48‑year‑old man with severe anemia, profound thrombocytopenia, low reticulocyte count, high ferritin, low serum iron, normal renal and hepatic function, on aspirin (acetylsalicylic acid) and chronic intracerebral hemorrhage—what is the likely etiology and how should he be acutely managed?

Acute Management of Bone Marrow Failure with Life-Threatening Cytopenias

This patient requires immediate hematology consultation and urgent packed red blood cell (PRBC) and platelet transfusion for life-threatening pancytopenia (Hgb 73 g/L, platelet count 6,000/mm³) with high risk of catastrophic bleeding given his history of chronic intracerebral hemorrhage. 1

Likely Etiology: Primary Bone Marrow Disorder

The constellation of findings strongly suggests bone marrow failure syndrome (likely myelodysplastic syndrome or aplastic anemia):

• Severe pancytopenia: Profound anemia (Hgb 73 g/L), critical thrombocytopenia (6,000/mm³), and absent differential counts 1
• Inappropriately low reticulocyte count (0.23%): Indicates inadequate bone marrow response to severe anemia, ruling out hemolysis or acute blood loss as primary etiology 1
• High ferritin (635 ng/mL) with normal serum iron: This pattern excludes simple iron deficiency and suggests anemia of chronic disease or primary bone marrow pathology 2, 3
• Negative H. pylori: Rules out infectious contribution to UGIB 2

This is NOT primarily aspirin-induced UGIB with secondary anemia. While aspirin may have contributed to bleeding, the profound pancytopenia with bone marrow failure (reticulocyte count 0.23%) indicates the primary problem is hematologic malignancy or severe aplastic anemia 1.

Immediate Life-Saving Interventions (Within Hours)

1. Transfusion Therapy

Transfuse PRBCs immediately to prevent cardiovascular collapse and cerebral hypoxia:

• Target Hgb >70-80 g/L initially, given chronic intracerebral hemorrhage risk 2
• Transfuse slowly (over 3-4 hours per unit) to avoid volume overload 2

Transfuse platelets emergently given catastrophic thrombocytopenia with prior ICH:

• Target platelet count >50,000/mm³ (higher threshold due to ICH history) 4
• Continuous platelet support will likely be needed 4
• Monitor closely for signs of new intracranial bleeding 4

2. Stop All Antiplatelet Agents

Discontinue aspirin immediately 2—while aspirin may have contributed to UGIB, the primary issue is bone marrow failure, not drug-induced bleeding.

3. Urgent Hematology Consultation

Refer to hematology within 24 hours for unexplained cytopenias to exclude myelodysplastic syndrome or aplastic anemia 1. The hematologist will:

• Perform peripheral blood smear to assess for dysplastic features, blasts, or abnormal morphology 1
• Arrange bone marrow biopsy urgently, as peripheral findings strongly suggest primary marrow pathology 1
• Rule out hemolysis with haptoglobin, LDH, and indirect bilirubin (though low reticulocyte count makes this unlikely) 1

Diagnostic Workup (Parallel to Resuscitation)

Essential Studies to Order Now:

• Vitamin B12 and folate levels: Severe folate deficiency can cause acute thrombocytopenia and pancytopenia, though typically with macrocytosis 5
• Peripheral blood smear: Look for dysplastic cells, blasts, schistocytes 1
• LDH, haptoglobin, indirect bilirubin: Rule out hemolysis despite low reticulocyte count 1
• Viral serologies: HIV, hepatitis B/C, parvovirus B19, EBV, CMV (can cause marrow suppression) 2
• Flow cytometry on peripheral blood: Screen for paroxysmal nocturnal hemoglobinuria or leukemia 1

Critical Pitfalls to Avoid

1. Do NOT give iron supplementation despite anemia—high ferritin (635 ng/mL) indicates iron overload risk, not deficiency 2. Iron will not improve anemia from bone marrow failure 2.

2. Do NOT delay transfusion waiting for diagnostic workup—this patient is at imminent risk of death from anemia/bleeding 2, 1.

3. Do NOT assume this is simple UGIB-related anemia—the pancytopenia with bone marrow failure (reticulocyte 0.23%) indicates primary hematologic disease 1.

4. Do NOT use ESAs (erythropoietin) in this setting—they are ineffective in bone marrow failure and contraindicated with history of stroke/ICH 2.

5. Monitor for transfusion-related complications: Given likely need for chronic transfusions, assess for alloantibodies and consider leukoreduced/irradiated products if transplant candidate 2.

Prognosis and Next Steps

Bone marrow biopsy is diagnostic priority after stabilization 1. If myelodysplastic syndrome is confirmed, treatment options include:

• Supportive transfusions 2
• High-dose ESAs (30,000-60,000 IU/week) in select MDS cases, though contraindicated here due to ICH history 2
• Hematopoietic stem cell transplantation if eligible 2

If aplastic anemia, consider immunosuppressive therapy or transplantation 4.

The chronic intracerebral hemorrhage significantly complicates management, as both severe anemia and thrombocytopenia increase rebleeding risk 4. Neurosurgical consultation may be warranted if clinical deterioration occurs 4.