neutropaenia in a cat

Re: neutropaenia in a cat

Marie Kubiak — Sat, 01 Mar 2014 11:27:27 GMT

Thanks Rory, in that case I shall leave retroviral testing alone for the time being. I'm learning lots about feline medicine so this is great CPD!

Marie

Re: neutropaenia in a cat

Rory Bell — Sat, 01 Mar 2014 10:53:23 GMT

Hi Marie

Regarding confirmatory testing for retroviral infection......short answer is no, I wouldn't do anything else at this stage.

Long answer (with apologies)...the diagnostic performance (accuracy) of the screening tests for retroviral infection (FeLV ELISA for antigenemia and FIV ELISA for antibodies) is very high. Your cat is healthy, and, despite his background (free ranging outdoor male) our pre-test probability that he actually has a retroviral infection is quite low. This in turn adversely affects the positive predictive value of any diagnostic test; i.e the chance of a false positive result increases.

IN terms of the specific diagnostic test used.....

Viral isolation is the 'gold standard' but is laborious and rarely performed. Glasgow will do FeLV isolation, but with a 1-3 week turnaround.

IFA for FIV does not perform as well as serology in terms of being somewhat less sensitive (it looks for virus in leucocytes, so false negatives become more likely in leucopaenic cats) and you need very competent lab staff as non specific staining in eosinophils can give rise to false positives.

Western blotting for FIV antibodies is more specific than ELISA, but is usually used for inconclusive results. Both tests are almost equally sensitive. In your cat, I'd be inclined to perform western blotting if the ELISA was positive to confirm the positive result...as mentioned above, the positive predictive value of even a very specific test is relatively low in this case.

PCR testing is bit of a minefield.

In terms of FIV, there are 5 different subtypes with about 25-30% genetic diversity between the subtypes. This makes it tough to design a PCR primer that will reliably amplify DNA from all the subtypes. Because of this, in most instances serology is more accurate (exceptions are in cats with late stage disease, early infections (prior to seroconversion) and kittens with maternally derived antibodies.

In terms of FeLV, its now recognised that cats generally do not completely eliminate virus following infection, and proviral DNA can be found in healthy cats that seemingly never go on to develop FeLV associated disease (so called regressive infection). This makes is VERY hard to interpret a positive PCR result in a healthy cat! PCR for FeLV RNA is probably more accurate in that a positive means the cats is in fact viraemic, but isn't yet commercially available.

If your cat actually becomes ill, then of course all bets are off, and I would be very keen to perform western blotting for FIV and probably viral isolation for FeLV on peripheral blood and if you got to the stage (hypothetically) of getting bone marrow, I'd also submit that for viral isolation and PCR (FeLV) and PCR (if available) and IFA (FIV).

Hope this helps, I think my short answer was probably more beneficial!

Re: neutropaenia in a cat

Marie Kubiak — Sat, 01 Mar 2014 09:27:36 GMT

That seems logical, thanks for the explanation.

Marie

Re: neutropaenia in a cat

John Flynn — Sat, 01 Mar 2014 09:22:12 GMT

[quote user="Marie Kubiak"]

[quote user="Andrew Kent"]Usually the stress response causes neutrophils to move from the marginating to circulating pools and so I would wonder with your samples whether the low ones are just normal for your cat and whether the higher one was associated with slightly more stress.[/quote]

Looking back, the only normal value was the sample collected at home so should have been lowest stress in theory (though this was a few days after surgery so perhaps a lag effect of this stress?)

[/quote]

Here's some more rambling thoughts to share that may or may not be correct/useful!

There's 2 different "stress" responses that might be confused here (and I think these might go for most mammals to a degree with the significance depending on factors such as percentage of marginated to circulating leukocytes etc?)

An adrenaline-"stress" response: This is where adrenaline associated with eg being restrained for a blood sample leads to an increase in blood flow that "washes" some of the marginated leukocyte population into the circulating population. When you take the blood sample, you are sampling the circulating population, so if more of the marginated wbcs are now in that circulating poplulation you will get higher numbers. I think in cats they have a particularly high percentage of marginated leukocytes - typically I'd expect the lymphocyte numbers to go up (esp in a cat) as well as neutrophil numbers as they both get "washed" off the sides of blood vessels by the incraesed blood flow.

