How to manage severe anemia in a patient with anaplastic large cell lymphoma (ALCL) and deep vein thrombosis (DVT) on apixaban (eliquis)?

Management of Severe Anemia in ALCL Patients on Apixaban for DVT

In patients with anaplastic large cell lymphoma and deep vein thrombosis on apixaban who develop severe anemia, you should continue apixaban while managing the anemia with red blood cell transfusion if hemoglobin is <7 g/dL (or <8-10 g/dL if symptomatic), as apixaban does not cause thrombocytopenia and can be safely continued during transfusion therapy. 1, 2, 3

Anticoagulation Management

Continue apixaban without interruption unless active bleeding is present. 1

• Apixaban is a preferred agent for cancer-associated thrombosis and does not require dose adjustment for anemia alone 1
• The 2023 ASCO guidelines specifically recommend apixaban as an alternative to LMWH for long-term anticoagulation in cancer patients with VTE, with at least 6 months of treatment required 1
• Apixaban does not interact with platelet factor 4 or cause immune-mediated platelet destruction, making it safe to continue during cytopenias 2
• The 2022 International guidelines confirm apixaban 10 mg twice daily for 7 days, then 5 mg twice daily, is appropriate for initial and long-term VTE treatment in cancer patients 1

Important caveat: Exercise caution if the patient has gastrointestinal or genitourinary malignancy involvement, as DOACs carry increased risk of clinically relevant non-major bleeding in these settings compared to LMWH 1

Anemia Management Algorithm

Step 1: Assess Severity and Symptoms

• Severe anemia with hemoglobin <7 g/dL: Transfuse regardless of symptoms 3, 4
• Hemoglobin 7-10 g/dL with symptoms (dyspnea, chest pain, tachycardia, orthostasis): Transfuse 3, 4
• Hemoglobin 7-10 g/dL without symptoms: Identify and treat underlying cause first 4

Step 2: Transfusion Strategy

• Use a restrictive transfusion threshold of <7 g/dL in hemodynamically stable patients without cardiac disease, as this approach reduces mortality, rebleeding, acute coronary syndrome, and infections 3
• Transfuse the minimum number of RBC units required to relieve symptoms or achieve hemoglobin >7 g/dL 3, 4
• Use leukocyte-reduced blood products for all cancer patients 1
• Irradiate all blood products if the patient is a potential stem cell transplant candidate 1
• Consider transfusing over 2-3 days in severely anemic patients to avoid volume overload 3

Step 3: Identify Underlying Cause

Evaluate for specific causes in ALCL patients:

• Bone marrow infiltration: Review bone marrow biopsy results from lymphoma staging 5, 6
• Chemotherapy-induced myelosuppression: Check timing relative to recent chemotherapy cycles 5, 7
• Nutritional deficiencies: Measure iron studies, vitamin B12, and folate levels 4
• Bleeding: Examine for occult gastrointestinal or genitourinary bleeding, particularly relevant given apixaban use 1
• Hemolysis: Check reticulocyte count, LDH, haptoglobin, and direct antiglobulin test 4

Step 4: Targeted Treatment Based on Cause

For iron deficiency (absolute or functional):

• Administer intravenous iron in cancer patients, as it is more effective than oral supplementation 4

For chemotherapy-related anemia:

• Consider erythropoiesis-stimulating agents (ESAs) if hemoglobin <10 g/dL in non-myeloid malignancies receiving chemotherapy 4
• Note: ESAs are not first-line; transfusion remains primary therapy for severe anemia 3, 4

For bone marrow infiltration:

• Optimize lymphoma-directed therapy (typically CHOP or CHOEP regimens for ALCL) 5, 6, 7
• Consider brentuximab vedotin in relapsed/refractory disease given high CD30 expression in ALCL 7

Monitoring During Concurrent Therapy

• Do not attribute thrombocytopenia to apixaban if it develops; investigate alternative causes including lymphoma progression, chemotherapy, or other drug effects 2
• Monitor hemoglobin every 3 days during active transfusion management 4
• Assess for signs of volume overload during transfusion, particularly in patients receiving multiple units 3
• Continue VTE prophylaxis monitoring for recurrent thrombosis symptoms 1

Special Considerations for ALCL

• ALK-positive ALCL has better prognosis than ALK-negative disease, but both require aggressive management of complications 5, 6
• Patients with multiple International Prognostic Index factors may have worse outcomes and require more intensive supportive care 5
• The combination of active lymphoma and anticoagulation creates competing risks that require careful balance 1

When to Consider Apixaban Interruption

Temporarily hold apixaban only if:

• Active major bleeding occurs (defined by ISTH criteria: fatal bleeding, symptomatic bleeding in critical area/organ, or bleeding causing fall in hemoglobin ≥2 g/dL or requiring ≥2 units transfusion) 1
• Emergency surgery or invasive procedure is required 1
• Platelet count falls below 50,000/mm³ (though this threshold is not well-established in guidelines, it represents standard clinical practice) 8

Resume anticoagulation as soon as bleeding is controlled or hemostasis is achieved post-procedure, as cancer patients remain at high risk for recurrent VTE 1