Polycythemia and erythrocytosis
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.
- Topic reviewThe full article, organized the way the exam asks it.
- ABIM-format MCQsVignettes with an explanation for every wrong answer.
- Key factsThe numbers and thresholds worth memorizing, up front.
- AI tutorMedBrain answers the question you're stuck on.
What this article covers
- Overview
Definition: polycythemia (erythrocytosis) is a true increase in red cell mass reflected by an elevated hemoglobin and hematocrit, which must first be distinguished from a spuriously elevated hematocrit caused by a contracted plasma volume.
- Epidemiology
PV is the most common MPN, with a median age of onset around 60 years.
- Risk factors
JAK2 V617F or JAK2 exon 12 mutation: the driver lesion in essentially all PV.
- Pathophysiology
PV: EPO-independent clonal proliferation.
- Clinical features
Often asymptomatic: many patients with PV are identified incidentally on a routine CBC showing an elevated hemoglobin, leukocytosis, and thrombocytosis.
- Differential diagnosis
Secondary erythrocytosis from chronic hypoxia: COPD, obstructive sleep apnea, smoking, high altitude, or cyanotic congenital heart disease; oxygen saturation often below 92%, EPO elevated, JAK2…
- Diagnosis
Confirm true erythrocytosis, then apply the WHO diagnostic criteria for PV: hemoglobin above 16.5 g/dL in men or above 16 g/dL in women establishes true erythrocytosis; PV is then diagnosed by this…
- Management
First, exclude and correct relative erythrocytosis: rehydrate or stop the offending diuretic and reassess the hematocrit before initiating PV-specific therapy, because phlebotomizing a normal red cell mass provides no benefit.
- Complications
Arterial and venous thrombosis: stroke, myocardial infarction, and venous thromboembolism, driven by hyperviscosity and, in PV, by accompanying thrombocytosis and neutrophilia; the leading cause of morbidity and mortality in PV.
- Prognosis
PV generally carries a favorable prognosis with treatment, and stem cell transplantation is not used because its mortality and morbidity are not justified given the otherwise good outlook with phlebotomy, aspirin, and cytoreduction.
- Prevention
Maintain the hematocrit below 45% in PV with ongoing phlebotomy, the single intervention shown to reduce major thrombosis and cardiovascular death, reassessing the interval by how quickly the hematocrit re-accumulates.
Read the whole article
Subscribing to Internal Medicine opens every article, the full question bank and MedBrain, on the web, iPhone and Android.
Related articles
- Myelofibrosis
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
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.
- Acute myeloid leukemia
Acute myeloid leukemia is a clonal proliferation of myeloid precursors that fails to differentiate, defined by myeloblasts at or above 20% of the bone marrow or blood, and it presents with cytopenias from marrow replacement plus, in acute promyelocytic leukemia, a coagulopathic emergency. Diagnosis rests on marrow blast count, immunophenotype, and cytogenetic and molecular testing that set both classification and risk, while treatment is intensive induction chemotherapy or ATRA-arsenic trioxide for APL, followed by risk-adapted consolidation.
- Renal cell carcinoma
Renal cell carcinoma is the most common kidney cancer, arising from renal tubular epithelium (most often clear cell), and is now diagnosed incidentally on imaging in most patients rather than through the classic triad of flank pain, hematuria, and mass. Contrast CT or MRI showing an enhancing solid renal mass is usually sufficient to diagnose and stage disease, and treatment is surgical for localized tumors versus tyrosine kinase inhibitors and immune checkpoint inhibitors for metastatic, chemo- and radio-resistant disease.
- Pheochromocytoma and paraganglioma
Pheochromocytoma and paraganglioma are catecholamine-secreting tumors of adrenal medullary chromaffin cells and extra-adrenal sympathetic ganglia, causing sustained or paroxysmal hypertension with headache, sweating, and palpitations, diagnosed by plasma free or 24-hour urine fractionated metanephrines before any imaging is obtained. First-line treatment is surgical resection preceded by alpha blockade with phenoxybenzamine (or off-label doxazosin) for 10 to 14 days, with a beta blocker added only after alpha blockade is established.
- Chronic obstructive pulmonary disease (COPD)
Chronic obstructive pulmonary disease is a persistent, usually progressive airflow obstruction driven mainly by cigarette smoke, confirmed by a postbronchodilator FEV1/forced vital capacity (FVC) ratio below 0.70 and staged by GOLD spirometric grade plus symptom/exacerbation group. Maintenance management is a stepwise ladder of smoking cessation, long-acting bronchodilators, add-on inhaled glucocorticoid, roflumilast, or azithromycin for frequent exacerbators, long-term oxygen for resting hypoxemia, and vaccination, with acute exacerbations managed as a separate protocol.