Familial polycythemia

• High Epo levels

  1. Low P₅₀: increased affinity of hemoglobin for oxygen

     • High-O₂-affinity hemoglobin variants

     • 2,3-bisphosphoglycerate (2,3-BPG) deficiency

     • Methemoglobinemia

  2. Normal P₅₀: defects in oxygen sensing

     • Homozygous Chuvash VHL mutation

     • Other VHL mutations

• Low or normal Epo levels

  1. Epo-R mutations: primary familial and congenital polycythemias

Familial thrombocytosis

• High Tpo levels: Tpo gene mutations

• Activating mutation of c-Mpl (Tpo-R)

• Others

Secondary polycythemia

• Physiologically appropriate: response to hypoxia

  1. Reduced P_aO₂

     • Chronic lung disease

     • Pickwickian (obesity-hypoventilation) syndrome

     • Sleep apnea

     • High altitude

     • Cyanotic heart disease

  2. Normal P_aO₂

     • Smokers' and CO-induced polycythemia

• Physiologically inappropriate

  1. Tumors

     • Renal cell carcinoma

     • Wilms tumor

     • Hepatoma

     • Uterine fibroma

     • Cerebellar hemangioma

     • Atrial myxoma

  2. Benign renal disease

     • Polycystic kidney disease

     • Hydronephrosis

     • Renal artery stenosis (rare)

  3. Postrenal transplantation erythrocytosis

  4. Endocrine disorders

     • Pheochromocytoma

     • Primary aldosteronism

     • Bartter syndrome

     • Cushing syndrome

  5. Administration of erythropoiesis-stimulating hormones

     • Epo

     • Androgens

Secondary thrombocytosis

• Transient processes

  1. Acute blood loss

  2. Recovery (“rebound”) from thrombocytopenia

  3. Acute infection or inflammation

  4. Response to exercise

  5. Drug reactions

• Sustained processes

  1. Iron deficiency

  2. Hemolytic anemia

  3. Asplenic state (eg, after splenectomy)

  4. Chronic inflammatory or infectious diseases

  5. Cancer