Leukogram Patterns in Disease
World Small Animal Veterinary Association World Congress Proceedings, 2003
Fred Reyers, MMedVet (KLD)
Section of Clinical Pathology, Faculty of Veterinary Science, University of Pretoria
Onderstepoort, Republic of South Africa

Interpreting a leukogram can be a daunting task. One has to interpret both the presence of as well as the degree of the abnormality. For instance, leukocyte counts of 5.5 and 0.5 x 109/l are both leukopenias, but the disease processes responsible are, in all probability, very different. Furthermore, the relationship of one numeric result to one or more other results may play a pivotal role in the interpretation. For instance, a neutropenia in the presence or absence of a "left shift" leads to quite different interpretations. There are also some "given truths" that need to be re-examined (e.g., lymphocytosis and viral disease) and certain definitions need clearing up (e.g., degenerative left shift).

In order to provide some guidelines for interpretation and address the latter problems, the Onderstepoort Academic Teaching Hospital computerized case database for the period March 1998 to June 2002 was merged with the Department of Companion Animal Clinical Studies, Clinical Pathology laboratory database for canine leukograms. Only first visit records were retained and only those cases where a diagnostic entry had been made were included. This yielded 5739 leukograms. The cases were classified into 25 diagnostic groups (principally based on organ systems) and most of these were further sub-classified to yield a total of 69 diagnostic categories. All reported cell counts, below, are in the SIU system (x 109/l).

Neutrophilia: This is common, being seen in 39.4% of cases. Most veterinarians would have expected patients with bacterial or purulent lesions to be those most strongly associated with neutrophilia. However, neutrophilia was recorded in 89% of primary immune-mediated haemolytic anaemia (IMHA) cases, with counts reaching 77 (half of the cases exceeding 30). By contrast, only 51% of the 144 cases that had trauma-induced purulent/septic lesions (dog fight wounds etc) had neutrophilia and only 8% had counts exceeding 30. The pattern for peritonitis and pancreatitis cases was very similar to the septic trauma cases. Canine babesiosis cases, on average, had very pronounced neutrophil responses, and those associated with secondary IMHA (usually with autoagglutination) had very similar levels of neutrophilia to the primary IMHA cases. In fact, the two very highest neutrophil counts (133.9 and 131.6) were found in two cases of Spirocerca lupi infection (a helminth parasite). So, although bacterial/purulent processes are very definitely associated with neutrophilia in just over half the cases, the inflammation caused by IMHA (sterile), canine babesiosis (protozoal) and spirocercosis (helminth) often induce more profound reactions.

The neutrophilic "left shift" Regenerative left shifts (RLS): The incidence closely parallels the picture seen in neutrophilia, above, and is seen in 24% of cases. In addition, a few other disease categories come to the fore. Pancreatitis cases, not unexpectedly, exhibit a RLS in 38% of patients. Immune-mediated thrombocytopenia (IMTP) cases exhibit a RLS in a third of cases (not surprising, considering the finding in IMHA). However, congestive heart failure patients have a RLS in 43% of cases (certainly not the sort of "inflammatory" disease we associate with RLS). Acute hepatopathies and rodenticide toxicoses both exhibit RLS in a third of cases (again, not the sort of conditions we look upon as being very inflammatory).

Degenerative left shifts (DLS): It is generally accepted that a DLS is a sign of a poor prognosis. However, there are numerous definitions of DLS. They include:

1.  Immature neutrophils exceed mature neutrophils

2.  Immature neutrophils are significantly raised while total neutrophils are normal or decreased

3.  Immature neutrophils are significantly raised while total neutrophils decreased

To decide which definition is the best "prognosticator", we compared the first two definitions, above (being the most commonly held) against the database records of deaths and euthanasia. Admittedly, euthanasia may be a decision based on financial or emotional considerations ("Fido will be better off dead"), but the findings were surprisingly similar. Considering the rule (Ni>Nmat), 7.1% of deaths were predicted and 2.5% of euthanasia decisions. Whereas, the rule (Ni increased and Ntot not increased) yielded the following: 15.7% of deaths predicted and 9.8% of euthanasia decisions (twice and four times as good, respectively). It would appear that the second definition is more useful as a prognostic indicator.

Neutropenias Neutropenia WITHOUT left shift: This is generally accepted to reflect myeloid suppression or marrow aplasia/failure. It is not commonly found (7.3% of all cases) but some 50% of chronic ehrlichiosis and canine parvoviral diarrhoea cases (CPV) exhibit this pattern.

Neutropenia WITH left shift: This pattern suggests that the marrow is still producing cells but is unable to keep up with the demand for neutrophils to leave circulation. It is a surprisingly rare finding (1.9% of cases), and occurs, not too surprisingly in one in six CPV cases. It is also seen in one sixth of Canine Distemper virus (CDV) cases, whereas these patients very rarely (less than 3% of cases) develop the marrow failure pattern seen in half the CPV cases. It is notable that this pattern was not seen at all in chronic ehrlichiosis cases and only once in any of the 140 ehrlichiosis cases.