A glucocorticoid-"stress" response: This is the effects of cortisol on the leukogram, classically considered in the human/dog as neutrophilia, lymphopenia, eosinopenia, monocytosis. Cats seem a little less subject to this in my personal experience than the dog, but I don't know what the modern consensus is.

Anyway, either "stress"-response could in theory cause an increased neutrophil count in a cat. So post-surgery, you could have a glucocorticoid-response leading to higher levels, even if in your home the adrenaline levels at time of restraint and sampling were lower than on other occasions.

Significance? Well, if the highest neutrophil count was obtained in a sample under the least stress, then it seems less likely that this was an adrenaline-response leading to sampling of more of the neutrophil pool as opposed to genuinely higher neutrophil numbers. That would reassure me somewhat as the implication might be that there was genuinely a higher neutrophil count and that the cat could (perhaps in response to surgery?) produce an increase in neutrophil numbers.

Re: neutropaenia in a cat

Marie Kubiak — Sat, 01 Mar 2014 09:04:07 GMT

Thanks everyone for the replies, I feel a bit happier now knowing that not subjecting him to a barrage of tests isn't the worst thing I can do!

[quote user="Rory Bell"]

On another tack, this neutropenia is not going to be due to consumption because he's otherwise well (unless he's got an immune mediated neutropenia which is vanishingly rare esp in cats), he's not got a retroviral infection (as far as we know) and bone marrow disease is unlikely (provided that jump in the haematocrit is real), so why not delay further investigation until he demonstrates that there is actually a problem?

let me know if you've any questions![/quote]

Do you think it is worth pursuing further retroviral tests at this stage? I know standard serology can give false negatives - my colleague has suggested western blot or virus isolation would be more sensitive and if these can be done on the same blood draw then I'm willing to do so.

Looking back, the only normal value was the sample collected at home so should have been lowest stress in theory (though this was a few days after surgery so perhaps a lag effect of this stress?)

[quote user="Braden Collins"]What would you do if it was a clients cat?[/quote]

Hand it on to a small animal vet and sigh with relief

Marie

Re: neutropaenia in a cat

Kate Richardson — Fri, 28 Feb 2014 15:28:58 GMT

[quote user="Marie Kubiak"]The first sample was under at least pre-med (ACP/buprenorphine) [/quote]

That would definitely explain the lower HCT on the first sample.

Re: neutropaenia in a cat

Braden Collins — Fri, 28 Feb 2014 09:14:08 GMT

What would you do if it was a clients cat? I think sometimes we start to overthink things when it is our own pet.

My feeling: treat the cat, not the numbers on the lab form. If the cat seems well, I wouldn't be doing anything else.

Re: neutropaenia in a cat

Andrew Kent — Fri, 28 Feb 2014 08:09:47 GMT

I would wonder how much of a problem this really is. Cats have very sticky neutrophils and so a large number of them sit within the marginating pool, as blood sampling only shows the circulating pool a neutropenia is not that uncommon. Usually the stress response causes neutrophils to move from the marginating to circulating pools and so I would wonder with your samples whether the low ones are just normal for your cat and whether the higher one was associated with slightly more stress.

You could test this by trying to exercise the cat (chase around the consult room?) prior to sampling and seeing what the neutrophils are doing.

Many people have neutrophil counts below the reference range without a problem, so personally I wouldn't investigate further unless I have more evidence of a problem.

Andy

Re: neutropaenia in a cat

Marie Kubiak — Thu, 27 Feb 2014 21:20:58 GMT

Sure, platelets have been lower end of reference range but never below it.

