Table 7.

Guideline recommendations on treatment of unusual sites of cancer‐associated venous thromboembolism

Unusual site thrombosis	American Society of Clinical Oncology 2020	International Initiative on Thrombosis and Cancer 2019	International Society of Thrombosis and Hemostasis 2018	National Comprehensive Cancer Network 2020	Spanish Society of Medical Oncology 2020
CVC thrombosis	Prophylaxis: No specific recommendations. Treatment: No specific recommendations.	Prophylaxis: Use of routine pharmacologic prophylaxis for CVC thrombosis is not recommended (grade 1A). CVC should be inserted on the right side, in the jugular vein, and the distal catheter tip should be located at the junction of the superior vena cava and the right atrium (grade 1B). In patients requiring CVC, we suggest the use of implanted ports over peripherally inserted CVC (guidance). Treatment: For the treatment of symptomatic CVC thrombosis, anticoagulation is recommended for a minimum of 3 months and as long as the CVC is in place; LMWHs are suggested. Direct comparisons between LMWHs, DOACs, and VKA have not been made (guidance). In patients with CVC thrombosis, the CVC can be kept in place if it is functional, well positioned, and not infected, with resolution of symptoms during anticoagulation. No standard duration of therapy is established (guidance).	Prevention: No specific recommendation. Treatment: Suggest (weak guidance) anticoagulation with LMWH without CVC removal if functional and required for ongoing therapy. Recommend (strong guidance) removal of a nonfunctional, infected, or incorrectly positioned catheter and suggest anticoagulation with LMWH. Suggest (weak guidance) a short duration of anticoagulation (3 to 5 days), if clinically practical, prior to removal of a CVC. Suggest (weak guidance) removal of CVC without anticoagulation if therapeutic anticoagulation cannot be safely administered because of the active risk of hemorrhage. Suggest (weak guidance) anticoagulation over no anticoagulation for an incidental CVC DVT. Alternative strategies such as serial ultrasound and/or catheter removal can be considered. Recommend (strong guidance) anticoagulation over thrombolysis for acute CVC thrombosis. Consideration of clot‐directed thrombolysis should be reserved for cases of massive clot burden and/or refractory thrombosis. In cases of thrombocytopenia without bleeding, the decision to use or withhold anticoagulation should be made on an individual basis. Suggest (weak guidance) 3 to 6 months of anticoagulation for a symptomatic, CVC upper‐extremity DVT. Suggest (weak guidance) LMWH over warfarin in patients with cancer. Suggest (weak guidance) anticoagulation for the duration the catheter remains in place for individuals with ongoing risk factors, such as persistent CVC.	Prevention: The panel does not recommend prophylactic anticoagulation for CVC. Treatment: If CVC is still needed, anticoagulation alone is recommended for CVC DVT. If CVC is no longer required, anticoagulation for 5–7 days is recommended before CVC removal, if feasible. If CVC is infected or symptoms of thrombosis fail to resolve, then CVC should be removed. If anticoagulation is contraindicated, CVC should be removed after consideration of thrombus burden and potential for embolization as well as feasibility of short course of anticoagulation prior to CVC removal. Anticoagulation for CVC DVT should be continued for at least 3 months or the life of the CVC should it remain in place.	Treatment: Recommend LMWH for 3–6 months or indefinitely if CVC is not removed (grade 2B). DOAC could be considered as a treatment option (grade 2C). Recommend against CVC removal unless it is no longer needed, infected, anticoagulation is contraindicated, or anticoagulation failure (grade 2B). Removal should be done after 5–7 days of anticoagulation.
Superficial vein thrombosis	No specific recommendations.	No specific recommendations.	No specific recommendations.	Prevention: No recommendations. Treatment: Distal upper extremity: Initial symptomatic treatment (warm compresses, elevation, NSAIDs) and remove catheter if present. If progression, consider anticoagulation. Proximal upper extremity: Same as above except consider initial anticoagulation if clot is within 3 cm of deep vein. Distal leg: Initial symptomatic treatment and remove catheter if present. If progression or clot within 3 cm of deep vein, consider anticoagulation. Proximal leg: Initial anticoagulation for at least 6 weeks. Remove catheter if present. At 6 weeks if persistent symptoms or risk factors for progression (advanced cancer, active cancer treatment, non–catheter‐related clots), consider longer course of therapy. Fondaparinux 2.5 mg daily and rivaroxaban 10 mg daily have been shown to be effective in studies with limited number of patients with cancer. Therapeutic anticoagulation at clinician discretion.	No specific recommendations.
Hepatic vein thrombosis	No specific recommendations.	No specific recommendations.	No specific recommendations.	Acute (symptoms/signs ≤8 weeks): If no contraindication, recommend anticoagulation. Hepatology evaluation. Consider catheter‐directed pharmacomechanical thrombolysis. If anticoagulation contraindicated, consider TIPS or surgical shunt. Hepatology evaluation. Reassess contraindication to anticoagulation regularly. Chronic (symptoms/signs >8 weeks): Hepatology evaluation. Consider TIPS or surgical shunt. Consider anticoagulation. Duration of anticoagulation at least 6 months for provoked hepatic vein thrombosis, indefinite for unprovoked event or persistent risk factor (i.e., cancer, thrombophilia).	No specific recommendations.
Portal, mesenteric, or splenic veins thrombosis	No specific recommendations.	No specific recommendations.	No specific recommendations.	Acute (symptoms/signs ≤8 weeks): If no contraindication, recommend anticoagulation. Surgery if bowel infarction present. Consider catheter‐directed pharmacomechanical thrombolysis. If anticoagulation contraindicated, GI and surgery evaluation. Surgery if bowel infarction. Reassess contraindication to anticoagulation regularly. Chronic (symptoms/signs >8 weeks): GI evaluation, beta blockade. Consider variceal banding; consider anticoagulation if no contraindication. Duration of anticoagulation at least 6 months for provoked hepatic vein thrombosis, indefinite for unprovoked event or persistent risk factor (i.e., cancer, thrombophilia).	No specific recommendations.

Abbreviations: CVC, central venous catheter; DVT, deep vein thrombosis; DOAC, direct oral anticoagulant; GI, gastrointestinal; LMWH, low‐molecular‐weight heparin; NSAID, nonsteroidal anti‐inflammatory drug; TIPS, transjugular intrahepatic portosystemic shunt; VKA, vitamin K antagonist.