真性紅血球增多症

Buzzwords → Dx

Diagnostic Criteria (WHO 5e)

Diagnosis requires all 3 majors OR first 2 majors + minor.

• Major:
  1. Hb >16.5 g/dL (M) or >16 g/dL (F), or Hct >49 % (M) / >48 % (F), or RBC mass >25 % above predicted.
  2. Marrow biopsy: hypercellular for age with trilineage proliferation (panmyelosis), pleomorphic mature megakaryocytes.
  3. JAK2 V617F or JAK2 exon 12 mutation.
• Minor: Subnormal serum EPO.

Workup

• CBC + smear (no specific morphology), CMP, LDH, uric acid.
• Serum EPO (low / normal-low favors PV).
• JAK2 V617F PCR → if neg and high suspicion → JAK2 exon 12 sequencing.
• Marrow biopsy for criterion 2 + cytogenetics + reticulin grade (rule out pre-PMF / MPN-overlap).
• Abdominal US (splenomegaly, splanchnic vein patency).
• Cardiopulmonary review to exclude secondary causes (OSA, COPD, R-L shunt, EPO-secreting tumor).

Treatment Algorithm

flowchart TD
  A[Confirmed PV] --> B[Risk stratification<br>Age >60 OR thrombosis hx → high-risk]
  B -- low-risk --> C[Phlebotomy goal Hct <45<br>+ low-dose aspirin 81 mg]
  B -- high-risk --> D[+ cytoreduction]
  D --> E{First-line cytoreduction}
  E -- under 60 / fertility / preferred --> F[Ropeginterferon alfa-2b<br>PROUD-PV]
  E -- standard --> G[Hydroxyurea 500-2000 mg/d]
  G --> H{HU response by ELN criteria?}
  H -- intolerance/resistance --> I[Ruxolitinib<br>RESPONSE/RESPONSE-2]
  F --> J[Aspirin continued; phlebotomy as needed]
  G --> J
  I --> J
  J --> K{Late myelofibrosis?<br>blasts ≥10 % or peripheral leukoerythroblastosis}
  K -- yes --> L[Re-stage as post-PV MF<br>per PMF algorithm; ruxolitinib for splenomegaly<br>HCT in fit candidates]

Pearls / Pitfalls

• Hematocrit target <45 % in all PV patients — CYTO-PV showed lower MACE/thrombosis vs <50 %. Picking "Hct <50" is wrong.²
• Aspirin contraindicated in extreme thrombocytosis (plt >1500 × 10⁹/L) due to acquired vWD (high-MW vWF multimers consumed) → bleeding. Cytoreduce platelets first.
• JAK2 V617F may also appear in ET/PMF/CMML — disease defined by lineage involvement + marrow features, not the mutation alone.
• Ropeginterferon alfa-2b is now first-line cytoreduction for younger PV pts (preserves fertility, may reduce JAK2 allele burden over years). PROUD-PV / CONTINUATION-PV showed superior molecular response vs HU.
• Hydroxyurea side effects: macrocytosis, leg ulcers, skin/oral cancers (NMSC), no clear AML/MDS link in PV when used alone.
• Ruxolitinib (RESPONSE) for HU-resistant/intolerant PV → improves Hct control, splenomegaly, symptoms; watch for HSV/VZV reactivation, hyperlipidemia, weight gain.
• Pregnancy in PV: continue aspirin; phlebotomy to keep Hct <45 %; interferon if cytoreduction needed (HU and ruxolitinib teratogenic).
• Splanchnic vein thrombosis (Budd-Chiari, portal vein): anticoagulate + screen for JAK2 V617F even if CBC is normal (latent MPN).
• Late myelofibrosis: post-PV MF behaves like PMF; re-stratify with MYSEC-PM (post-PV/ET-specific) score.

Cross-references

• Cytogenetics Atlas — JAK2 V617F, exon 12
• Drug Regimens — hydroxyurea, ropeginterferon, ruxolitinib
• ET — JAK2/CALR/MPL contrast
• PMF — fibrotic phase MPN
• VTE — splanchnic thrombosis screening
• Acquired vWD in extreme thrombocytosis

相關題目

• Q-023 — PV — hematocrit target (CYTO-PV)
• Q-024 — PV/ET — extreme thrombocytosis and acquired vWD
• Q-025 — PV — Budd-Chiari syndrome and JAK2 screening
• Q-131 — High-affinity hemoglobin — distinguishing from PV

Sources