Essential Erythrocytosis in a Cat

WHAT IS YOUR DIAGNOSIS? A 12 year old, female neutered domestic shorthaired cat was presented to the R(D)SVS Feline Clinic with a 6 week history of polydipsia and polyuria, which was not quantified. The cat had previously been polyphagic for a few weeks, but the appetite was currently reported to be normal. No respiratory or gastro-intestinal signs were reported, but the owners had noticed that the cat seemed to be having difficulty jumping onto things. No other neurological signs were reported. Physical examination indicated the cat to be in good body condition (4/9), bright and interactive. Heart rate was 220 bpm with a II/VI systolic murmur and intermittent gallop. Respiratory rate was 12/min with no adventitious lung sounds. Abdominal palpation and peripheral lymph nodes were within normal limits and she was normothermic at 37.9°C. The nasal planum, pads of the paws and clipped skin were all noted to be hyperaemic. A blood sample was obtained to investigate the polydipsia and polyuria, with the following haematology and biochemistry results. HAEMATOLOGY Parameter Reference Range RBC count 5.5-10.0 x 10 /l 16.83 PCV 0.24-0.45 l/l 0.66 Haemoglobin 8.0-14.0 g/dl 21.5 MCV 39.0-55.0 f/l 39.2 MCHC 30.0-36.0 % 32.5 Total WBC count 7.0 – 20.0 x 10 /l Neutrophils 2.5 – 12.8 x 10 /l 12 Patient Result 9 6.8 9 3.9 Lymphocytes 1.5 – 7.0 x 10 /l 2.4 Monocytes 0.07-0.85 x 10 /l Eosinophils 0.00-1.00 x 10 /l Manual platelets 300-600 x 10 /l 9 9 9 0.41 9 0.14 128 page 1 of 6 BIOCHEMISTRY Parameter Reference Range Patient Result Total Protein 69.0-79.0 g/l 83.5 Albumin 28.0-39.0 g/l 36.5 Globulin 23.0-50.0 g/l 47.0 Bile acids 0.0-7.0 µmol/l 0.7 Total bilirubin 0.0-6.8 µmol/l 2.1 Chloride 117-140 mmol/l 115 Creatinine 40.0-177.0 µmol/l 190 Glucose 3.3-5.0 mmol/l 5.8 Urea 2.8-9.8 mmol/l 11.0 AP 10.0-100.0 IU/l 48 ALT 6.0-83.0 IU/l 46 Calcium 2.10-2.90 mmol/l 2.67 Inorganic phosphate 1.40-2.50 mmol/l 1.16 Sodium 145-156 mmol/l 159 Potassium 4.0-5.0 mmol/l 5.7 Thyroxine 15-45 nmol/l 23 1) What are your differential diagnoses for the abnormal red blood cell parameters? 2) What investigations would you perform? page 2 of 6 1) Differential Diagnoses Relative polycythaemia (pseudoerythrocytosis) • • Dehydration Splenic contraction (dogs, not cats!) Absolute polycythaemia • • • Primary (Essential erythrocytosis) Secondary o Appropriate (to make up for inadequacies in O2 carrying capacity)  Cardiac disease (right to left shunts e.g. Tetralogy of Fallot, reversed PDA, VSD)  Pulmonary disease  High altitude  Haemoglobinopathies (e.g. methaemoglobin reductase deficiency) o Inappropriate (no inadequacy in O2 carrying capacity)  Renal disease – primarily neoplasia; polycystic kidney disease, amyloidosis  Other neoplasms (hepatic; caecal leiomyosarcoma) Endocrinopathies (elevations usually mild) o Hyperthyroidism o Hyperadrenocorticism o Acromegaly 2) Further Investigations Urinalysis: the specific gravity was 1.022, making dehydration very unlikely. The cat did not appear clinically dehydrated, however if suspected fluid therapy can be administered and the PCV re-assessed. The specific gravity supported that the azotaemia identified was due to renal disease. Echocardiography: this identified mild hypertrophic cardiomyopathy, but no evidence of right to left shunting. Thoracic radiography: no evidence of lung disease was identified Abdominal ultrasonography: the spleen appeared slightly enlarged, attributed to sedation, as an FNA of the spleen did not identify any neoplastic cells. There was no evidence of renal, hepatic or colic neoplasia. 