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NCCN Flash Updates: NCCN Guidelines Updated for Cancer-Associated Venous Thromboembolic Disease

NCCN has published updates to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines^®), and the NCCN Drugs & Biologics Compendium (NCCN Compendium^®) for Cancer-Associated Venous Thromboembolic Disease. These NCCN Guidelines^® are currently available as Version 1.2025.

Link directly to the Updates section of the NCCN Guidelines: Cancer-Associated Venous Thromboembolic Disease

Global Updates

• References have been updated throughout the guidelines.

VTE-A

• Contraindications to Prophylactic Anticoagulation, bullet added: Pork product allergy (contraindication for LMWH and UFH)

VTE-B (1 of 5)

• Enoxaparin
  • Dosing for BMI ≥40 kg/m2, options removed: BMI >50 kg/m2: Consider 60 mg SC every 12 hours OR 0.5 mg/kg actual body weight SC daily
• UFH
  • Dosing for Actual Body Weight 25-50 kg, option modified: Weight <40 50 kg: 2500 units SC every 8–12 hours
• Note added: § Refer to package insert for full prescribing information: https://www.accessdata.fda.gov/scripts/cder/daf/ (Also for VTE-B 2 of 5, VTE-B 3 of 5, VTE-B 4 of 5, VTE-D 2 of 6, VTE-D 3 of 6, VTE-D 4 of 6, and as footnote c on HIT-B)
• Footnote a added: LMWH (enoxaparin and dalteparin) are preferred over UFH unless contraindicated (eg, poor renal function). (Also for VTE-B 3 of 5)
• Footnote f modified: "Dosing recommendations for patients weighing 25–4050 kg are included as guidance and based on expert opinion..." (Also for VTE-B 3 of 5)

DVT-2

• Proximal lower extremity, contraindication to anticoagulation
  • No, bullet 3 modified: Consider GCS compression therapy for symptom control if the patient tolerates therapeutic anticoagulation

PE-2

• Contraindication to anticoagulation, no, acute management using anticoagulation
  • Bullet 3, sub-bullet 1 modified: Systemic or catheter-directed thrombolysis or embolectomy for hemodynamically unstable PEin patients with lower bleeding risk
• Footnote j modified: "...Consider echocardiography or CTA to assess right ventricular overload, NT-proBNP, and troponin, and lactate levels (Galić K, et al. Croat Med J 2018;59:149-155)..."

SPVT-1

• Footnote a, bullet 2 modified: Abdominal mass/cancer (hepatobiliary, luminal GI, pancreatic cancers)

VTE-D (2 of 6)

• Warfarin, bullet 3 added: The PT/INR can be prolonged by lupus inhibitors/anticoagulants, particularly point-of-care PT/INR. See Discussion for further discussion of management.

VTE-D (4 of 7)

• Agent modified: LMWH: Dalteparin and enoxaparin
  • LMWH, contraindications and warnings, bullet added: Pork product allergy
• DOACs, contraindications and warnings, bullet added: Antiphospholipid syndrome (APS)
• Footnote k modified: Although stage IV chronic kidney disease is not listed as a contraindication in the FDA-approved label for apixaban, the NCCN Panel acknowledges that there are insufficient observational data to support safe apixaban dosing in these patients, especially those who are on hemodialysis.
• Footnote l added: Warfarin is the preferred anticoagulant for most patients with APS. This is particularly true in patients with triple-positive APS or lupus inhibitors/anticoagulants but it has also been seen in patients with in single-and double-positive disease. DOACs should be used with caution (Knight JS, et al. BMJ. 2023:380:e069717).

VTE-D (5 of 7)

• DOACs and GI Tract Surgery Considerations
  • Bullet 1 modified: DOACs are absorbed primarily in the stomach and proximal small bowel (with the exception of apixaban, which is also partially absorbed in the distal small bowel and proximal colon), so they may not be appropriate for patients who have had significant resections of these portions of the intestinal tract. The table below provides absorption guidance following GI surgical interventions based on available data.
  • Bullet 2 added: Retrospective cohort studies of patients who had bariatric and cancer GI surgery support the conclusion that apixaban drug levels are more likely to remain in the expected peak on treatment range than rivaroxaban after gastric or proximal small bowel resections. Dabigatran drug levels were below the peak on therapy range. Limited information is available for edoxaban but in the few patients studied, drug levels were in the expected peak on treatment range.
  • Bullet 3 modified: Although uncertainty remains about the association of drug levels and clinical outcomes, we recommend considering drug levels in patients taking DOACs post-GI tract surgery.Due to limited data, consider checking a drug-specific anti-Xa level for Xa-inhibitors or a dabigatran level to ensure adequate absorption.

VTE-G (1 of 3)

• Column 2, bullet added: Consider HIT and APS testing
• Subtherapeutic level, bullet 2 added: Consider drug-drug interactions, especially for DOACs
• Therapeutic level, consideration removed: Consider HIT and antiphospholipid syndrome (APS) testing
• Footnote b modified: Conditions associated with venous stasis such as vascular compression by tumors or lymphatic masses or stasis associated with IVC filters can cause recurrent thrombosis despite therapeutic anticoagulation. Uncontrolled myeloproliferative neoplasms or paroxysmal nocturnal hemoglobinuria can also be responsible for this phenomenon. Relief of vascular stasis or treatment of MPN/PNH can reduce the risk of recurrence.

