for bleeding and no drug interactions. Discuss the relative benefits and harms, drug cost, and duration of prophylaxis with the patient. C Administer thromboprophylaxis with either aspirin (only in lower-risk patients) or LMWH in patients with multiple myeloma receiving thalidomide- or lenalidomide-based regimens with chemotherapy and/or dexamethasone. B As per ASH 2023 guidelines, consider obtaining testing for hereditary thrombophilia in ambulatory patients with cancer receiving systemic therapy, having a family history of VTE, and otherwise being determined to be at low or intermediate risk for VTE. Consider administering ambulatory thromboprophylaxis in patients with thrombophilia. Do not administer thromboprophylaxis in patients without thrombophilia. C As per ESMO 2023 guidelines, consider administering LMWH at a higher dose (150/IU/kg dalteparin or 1 mg/kg enoxaparin) for a maximum of 3 months in ambulatory patients with pancreatic cancer on first-line systemic anticancer treatment. C Show 7 more As per ITAC 2022 guidelines, administer prophylaxis with LMWH or fondaparinux in patients with CrCl 30 mL/min, or with UFH in hospitalized patients with reduced mobility. B Do not use direct OACs routinely in this setting. B Show 4 more Landmark trials: SAVE-ONCO In patients with metastatic or locally advanced solid tumors who were beginning to receive a course of chemotherapy, semuloparin was superior to placebo with respect to the composite outcome of symptomatic deep vein thrombosis, nonfatal PE, and death related to VTE. https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 12/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway Giancarlo Agnelli et al. N Engl J Med. 2012 Feb 16. As per ASH 2021 guidelines, do not administer parenteral thromboprophylaxis in ambulatory patients with cancer at low risk for thrombosis receiving systemic therapy. D Show 6 more Landmark trials: CASSINI In high-risk ambulatory adults with cancer, rivaroxaban was not superior to placebo with respect to thrombotic events at 6 months. Alok A Khorana et al. N Engl J Med. 2019 Feb 21. As per BCSH 2015 guidelines: Do not administer routine thromboprophylaxis in patients without a history of VTE receiving adjuvant hormonal therapies for cancer. D Assess the risk of VTE in patients with myeloma receiving thalidomide or lenalidomide and administer thromboprophylaxis unless contraindicated. A As per CCG-VTEC 2015 guidelines: Consider administering prophylactic anticoagulant therapy in outpatients with active malignancy receiving chemotherapy at high risk of thrombosis. C Reassess the risks, discomfort, and inconvenience of taking anticoagulant therapy versus the benefits of preventing recurrent VTE once cancer therapy is withdrawn. B Thromboprophylaxis, patients undergoing surgery, general principles: As per ASCO 2023 guidelines, administer pharmacologic thromboprophylaxis with either UFH or LMWH in all patients with malignant disease undergoing major surgical intervention unless contraindicated because of active bleeding, high bleeding risk, or other contraindications. A Continue thromboprophylaxis preoperatively. B Show 4 more As per ESMO 2023 guidelines, administer pharmacological VTE prophylaxis, preferably with LMWH, or UFH, A or alternatively with fondaparinux, B in patients undergoing major cancer surgery, unless contraindicated because of the high risk of bleeding. A Show 4 more As per ITAC 2022 guidelines, administer LMWH at the highest prophylactic dose once daily (when CrCl is 30 mL/min) or low-dose UFH TID for the prevention of postoperative VTE in patients with cancer. Initiate pharmacological prophylaxis 2-12 hours preoperatively and continue for at least 7-10 days. A Show 4 more As per ASH 2021 guidelines, consider administering pharmacological in patients with cancer without VTE undergoing surgical procedures at lower bleeding risk. C https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 