Guideline sources The following summarized guidelines for the evaluation and management of catheter-related thrombosis (CRT) are prepared by our editorial team based on guidelines from the European Society of Medical Oncology (ESMO 2023; 2015), the International Initiative on Thrombosis and Cancer (ITAC 2022), the European Society for Vascular Surgery (ESVS 2021), the American Society of Hematology (ASH 2021), the Canadian Consensus Group on Cancer-Associated Thrombosis (CCG-CAT 2015), the Canadian Consensus Group on Venous Thromboembolism in Cancer (CCG-VTEC 2015), the International Society on Thrombosis and Haemostasis (ISTH 2014), the American Society of Clinical Oncology (ASCO 2013), and the American College of Chest Physicians (ACCP 2012). 1 2 3 4 5 6 7 8 9 10 11 12 12 12 13 Definition Central venous catheter thrombosis is a common complication of central venous catheter insertion characterized by thrombus formation around the site of the catheter. 28979481]. Epidemiology Central venous catheter thrombosis is caused by activation of the coagulation cascade and formation of thrombin and clot associated with an indwelling catheter. Circulatory stasis, vascular https://web.pathway.md/diseases/rectoiqw9WzeJF19r 1/8 6/29/23, 3:46 AM Catheter-related thrombosis Pathway endothelial injury, and hypercoagulable states predispose to the development of thrombus. 12 12 Disease course Central venous catheter thrombosis may be asymptomatic or cause pain, swelling in the arm, shortness of breath, vena cava obstruction. Disease progression may lead to PE. Long-term sequelae may include postphlebitic syndrome. 12 Prognosis and risk of recurrence The 28-day mortality rate in critically ill patients with central venous catheter thrombosis is estimated at 14.1%. 13 Calculator Michigan risk score for peripher Guidelines 1. Diagnostic investigations Diagnostic imaging: As per CCG-CAT 2015 guidelines: Obtain ultrasound in patients with suspected symptomatic catheter-related upper-extremity deep vein thrombosis. B Consider obtaining further diagnostic testing (such as contrast venography or CTV) in patients with negative ultrasound findings but with a high index of suspicion for catheter-related upper extremity deep vein thrombosis. Do not obtain serial ultrasound in this setting. C As per ESMO 2015 guidelines: Obtain Doppler ultrasound if central venous catheter thrombosis is suspected. B Obtain venography or alternative imaging (MRI, CT, gadolinium-enhanced MRV, or contrast- enhanced CT) in case of normal ultrasound results and suspected thrombosis or occlusion. B As per ISTH 2014 guidelines: Obtain ultrasound as the initial test of choice for the diagnosis of suspected catheter-related upper extremity thrombosis. E Consider obtaining standard contrast venography in patients with high clinical suspicion and negative (or nondiagnostic) ultrasound testing. Consider obtaining less invasive imaging modalities such as CTV or MRV if contrast venography is not available or practical. E D-dimer: do not obtain D-dimer to exclude the diagnosis of suspected catheter-related upper extremity DVT. D https://web.pathway.md/diseases/rectoiqw9WzeJF19r 2/8 6/29/23, 3:46 AM Catheter-related thrombosis Pathway 2. Medical management Anticoagulant therapy: 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 thromboses in patients with cancer. B Consider extending anticoagulation until catheter removal if the bleeding risk is low in patients with CRT 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 CRT in patients with cancer. B As per ESVS 2021 guidelines, consider initiating anticoagulation with LMWH or LMWH followed by vitamin K antagonists for a minimum of 3 months in patients with CRT. 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. 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 https://web.pathway.md/diseases/rectoiqw9WzeJF19r 3/8 6/29/23, 3:46 AM Catheter-related thrombosis Pathway 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 contraindications to tPA. 3. Nonpharmacologic interventions 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 ESVS 2021 guidelines, consider removing catheter in patients with CRT 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 CRT 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 CRT 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. 4. Specific circumstances https://web.pathway.md/diseases/rectoiqw9WzeJF19r 4/8 6/29/23, 3:46 AM Catheter-related thrombosis Pathway Pediatric patients: administer continuous infusion of UFH at 0.5 units/mL at 1 mL/hour in neonates and children with peripheral arterial catheters in situ. A Show 7 more 5. Preventative measures Thromboprophylaxis: As per ESMO 2023 guidelines, do not administer routine pharmacological prophylaxis for CRT. D As per ITAC 2022 guidelines, do not administer anticoagulation for routine prophylaxis of CRT 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. 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 systemic anticoagulants (warfarin, LMWH, UFH) 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 Landmark trials: WARP (warfarin evaluation) https://web.pathway.md/diseases/rectoiqw9WzeJF19r 5/8 6/29/23, 3:46 AM Catheter-related thrombosis Pathway In patients aged 16 years with cancer receiving chemotherapy through central venous catheters, warfarin was not superior to no warfarin with respect to a catheter-related thrombotic events. Annie M Young et al. Lancet. 2009 Feb 14. 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 Catheter flushing: As per ESMO 2015 guidelines, perform flushing with 0.9% normal saline. B 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. Clinical findings Symptoms Past medical history Arm pain Inserted central venous catheter Arm swelling Inserted venous catheter Facial pain Malignancy Headache Thrombophilia Hoarseness Vascular exam Jaw pain Neck pain Signs of upper extremity deep vein thrombosis Shortness of breath Shoulder pain Signs of upper extremity superficial vein thrombosis Skin flushing Past surgical history Recent surgery Integument exam Erythema of upper extremity Upper extremity edema https://web.pathway.md/diseases/rectoiqw9WzeJF19r 6/8 6/29/23, 3:46 AM Catheter-related thrombosis Pathway 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. 2009 WARP (warfarin evaluation) In patients aged 16 years with cancer receiving chemotherapy through central venous catheters, warfarin was not superior to no warfarin with respect to a catheter-related thrombotic events. Annie M Young et al. Lancet. 2009 Feb 14. References 1. 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 2. 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 3. 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 4. Schiffer CA, Mangu PB, Wade JC et al. 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