Non-regenerative anaemias Flashcards

1
Q

What are the 4 Hs of non regenerative anaemias?

A
Haemolysis at precursor stage
Per acute haemorrhage
Haemodilution
Hypoplasia - BM damage/ Fe deficiency due to chronic haemorrhage
Anaemia of chronic dz
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2
Q

When may you see Pica?

A

chronic Fe of anaemia

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3
Q

When may you see retinal bleeding without hypertension?

A

anaemia

possibly due to vasodilation and vascular leak

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4
Q

What do you see on clin path with the 4 non regenerative anaemias?

A

Haemolysis at precursor stage - inflammation, other cytopaenias, normal MCHC and MCV
Per acute haemorrhage - Low TP, low platelets, normal MCV and MCHC
Haemodilution - mild anaemia, low TP and albumin, lack of clinical signs, normal MCHC and MCV
Hypoplasia - BM damage - cytopaenias, normal MCV and MCHC
Fe deficiency due to chronic haemorrhage - moderate anaemia, rarely severe, Low MCHC and MCV
Anaemia of chronic dz - mild to moderate anaemia, normal MCHC and MCV

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5
Q

What are the differentials for non regenerative anaemia of non BM origin?

A
Inflammatory disease/ cancer - d/t cytokine derangements, low EPO, functionally altered metabolism
CKD/ kidney failure
Low T4
Addisons
Liver disease (chronic)
Fe deficiency
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6
Q

What are the differentials for non regenerative anaemia of BM origin?

A

• Auto‐immunity
– None regenerative IMHA / PRCA / aplastic anaemia / immune mediated neutropenia

• Infectious disease

• Neoplasia
– Haemophagocytic syndrome
– Neoplasia ablating affecting bone marrow (Myeloma, lymphoma leukaemia)

• Toxin / drug induced dyscrasias / dysmyelopoesis

• Haematologic disorders secondary to other diseases
– Particularly lack of EPO associated with kidney failure

• Myelonecrosis/fibrosis – end stage

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7
Q

What are the 3 types of immune-mediated disease of RBCs?

A

Of rubriblasts - pure red cell aplasia
Of precursor cells - non regenerative IMHA
In blood - regenerative IMHA

So in a precursor IMHA, will see low numbers from the level that is being destroyed, and higher levels of precursors to this
Clin pathologists will assess the ratio or erythroid v myeloid cells.
Earlier in the process the destruction is, the longer it will take to see an improvement

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8
Q

How do you diagnose a non regenerative IMHA

A

Will not see spherocytes, agglutination, -ve coombs

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9
Q

What are the initial DDx you should rule out for non regenerative IMHA?

A

Cats - FeLV, FIV, FIP, mycoplasma
drug reactions, myelodysplastic syndrome

Dogs - drug reactions, toxins (esp lead)
infections -erlichia, leishmania, babesia

then move onto BM ddx

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10
Q

What are the BM ddx you need to rule out to diagnose non regenerative IMHA?

A

– Erythroid hyperplasia, maturation arrest or PRCA
– Dysplastic changes, dysmyelopoesis, myelofibrosis, myelonecrosis and inflammation
– Dogs ‐ marrow plasma cell hyperplasia
– Cats – marrow and peripheral lymphocytosis

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11
Q

Outline pure red cell aplasia

A

– More common in cats than dogs
– Immune mediated +/‐ FeLV subgroup C in cats
– Severe non‐regenerative anaemia normochromic,
normocytic anaemia and marked erythroid hypoplasia.
– Early precursor targeted
– Lymphocytosis in cats
– Normal plts and neutrophils

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12
Q

What is myelopthisis?

Give some examples

A
• Normal precursors are crowded out
• Malignant cells
– Competing for nutrients
– Releasing immunosuppressive cytokines
– Immune mediated destruction of normal cells
• Examples: 
– Leukaemia especially AML
– Lymphoma
– Myeloma
– Malignant histiocytosis
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13
Q

outline erlichia and anaplasma as a cause of cytopaenias

A

– Dogs
• Acute disease - thrombocytopenia
• Chronic disease - pancytopenia due to decreased
bone marrow production
– Cats
• Non‐regenerative anaemia +/‐ neutropenia and
thrombocytopenia

Consider Leishmania and enzootic fungal disease if
travelled to appropriate areas

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14
Q

Outline FeLV as a cause of cytopaenias

A

• Several conditions including:
– IMHA, PRCA, Aplastic anaemia, myelodysplastic syndrome, myelofibrosis, leukaemia and lymphoma

• Anaemia macrocytic and nonregenerative.

• Sometimes thrombocytosis with increased MPV or
thrombocytopenia

• Bone marrow – MDS ‐ dysplasia, granulocyte
hypoplasia or maturation arrest of precursors

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15
Q

Outline FIV as a cause of cytopaenias

A

• May cause dysplasia in red blood cell and platelet
precursor via infection of T cells regulating
haematopoiesis
• Does not cause infect erythroid precursors directly
• Infected animals at increased risk of neoplasia,
mycoplasma

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16
Q

Outline aplastic anaemia

A

• Severe Bi or Pancytopenia.
• Marrow containing 95% adipose tissue – dx requires core
Clinical signs ‐ related to sepsis or bleeding
• Treatment – remove inciting cause and supportive
• Prognosis poor but some do recover

17
Q

What can cause aplastic anaemia in dogs?

