Polycythemia (Erythrocytosis), Polycythemia Rubra Vera, and Secondary Polycythemia
Polycythemia
Sample for Polycythemia
- EDTA blood sample is needed.
Definition of Polycythemia
- Polycythemia is an increase in the total blood RBCs, more than the normal upper limit.
- This is an uncontrolled proliferation of red blood cells.
- There is increased hemoglobin concentration above the upper limit of normal.
- Criteria to label polycythemia are:
- RBCs = count increased, more than the normal upper limit.
- PCV = Increased.
- Hemoglobin = Increased > 18 g/dL (180 g/L).
- Male 18 g/dL (170 g/L)
- Female 16 g/dL (160 g/L).
- Hematocrit = Increased.
- Male >60%
- Female >56%
Pathophysiology of Polycythemia
- Types of Polycythemia. There are three types :
- Primary polycythemia (also known as polycythemia rubra vera).
- Secondary polycythemia.
- Relative polycythemia.
- There is pseudopolycythemia, where red cell volume is normal, but the plasma volume is reduced.
Test | Normal value | Relative Polycythemia | Primary/secondary polycythemia |
Plasma volume | 40 to 50 mL/Kg | Decreased | Normal |
Total red blood cell volume | male =25 to 35 mL/Kg | Normal | Increased |
Female = 22 to 32 mL/Kg |
Polycythemia facts:
- There is hyperviscosity.
- In primary polycythemia, there is an uncontrolled clonal proliferation of stem cells.
- There is a chromosomal abnormality of the deletion of 9p or 20q found in the minority of the cases.
Polycythemia Rubra Vera (primary)
- Polycythemia vera is also called polycythemia rubra vera.
Polycythemia vera facts:
- This is a bone marrow disorder where the bone marrow produces an uncontrolled RBC proliferation.
- This is basically a myeloproliferative disorder.
- This is a stem cell disorder.
- Erythrocytosis is not dependent on erythropoietin.
- The median age at diagnosis is 60 years.
- This is more common in men than in women.
- This is a chronic disease; many patients die from thrombosis or cardiac arrest.
- Polycythemia vera also may result in the production of too many of the other types of blood cells like white blood cells and platelets.
- Polycythemia vera is also called primary polycythemia.
- It is rare and usually develops slowly.
- Polycythemia vera is often found during a blood test for some other reason.
- These patients who survive long may develop myelofibrosis or myeloid leukemia.
- Laboratory findings are increased RBC count, Hb, and Hct. Normal MCV and MCH. Increased WBCs and platelets.
- Bone marrow shows panhyperplasia.
Causes of polycythemia (Rubra) vera:
- Unknown.
- Bone marrow abnormality
- 95 % of the cases have a genetic abnormality.
Signs and Symptoms of Polycythemia (Rubra) vera:
- This is often found incidentally where it is found raised hemoglobin and RBCs count.
- This is the disease of old age with equal sex distribution.
- Rarely seen under the age of 40 years
- The symptoms are due to the following:
- Hyperviscosity.
- Hypervolemia.
- Hypermetabolism.
- There is a history of epistaxis and bleeding from the GI tract.
- There is easy bruising and bleeding.
- The patient may have neurologic symptoms like vertigo, tinnitus, headache, and eye problems, particularly after a hot bath, and may become a severe problem.
- Hypertension is seen in 1/3 of the patient.
- There may be generalized pruritus.
- The spleen may be palpable in 75% of the cases.
- Gout may be seen due to a raised level of uric acid.
- Peptic ulceration is seen in 5% to 10% of the patients.
Lab findings in Polycythemia (Rubra) Vera:
- Hemoglobin is raised.
- Hct may be >60%.
- Total red cell mass:
- Male >35 mL/Kg
- Female = >32 ml/Kg.
- Arterial oxygenation is >92%.
- There is an increased number of WBCs and platelets.
- Raised platelet count is seen in half of the patients.
- Increased leucocytosis is seen in more than half of the patients, and even may see increased basophils.
- Increased neutrophil alkaline phosphatase score (NAP).
- Bone marrow is hypercellular with prominent megakaryocytes.