Lymphopenia is common, occurring in 29% of all cases, but is most consistently present in canine distemper virus infection (23 of 33 cases, 70%), followed by canine ehrlichiosis (60% in chronic and 43% in early cases-quite at variance with recent literature). As expected, in canine Cushing's disease, lymphopenia is seen in many cases (51%). However, the finding that Diabetes mellitus has the same frequency of lymphopenia, is unexpected, possibly indicating a large proportion of secondary DM. Renal disease (acute {47%}, chronic {46%} and glomerular {54%}) was also not entirely predictable, as was hepatic neoplasia (47%), although the stress of being very ill may play a role. A well known, though counterintuitive, lymphopenia in 48% of lymphoma cases was recorded. In contrast, 49% of general immune-induced disease (such as lupus, pemphigus etc), present with lymphopenia.

Lymphocytosis, by contrast is relatively rare (4.5% of cases). Lymphoid leukaemia (72%) predictably led the field. Of the top 12 lymphocyte counts, 5 were lymphoid leukaemia and 3 Stage V lymphomas. Far behind, but still significantly above the average were glomerulonephropathy (15%), hepatic portosystemic shunting (14%) and primary (11%) as well as secondary IMHA (12%). Striking, is the finding that none of the 55 canine Cushing's and 47 diabetics, had a lymphocytosis.

Monocytosis was a common finding in our database (33.3%), probably due to the high prevalence of canine babesiosis. Babesiosis cases made up 68% of the 40 highest monocyte counts (10 to 22). IMHA (secondary and primary) had the highest incidence (64% and 53%) respectively. Babesiosis, is very frequently associated with monocytosis (40%). About one third of spirocercosis, glomerulopathy, acute renal, pancreatitis, peritonitis/pleuritis and general immune-induced disease, presented with monocytosis. Surprisingly low on this list was ehrlichiosis (2%), but see below.

Monocytopenia, an infrequently discussed pattern was quite rare (7.75% of cases). However, well above the average were chronic ehrlichiosis (60%) and acute ehrlichiosis (20%). This is, of course, quite different from the pattern that is reported in the literature. Addison's disease (19%), intestinal malassimilation (19%) as well as CDV and CPV (both at 15%) were the only other disease categories with a significant prevalence of monocytopenia.

Eosinopenia is very common, occurring in 41% of all cases. Babesiosis (58%),congestive heart failure (CHF) (57%), CPV (47%), IMHA (45%), acute ehrlichiosis (40%) and CPV (36%) stood out.

Eosinophilia, by contrast, is relatively uncommon and was seen in only 6.0% of cases in the database. As expected, verminosis (26%), led the way, although 23% were eosinopenic. Also expected, due to the prevalence of PIE, tracheo-bronchial disease (26%) cases exhibited eosinophilia as frequently as verminosis cases. Five of the 12 highest eosinophil counts (7 to 42) were tracheo-bronchial with only one verminosis. More unexpected, were hypothyroidism (22%), chronic hepatopathies and gynaecological cases (both 20%). Even more unexpected was the finding that 23 of the 116 cases of epilepsy (20%) had eosinophilia. Only 14% of Addison's disease cases had eosinophilia.

Basophilia (defined as "basophils reported"), tended to parallel eosinophilia, being as efficient a predictor of verminosis (26%), eosinophil-associated pulmonary disease (21%) and hypothyroidism (25%) as eosinophilia. Interesting "oddities" included otitis (23%), snake bite toxicosis (25%, none of which had eosinophilia), lower urinary tract disease and myopathies (both 25%) as well as chronic ehrlichiosis (20%). Basophils were also a more consistent indicator of Addison's disease (29%) than eosinophils (14%).

Thrombocyte counts. Thrombocytopenia is common (42%), but the outstanding thrombocytopenia-related diseases (below a count of 25) were babesiosis (94%), ehrlichiosis (90%) and IMTP (87%).

Thrombocytosis was quite uncommon (9%) with three endocrinopathies standing out: hypothyroidism (44%), diabetes mellitus (40%) and canine Cushing's (36%). The 12 highest platelet counts (all exceeding 900) included 5 diabetes, 2 hyperestrogenism and two IMHA cases.

Leukocyte response combinations

These may also provide some interesting insights or pose some searching questions into the underlying pathophysiology of diseases. For instance, although babesiosis and IMHA present as similar clinical cases and have many leukocyte reactions in common (see above), a combination of neutrophilia and monocytosis acts as a very useful distinguishing criterion (78% in babesiosis and only 8% of IMHA cases). Concurrent monocytosis and thrombocytopenia is also a useful discriminating factor for these two diseases (babesiosis 31% and IMHA 11%). Neutrophilia with monocytosis is quite common (23%) but is seen, particularly in neoplasia (59%) although only in 10% of lymphomas. A combination of neutropenia and lymphopenia is uncommon (4%) and besides ehrlichiosis (at 30%, expected from a pan-cytopenia point of view but unexpected from the recent lymphocytosis report) was found in 44% of CPV and only 6% of CDV giving a fairly clear indication of the different effects of the two viruses on leukocytes (70% of CDV lymphopenic and 65% of CPV neutropenic). An interesting incidental observation is that 13% of spinal disc disease cases present with this pattern.

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Fred Reyers, MMedVet (KLD)
Section of Clinical Pathology, Faculty of Veterinary Science
University of Pretoria
Onderstepoort, Republic of South Africa


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