Polycythemia (Erythrocytosis), Polycythemia Rubra Vera, and Secondary Polycythemia
- EDTA blood sample is needed.
- 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.
- PCV = raised
- Hemoglobin = raised > 18 g/dL
- male 17 g/dL
- female 15 g/dL
- hematocrit = raised
- male >60%
- female >56%
- Types of absolute Polycythemia. There are two types :
- Primary polycythemia (also known as polycythemia rubra vera).
- Secondary 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
- There is a hyperviscosity.
- In the primary polycythemia, there is a clonal uncontrolled proliferation of stem cells.
- There is a chromosomal abnormality of the deletion of 9por 20q found in the minority of the cases.
Polycythemia Rubra Vera (primary)
- This is a bone marrow disorder where the bone marrow produces an uncontrolled proliferation of RBCs.
- This Is basically a myeloproliferative disorder.
- This is a stem cell disorder.
- Erythrocytosis is not dependant on erythropoietin.
- The median age at diagnosis is 60 years.
- This is more common in men than in women.
- This is a chronic disease and many patients die due to thrombotic disease 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 also called primary polycythemia.
- It is rare and usually develops slowly.
- Often, polycythemia vera is found during a blood test done for some other reason.
- These patients who survive long may develop myelofibrosis or myeloid leukemia.
- Laboratory findings are increased RBC count, Hb, Hct. Normal MCV and MCH. Increased WBCs and platelets.
- Bone marrow show panhyperplasia.
Causes of polycythemia (Rubra) vera:
- Bone marrow abnormality
- 95 % of the cases have a genetic abnormality.
Signs and Symptoms
- 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:
- 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 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 >35mL/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 the chemotherapy. Phosphorus -32 therapy 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 is caused by either natural or artificial increases in the production of erythropoietin leads 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.
- Adrenal adenoma with Cushing’s syndrome.
- Anabolic steroids use (athletes abuse of 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:
- Dehydration in case of water deprivation and vomiting.
- Plasma loss in burn and enteropathy.
- This is characterized by :
- 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.
- 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. 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|