- The serum erythropoietin level is usually low.
- Blood viscosity is increased.
- Serum LDH level is normal, and uric acid is increased.
- There is splenomegaly.
- The JAK2 mutation is seen in granulocytes in almost 100% of the cases.
- There is increased serum vitamin B12 and B12 –binding capacity.
Treatment of polycythemia Rubra Vera
- Venesection to keep hematocrit low.
- Cytotoxic myelosuppression by chemotherapy. Phosphorus-32 therapy is used in older patients.
- Interferon (α-interferon) suppresses the bone marrow.
- Aspirin prevents thrombotic complications.
Prognosis of polycythemia Rubra Vera
- Mostly prognosis is good, and the median survival is 10 to 16 years.
- The major complications are thrombosis and hemorrhage.
Secondary polycythemia
- Secondary polycythemia is caused by either natural or artificial increases in erythropoietin production, leading to increased RBC production.
- RBCs count maybe 6 to 8 million (occasionally 9 million cmm).
- Secondary polycythemia resolves when the underlying cause is treated.
Causes of secondary polycythemia:
- Or physiological polycythemia may be caused by:
- High Altitude (altitude sickness).
- Hypoxic disease.e.g., cyanotic heart and hypoxic lung disease (COPD). And chronic obstructive sleep apnea.
- Idiopathic or Iatrogenic can be induced directly by phlebotomy, which can concentrate the erythrocytes.
- Genetic abnormalities in hemoglobin oxygen release.
- Renal diseases like cystic disease and hydronephrosis.
- Neoplasms e.g.
- Renal-cell carcinoma.
- Liver tumors.
- Pheochromocytoma.
- Adrenal adenoma with Cushing’s syndrome.
- Anabolic steroids use (athletes abuse steroids).
- Testosterone replacement for hypogonadism.
- People who take erythropoietin may develop secondary polycythemia.
Laboratory findings in Secondary polycythemia show:
- Increased RBC count.
- Increased hemoglobin.
- Increased hematocrit.
- Normal MCV and MCH.
- White cells and platelets are normal.
Relative polycythemia (Pseudopolycythemia):
- It is caused by:
- Stress,
- Smoking.
- Dehydration in case of water deprivation and vomiting.
- Plasma loss in burn and enteropathy.
- This is characterized by the following:
- Raised hemoglobin.
- Normal TLC.
- Normal platelets.
- Normal red cell mass.
- Decreased plasma volume.
- Laboratory findings are Increased RBC count, Hb, Hct, and normal WBCs and platelets.
- Relative polycythemia is seen in decreased plasma volume and may be seen in dehydration or hemoconcentration.
Treatment of Polycythemia
- The treatment of the choice is phlebotomy.
- Donate one point of blood until the Hct is <45%.
- The patient should be given a low-iron diet.
- Chemotherapy like myelosuppressive drugs may be given.
Summary of the clinical finding of various types of polycythemia:
Clinical and laboratory findings | Relative polycythemia | Secondary polycythemia | Primary polycythemia Rubra |
1. Red cell mass | Normal | increased | Increased |
2. Erythropoietin | Normal | Increased (rarely normal) | Decreased (rarely normal) |
3. White blood cells | Normal | Normal | Increased in 80% of the cases |
4. Platelets count | Normal | Normal | Increased by 50% of the cases |
5. Nucleated RBCs | Absent | Absent | Usually present |
6. Bone marrow | Normal | increased erythropoiesis | Hypercellular increased erythropoiesis and leucopoiesis |
7. Leucocyte alkaline phosphatase score | Normal | Normal | Increased in 70% of the cases |
8. Serum vitamin B12 | Normal | Normal | Increased in 75% of the cases |
9. Splenomegaly | Absent | Absent | Present in 75% of the cases |
10. Hepatomegaly | Absent | Absent | present in 35% of the cases |
11. Heart or lung disease | Absent | Present | Absent |
12. Cyanosis | May be present | Present | Absent |
questions and answers:
Question 1: Is there any association of heart/lung disease with polycythemia vera?
Question 2: Do you see cyanosis in polycythemia vera?