Polycythemia (Erythrocytosis), Polycythemia Rubra Vera, and Secondary Polycythemia

Sample

• EDTA blood sample is needed.

Definition

1. This is an uncontrolled proliferation of red blood cells.
   1. There is increased hemoglobin concentration above the upper limit of normal.
2. Criteria to label polycythemia are :
   1. RBCs = count increased.
   2. PCV = raised
   3. Hemoglobin = raised > 18 g/dL
      1. male 17 g/dL
      2. female 15 g/dL
   4. hematocrit = raised
      1. male >60%
      2. female >56%

Pathophysiology

1. Types of absolute Polycythemia. There are two types :
   1. Primary polycythemia (also known as polycythemia rubra vera).
   2. Secondary polycythemia.
2. 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

3. There is a hyperviscosity.
4. In the primary polycythemia, there is a clonal uncontrolled proliferation of stem cells.
   1. There is a chromosomal abnormality of the deletion of 9por 20q found in the minority of the cases.

Polycythemia Rubra Vera (primary)

1. This is a bone marrow disorder where the bone marrow produces an uncontrolled proliferation of RBCs.
   1. This Is basically a myeloproliferative disorder.
   2. This is a stem cell disorder.
2. Erythrocytosis is not dependant on erythropoietin.
3. The median age at diagnosis is 60 years.
   1. This is more common in men than in women.
4. This is a chronic disease and many patients die due to thrombotic disease or cardiac arrest.
5. Polycythemia vera also may result in the production of too many of the other types of blood cells like white blood cells and platelets.
6. Polycythemia vera also called primary polycythemia.
7. It is rare and usually develops slowly.
8. Often, polycythemia vera is found during a blood test done for some other reason.
9. These patients who survive long may develop myelofibrosis or myeloid leukemia.
10. Laboratory findings are increased RBC count, Hb, Hct.  Normal MCV and MCH. Increased WBCs and platelets.
11. Bone marrow show panhyperplasia.

Causes of polycythemia (Rubra) vera:

1. Unknown.
2. Bone marrow abnormality
3. 95 % of the cases have a genetic abnormality.

Signs and Symptoms

1. This is often found incidentally where it is found raised hemoglobin, and RBCs count.
2. This is the disease of old age with equal sex distribution.
3. Rarely seen under the age of 40 years
4. The symptoms are due to:
   1. Hyperviscosity.
   2. Hypervolemia.
   3. Hypermetabolism.
5. There is a history of epistaxis and bleeding from the GI tract.
6. There is easy bruising and bleeding.

7. The patient may have neurologic symptoms like vertigo, tinnitus, headache, and eye problems particularly after a hot bath, and may become a severe problem.
8. Hypertension is seen in 1/3 of the patient.
9. There may generalized pruritus.
10. The spleen may be palpable in 75% of the cases.
11. Gout may be seen due to a raised level of uric acid.
12. Peptic ulceration is seen in 5 to 10% of the patients.
13. Lab findings in Polycythemia (Rubra) Vera:
    1. Hemoglobin is raised.
    2. Hct may be >60%.
    3. Total red cell mass:
       1. Male >35mL/Kg
       2. Female = >32 ml/Kg.
    4. Arterial oxygenation is >92%.
    5. There is an increased number of WBCs and platelets.
       1. Raised platelet count is seen in half of the patients.
       2. Increased leucocytosis is seen in more than half of the patients and even may see increased basophils.
       3. Increased neutrophil alkaline phosphatase score (NAP).
    6. Bone marrow is hypercellular with prominent megakaryocytes.
    7. The serum erythropoietin level is usually low.
    8. Blood viscosity is increased.
    9. Serum LDH level is normal and uric acid is increased.
    10. There is splenomegaly.
    11. The JAK2 mutation is seen in granulocytes in almost 100% of the cases.
    12. There is increased serum vitamin B₁₂ and B_{12 ^–}binding capacity.

Treatment of polycythemia Rubra Vera

1. Venesection to keep hematocrit low.
2. Cytotoxic myelosuppression by the chemotherapy. Phosphorus -32 therapy used in older patients.
3. Interferon (α-interferon) suppresses the bone marrow.
4. 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

1. Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin leads to increased RBC production.
2. RBCs count maybe 6 to 8 million (occasionally 9 million cmm).
3. Secondary polycythemia resolves when the underlying cause is treated.
4. Causes of secondary polycythemia or physiological polycythemia may be caused by:
   1. High Altitude (altitude sickness).
   2. Hypoxic disease.e.g. cyanotic heart and hypoxic lung disease (COPD). and chronic obstructive sleep apnea.
   3. Idiopathic or Iatrogenic can be induced directly by phlebotomy which can concentrate the erythrocytes.
   4. Genetic abnormalities in hemoglobin oxygen release.
   5. Renal diseases like cystic disease and hydronephrosis.
   6. Neoplasms e.g.
      1. Renal-cell carcinoma.
      2. Liver tumors.
      3. Pheochromocytoma.
      4. Adrenal adenoma with Cushing’s syndrome.
   7. Anabolic steroids use (athletes abuse of steroids).
   8. Testosterone replacement for hypogonadism.
   9. People who take erythropoietin may develop secondary polycythemia.

1. Laboratory findings in Secondary polycythemia show:

   1. Increased RBC count.
   2. Increased hemoglobin.
   3. Increased hematocrit.
   4. Normal MCV and MCH.
   5. White cells and platelets are normal.

Relative polycythemia (Pseudopolycythemia):

1. It is caused by:
   1. Stress,
   2. Smoking.
   3. Dehydration in case of water deprivation and vomiting.
   4. Plasma loss in burn and enteropathy.
2. This is characterized by :
   1. Raised hemoglobin.
   2. Normal TLC.
   3. Normal platelets.
   4. Normal red cell mass.
   5. Decreased plasma volume.
   6. Laboratory findings are Increased RBC count, Hb, Hct, and normal WBCs and platelets.
3. Relative polycythemia is seen in decreased plasma volume and may be seen in dehydration or hemoconcentration.

Treatment

1. The treatment of the choice is phlebotomy.
2. Donate one point of blood until the Hct is <45%.
3. The patient should be given a low iron diet.
4. Chemotherapy like myelosuppressive drugs may be given.

Summary of the clinical finding of various types of polycythemia

normal

Clinical and laboratory findings	Relative polycythemia	Secondary polycythemia	Primary polycythemia Rubra
1. Red cell mass	normal	increased	increased
2. White blood cells	normal	normal
3. Platelets count	normal	normal	increased by 50% of the cases
4. Nucleated RBCs	absent	absent	usually present
5. Bone marrow	normal	increased erythropoiesis	hypercellular increased erythropoiesis and leucopoiesis
6. leucocyte alkaline phosphatase score	normal	normal	increased in 70% of the cases
7. Serum vitamin B12	normal	normal	increased in 75% of the cases
8. Splenomegaly	absent	absent	present in 75% of the cases
9. Hepatomegaly	absent	absent	present in 35% of the cases
10. Heart or lung disease	absent	present	absent
11. Cyanosis	maybe present	present	absent

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