Help with Non-regenerative anemia -> steroids or not?

RE: Help with Non-regenerative anemia -> steroids or not?

Andrew Kent — Sat, 02 Jan 2021 20:10:59 GMT

Thanks for the update Beats - hopefully you will get a response in the coming weeks.

Andy

RE: Help with Non-regenerative anemia -> steroids or not?

Beats — Sat, 02 Jan 2021 13:59:42 GMT

Follow-up:

Gave 1st (untyped) blood transfusion on Tuesday, when PCV had reduced to 9% and was becoming symptomatic and tired and started on 25mg azathioprine once daily (having relatively severe PUPD on steroids at this early stage).

RE: Help with Non-regenerative anemia -> steroids or not?

Andrew Kent — Sun, 27 Dec 2020 17:00:35 GMT

Great - glad the results have been helpful and more definitive. It may be worth adding a second immunosuppressant as these cases can often take a while to respond to treatment.

Andy

RE: Help with Non-regenerative anemia -> steroids or not?

Beats — Sun, 27 Dec 2020 14:05:50 GMT

Idexx were great (in terms of speed, responsiveness, detail and bone marrow expertise - very impressive day before Christmas!) and beyond my expectations got the blood smear looked at again AND bone marrow checked on Christmas Eve. Seems consistent with non-regenerative IMHA (precursor-directed immune-mediated anaemia) and was plenty of iron, so just continued with steroids (and omeprazole) over Christmas and crossed fingers would manage without blood transfusion...

"Erythrocytes:
Mild anisocytosis, rare ghosts are noted

Platelets:
Clumping present thus the reported concentration is a minimum value.

Leucocytes:
Occasional band neutrophil noted. Neutrophils occasionally have a foamy cytoplasm with increased basophilia (toxic change). Occasional lymphocyte has an increased amount of deep blue cytoplasm (reactive change)."

"SITE
Bone marrow

CYTOLOGICAL INTERPRETATION
1. Hypercellular marrow with erythroid predominance
2. Moderate to marked erythroid hyperplasia with moderate left shift
3. Evidence of erythrocyte destruction
4. Slight to mild reactive lymphoid hyperplasia

CYTOLOGICAL DESCRIPTION
Nine submitted slides, a direct and concentrated preparation are examined. Submitted smears have low to moderate cellularity variable preservation and erythrocytes and a light pink background. Fragments of spicules are noted which appear hypercellular comprising greater than 75% haematopoietic cells and less than 25% adipocytes.
The erythroid line is not complete with absence of polychromasia and low numbers of metarubricytes and polychromatophilic rubricytes. Nucleated differential count gives 50% late stage erythroid precursors and 12% erythrobalsts/early stages. Rare macrophage is noted containing late stage erythroid precursors.
Myeloid line is complete with the majority of cells being late stage precursors. A differential count gives 35% late stage cells (predominantly neutrophils and band neutrophils).
M:E is approx 0.5.
Other nucleated cells include low numbers of lymphocytes (approximately 4% of the total nucleated cell count) with scattered plasma cells noted.
Megakaryocytes are noted and with a mild increase in earlier stages.
Stainable iron is present and appears focally increased.

COMMENT
The cytological features are consistent with increased bone marrow cellularity due to erythroid hyperplasia. The absence of late stages and the evidence of destruction reflect ineffective erytopoiesis due to IMHA as you suspect. Immune mediated destruction targets metarubricytes and reticulocytes and the anaemia may be augmented due to vascular injury, inflammation, macrophage activation, myelodysoplasia and myelofibrosis. The negative Coombs test is noted but this would only be positive if antigens common to erythroid precursors and mature erythrocytes were targeted. Haemosiderin is commonly increased in cases of immune mediated haemolytic anaemia but is increased in other pathology also. Less common reasons for ineffective erythropoesis include severe iron deficiency, myeloid neoplasia and congenital dyserythropoesis.I note the peripheral indicies (although MCV is normal but this can be due to swelling or agglutination which I was not convinced for) and while Fe deficiency was a consideration initially there is sufficient/increased iron in the marrow and with the destruction it points to IMHA."

