ISRAEL JOURNAL OF
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VETERINARY MEDICINE home archive journal |
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THE
USE OF RECOMBINANT HUMAN GRANULOCYTE COLONY STIMULATING FACTOR AND
RECOMBINANT HUMAN ERYTHROPOIETIN IN THE TREATMENT OF SEVERE PANCYTOPENIA DUE
TO CANINE MONOCYTIC EHRLICHIOSIS I.
Aroch and S. Harrus Koret
School of Veterinary Medicine, The Hebrew University of Jerusalem, P.O. Box
12, 76100 Rehovot, Israel |
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Abstract
The chronic severe form of canine monocytic ehrlichiosis (CME) is
characterized by severe pancytopenia, and carries a grave prognosis
despite treatment. Treatment options are usually limited to supportive
care, anti-ehrlichial drugs and blood component therapy. This case report
describes for the first time successful treatment of a dog with severe
chronic pancytopenia caused by CME. The treatment included a combination
of haematopoietic growth factors (recombinant human granulocyte colony
stimulating factor and recombinant human erythropoietin) and a long course
of glucocorticoid therapy. |
Canine
monocytic ehrlichiosis (CME) is a tick-borne (Rhipicephalus sanguineus)
disease of canids, caused by the rickettsia Ehrlichia canis, and is now
recognized worldwide (1). CME consists of acute, subclinical and chronic phases.
Dogs may recover from the acute phase of the disease without treatment, however
some remain subclinically infected, and several months to years later may
develop the severe pancytopaenic chronic stage. This pancytopaenic chronic phase
of CME has a grave prognosis despite therapy (1,2,3,4,5). Hematopoietic growth
factors have been proposed as a rational treatment for the chronic pancytopaenic
phase (5). However, no clinical trials using this mode of therapy have been
published. This report describes the successful treatment of a severely
pancytopaenic dog in the chronic stage of CME, with long-term corticosteroid
therapy in combination with two synthetic recombinant haematopoietic factors:
human granulocyte colony stimulating factor (rhG-CSF) and human erythropoietin (rh-EPO).
A
three-year old male weimaraner dog was referred to the Hebrew University
Veterinary Teaching Hospital with chief complaints of exercise intolerance for
the last 3 months, fever, and a history of tick infestation. Two weeks prior to
presentation, the referring veterinarian performed a complete blood count (CBC)
which revealed a severe pancytopenia {white blood cells (WBC) - 0.29x103/mm3,
platelets (Plt) - 2x103/mm3,
red blood cells (RBC) - 3.94x106/mm3}.
Serologic testing for E. canis with a commercial dot-blot enzyme-linked
immunosorbent assay kit (Biogal Laboratories, Galed, Israel) was strongly
positive. A presumptive diagnosis of CME was made, and the dog was treated with
doxycycline (5mg/kg q12h PO for 14 days) and imidocarb-dipropionate (5mg/kg IM,
single injection).
On the day of presentation (day 1) the dog’s general condition had deteriorated, it was lethargic, anorexic, emaciated and had a fever (40.60C), tachycardia (160/min), tachypnea (60/min), severe dyspnea, increased respiratory sounds and pale mucous membranes. CBC revealed severe pancytopenia (Table 1), severe anemia (RBC - 2.48x106/mm3), and no evidence of RBC regeneration in peripheral blood smears (reticulocyte count was 0%). The dog had hyperglobulinemia (globulin - 6.2g/dl), mild hypoalbuminemia (albumin — 2.4 g/dl), with an A/G ratio of 0.39. Thoracic radiographs showed signs consistent with severe bronchopneumonia. The E. canis IgG indirect immunofluorescence antibody test (IFA) titer was 1:5120. Severe chronic CME, with secondary bronchopneumonia, were diagnosed.
Table
1:
Hematological values of a dog with severe chronic pancytopenia due to CME,
successfully treated with hematopoietic growth factors and prednisone, during a
476 day period
|
Day |
WBC
(103/mm3) |
RBC |
HB
(g/dl) |
Ht
|
MCV
(fl) |
MCH |
MCHC |
Plt
( |
TS
(g/dl) |
|
1 |
0.2 |
2.84 |
6.4 |
19.5 |
69 |
22.5 |
32.8 |
6 |
86 |
|
4 |
1.0 |
3.24 |
7.4 |
21.4 |
66 |
22.8 |
34.5 |
30 |
82 |
|
10 |
2.1 |
2.66 |
6.1 |
18.0 |
68 |
22.9 |
33.8 |
12 |
92 |
|
11 |
2.7 |
2.97 |
7 |
20.5 |
69 |
23.5 |
34.1 |
5 |
80 |
|
16 |
2.0 |
2.63 |
6.4 |
18.7 |
71 |
24.3 |
34.2 |
21 |
80 |
|
26 |
1.3 |
2.41 |
5.9 |
17.7 |
73 |
24.4 |
33.3 |
22 |
72 |
|
41 |
1.8 |
2.00 |
5.3 |
16.4 |
82 |
26.5 |
32.3 |
13 |
74_ |
|
64 |
2.2 |
2.21 |
6.3 |
19.7 |
89 |
28.5 |
31.9 |
40 |
72 |
|
95 |
1.8 |
4.19 |
10.7 |
32.2 |
77 |
25.5 |
33.2 |
33 |
80 |
|
113 |
3.67 |
4.39 |
10.8 |
34.6 |
79 |
24.6 |
31.2 |
13 |
Nd |
|
142 |
4.5 |
4.92 |
10.8 |
33.1 |
67 |
21.9 |
32.6 |
64 |
78 |
|
191 |
11.8 |
5.14 |
11.5 |
33.7 |
66 |
22.4 |
34.1 |
3 |
Nd |
|
196 |
11.4 |
5.91 |
12.6 |
38.0 |
64 |
21.3 |
33.1 |
21 |
88 |
|
212 |
19.3 |
5.13 |
12.8 |
32.4 |
63 |
24.9 |
39.5 |
92 |
90 |
|
356 |
9.2 |
5.98 |
12.6 |
35.8 |
60 |
21.0 |
35.1 |
251 |
90 |
|
476 |
15.4 |
6.66 |
14.9 |
0.426 |
64 |
22.3 |
34.9 |
378 |
74 |
|
Reference
intervals |
5.5-17 |
5.5-8.5 |
12-18 |
37.0-55.0 |
55-77 |
19.5-24.5 |
32-36 |