Polycythemia is a group of disorders that produces an excess of red blood cells and/or one or more of the bone marrow elements (panmyelosis). This is one instance in which an over-production of cells can cause dysfunction, as well as any deficiency of these same cells.
Polycythemia vera is an unusual, chronic, myeloproliferative red cell disease that causes erythrocytosis (excessively large numbers of erythrocytes in the blood). It is also marked by leukocytosis (increased leukocytes), thrombocytosis (increased platelets), and increased hemoglobin concentration, all the while maintaining a normal or decreased plasma volume. Controversy does exist as to whether it should be classified as a leukemia or a problem of marrow hyperplasia, that is, a myeloproliferative disorder.
The danger from erythrocytosis is that it causes blood volume and blood viscosity to increase, along with the erythrocyte count. The liver and spleen become increasingly congested with erythrocytes as viscosity causes blood flow to slow. Eventually, the thick, sticky, slow-flowing blood becomes an ideal environment for clotting and acidosis. If thrombi obstruct vessels, the result is blood deprivation (infarction) of tissues and organs.
Polycythemia vera was first described in 1892 by a French physician, M.H. Vaquez. In the early 1900s, William Osler undertook an extensive investigation of the disease; but not much more was learned until the 1960s when researchers began to investigate a link between all polycythemias and the formation of any tumors (neoplasia) affecting stem cells. Because polycythemia vera is caused by an excessive proliferation of erythrocyte precursors in the marrow and is typically accompanied by increases of circulating platelets and granulocytes, it suggests that the disease is caused by an abnormality of the pluripotential stem cell.
There are three types of polycythemia: primary, secondary, and familial.
- Primary: The primary form is relatively rare and the cause is unknown; but it tends to occur in men between the ages of 40 and 60 and is more common in whites, particularly Jews of European ancestry.
- Secondary: The seconday type is the more commonly seen form of the disorder. It is an essentially physiologic response to hypoxia. Therefore, it is not uncommon to find an increased red cell count in individuals living at high altitudes (over 10,000 feet), in smokers, and in individuals with congestive heart failure or COPD (chronic obstructive pulmonary disease).
- Familial: This form is extremely rare and not all within the family are affected.
Clinical manifestations of polycythemia vera include the following:
- a ruddy, red color of the face, hands, feet, ears, and mucous membranes (plethora)
- engorgement of retinal and sublingual veins
- Vascular disease may predominate, including angina, calf pain associated with walking, thrombotic disease, and cerebral insufficiency. Thrombosis of gastric vessels can cause ulcers and mesenteric pain.
Symptoms include headache, a feeling of fullness in the head, dizziness, weakness, elevated blood pressure, itching, sweating, weight loss, epigastric disturbances, fatigue on exertion, backache, and visual disturbances caused by congestion of the conjunctiva, retina, retinal veins. The eyes may be bloodshot and the gums will often bleed, as will the gastrointestinal and genitourinary tracts. There may be an unusual sensation in the fingers, as burning or prickling. There may also be such intense itching after bathing that some individuals avoid bathing with warm water. Joint symptoms may also occur and repiratory infections are common, as is hoarseness. Symptoms do not respond to antihistamines.
Diagnosis is determined by an absolute increase in red blood cells and in the total blood volume, although it is not unusual to also have increases in white blood cells and platelets. A bone marrow examination may be done. However, it is not functional in determining a definitive diagnosis.
Laboratory studies confirm the diagnosis by showing increased RBC mass and normal arterial oxygen saturation in association with splenomegaly (spleen enlargement) or two of the following: thrombocytosis, leukocytosis, elevated leukocyte alkaline phosphatase level, or elevated serum vitamin B12 or unbound B12-binding capacity.
Other studies may reveal increased serum uric acid, increased blood histamine, decreased serum iron concentration, and decreased or absent urinary erythropoietin. Bone marrow biopsy reveals panmyelosis.
The treatment of choice is phlebotomy, aimed at reducing erythrocytosis and blood volume, controlling symptoms, and preventing thrombosis. Phlebotomy is a procedure in which a vein is opened and blood is removed. (Phlebotomy is just the modern term used for the ancient art of ‘blood-letting’).
Typically, 350-500 ml of blood may be removed every other day until the patient’s hematocrit falls to the low-normal range. After that, phlebotomy may be done every three or four months. After repeated phlebotomies, the patient develops iron deficiency, which stabilizes RBC production and reduces the need for this treatment.
Phlebotomy does not reduce white blood cell (WBC) or platelet counts and will not control the hyperuricemia (excessive uric acid) associated with marrow cell proliferation.
Radioactive phosphorus is sometimes given orally or intravenously to suppress the over-production of erythrocytes. Unfortunately, a side effect of this can be the general suppression of all blood cells (hematopoiesis), resulting in anemia, leukopenia, or thrombocytopenia. Radioactive phosphorus is not given at frequent intervals and as many as eighteen months may elapse between treatments. Myelosuppressive drugs (marrow suppressants) are also used, but their effects can be more unpleasant than the disease.
Prognosis depends on age at diagnosis, treatment used, and complications. Mortality is high if it is untreated or is associated with leukemia or myeloid metaplasia. Without proper intervention, half of all individuals with polycythemia vera die within eighteen months of the onset of initial symptoms. The major cause of death results from thrombosis or hemorrhage. Although polycythemia vera is a chronic disorder, appropriate therapy can result in remission and prevention of early death.