13/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway Show 5 more Thromboprophylaxis (patients undergoing surgery, thoracic: lobectomy/segmentectomy): consider administering parenteral anticoagulation with subcutaneous LMWH or UFH for VTE prevention in patients undergoing lobectomy or segmentectomy. C Consider preferring LMWH over UFH. C Show 7 more Thromboprophylaxis (patients undergoing surgery, thoracic: pneumonectomy): consider administering parenteral anticoagulation with subcutaneous LMWH or UFH for VTE prevention in patients undergoing pneumonectomy or extended lung resection. C Consider preferring LMWH over UFH. C Show 6 more Thromboprophylaxis (patients undergoing surgery, thoracic: esophagectomy): consider administering parenteral anticoagulation with subcutaneous LMWH or UFH for VTE prevention in patients undergoing esophagectomy. C Consider preferring LMWH over UFH. C Show 6 more Thromboprophylaxis, patients undergoing surgery, abdominopelvic: As per ASCO 2023 guidelines, continue thromboprophylaxis with LMWH for up to 4 weeks postoperatively in patients after a major open or laparoscopic abdominal or pelvic surgery for cancer and having high-risk features, such as restricted mobility, obesity, history of VTE, or with additional risk factors. B As per ESMO 2023 guidelines, administer extended postoperative VTE prophylaxis for 4 weeks with LMWH after open abdominal or pelvic surgery or laparoscopic colorectal cancer surgery. A As per ITAC 2022 guidelines, administer extended prophylaxis (4 weeks) for the prevention of postoperative VTE after major abdominal or pelvic surgery (either laparotomy or laparoscopy) in patients with cancer not at high risk of bleeding. A As per ASH 2021 guidelines, consider continuing pharmacological thromboprophylaxis after hospital discharge in patients with cancer after a major abdominal/pelvic surgical procedure. C As per BCSH 2015 guidelines, consider administering extended thromboprophylaxis in patients undergoing abdominal or pelvic surgery for cancer. C As per CCG-VTEC 2015 guidelines: Administer prophylactic anticoagulant therapy in outpatients undergoing major abdominal or pelvic cancer surgery. A Consider administering extended prophylaxis for deep vein thrombosis for up to 4 weeks postoperatively in patients undergoing major abdominal or pelvic cancer surgery, especially in patients at high risk. C Thromboprophylaxis, patients undergoing other procedures: As per ASCO 2023 guidelines, do not administer routine pharmacologic thromboprophylaxis in patients admitted for the sole purpose of minor procedures or chemotherapy infusion, nor in patients undergoing stem-cell/BMT. D https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 14/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway As per CCG-VTEC 2015 guidelines, insufficient evidence to recommend prophylactic anticoagulation in outpatients undergoing lower-risk surgeries (such as biopsies, cutaneous excisions). I Thromboprophylaxis (monitoring): do not obtain routine monitoring of anti-factor Xa levels in most patients receiving prophylactic anticoagulation. D 9. Follow-up and surveillance Follow-up: Schedule an initial follow-up at 1-4 weeks. B Ensure that SC injections are being administered properly and assess for bleeding and recurrent thrombotic complications. B Management of recurrence: As per ITAC 2022 guidelines: Consider offering the following options in patients with VTE recurrence: increase LMWH by 20-25% or switch to direct OACs switch to LMWH if on direct OACs switch to LMWH or direct OACs if on vitamin K antagonists. C Consider placing an IVC filter in patients with PE recurrence occurring under optimal anticoagulation. C Landmark trials: CLOT In patients with cancer who had acute, symptomatic proximal deep vein thrombosis, PE, or both, subcutaneous dalteparin was superior to oral anticoagulation with respect to recurrent VTE at 6 months. Lee AY et al. N Engl J Med. 2003 Jul 10. As per ASH 2021 guidelines: Consider increasing the LMWH dose to a supratherapeutic level or continuing with a therapeutic dose in patients with cancer and recurrent VTE despite receiving therapeutic LMWH. C Avoid using IVC filters in patients with cancer and recurrent VTE despite anticoagulation treatment. D As per CCG-VTEC 2015 guidelines: Increase the dose of LMWH by 20-25% in patients with recurrent VTE while on LMWH. B Extend anticoagulation therapy (> 3 months) in patients with recurrent VTE. B https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 15/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway Clinical findings Past medical history Past obstetric history CKD Pregnancy Catheter-related thrombosis Social history Cerebral venous thrombosis DVT Tobacco use Exposure to chemotherapy Immobility Inserted central venous catheter Malignancy Migratory thrombophlebitis Obesity PE Splanchnic vein thrombosis Superficial vein thrombosis Trousseau's syndrome Past surgical history Recent surgery Lab findings serum D-dimer serum lactate Studies 2022 AVERT (subgroup analysis) In patients with cancer-initiating chemotherapy who were at intermediate-to-high risk of VTE, apixaban was superior to placebo with respect to VTE at 180 days. Willem Brandt et al. Thromb Res. 2022 May 29. 2019 CASSINI In high-risk ambulatory adults with cancer, rivaroxaban was not superior to placebo with respect to thrombotic events at 6 months. Alok A Khorana et al. N Engl J Med. 2019 Feb 21. Show 7 more References https://web.pathway.md/diseases/recIVmB3RkdyvcT1J 16/18 6/29/23, 3:25 AM Cancer-associated thrombosis Pathway 1. Henry G Watson, David M Keeling, Mike Laffan et al. Guideline on aspects of cancer-related venous thrombosis. Br J Haematol. 2015 Sep;170 5 640 8. Open 2. Dominique Farge, Corinne Frere, Jean M Connors et al. 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. Open 3. M Carrier, A Lazo-Langner, S Shivakumar et al. Clinical challenges in patients with cancer-associated thrombosis: Canadian expert consensus recommendations. Curr Oncol. 2015 Feb;22 1 49 59. Open 4. J C Easaw, M A Shea-Budgell, C M J Wu et al. Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 1 prophylaxis. Curr Oncol. 2015 Apr;22 2 133 43. Open 5. Stavros K Kakkos, Manjit Gohel, Niels Baekgaard et al. Editor's Choice European Society for Vascular Surgery ESVS 2021 Clinical Practice Guidelines on the Management of Venous Thrombosis. Eur J Vasc Endovasc Surg. 2021 Jan;61 1 9 82. Open 6. Gary H Lyman, Marc Carrier, Cihan Ay et al. American Society of Hematology 2021 guidelines for management of venous thromboembolism: prevention and treatment in patients with cancer. Blood Adv. 2021 Feb 23;5 4 927 974. Open 7. A Falanga, C Ay, M Di Nisio et al. Venous thromboembolism in cancer patients: ESMO Clinical Practice Guideline. Ann Oncol. 2023 Jan 3;S0923 7534 22 04786 X. Open 8. Nigel S Key, Alok A Khorana, Nicole M Kuderer et al. Canadian Urological Association consensus guideline: Management of testicular germ cell cancer. J Clin Oncol. 2023 Apr 19;JCO2300294. Open 9. J I Zwicker, G Connolly, M Carrier et al. Catheter-associated deep vein thrombosis of the upper extremity in cancer patients: guidance from the SSC of the ISTH. J Thromb Haemost. 2014 May;12 5 796 800. Open 10. Schiffer CA, Mangu PB, Wade JC et al. Central venous catheter care for the patient with cancer: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. 2013 Apr 1;31 10 1357 70. Open 11. J C Easaw, M A Shea-Budgell, C M J Wu et al. Canadian consensus recommendations on the management of venous thromboembolism in patients with cancer. Part 2 treatment. Curr Oncol. 2015 Apr;22 2 144 55. Open 12. Yaron Shargall, Wojtek Wiercioch, Alessandro Brunelli et al. Joint 2022 European Society of Thoracic Surgeons and The American Association for Thoracic Surgery guidelines for the prevention of cancer- associated venous thromboembolism in thoracic surgery. Eur J Cardiothorac Surg. 2022 Dec 2;63 1):ezac488. Open