Essential thrombocythemia

Clonal platelet overproduction; JAK2/CALR/MPL (10–20% triple-negative → marrow biopsy). Symptoms: often asymptomatic; vasomotor symptoms, TIAs, ocular migraines, 1st-trimester loss.

ASK: "Differential for thrombocytosis?" Reactive (iron-deficiency anemia — commonly missed; infection/inflammation; post-splenectomy) vs primary (the 4 MPNs).

Pearl: Platelet count magnitude does NOT predict thrombosis — don't reflexively start aspirin for reactive thrombocytosis.

Polycythemia vera

Most common MPN; erythrocytosis (± leukocytosis/thrombocytosis); >95% JAK2 V617F. Suspect with Hgb >16.5 (M)/>16.0 (F), 25% rise in RBC mass, or thrombosis. Symptoms: aquagenic pruritus, headache, thrombosis, bleeding (acquired vWD), TIA/ocular migraine.

Pearl: Splanchnic-vein thrombosis (Budd-Chiari, portal/splenic/mesenteric) should trigger a PV hunt — portal hypertension can mask the lab signs.

ASK: "Walk the erythrocytosis differential by EPO level." Build the EPO physiology (hypoxia → renal EPO → marrow RBCs), then:

Type	Primary problem	Examples	EPO
Relative	Hemoconcentration	Diuretics, vomiting, diarrhea (dehydration)	Normal
Secondary	Hypoxia or ↑EPO	COPD/OSA, altitude, renal artery stenosis; EPO-secreting tumor (HCC, RCC, pheo)	High
PV	Marrow (autonomous)	JAK2 V617F	Low (normal in ~15%)

Primary myelofibrosis

Marrow replaced by fibrosis → extramedullary hematopoiesis; JAK2/CALR/MPL; can evolve from PV or ET. Hepatosplenomegaly, bone pain, cytopenias. Classic findings: teardrop cells (dacrocytes) on smear, "dry tap" with megakaryocyte hyperplasia on biopsy.

Chronic myeloid leukemia

Mature granulocyte excess; BCR-ABL1 (Philadelphia chromosome, t(9;22)) → ↑tyrosine kinase activity; low LAP score. Chronic phase (85% at dx) → accelerated → blast crisis.

ASK: "Differential for leukocytosis?" Leukemoid reaction (infection, stress, meds, tobacco) vs malignancy. Suspicious for CML: neutrophilia with left shift, basophilia, eosinophilia, constitutional symptoms, splenomegaly; WBC can exceed 100k but leukostasis is rare (vs acute leukemia).

ASK: "Sort the four leukemias on smear and marrow." Use the board's table:

	AML	CML	ALL	CLL
Smear	Myeloblasts, Auer rods	Eosinophilia/basophilia, median WBC 100k	Lymphoblasts	Lymphocytosis, smudge cells
Marrow	>20% myeloblasts	Granulocytic hyperplasia, <20% blasts	>20% lymphoblasts	Lymphocytic hyperplasia
Demographic	Adults > children	Median age 50	Children > adults	Median age 70
Unique	DIC (esp. APL)	t(9;22) BCR-ABL1	LN/CNS infiltration (LP before tx)	Richter transformation, autoimmune cytopenias