What is the best management approach for a 50-year-old female with a history of stroke on Eliquis (apixaban), experiencing menorrhagia-induced anemia, thrombocytosis, and active hepatitis C infection with elevated liver enzymes?

Management of Complex Case: Stroke Patient on Anticoagulation with Menorrhagia-Induced Anemia, Thrombocytosis, and Active Hepatitis C

The priority is to treat the hepatitis C with modern direct-acting antivirals (DAAs) while continuing Eliquis, addressing the menorrhagia with gynecologic intervention, and correcting the iron deficiency anemia—the thrombocytosis will resolve with iron repletion and does not require specific treatment.

Immediate Management Priorities

1. Hepatitis C Treatment

• Initiate DAA therapy immediately using pangenotypic regimens (sofosbuvir/velpatasvir or glecaprevir/pibrentasvir) as these are highly effective, well-tolerated, and do not cause the severe anemia associated with older interferon-based regimens 1.

• The mildly elevated transaminases (AST 43, ALT 40) indicate active hepatitis but preserved liver function, making this an ideal time for treatment 1.

• Continue Eliquis during HCV treatment as modern DAAs do not have significant drug interactions with apixaban and the bleeding risk from anticoagulation does not contraindicate HCV therapy 1.

• Avoid older interferon/ribavirin-based regimens entirely, as ribavirin causes severe hemolytic anemia that would be catastrophic in a patient already anemic with a history of stroke requiring anticoagulation 1.

2. Anemia Management

• Characterize the anemia type by checking iron studies (ferritin, transferrin saturation), B12, folate, and reticulocyte count to confirm iron deficiency from menorrhagia 1.

• Initiate intravenous iron replacement (iron sucrose or ferric carboxymaltose) rather than oral iron, as IV iron provides faster correction and better tolerability in severe anemia 2, 3.

• The hemoglobin of 9.2 g/dL is stable but symptomatic management may be needed—transfusion is only indicated if hemoglobin drops below 7.5 g/dL or if there are clinical symptoms of hemodynamic compromise 1.

• Do not reduce or discontinue Eliquis for stable anemia at this level, as the stroke prevention benefit outweighs bleeding risk when hemoglobin is >7-8 g/dL 4.

3. Thrombocytosis Management

• The elevated platelet count (558) is reactive thrombocytosis secondary to iron deficiency anemia and will normalize with iron repletion—this is well-documented in the literature 2, 3, 5, 6.

• While thrombocytosis with iron deficiency has been associated with thrombotic events including stroke in case reports, the patient is already adequately anticoagulated with Eliquis 5, 6, 7.

• No additional antiplatelet therapy is needed as the patient is on therapeutic anticoagulation, and adding aspirin would significantly increase bleeding risk, particularly with ongoing menorrhagia 4.

• Monitor platelet count monthly—expect normalization within 2-3 months of iron repletion 2, 3.

4. Menorrhagia Control

• Urgent gynecology referral is essential to address the source of ongoing blood loss and prevent recurrent anemia 1.

• Consider hormonal management (levonorgestrel IUD, combined oral contraceptives if no contraindications) or procedural interventions (endometrial ablation, hysterectomy if appropriate) 3.

• The menorrhagia must be controlled to prevent ongoing iron loss and allow successful anemia correction while maintaining anticoagulation 2, 3.

Monitoring Protocol

• Weekly CBC until hemoglobin stabilizes and begins rising, then every 2-4 weeks until normalized 1.

• Monthly liver function tests during HCV treatment to monitor for any hepatotoxicity 1.

• Iron studies (ferritin, transferrin saturation) at 4-6 weeks to assess response to IV iron and guide continued supplementation 1.

• HCV RNA at week 4 and week 12 post-treatment to confirm sustained virologic response 1.

• Platelet count monitoring monthly—expect decline toward normal as iron deficiency resolves 2, 3.

Critical Pitfalls to Avoid

• Never use interferon-based HCV regimens in this patient—the ribavirin-induced hemolytic anemia would be life-threatening given her baseline anemia and anticoagulation 1.

• Do not discontinue Eliquis due to menorrhagia or anemia unless there is active life-threatening bleeding—premature discontinuation dramatically increases stroke risk 4.

• Do not treat the thrombocytosis as a primary disorder—it is reactive to iron deficiency and will resolve with iron repletion; unnecessary antiplatelet therapy would increase bleeding risk 2, 3, 5.

• Avoid oral iron as monotherapy in severe iron deficiency with ongoing losses—IV iron provides superior and faster repletion 2, 3.

• Do not delay HCV treatment waiting for anemia correction—modern DAAs are safe in anemic patients and do not worsen anemia like older regimens 1.

Specific Treatment Algorithm

1. Day 1-7: Start IV iron infusion, obtain gynecology consultation, initiate DAA therapy for HCV, continue Eliquis
2. Week 2-4: Repeat IV iron if needed, implement gynecologic intervention for menorrhagia control, monitor CBC weekly
3. Week 4-12: Continue DAA therapy, transition to oral iron supplementation once ferritin >100 ng/mL and transferrin saturation >20%, monitor CBC every 2 weeks 1
4. Week 12+: Confirm HCV cure with SVR12, ensure hemoglobin normalized, verify platelet count returned to normal range 1