Summary

The 2022 ITAC international clinical practice guidelines provide GRADE-based recommendations for treatment and prophylaxis of venous thromboembolism (VTE) in patients with cancer, including those with COVID-19. This update incorporates new RCT evidence supporting direct oral anticoagulants (DOACs) as first-line options alongside LMWH for cancer-associated thrombosis, addresses primary prophylaxis with DOACs in ambulatory patients with elevated Khorana scores, and adds new guidance for cancer patients with COVID-19.

Key Recommendations

Initial VTE treatment (0–10 days): LMWH preferred over UFH given lower mortality and recurrence; DOACs (apixaban, rivaroxaban, edoxaban) are acceptable first-line alternatives in patients without high GI bleeding risk.
Early maintenance and long-term treatment (up to 6 months): use LMWH or a DOAC; DOACs are non-inferior or superior to LMWH for recurrent VTE but increase clinically relevant non-major bleeding, especially with GI or genitourinary cancers.
Anticoagulation should be continued beyond 6 months in patients with active cancer, metastatic disease, or ongoing chemotherapy; reassess benefit/risk periodically.
Avoid DOACs in patients with luminal GI cancers, unresected GU lesions, drug–drug interactions with strong P-gp/CYP3A4 modulators, or severe thrombocytopenia.
IVC filters are not routinely recommended; reserve for absolute contraindication to anticoagulation, with anticoagulation resumed when feasible.
Surgical prophylaxis: give LMWH once daily (or UFH TID) starting 2–12 hours preoperatively; extend prophylaxis to 4 weeks after major open or laparoscopic abdominal/pelvic cancer surgery.
Hospitalized medical cancer patients with reduced mobility: give LMWH, UFH, or fondaparinux prophylaxis during admission.
Ambulatory cancer patients on chemotherapy with Khorana score ≥2: offer primary prophylaxis with apixaban 2.5 mg BID or rivaroxaban 10 mg daily; LMWH is an alternative, particularly in locally advanced/metastatic pancreatic cancer.
Myeloma patients on IMiD-based therapy: give prophylaxis with aspirin, LMWH, apixaban, or warfarin based on individual VTE risk.
Central venous catheters: insert in right jugular vein with tip at SVC–RA junction; do not routinely use anticoagulant prophylaxis for CRT.
Established catheter-related thrombosis: treat with at least 3 months of anticoagulation (LMWH preferred); do not remove a functional, well-positioned, non-infected catheter.
Brain tumor patients with VTE: anticoagulate with LMWH or DOAC (DOACs may carry lower ICH risk in retrospective data); thrombocytopenia <50×10⁹/L warrants modified-dose anticoagulation or platelet transfusion support.

Thresholds & Doses

Apixaban for CAT: 10 mg BID × 7 days, then 5 mg BID for ≥6 months
Rivaroxaban for CAT: 15 mg BID × 21 days, then 20 mg daily for ≥6 months
Edoxaban for CAT: 60 mg daily after ≥5 days of parenteral anticoagulation (30 mg if CrCl 15–50 mL/min, weight ≤60 kg, or strong P-gp inhibitor)
Dalteparin for CAT: 200 IU/kg SC daily × 30 days, then 150 IU/kg SC daily for ≥6 months
Tinzaparin for CAT: 175 IU/kg SC daily for ≥6 months
Enoxaparin treatment dose: 1.5 mg/kg SC daily (or 1 mg/kg BID)
Fondaparinux treatment: 5 mg (<50 kg), 7.5 mg (50–100 kg), 10 mg (>100 kg) SC daily
Surgical prophylaxis dalteparin: 5000 IU SC daily; enoxaparin 40 mg SC daily
Extended postoperative prophylaxis after major abdominal/pelvic cancer surgery: 4 weeks
Apixaban primary prophylaxis (AVERT): 2.5 mg BID × 6 months in patients with Khorana score ≥2
Rivaroxaban primary prophylaxis (CASSINI): 10 mg daily × 6 months in patients with Khorana score ≥2
Khorana score threshold for ambulatory prophylaxis: ≥2
Renal cutoffs: avoid LMWH/fondaparinux if CrCl <30 mL/min (tinzaparin <20); avoid dabigatran if CrCl <30; avoid apixaban/edoxaban/rivaroxaban if CrCl <15 mL/min
Severe thrombocytopenia threshold for dose modification: platelets <50×10⁹/L
VKA target INR for CAT (when used): 2.0–3.0

Citations

Q1/Q2 Treatment of established VTE — DOAC vs LMWH RCTs (Hokusai-VTE Cancer, SELECT-D, ADAM-VTE, CARAVAGGIO, CASTA-DIVA, CANVAS)
Appendix 6 Q1 Conclusions — Initial treatment of VTE; IVC filter and thrombolysis recommendations
Appendix 6 Q2 Conclusions — Early maintenance and long-term anticoagulation duration
Appendix 6 Q4 Conclusions — Surgical prophylaxis: LMWH dose, extended duration 4 weeks
Appendix 6 Q5 Conclusions — Ambulatory thromboprophylaxis with Khorana score ≥2; DOACs (CASSINI, AVERT)
Appendix 6 Q7 Conclusions — CVC type, position, and prophylaxis recommendations
Appendix 6 Q8 Conclusions — Special populations: brain tumors, thrombocytopenia, renal failure, children
Appendix 10 — Anticoagulant pharmacokinetics, dosing, and renal cutoffs