Suspected Reactive Marrow Fibrosis (MF3) Following Evolocumab Exposure

Discordant findings: MF-3 histology with no clonal mutation and recovering blood counts
1. Patient Information
Patient: 73-year-old Asian individual with hypercholesterolemia and statin intolerance. No prior
hematologic disease, autoimmune disease, or malignancy. Baseline blood counts normal prior to
Evolocumab.
2. Suspected Drug
Drug: Evolocumab (Repatha®), Amgen Inc., subcutaneous injection, standard dosing. No concurrent
lipid-lowering therapy.
3. Clinical Course
Initial exposure (Dec 2024–Jul 2025) resulted in severe thrombocytopenia (nadir ~19×10^9/L) and
anemia, requiring hospitalization. No malignancy detected. Splenectomy performed Sept 2025 with
rapid normalization of counts. Rechallenge Jan 2026 resulted in recurrent cytopenia within 4–6 weeks,
again resolving partially upon drug discontinuation.
4. Hematology Timeline
Date Repatha Hb Platelets Notes
Dec 2024 Started 126 195 Baseline
Jul 2025 On ↓ 19 Severe cytopenia
Sep 2025 Stopped - - Splenectomy
Nov 2025 Off 129 197 Recovered
Jan 2026 Off 125 153 Pre-rechallenge
Feb 2026 On 109 133 Decline begins
Apr 2026 On 84 51 Drug stopped
May 12 2026 Off 88 54 Recovery phase
May 19 2026 Off 84 48 Stable plateau
5. Bone Marrow Findings
Bone marrow biopsy (May 2026): Reticulin fibrosis MF-3, collagen fibrosis grade 0. Megakaryocytes
reduced but without clustering or atypia. Flow cytometry normal. JAK2/CALR/MPL mutations negative.
6. Clinical Interpretation
Overall pattern suggests drug-associated, splenic-dependent cytopenia with secondary/reactive
marrow fibrosis rather than primary myeloproliferative neoplasm. Recovery trend supports reversible
process.
7. Key Questions for Expert Consultation
- Is MF-3 with collagen 0 indicative of reversible fibrosis?
- Is reactive fibrosis consistent with improving platelet trend?
- Should JAK inhibitor therapy be deferred in absence of clonal mutation