In an 81‑year‑old man with a history of basal cell carcinoma resection, aortic valve replacement (AVR) on apixaban (Eliquis) 2.5 mg twice daily, atrial fibrillation (AF) post‑ablation, hypertension (HTN), obstructive sleep apnea (OSA) treated with Inspire, chronic alcohol use, thrombocytopenia, former smoker (22 pack‑years, quit >45 years ago), possible chronic obstructive pulmonary disease (COPD) requiring intermittent home oxygen, and ankylosing spondylitis who recently underwent a minimally invasive (MIS) L3–S1 transforaminal lumbar interbody fusion (TLIF), what is the recommended diagnostic work‑up for his new‑onset anemia and persistent thrombocytopenia?

Diagnostic Work-Up for New-Onset Anemia and Persistent Thrombocytopenia Post-Spinal Fusion

In this 81-year-old man with recent major spinal surgery, chronic alcohol use, and baseline thrombocytopenia, the recommended work-up should prioritize distinguishing perioperative blood loss and hemodilution from underlying hematologic disorders, while recognizing that his chronic alcohol use and possible myelosuppression require systematic evaluation.

Immediate Laboratory Assessment

Obtain the following baseline studies to characterize the cytopenias:

• Complete blood count with differential and reticulocyte count to assess bone marrow erythropoietic response and identify the degree of anemia and thrombocytopenia 1, 2
• Peripheral blood smear to detect abnormal cell morphology, hemolysis, or dysplastic features that may suggest myelodysplastic syndrome or other bone marrow pathology 2, 3
• Iron studies (serum iron, total iron binding capacity, transferrin saturation, and ferritin) performed now to establish baseline, recognizing that ferritin may be falsely elevated in the acute postoperative inflammatory state 1, 4
  • Transferrin saturation <20% and ferritin <100 ng/mL indicate iron deficiency 1, 4
  • In surgical patients, iron deficiency is responsible for 40-50% of anemia cases 1

Perioperative Blood Loss Assessment

Evaluate for surgical blood loss and hemodilution:

• Review intraoperative records for estimated blood loss during the L3-S1 TLIF procedure and any intraoperative transfusions 1
• Assess for ongoing bleeding by monitoring hemoglobin trends, examining surgical drains if present, and checking stool guaiac 1
• Postoperative anemia is associated with myocardial injury, type 2 MI, and mortality proportional to the lowest hemoglobin concentration 1

Alcohol-Related and Nutritional Deficiency Evaluation

Given chronic alcohol use, screen for nutritional deficiencies and direct marrow toxicity:

• Serum vitamin B12 and folate levels to identify deficiencies that can blunt erythropoiesis and cause macrocytic anemia 1, 3
• Liver function tests to assess for cirrhosis-related hypersplenism or synthetic dysfunction 1
• Inflammatory markers (CRP, ESR) if functional iron deficiency is suspected (elevated ferritin with low transferrin saturation) 3

Thrombocytopenia-Specific Work-Up

Distinguish between dilutional, consumptive, and production defects:

• Review baseline platelet counts prior to surgery to determine if thrombocytopenia is new or chronic 2
• Assess for medication-induced thrombocytopenia by reviewing all medications, particularly apixaban, though direct oral anticoagulants do not typically cause thrombocytopenia 1, 2
• Consider heparin-induced thrombocytopenia (HIT) if the patient received heparin perioperatively, though timing (typically 5-10 days post-exposure) may not fit 2
• Severe thrombocytopenia is defined as platelet count <25,000/mm³ requiring more aggressive management 2

Bone Marrow Evaluation Criteria

Proceed to bone marrow biopsy if:

• Cytopenias persist beyond 4-6 weeks postoperatively without clear etiology 2
• Peripheral smear shows dysplastic features or unexplained abnormalities 2, 3
• Multiple cell lines are affected (bicytopenia or pancytopenia) suggesting primary marrow pathology 2
• Chronic alcohol use raises concern for myelodysplastic syndrome, which requires persistent cytopenia for 4-6 months unless accompanied by specific karyotype or bilineage dysplasia 2

Hemolysis and Coagulopathy Assessment

If anemia is disproportionate to surgical blood loss:

• Hemolysis panel: Coombs test, haptoglobin, indirect bilirubin, LDH 1
• Disseminated intravascular coagulation (DIC) panel: PT/INR, aPTT, fibrinogen, D-dimer if clinical suspicion exists 1

Apixaban Management Considerations

Address anticoagulation in the context of recent surgery and bleeding risk:

• Apixaban 2.5 mg BID is the appropriate dose for this patient given his age ≥80 years and body weight considerations per drug labeling 1
• Do not attribute thrombocytopenia to apixaban as direct oral anticoagulants do not cause immune-mediated thrombocytopenia 1
• If major bleeding occurs, consider four-factor prothrombin complex concentrate or andexanet-alpha for life-threatening bleeding, though availability may be limited 1
• Blood transfusion may be considered if hemoglobin <8 g/dL or hematocrit <25% with compromised hemodynamic status 1

Timing of Iron Studies Re-Assessment

Critical pitfall to avoid:

• Do not recheck ferritin within 4 weeks of any IV iron administration if given, as falsely elevated levels will not reflect true iron stores 4, 3
• Optimal laboratory window is 4-8 weeks after the final iron dose to obtain accurate ferritin and transferrin saturation values 4, 3

Transfusion Thresholds in This High-Risk Patient

Given AVR, atrial fibrillation, and cardiovascular disease:

• A restrictive transfusion threshold of 8 g/dL is recommended for orthopedic surgery patients and those with cardiovascular disease 1
• Transfusion decisions should not be based solely on hemoglobin triggers but must account for symptoms, comorbidities (AVR, AF, HTN, possible COPD), and hemodynamic stability 1
• Symptomatic patients should receive transfusion; asymptomatic patients with significant cardiovascular comorbidities should have transfusion considered 1

When to Refer Back to Hematology

Specific indications for ongoing hematology involvement:

• Unexplained cytopenias after initial work-up is complete 2
• Persistent cytopenia without obvious cause (surgical blood loss, hemodilution, nutritional deficiency) 2
• Thrombocytopenia where medication-related destruction or disease progression cannot be identified 2
• Need for bone marrow biopsy to evaluate for myelodysplastic syndrome or other primary marrow disorders 2, 3

Common Pitfalls to Avoid

• Assuming all postoperative anemia is simple blood loss; lack of appropriate reticulocyte response after adequate time mandates broader work-up 3
• Measuring ferritin too early in the postoperative inflammatory state produces falsely high results and misguides treatment decisions 4, 3
• Overlooking alcohol-related marrow suppression and nutritional deficiencies (B12, folate) that are highly prevalent in chronic alcohol users 1
• Delaying specialist follow-up when hemoglobin remains <9 g/dL or thrombocytopenia persists, as timely hematology input improves outcomes 2, 3