Eyrthrocytosis and polycythaemia

Question 1

Briefly describe the processes of normal erythropoiesis

Answer 1

• Hypoxia is sensed within the kidney and stimulates production of hypoxia inducible factor 1
• HIF-1 stimulates renal interstitial fibroblasts to produce EPO
• EPO is synergised by thyroid hormone and glucocorticoids
  
  • T4 stimulates proliferation of erythroid progenitor cells
  • glucocorticoids synergise with HIF to stimulate BFU-erythroid
• EPO stimulates RBC progenitor cells to proliferate

Question 2

List the basic categories and causes of erythrocytosis

Answer 2

1. Relative (appropriate)
   
   • Typically due to dehydration / fluid loss
2. Secondary appropriate
   
   • In response to hypoxaemia
   • Pulmonary of cardiac disease
3. Secondary inappropriate
   
   • No hypoxaemia
   • Increased EPO independent of hypoxaemia
   • paraneoplastic, endocrine disease (hyperA, hyperT, hypersomatotropism), renal disease
4. Primary polycythemia
   
   • Genetic mutation versus neoplasia.

Question 3

Describe the diagnostic pathway for erythrocytosis

Answer 3

1. Basic blood tests reveal elevated RCC with normal protein
2. History/physical examination: Assess for low oxygen environment (recent travel?), pulmonary disease, heart disease, palpable mass, possible endocrinopathy
3. Diagnostic testing:
   
   • arterial blood gas (<92% suggests hypoxaemia)
   • Thoracic radiographs +/- bronchoscopy if pulmonary signs (and for neoplasia search)
   • Echo if concern for right to left shunt
   • Abdominal ultrasound to assess renal structure and to assess for neoplasia
4. EPO measurement?
   
   • Lack of readily available test validated for the species
   • overlap between normal animals and with primary polycythaemia
   • Increased EPO suggests secondary polycythaemia

Question 4

Discuss the treatment options for polycythaemia / erythrocytosis

Answer 4

1. Relative polycythaemia - treat with fluid volume replacement
2. Treat underlying cause if one can be found
3. Cardiac disease: secondary polycythaemia
   
   • Phlebotomy with a target of 58%-65% based on clinical signs
4. Phlebotomy: remove 15-20 ml/kg blood +/- replace with crystalloids.
5. Hydroxyurea: if phlebotomy is required more than once a month or is not tolerated.
   
   • Dosage is empirical and titrated to lowest effective dose.