"DIAGNOSIS

1. Hypercellular marrow
2. Marked erytroid hyperplasia with moderate left shift
3. Mild reactive lymphoid hyperplasia

CLINICAL HISTORY
Please see cytology report

HISTOLOGY
Sections of core biopsy microscopically examined. Sections comprise marked haematopoietic tissue between moderately preserved trabecular bone. Sections are hypercellular.
The majority of cells are erythroid with an increase proportion of erythroblasts noted and lesser numbers of very late stage precursors noted. 
Myeloid cells are present and are predominantly late stage myeloid.
Megakaryocytes are noted and are predominantly mature.
Scattered plasma cells and small lymphocytes are noted. 
Occasional macrophage is encountered.
Stainable iron is abundant 

COMMENT
The findings reflect the cytological suspicion of a hypercellular marrow. The majority of cells are erythroid with low numbers of late stage and a lack of normal progression. This reflects cytology and further evidence of ineffective haematopoiesis. Destruction is difficult to identify on histology.
Stainable iron is abundant which we see with IMHA. There is no evidence currently of myelofirbosis which can occur with prolonged IMHA. No neoplastic cells are encountered."

RE: Help with Non-regenerative anemia -> steroids or not?

Beats — Wed, 23 Dec 2020 21:48:19 GMT

Thanks Andy! Really appreciate your response on Christmas Eve Eve!!

I can't decide whether to trust the lab smear assessment or my own (and not sure I'll get anything further this side of holidays, but I might yet). I was perhaps just seeing what I expected to see and biased by the fact that its face looked like it had IMHA, while the lab is going to be more objective, so perhaps I should trust that one more.

I'll start some oral iron - I have some sytron on the shelf in-date I think so will probably start with that.

I didn't send serum, so options I see at Idexx of Iron (Total) [FE] or Total Iron Binding Capacity (TIBCR) can't be done for week yet. If I take a sample pre-iron supplementation starting tomorrow, do you know if better to keep in fridge or freeze? I can't readily find that information? Don't see Ferritin as an Idexx test, but can send elsewhere if this would be useful potentially - is that on serum also? Will ask to stain the bone marrow for iron if that still seems a worthwhile thing once more results come in from lab next week.

Still not sure what I think best with steroid dose... if might be IMHA, then no steroids for a week might be fatal (Pet Blood Bank no longer delivering to Northern Ireland + all staff donor dogs used in last month...)... if might be nsaid induced GI ulceration then continuing steroids may be fatal... I guess that's where the imaging should be coming in in helping to decide...

Coombs has also come back negative (had been on steroids for a week), not clear if run on peripheral blood or bone marrow sample.

RE: Help with Non-regenerative anemia -> steroids or not?

Andrew Kent — Wed, 23 Dec 2020 21:30:33 GMT

Difficult when there is a discrepancy between what you saw and what the lab report. Although the response to iron is often quite quick so you lose nothing by seeing if this helps.

Would certainly be worth getting iron evaluated. In simple terms you can look at serum iron or you can get more complex and look at ferritin or iron saturation. You could also get bone marrow stained for iron.

A bone marrow disease is also possible with immune mediated most common - these are a challenge as the time to get a response can be long.

the review of the smear and the bone marrow will help but until you clear it up I would be cautious giving too much steroid and likely give some iron.

Andy

RE: Help with Non-regenerative anemia -> steroids or not?

Beats — Wed, 23 Dec 2020 21:18:27 GMT

And the rbcs looked normochromic to me last week and at weekend. I've only seen couple of cases of iron-deficiency anemia in past, and these would presumably have been much more chronic and maybe extreme, but the rbcs looked pale and hollow and there were obvious what I would call leptocytes. These rbcs looked mostly rather normal to my non-expert eye.

