2 Diagnosis of PV

10 to 20% MF transformation at 15-20 years of follow-up
2-5% blast phase, fundamentally altered prognosis
Thrombosis leading cause of morbidity even in well-controlled patients

Code

library(tidyverse)

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Code

library(gt)
library(kableExtra)


Attaching package: 'kableExtra'

The following object is masked from 'package:dplyr':

    group_rows

The diagnosis of PV previously required isotopic dilution studies to demonstrate a true polycythaemia and exclude relative polycythaemia (elevation of the Hb because of reduction of plasma volume).
Following the discovery that almost all patients with PV have a detectable acquired JAK2 mutation, providing evidence of a clonal bone marrow disorder, the importance of estimating the red cell mass has greatly declined.

2.1 Incidence of PV

The incidence is increased after treatment of thyroid cancer (possibly resulting from irradiation) and also after the occurrence of parathyroid adenoma or melanoma
a familial predisposition, sometimes attributable to a gain‐of‐function mutation in EPOR

2.2 Symptoms of PV

Pruritus can occur, probably consequent on histamine secretion by basophils.

2.3 Bone Marrow Morphology

2.4 # WHO 2022 Diagnostic Criteria for Polycythemia Vera

Code

# Create diagnostic criteria table
pv_criteria <- tribble(
  ~Category, ~Criterion, ~Details,
  "Major 1", "Erythrocytosis", "Hemoglobin >16.5 g/dL OR Hematocrit >49% (men)\nHemoglobin >16.0 g/dL OR Hematocrit >48% (women)\n\nOR Sustained absolute erythrocytosis:\nHemoglobin ≥18.5 g/dL OR Hematocrit ≥55.5% (men)\nHemoglobin ≥16.5 g/dL OR Hematocrit ≥49.5% (women)",
  
  "Major 2", "Bone Marrow Histology", "Hypercellularity for age with trilineage growth (panmyelosis)\nIncluding:\n• Prominent erythroid proliferation\n• Granulocytic proliferation\n• Megakaryocytic proliferation with pleomorphic, mature megakaryocytes",
  
  "Major 3", "Molecular", "Presence of JAK2 V617F mutation (exon 14)\nOR\nJAK2 exon 12 mutation",
  
  "Minor", "Erythropoietin", "Subnormal serum erythropoietin (EPO) level"
)

# Display as formatted table
pv_criteria %>%
  gt() %>%
  tab_header(
    title = "WHO 2022 Diagnostic Criteria for Polycythemia Vera"
  ) %>%
  cols_label(
    Category = "Category",
    Criterion = "Type",
    Details = "Criteria"
  ) %>%
  tab_style(
    style = cell_text(weight = "bold"),
    locations = cells_column_labels()
  ) %>%
  tab_style(
    style = cell_fill(color = "#E8F4F8"),
    locations = cells_body(rows = Category %in% c("Major 1", "Major 2", "Major 3"))
  ) %>%
  tab_style(
    style = cell_fill(color = "#FFF4E6"),
    locations = cells_body(rows = Category == "Minor")
  ) %>%
  fmt_markdown(columns = Details)

Category	Type	Criteria
WHO 2022 Diagnostic Criteria for Polycythemia Vera
Major 1	Erythrocytosis	Hemoglobin >16.5 g/dL OR Hematocrit >49% (men) Hemoglobin >16.0 g/dL OR Hematocrit >48% (women) OR Sustained absolute erythrocytosis: Hemoglobin ≥18.5 g/dL OR Hematocrit ≥55.5% (men) Hemoglobin ≥16.5 g/dL OR Hematocrit ≥49.5% (women)
Major 2	Bone Marrow Histology	Hypercellularity for age with trilineage growth (panmyelosis) Including: • Prominent erythroid proliferation • Granulocytic proliferation • Megakaryocytic proliferation with pleomorphic, mature megakaryocytes
Major 3	Molecular	Presence of JAK2 V617F mutation (exon 14) OR JAK2 exon 12 mutation
Minor	Erythropoietin	Subnormal serum erythropoietin (EPO) level

Code

# Diagnostic algorithm
diagnostic_rules <- tibble(
  Rule = c("Standard Diagnosis", "Alternative Diagnosis", "Bone Marrow Waiver"),
  Requirements = c(
    "ALL 3 Major Criteria",
    "First 2 Major Criteria + Minor Criterion",
    "If sustained absolute erythrocytosis* present:\nMajor 3 + Minor Criterion may be sufficient\n(bone marrow biopsy not required)"
  ),
  Note = c(
    "Most comprehensive approach",
    "When EPO is low",
    "*Hgb ≥18.5 (M) or ≥16.5 g/dL (F)\nHct ≥55.5% (M) or ≥49.5% (F)"
  )
)

diagnostic_rules %>%
  gt() %>%
  tab_header(
    title = "Diagnostic Algorithm"
  ) %>%
  cols_label(
    Rule = "Diagnostic Path",
    Requirements = "Criteria Required",
    Note = "Comments"
  ) %>%
  fmt_markdown(columns = everything())

Diagnostic Path	Criteria Required	Comments
Diagnostic Algorithm
Standard Diagnosis	ALL 3 Major Criteria	Most comprehensive approach
Alternative Diagnosis	First 2 Major Criteria + Minor Criterion	When EPO is low
Bone Marrow Waiver	If sustained absolute erythrocytosis* present: Major 3 + Minor Criterion may be sufficient (bone marrow biopsy not required)	*Hgb ≥18.5 (M) or ≥16.5 g/dL (F) Hct ≥55.5% (M) or ≥49.5% (F)

Code

# Key clinical notes

cat("\n## Important Clinical Notes\n\n")


## Important Clinical Notes

Code

cat("• >95% of PV patients harbor JAK2 V617F mutation (exon 14)\n")

• >95% of PV patients harbor JAK2 V617F mutation (exon 14)

Code

cat("• ~3% have JAK2 exon 12 mutations (in JAK2 V617F-negative cases)\n")

• ~3% have JAK2 exon 12 mutations (in JAK2 V617F-negative cases)

Code

cat("• Serum EPO is subnormal in >85% of PV patients\n")

• Serum EPO is subnormal in >85% of PV patients

Code

cat("• Bone marrow biopsy can detect initial myelofibrosis (present in up to 20%)\n")

• Bone marrow biopsy can detect initial myelofibrosis (present in up to 20%)

Code

cat("• WHO 2022 removed red cell mass measurement requirement\n")

• WHO 2022 removed red cell mass measurement requirement

Code

cat("• ~2.6% of PV patients may present with Hct/Hgb below WHO thresholds ('early-stage' PV)\n")

• ~2.6% of PV patients may present with Hct/Hgb below WHO thresholds ('early-stage' PV)