Marie

Date of Sampling: 07/02/2014 Tests Requested:
Basic Screen Interpreted

HAEMATOLOGY

Test Result Alert Units Reference Range

*Red cells 5.53 10^12/L 5.00 - 10.00
*Haemoglobin 8.9 Low g/dL 9.0 - 15.0
*Hct 0.286 l/L 0.260 - 0.470
*MCV 51.7 fL 35.1 - 53.9
*MCH 16.1 pg 13.0 - 17.5
*MCHC 31.1 g/dL 28.0 - 36.0
*Absolute retic. count 5.5 10^9/L <= 50.0
*White Cells 3.0 Low 10^9/L 6.0 - 15.0
*Neutrophils (Absolute) 1.68 Low 10^9/L 2.50 - 12.50
*Neutrophils 56 %
*Lymphocytes (Absolute) 1.05 Low 10^9/L 2.00 - 7.00
*Lymphocytes 35 %
*Monocytes (Absolute) 0.12 10^9/L <= 0.60
*Monocytes 4 %
*Eosinophils (Absolute) 0.15 10^9/L 0.00 - 0.70
*Eosinophils 5 %
*Platelet count 193 10^9/L 150 - 550
*Analyser ID Results generated by SYSMEX XT2000
*Morphological Assessment : No abnormal cells seen.

Feline Leukaemia Virus, FIV Antibody Test both negative

Fresh and EDTA films: the morphological features are as described. Film
examination verifies the low white cell count. No left shift is identified
but there are small numbers of small Dohle bodies in the fresh film. Small
platelet aggregates in both films suggest that the platelet count given is
a minimum estimate.

---------------------------------------------------------------------------------------------

Date of Sampling: 12/02/2014 Tests Requested:
FULL BLOOD COUNT (SMALL)

HAEMATOLOGY

Test Result Alert Units Reference Range

Full Blood Count
*Red cells 7.93 10^12/L 5.00 - 10.00
*Haemoglobin 12.5 g/dL 9.0 - 15.0
*Hct 0.454 l/L 0.260 - 0.470
*MCV 57.3 High fL 35.1 - 53.9
*MCH 15.8 pg 13.0 - 17.5
*MCHC 27.5 Low g/dL 28.0 - 36.0
*Absolute retic. count 25.4 10^9/L <= 50.0
*White Cells 6.2 10^9/L 6.0 - 15.0
*Neutrophils (Absolute) 3.53 10^9/L 2.50 - 12.50
*Neutrophils 57 %
*Lymphocytes (Absolute) 1.80 Low 10^9/L 2.00 - 7.00
*Lymphocytes 29 %
*Monocytes (Absolute) 0.37 10^9/L <= 0.60
*Monocytes 6 %
*Eosinophils (Absolute) 0.50 10^9/L 0.00 - 0.70
*Eosinophils 8 %
*Platelet count 167 10^9/L 150 - 550
*Analyser ID Results generated by SYSMEX XT2000
*Morphological Assessment : Small platelet clumps seen. Platelet count and
estimate should be considered minimum value.
No abnormal cells seen.

--------------------------------------------------------------------------------------------------

Date of Sampling: 22/02/2014 Tests Requested:
FULL BLOOD COUNT (SMALL)

HAEMATOLOGY

Test Result Alert Units Reference Range

Full Blood Count
*Red cells 7.72 10^12/L 5.00 - 10.00
*Haemoglobin 12.5 g/dL 9.0 - 15.0
*Hct 0.436 l/L 0.260 - 0.470
*MCV 56.5 High fL 35.1 - 53.9
*MCH 16.2 pg 13.0 - 17.5
*MCHC 28.7 g/dL 28.0 - 36.0
*Absolute retic. count 28.6 10^9/L <= 50.0
*White Cells 3.9 Low 10^9/L 6.0 - 15.0
*Neutrophils (Absolute) 1.48 Low 10^9/L 2.50 - 12.50
*Neutrophils 38 %
*Lymphocytes (Absolute) 2.03 10^9/L 2.00 - 7.00
*Lymphocytes 52 %
*Monocytes (Absolute) 0.16 10^9/L <= 0.60
*Monocytes 4 %
*Eosinophils (Absolute) 0.23 10^9/L 0.00 - 0.70
*Eosinophils 6 %
*Platelet count 172 10^9/L 150 - 550
*Analyser ID Results generated by SYSMEX XT2000
*Morphological Assessment : No abnormal cells seen.