No abdominal imaging done to-date. Abdomen has been soft and comfortable and easily palpated throughout. I'm not sure my skills as an ultrasonographer would add too much at this point, especially in non-fasted patient. I've got an endoscope of sorts, but again my skills make that more limited than what you might imagine the value to be... I can usually take a lovely xray though :-)

RE: Help with Non-regenerative anemia -> steroids or not?

Beats — Wed, 23 Dec 2020 21:10:56 GMT

Thanks Andy!!! I wasn't expecting a response, only hoping!

7 to 8 year old. Fit as a fiddle - still very lively and chasing ball at PCV=14%. Previous bilateral cruciate surgery within last 12 months, and recent pin removal in October (believe was irritating as exiting caudal cortex of proximal tibia rather than thought infection etc) only health issues.

Today's lab results (yesterday's blood) retyped with last week's lasercyte ones in [brackets] after:

Parameter x.xx (reference interval x.xx-y.yy) [last week's in-house lasercyte restults for comparison x.xx]

RBC 2.24 (5.39-8.7) [Last week in-house lasercyte = 3.10]

HCT 0.159 (0.282-0.565) [0.197]

Hgb 48 (134-207) [73]

MCV 71 (59-76) [63.6]

MCH 21.4 (21.9-26.1) [23.4]

MCHC 302 (326-392) [369]

Retics 21.5 (<=110) [41.7]

Retic Hgb 23 (24.5-31.8) [not given by lasercyte on sample last week]

WBC 15.8 (4.9-17.6) [8.81]

Neuts 12.8 (2.94-12.67) [5.94]

Lymph 0.95 (1.06-4.95) [2.07]

Monocytes 1.58 (0.13-1.15) [0.64]

Eosin 0.47 (0.07-1.49) [0.15]

Platelets 462 (143-448) [518]

Red cells appear microcytic and hypochromic. Rare ghost cells seen.
No increase in polychromasia observed.
No abnormal white cells seen. Smear confirms mature neutrophilia.
Blood film suggests platelet numbers are increased.

=========================== FURTHER REPORT =============================  

The marked anaemia is non-regenerative, as you reported. The technician reports microcytosis and hypochromasia that is compatible with iron deficiency, typically associated with chronic external (usually GI) blood loss, rarely dietary. However ghost cells have also been reported therefore potentially there is concurrrent intravascular haemolysis; a clinical pathologist will review the fresh blood smear(s) and a further report will follow. Low reticulocyte Hgb suggests either iron sequestration or absolute deficiency is limiting erythroid regeneration, although this may not be the only factor; further pathologist assessment pending.

The leukogram reflects a stress/steroid response, potentially with concurrent inflammation. Thrombocytosis is commonly associated with iron deficiency.

My Q's (I added at end of first post, but you might not have seen there as done as edit)

The rbcs on smear last week and again at weekend had looked fairly unremarkable to me, and the MCV seems normal enough (I guess could be ageing artifact increasing it compared to fresh smears sent to lab, but only 24hours in post), so I'm not too sure what to make of this lab report. I had been thinking IMHA (primaily directed at bone marrow?) to be more likely than NSAID induced GI bleeding, but now I'm not so sure...

Do I continue the steroids while waiting for more results?

Is it worth requesting iron measurements or any other tests on submitted samples urgently tomorrow morning while lab still open on chance that get result before close at lunch (if so what ones and on peripheral blood or bone marrow)?

RE: Help with Non-regenerative anemia -> steroids or not?

Andrew Kent — Wed, 23 Dec 2020 20:52:02 GMT

Hi Beats

difficult to read the blood results in that format could you try in a different way?

from the half lines I can see looks like the lab is suspicious of iron deficiency which could be due to chronic bleeding from NSAID or something else. How old is the dog? Any abdo imaging performed?

I would be cautious with steroid at this stage and perhaps treat with iron and antacids first?

Andy