3) Based on these results, what is your diagnosis, and how would you treat it? page 3 of 6 3) Diagnosis Essential erythrocytosis (Polycythaemia vera) Treatment options include phlebotomy, hirudotherapy and/or chemotherapy. The patient received all three, as follows. Phlebotomy was performed to reduce the PCV, as neurological signs such as seizures can occur due to the hyperviscosity associated with the elevated red blood cell numbers. Under sedation, 15ml/kg of blood was removed via a 21G needle and extension set. Removing this volume of blood over a relatively rapid period (20 minutes) can lead to hypotension, therefore an IV catheter was placed and the blood volume removed was replaced with Hartmann’s solution. The aim of phlebotomy is to reduce the PCV to below 50% (55% for dogs), and this was achieved, with the patients PCV dropping to 45%. Hirudotherapy (leech therapy) was used 1 month later, when the PCV had returned to 57% and the red blood cell count was 14.05 x 1012/l. Benefits of hirudotherapy over traditional phlebotomy include reduced requirement for sedation and a more insidious bleed. This was considered beneficial in this case, as a rapid drops in blood volume (and hence blood pressure) could be detrimental to the kidneys. In addition, polycythaemic patients can be difficult to phlebotomise, and larger gauge needles may be required. This can be particularly problematic in cats. 4 medical leeches were applied to a clipped area of fur and fed for between 10 and 40 minutes (figure 1). The leeches detach when they have finished feeding, having ingested approximately 6ml blood per leech. Due to the leeches injecting an anti-coagulant (hirudin) the sites of attachment continue to ooze blood, leading to a loss of up to a further 10ml/site over the following 12 hours. The leeches are well tolerated, as in addition to injecting hirudin, they also inject a local anaesthetic. Following hirudotherapy, the patient’s PCV reduced to 43%. Chemotherapy was started subsequent to the hirudotherapy. Whilst patients can be managed long term on phlebotomy (or hirudotherapy) alone, provided iron supplementation is administered this does not address the primary problem. It was also felt that the frequency at which this would be required (every 5-6 weeks) would necessitate repeated sedations which may be detrimental to the patient,(and more expensive for the owner!). Hydroxycarbamide (hydroxyurea) is a chemotherapeutic agent that inhibits DNA synthesis. The initial dose is given as 30mg/kg daily for 7 days then reducing to 15mg/kg, but a lower dose was chosen in this case, as a normal PCV had been attained and the cat had chronic kidney disease. Reformulation of the human capsules into 100mg capsules was performed to reduce the risk of toxicity, signs of which include myelosuppression, macrocytosis, sloughing of toe-nails and development of methaemoglobinaemia. Haematology will be monitored every 7-14 days initially, then every 3 months once we are happy she is stable. page 4 of 6 Discussion Essential erythrocytosis is a primary bone marrow disorder which results in clonal expansion of red blood cells due to a myeloproliferative disease. In humans it can be associated with splenomegaly and thrombocytosis or leukocytosis, although these are not consistent findings in veterinary patients. This patient was slightly older than most at time of diagnosis, with a median age of 6-7 years, and the condition more commonly affects male cats than female cats. Erythropoietin may be expected to be low or at the low end of the reference range in these patients, whereas it might be expected to be high with secondary erythrocytosis. However measurement of this hormone is not considered particularly useful, as there is a lot of overlap between the 2 categories of disease. Bone marrow evaluation also was not performed, as it is not possible to differentiate between primary disease and bone marrow hyperplasia in response to erythropoietin. The diagnosis is therefore usually made, as in this case, by excluding common causes of secondary erythrocytosis. The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. www.ed.ac.uk/vet/hfsa-int-med page 5 of 6 Figure 1 – Medical leeches on the flank of the patient (one leech has already detached) The University of Edinburgh is a charitable body, registered in Scotland, with registration number SC005336. www.ed.ac.uk/vet/hfsa-int-med page 6 of 6