Re: neutropaenia in a cat

Rory Bell — Thu, 27 Feb 2014 21:18:18 GMT

Marie

I'd agree with what Martin and Kate have said; watch and wait. I've investigated a few neutropaenic cats who are otherwise healthy, enough to make me reticent to do so in the future......simply because I've seldom found anything wrong with those cats. Don't get me wrong, I'd completely agree with the investigation that you're colleague suggested, all I'm saying is that I've done that, including a bone marrow, and rarely found anything wrong.

let me know if you've any questions!

Re: neutropaenia in a cat

Christopher Saul — Thu, 27 Feb 2014 20:29:04 GMT

Hi Marie

I'm so sorry for the exceptionally quick reply to this but I'm just on my mobile phone whilst waiting for an emergency which is about due to arrive

What were the platelets doing? can you post the full blood count? The 3 cell lines I tend to look at first are: neutrophils, PLT and RBC. If there are cytopenias in more than one of these 3 then there is more suspicion of bone marrow disease..

Will try to reply in depth later but to be honest what others have already posted sounds sensible so far....

Cheers

Chris

Re: neutropaenia in a cat

Marie Kubiak — Thu, 27 Feb 2014 19:59:01 GMT

Hi,

The first sample was under at least pre-med (ACP/buprenorphine) as he wasn't very co-operative for my colleagues and was having a GA at this point anyway. I did wonder if it was done after IV fluids with the Hct variation but I'm sure she wouldn't have left sampling till late on in the anaesthetic but will double check that. The rest I have done conscious with a bit of a fight as he is slightly better with me so will continue to do this.

Marie

Re: neutropaenia in a cat

Kate Richardson — Thu, 27 Feb 2014 19:18:03 GMT

Hi Marie, I also agree with monitoring if your cat is well. I would probably do every 2-4 weeks though unless he shows signs of illness, maybe check his temperature at home periodically? Re Toxo serology- be careful interpreting especially in the abscence of any clinical signs. Out of interest, was the first sample taken under sedation? As John pointed out quite a jump from HCT of 0.28 to 0.45! Also remember normal ranges are normal for most of the population, but not all; there will always be some who sit on the boundaries. Kate

Re: neutropaenia in a cat

Marie Kubiak — Thu, 27 Feb 2014 15:05:55 GMT

Hi, thanks both.

He is on amoxy-clav now and I plan to do weekly monitoring bloods (plus viral and toxo serology).

Spleen doesn't feel large/irregular and he remains apparently clinically normal. I think I may be more inclined to consider more invasive testing if this is a persisting problem or he shows even the slightest sign of being unwell but for now will stay fairly conservative.

Marie

Re: neutropaenia in a cat

Martin Atkinson — Tue, 25 Feb 2014 19:25:15 GMT

Some cats have idiopathic leucopaenia and suffer no symptoms. You've done retroviruses and looking at Toxo, and although unlikely it might be worth an FIP/FCoV and FPV tests while you've got some blood as well. You've said abdominal palpation is NAD but what did the spleen feel like?Bone marrow biopsy may be next but you have said you don't want to anything invasive so as John says, if the cat is well just monitor for now.

Re: neutropaenia in a cat

John Flynn — Tue, 25 Feb 2014 19:02:40 GMT

Here's a few thoughts (or probably more questions to spark thoughts):

1) Those haematology results all look a bit funny to me. Firstly as a ball-park the HCT is usually about 3 times the Hb. Secondly, I very much doubt that a true HCT changed from 29% to 45% in 4 days given a description of no regeneration on day1! That's enough funny business to make me question things... was the cat sedated for one or more of these blood samples for instance? Are they all external lab ones? Were manual HCTs and blood smears done fresh on all occasions etc etc.

2) I would treat the cat foremost. The haemtology was done because he was having a lump removed, not because he was noted to be ill. He may have had wbcs in this range for years if they are genuine results. OK it might have flagged something up, but I'd do little more than monitor the haematology (along with his weight, general health etc) at most personally.