Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (353 page)

   Patients, especially females, with persistent thrombocytosis without an underlying cause, not meeting criteria for polycythemia vera, primary myelofibrosis, chronic myelogenous leukemia, myelodysplastic syndromes, or other myeloid neoplasms.

   Patients with unexplained splenomegaly.

   Patients with unexplained thrombosis or hemorrhages.

   No evidence of reactive thrombocytosis.

   Laboratory Findings

   
CBC
: sustained platelet count >450,000 (some recommend persistent elevated counts for ≥8 months).

   
Bone marrow biopsy
shows proliferation of the megakaryocytic lineage with increased numbers of enlarged, mature megakaryocytes; no increase and no left shift of granulopoiesis or erythropoiesis. Iron stores are normal.

   
Genetic test
: V617F JAK2 mutation can be demonstrated in about half the cases of ET; in its absence, reactive thrombocytosis should be ruled out, especially by demonstrating normal serum ferritin to exclude iron deficiency.

Cytogenetics
: No cytogenetic abnormalities are specific for ET. The incidence of clonal cytogenetic abnormalities is approximately 5–10%. Abnormalities include +8, +9, and 20q−. The absence of BCR-ABL1 (t[9;22]) must be documented to exclude CML.

Suggested Reading

Passamonti F, Thiele J, Girodon F, et al. A prognostic model to predict survival in 867 World Health Organization-defined essential thrombocythemia at diagnosis: a study by the International Working Group on Myelofibrosis Research and Treatment.
Blood.
2012;120:1197–1201.

PRIMARY MYELOFIBROSIS (PMF)

   Definition

PMF is a Philadelphia (Ph) chromosome–negative chronic myeloproliferative neoplasm (MPN) characterized by progressive bone marrow fibrosis, clonal proliferation of myeloid cells, and ineffective hematopoiesis. All patients have marked splenomegaly. It may follow transformation of PV or ET into myelofibrosis (no longer “primary”). PMF has a prefibrotic (initial) and a fibrotic stage. The prefibrotic stage is frequently difficult to diagnose. PMF is characterized by a leukoerythroblastic blood picture, teardrop poikilocytosis of red cells, and extramedullary hematopoiesis, with progressive hepatosplenomegaly. Other causes of marrow fibrosis must be excluded.

   Classification

   The WHO-proposed revision requires the presence of major and minor criteria:

   
Major criteria