The term polycythemia identifies any generic increase in the number of red blood cells in the blood, an event which in clinical practice usually results in an increase in plasma hemoglobin and hematocrit (blood viscosity).
Secondary polycythemia
Secondary polycythemias are mostly related to chronic hypoxemia, or a lack of oxygen in the blood. This condition induces an adaptive physiological response which - mediated by the increased synthesis of erythropoietin in the kidney - leads to an increase in the synthesis of red blood cells. In this way the organism is able to capture more oxygen from the atmospheric air and make up for the deficiencies within certain limits. Not surprisingly, polycythemia is a typical trait of numerous high altitude ethnic groups, appreciable even in those who stay for several weeks on the high ground; as anticipated, it is an adaptive response to the reduced partial pressure of oxygen that characterizes these environments. The physiological polycythemia from high altitudes explains why various athletes, especially practicing cross-country sports (running, cycling, etc.), train for some periods to high altitude: the increase in red blood cells will ensure an improvement in sports performance.
Causes of secondary polycythemia:
From increased erythropoietin synthesis in response to arterial hypoxemia
- extended stay in the high mountains
- respiratory disorders with alveolar hypoventilation (e.g. COPD)
- congenital heart disease with right-to-left shunt
- methemoglobinemia
- carboxyhemoglobinemia
- sleep apnea in the course of excessive obesity
From inappropriate erythropoietin secretion
- hypernephroma
- kidney cysts (polycystic kidney)
- uterine fibroma
- hepatic neoplasms
- pheochromocytoma
By increasing the intake of erythropoietin or other drugs with similar action (epoetin), both for therapeutic and doping purposes
For what has been said, secondary polycythemia is a reversible phenomenon: when the individual descends to low altitude or the cause of hypoxia disappears, the number of red blood cells gradually re-establishes.
Primary polycythemia
For further information: Polycythemia Symptoms
Also known as primary polycythemia or erythremia / Vaquez-Oslere disease, polycythemia vera is an autonomous myeloproliferative disease, characterized by an "abnormal proliferation of haemocytoblasts on a genetic basis [mutation of the JAK2 tyrosine kinase in stem cells of 90% of patients with polycythemia vera ].
It takes the form of an elevated synthesis of red blood cells, generally accompanied also by an "enhanced synthesis of white blood cells and platelets. The result is an increase in the hematocrit and total blood volume (plasma hyperviscosity and hypervolemia); the increased blood viscosity and the blood pressure on the vascular walls can cause important alterations in the blood flow and determine rather dangerous consequences for the health of the patient suffering from polycythemia vera: the capillaries become clogged due to the excessive viscosity of the blood, thrombotic phenomena increase (the risk of stroke, angina pectoris, myocardial infarction, superficial and deep thrombophlebitis and, more rarely, pulmonary embolism increases). Generally there are dizziness, headache, mild hypertension, hepatomegaly, splenomegaly and haemorrhagic phenomena (nosebleeds, bleeding from the gums and bruising); the skin takes on reddish shades (due to the increased presence of oxygenated hemoglobin) and bluish - cyanotic (due to the increased presence of deoxygenated hemoglobin), and is often the subject of itching after bathing.
The diagnosis of polycythemia vera is based on the study of the blood count:
- the values of hemoglobin and hematocrit, higher than normal, can respectively reach 22-24 g / dl and 55-60%, while the finding of neutrophilic leukocytosis and platelet disease is common
and other biohumoral parameters:
- increase in blood levels of cholesterol, uric acid, vitamin B12, LDH, intraleukocyte ALP
Erythroid hyperplasia is recorded on bone marrow biopsy and subsequent morphological examination of the bone marrow; moreover it is possible to demonstrate the presence of the aforementioned JAK2 V617F mutation. Ultrasonography and objective evaluation may show an increase in the size of the liver and spleen.
The therapy, originally based on bloodletting or phlebotomy - that is, the removal of 300-500 ml of blood every 2-3 days until the hematocrit falls below the 50% threshold, possibly compensated by reinfusion of plasma or administration of its substitutes - can make use of cytotoxic / chemotherapeutic drugs (busulfan, hydroxyurea, cyclophosphamide, chlorambucil, cytosine arabinoside, melphalan) or radiotherapy. These last interventions are aimed at depressing the abnormal proliferative activity of the bone marrow, in which polycythemia vera recognizes its own pathogenetic center. New generation drugs capable of inhibiting the activity of the abnormal protein tyrosine kinase (JAK2) responsible for the disease are being developed and tested.