VTE-G (2 of 3)

• UFH, adjustment bullet 2 added: In patients with lupus inhibitor/anticoagulant or prolonged baseline aPTT, UFH anti-Xa level should be used for dose titration
• Warfarin, adjustment bullet 1 modified: Goal 2–3 if baseline INR is normal
• Warfarin, adjustment bullet 2 added: In patients with prolonged baseline PT/INR or lupus inhibitor/anticoagulant, target INR range should be confirmed with factor X activity or chromogenic factor X activity, respectively

VTE-G (3 of 3)

• UFH, alternative anticoagulant, bullet 1 added: Confirm therapeutic aPTT with UFH anti-Xa level
• UFH, alternative anticoagulant, bullet 3 modified: Increase dose of UFH. Use UFH anti-Xa levels to titrate UFH (in the event of recurrence in setting of subtherapeutic anti-Xa levels).
• Warfarin, alternative anticoagulant, bullet 1 added: If factor X activity or chromogenic factor X activity is low despite therapeutic PT/INR, increase dose of warfarin and titrate to PT/INR range based upon therapeutic factor X or chromogenic factor X activity
• Apixaban, alternative anticoagulant, bullet modified: Switch to LMWH, UFH, fondaparinux (Also for dabigatran, edoxaban, rivaroxaban)
• Footnote f added: Ensure taking with largest meal of the day to promote absorption.

VTE-I

• Contraindications to thrombolysis, absolute sub-bullet 1 modified: History of hemorrhagic stroke or stroke of unknown origin intracranial hemorrhage
• Indications for thrombolysis, bullet 2 modified: Severely symptomatic iliofemoral thrombosis (select patients)

VTE-K (1 of 8)

• Bullet 3
  • Reversal of anticoagulation agent removed: Desmopressin (DDAVP)
  • Reversal of anticoagulation agent removed: Fresh frozen plasma (FFP)
• Precautions/additional considerations, bullet 1 modified: Protamine can cause anaphylaxis if administered too rapidly. Protamine can also cause significant hypotension, bradycardia, and pulmonary hypertension, so monitor blood pressure, heart rate, and oxygenation closely during administration.

VTE-K (2 of 8)

• DTI, reversal of anticoagulation
  • Bullet 2, sub-bullet added: Monitor reversal with aPTT.
  • Bullet 2, sub-bullet removed: DDAVP 0.3 mcg/kg reduced bleeding in animal and ex-vivo models, and if used should be administered over 15–30 minutes.
• Argatroban, reversal of anticoagulation
  • Bullet 2, sub-bullet removed: DDAVP (0.3 mcg/kg) reduced bleeding in animal and ex-vivo models.
• Precautions/additional considerations, bullet 2 removed: Repeated doses (more than 3 or 4) of DDAVP are associated with tachyphylaxis and hyponatremia.

VTE-K (4 of 8)

• Reversal of anticoagulation
  • Bullet 2, sub-bullet 2 removed: Alternative options may include: PCC
    • Sub-sub-bullet removed: aPCC 25–50 units/kg IV

VTE-K (6 of 8)

• Warfarin management of urgent surgery
  • Reversal of anticoagulation
    • Within 24 hours, bullet 3 modified: Repeat INR preoperative to determine need for supplemental FFP PCC
    • Within 48 hours, bullet 3 modified: Repeat INR at 24 and 48 hours to assess need for supplemental vitamin K1 or FFP PCC
  • Precautions/additional considerations
    • Bullet removed: Excessive intravascular volume (FFP
    • Bullet removed: Transfusion-related acute lung injury (FFP)
    • Bullet removed: Pulmonary edema (FFP)
    • Bullet removed: Agglutination reactions/hemolysis due to blood-type incompatibility (FFP)
    • Bullet removed: Transfusion-associated graft-versus-host disease (if not irradiated FFP)
    • Bullet removed: Febrile nonhemolytic transfusion reactions (FFP)
• Note modified: §Prescribing information for coagulation factor Xa (recombinant), inactivated-zhzo. Lyophilized powder for solution for intravenous injection 2022. Available at: https://www.fda.gov/media/113279/download. Refer to package insert for full prescribing information: https://www.accessdata.fda.gov/scripts/cder/daf/ (Also for VTE-K 7 of 8)

PMA-A

• Table 1: Spinal injections moved from low to moderate risk.

HIT-2

• Additional recommendations for patients with confirmed HIT
  • Bullet 3 added: Intravenous immunoglobulin has been shown to be effective in patients with refractory HIT as well as autoimmune HIT. It is also a useful treatment for patients at high risk of bleeding who have HIT.

HIT-B

• Therapeutic option added: Intravenous Immunoglobulin (refractory HIT, autoimmune HIT, or patients at high risk of bleeding who have HIT)
  • Bullet 1 added: 1 g/kg IV daily x2

 

 

 

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