Polycythemia: Causes

Pathogenesis (disease development)

Polycythaemia vera (primary polycythemia; primary polyglobulia) is due to a disorder of the myeloid stem cell characterized by autonomous proliferation of the three cell series:

  • EPO (erythropoietin)-independent, irreversible, and progressive increase in erythrocyte (red blood cell) production.
  • Increased proliferation of granulopoiesis (development of granulocytes/a group of white blood cells) and megakaryopoiesis (development of megakaryocytes in the bone marrow; it is part of thrombopoiesis/formation of platelets, i.e., blood platelets)
  • Erythrocytosis is in the foreground and determines the clinical picture
  • Increased blood viscosity due to the increase in hematocrit (Hkt; proportion of all cellular components in the volume of blood) → symptomatic microcirculatory disorders and an increased risk of thromboembolic complications.

Secondary polycythemia (polyglobulia) can be caused by a number of conditions (e.g., renal polyglobulia, hypertensive polyglobulia, etc.), among others. For other causes, see below. Relative polycythemia (pseudopolyglobulia) – due to a decrease in plasma volume with an isolated borderline or moderate increase in red cell count (stress erythrocytosis).

Etiology (causes) of polycythemia

Biographic causes

  • Genetic burden
    • Genetic diseases
      • Polycystic kidney disease – kidney disease due to multiple cysts (fluid-filled cavities) in the kidneys
        • Partly with autosomal dominant as well as autosomal recessive inheritance (see below Cystic Kidney Disease).

Causes related to disease

Respiratory system (J00-J99)

  • Chronic pulmonary disease, unspecified [secondary erythrocytosis due to arterial hypoxia/oxygen deficiency).

Blood, hematopoietic organs – immune system (D50-D90).

  • Erythropoietin receptor mutations leading to increased EPO sensitivity of erythroid progenitors.
  • Essential thrombocythemia (ET) – chronic myeloproliferative disorder (CMPE, CMPN) characterized by chronic elevation of platelets (thrombocytes).
  • Chuvash polycythemia – impaired EPO gene regulation.
  • Hemoglobinopathy (disease caused by disorders of hemoglobin (red blood pigment)) with increased oxygen affinity or 2,3-DPG deficiency (e.g., 2,3-DPG mutase deficiency)
  • Congenital methemoglobinemia – congenitally increased concentration of methemoglobin in erythrocytes.
  • Disorders of hemoglobin formation in the presence of normal O2 affinity of hemoglobin (heterozygous beta-thalassemia, alpha-thalassemia minor, mild iron deficiency anemias; hemoglobin concentration, hematocrit (proportion of all cellular components in the volume of blood) and mean red cell volume (MVC) are decreased in this case).

Cardiovascular system (I00-I99).

  • Known congenital heart conditions such as septal defects (structural damage to the heart wall, or holes in the septum), left-to-right shunt (disorder of the circulatory system in which oxygenated blood from the arterial limb of the circulatory system (e.g. E.g., from the left side of the heart) passes directly into the venous limb of the circulation (e.g., the right side of the heart)) [secondary erythrocytosis due to arterial hypoxia/oxygen deficiency).
  • Hypertension (high blood pressure)

Neoplasms – tumor diseases (C00-D48)

  • Wg. autonomous EPO (erythropoietin) production in tumors:
    • Hemangioblastoma (vascular tumor that can occur in the central nervous system but also in soft tissue).
    • Hepatoma (malignant (malignant) or benign (benign) adenomas / neoplasms of the liver).
    • Hepatocellular carcinoma
    • Renal cell carcinoma
    • Paraneoplastic syndromes, for example in ovarian cancer (ovarian cancer), cerebellar tumors, etc.
    • Pheochromocytoma (tumors of the adrenal medulla or sympathetic paraganglia).
  • Myeloproliferative neoplasms:
    • Chronic myeloid leukemia (CML) – leukemia associated with a marked proliferation of leukocytes (white blood cells), specifically granulocytes and their precursors, in the blood and hematopoietic bone marrow
    • Essential thrombocythemia (ET) – chronic myeloproliferative disorder (CMPE, CMPN) characterized by chronic elevation of platelets (thrombocytes).
  • Wilms tumor (nephroblastoma) – malignant neoplasm of the kidney occurring in childhood.

Psyche – nervous system (F00-F99; G00-G99).

Genitourinary system (kidneys, urinary tract – sex organs) (N00-N99).

  • Renal dysfunction, unspecified
  • Polycystic kidney disease – refers to the presence of multiple cysts in the kidneys.

Medication

  • Androgens (by stimulating erythropoiesis/blood formation).
  • EPO supply, e.g., in doping.
  • Steroids (by stimulating erythropoiesis).

Other causes

  • Staying at high altitudes
  • Posttransplant erythroblastosis – increased occurrence of precursor red blood cells after organ transplantation.
  • Smoker’s polycythemia – increased in heavy smokers due to increased levels of carbon monoxide hemoglobin (COHb).
  • Severe exsiccosis (dehydration) – passive erythrocytosis with concomitant increase in hematocrit and hemoglobin concentration.