原發性血小板增多症

Buzzwords → Dx

Diagnostic Criteria (WHO 5e)

Diagnosis requires all 4 majors OR first 3 majors + minor.

• Major:
  1. Plt ≥450 × 10⁹/L sustained.
  2. Marrow biopsy: megakaryocytic hyperplasia with mature, hyperlobulated megs; no significant erythroid/granulocytic increase, no relevant fibrosis.
  3. Not meeting WHO criteria for CML, PV, PMF, MDS, or other myeloid neoplasm.
  4. JAK2 V617F or CALR or MPL mutation.
• Minor: Clonal marker present (other than driver) or no evidence for reactive thrombocytosis.

Reactive thrombocytosis (rule out!)

• Iron deficiency, infection/inflammation (CRP, ESR), splenectomy/asplenia, surgery, malignancy, hemolysis. Only ~10 % of plt >450 in adults are clonal.

Workup

• CBC + smear, ferritin (rule out iron deficiency).
• JAK2 V617F, then CALR and MPL (sequential or panel).
• Marrow biopsy with reticulin staining (rule out pre-PMF).
• Karyotype (typically normal in ET).
• vWF panel (RCo, antigen, multimers) if plt >1000–1500.
• Cardiovascular risk assessment: HTN, DM, smoking, dyslipidemia.

Treatment Algorithm (per IPSET-thrombosis)

flowchart TD
  A[Confirmed ET] --> B[IPSET-thrombosis<br>age >60 = 1, JAK2 V617F = 2,<br>thrombosis hx = 2, CV risk = 1]
  B -- very low <2 --> C[Aspirin 81 mg ONCE daily<br>or observation if triple-neg + no CV risk]
  B -- low 2 --> D[Aspirin 81 mg]
  B -- intermediate 2-3 --> E[Aspirin + cytoreduction<br>esp. if JAK2+ or CV risk]
  B -- high ≥3 --> F[Aspirin + cytoreduction<br>± full anticoagulation if hx VTE]
  E --> G{Cytoreduction agent}
  F --> G
  G -- under 60 / fertility --> H[Pegylated interferon<br>or ropeginterferon]
  G -- ≥60 / standard --> I[Hydroxyurea 500-2000 mg/d]
  G -- HU-intolerant --> J[Anagrelide<br>or interferon switch<br>or ropeginterferon]
  I --> K{Plt >1500?<br>acquired vWD?}
  H --> K
  J --> K
  K -- yes --> L[Hold aspirin until plt <1000<br>cytoreduce first]

Pearls / Pitfalls

• CALR-mutated ET has the lowest thrombosis rate but the highest myelofibrosis transformation rate (CALR type 1 worse). Picking "JAK2 V617F is the lowest-risk genotype" is wrong.
• Hold aspirin if plt >1000–1500 until cytoreduced — acquired vWD consumes high-MW multimers → bleeding. Bleeding ≠ aspirin; check vWF panel.
• IPSET-thrombosis includes JAK2 V617F (2 pts) in addition to age >60 (1) and thrombosis hx (2) → "high-risk" is ≥3 (per revised IPSET-thrombosis).
• Hydroxyurea-resistance/intolerance criteria (ELN): plt >600 after 3 mo HU at ≥2 g/d, or HU-related cytopenias (ANC <1, Hb <10), or unacceptable mucocutaneous toxicity (leg ulcers, NMSC).
• Anagrelide is reserved for HU-intolerant ET — selective for megakaryocytes; AEs include palpitations, fluid retention, headache, and increased risk of MF transformation (vs HU per PT-1 trial).
• Aspirin twice daily may be considered for high-risk JAK2+ ET, esp. with microvascular events (small data).
• Pregnancy in ET: aspirin 81 mg/d; interferon if cytoreduction needed; LMWH if previous VTE; postpartum LMWH × 6 wk (high VTE risk).
• Acquired hemophilia / inhibitor screen in ET with bleeding without other cause (rare).
• Pre-PMF is the ET-mimic that's actually early PMF — needs reticulin staining + meg morphology to differentiate. Pre-PMF outcomes worse than true ET; manage as PMF if MF-1 fibrosis present.

Cross-references

• Cytogenetics Atlas — JAK2, CALR, MPL
• Drug Regimens — hydroxyurea, ropeginterferon, anagrelide
• PV — JAK2 contrast
• PMF — fibrotic MPN
• Acquired vWD
• VTE risk in MPN

相關題目

• Q-024 — PV/ET — extreme thrombocytosis and acquired vWD
• Q-026 — ET — IPSET-thrombosis risk stratification
• Q-027 — ET — driver mutation prognostic implications
• Q-028 — ET — anagrelide adverse effects

Sources