Essential thrombocythemia

Polycythemia (erythrocytosis) is a true increase in red cell mass that must be sorted into primary polycythemia vera, a JAK2-mutated myeloproliferative neoplasm with a low erythropoietin level, versus secondary erythrocytosis driven by hypoxia or ectopic erythropoietin, versus relative erythrocytosis from plasma volume contraction. Diagnosis rests on the hemoglobin threshold plus JAK2 V617F testing and a serum erythropoietin level, and management of polycythemia vera centers on therapeutic phlebotomy to a hematocrit target below 45%, low-dose aspirin, and cytoreduction in higher-risk patients.

Primary myelofibrosis is a BCR-ABL-negative myeloproliferative neoplasm driven by JAK2, CALR, or MPL mutations that produces marrow fibrosis, extramedullary hematopoiesis, massive splenomegaly, and a leukoerythroblastic smear with teardrop cells. Diagnosis rests on bone marrow biopsy showing fibrosis with a clonal marker or exclusion of reactive causes, and management is risk-stratified with the JAK inhibitor ruxolitinib for symptomatic disease and allogeneic transplant as the only cure.

Chronic myeloid leukemia is a myeloproliferative neoplasm driven by the Philadelphia chromosome t(9;22), which produces the constitutively active BCR-ABL1 tyrosine kinase and marked, left-shifted granulocytosis with a low leukocyte alkaline phosphatase score. Diagnosis is confirmed by cytogenetics or molecular testing for BCR-ABL1, and a BCR-ABL tyrosine kinase inhibitor such as imatinib is first-line, continued indefinitely with molecular-response monitoring, reserving allogeneic transplant for TKI failure or blast crisis.

Thrombocytopenia, a platelet count below 150,000/microL, is a laboratory finding rather than a single disease, so evaluation starts with the smear to exclude pseudothrombocytopenia and identify the can't-miss consumptive emergencies TTP, HIT, and DIC before working through production, destructive, and sequestration causes. Management treats the underlying cause, reserves platelet transfusion for bleeding or procedural thresholds, and specifically avoids platelet transfusion in TTP and HIT except for life-threatening hemorrhage.

Anemia is a hemoglobin below 12 g/dL in women or 13 g/dL in men, from underproduction, destruction, or loss of erythrocytes, never a final diagnosis in itself. The mean corpuscular volume (MCV) and reticulocyte count sort the differential, and management means treating the identified cause, iron or vitamin repletion, immunosuppression, or transfusion for symptomatic or severe disease.

Antiplatelet agents block platelet activation and aggregation to prevent arterial thrombosis. Aspirin irreversibly inhibits cyclooxygenase-1, and P2Y12 inhibitors such as clopidogrel, ticagrelor, and prasugrel block adenosine diphosphate-driven platelet activation. Aspirin 81 mg daily anchors secondary prevention, and dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor is first-line after acute coronary syndrome or coronary stenting.

Deep vein thrombosis or pulmonary embolism occurring in a patient with active malignancy, driven by tumor-derived procoagulant activity plus stasis and vascular injury. Diagnosis is confirmed by compression ultrasonography or CT pulmonary angiography, and first-line treatment is apixaban, rivaroxaban, or low molecular weight heparin continued while cancer is active.