A

– Infectious disease (Ehrlichia, Parvovirus)
– Drugs/Toxins
TMPS, chemotherapeutic agents, thiacetersamide + others
- Estrogen producing tumour
– Idiopathic

18
Q

What can cause aplastic anaemia in cats?

A
FeLV
methimazole
griseofulvin
renal failure
idiopathic
19
Q

Which drugs can cause drug induced haematologic dyscrasia?

A

• Typically immune mediated or toxic bone marrow
injury
• Common examples include:
– Chemotherapy agents, estrogens (including estrogen
producing tumours), paracetamol, aspirin, TMPS, phenobarbital (dogs), propylthiouracil (cats), methimazole (cats) and griseofulvin and lead amongst others
• Others include:
– Cephalosporins, carprofen, chloramphenicol, phenytoin, metronidazole, levamisole, albenazole, fenbenazole, thiacetarsemide, amiodarone, captopril, colchicine and mitotane amongst others

Technically anything could induce a reaction

20
Q

What is dysmyelopoiesis?

A

• Definition ‐ Presence of morphological abnormalities
in one or more cell lines
• Types ‐ Myelodysplastic syndrome, secondary
dysmyelopoiesis, congenital dysmyelopoiesis

21
Q

What congenital dysmyelopoiesis types are there?

A

• Macrocytosis ‐ poodle
• Congenital dyserythropoiesis ‐ Springer Spaniel
• Selective Vit B12 malabsorption and megaloblastic
anaemia ‐ Giant Schnauzer
• Thrombocytopenia and macroplatelets ‐ CKCS
• Microcytosis – Akitas and Shiba Inus

22
Q

What is myelodysplastic syndrome?

A

• MDS – clonal proliferative disorders often
progress to AML
– Most cases have FeLV in cats
– MDS several subtypes have < 20 – 30% blasts
– AML >20 ‐ 30% blasts
– Clin path changes depend upon level at which
dysplastic change takes place
– Some show anaemia +/‐ circulating normoblasts
only, others bi/pancytopenia

23
Q

What is secondary dymyelopoiesis

A
• Cytologically appears similar to MDS’s
• Secondary dysmyelopoiesis
– No increase in blasts
– Associated disease present
• Causes – dogs
IMHA, IMTP, lymphoma, myelofibrosis and multiple myeloma, drugs 
(chemotherapeutics, estrogen, cephalosporin, chloramphenicol, phenobarbital and colchicine)
• Causes – cats
IMHA, IMTP, lymphoma, chemotherapy
24
Q

How can inflammation be a cause of a cytopaenia?

A

Acute or granulomatous/ pyogranulomatous inflammation

haemophagocytic syndrome

25
Q

Outine acute or granulomatous/pyogranulomatous inflammation as a cause of cytopaenias

A

Causes - Acute – Sepsis, IMHA, FIP
• Granulomatous – Systemic fungal infections
• Pyogranulomatous – Histoplasmosis if travelled

26
Q

Outline haemophagocytic syndrome

A

bi/ pan cytopaenia d/t immune stimulated macrophages
Causes - 20% idiopathic, SLE, IMHA, myelodysplasia, E.Canis infection, lymphoma, sepsis, histiocytic sarcoma
• Infection associated cases do better than immune associated

27
Q

What is myelonecrosis?

A

Secondary to toxic or inflammatory response
Chronic myelonecrosis leads to myelofibrosis
tx is supportive
Prognosis is good if can resolve

28
Q

What are the possible causes of myelonecrosis?

A

Dogs
Sepsis, IMHA, SLE, lymphoma, drugs including (phenobarbital, carprofen, metronidazole, mitotane, cyclophosphamide, vincristine, colchicine and fenbendazole)

Cats
IMHA, FeLV, myelodysplastic syndrome and acute leukaemia

29
Q

What can cause myelofibrosis?

A

Causes of secondary disease – Dogs
IMHA, IMTP, neoplasia, drugs (phenytoin, phenobarbitone, phenylbutazone and colchicine)

Causes of secondary disease ‐ Cats
IMHA, myelodysplastic syndrome, chronic renal failure

30
Q

What is myelofibrosis?

A
  • Proliferation of fibroblasts usually secondary to marrow injury but can see idiopathic primary fibrosis – diagnosis requires core
  • Moderate to severe nonregenerative anaemia
  • Occasional animals thrombocytopenic or neutropenic
  • May see circulating precursors or dysplastic RBCs
  • Treatment – treat underlying cause
  • Prognosis – 50% of dogs recover
31
Q

When can you see nucleated RBCs?

A

usually reflect active regeneration but are also seen with splenic dysfunction, shock or bone marrow disorders

32
Q

Outline punctate and aggregate reticulocytes (these are only present in cats)

A

Aggregate reticulocytes have multiple (more than six) small dark blue cytoplasmic granules, in lines, chains or clumps, whereas punctate reticulocytes have only a few (two to six) cytoplasmic dots
Aggregates last in the circulation for about a day before maturing further into punctates that then survive in the circulation for up to 10 days.
Only aggregates reflect recent bone marrow RBC production so these are the reticulocytes included in feline reticulocyte counts, especially when evaluating cats with moderate to pronounced anaemia

33
Q

How can systemic amyloidosis cause regenerative anaemia?

A

rare condition seen in young to middle-aged Siamese and related breeds, can cause spontaneous liver rupture and abdominal haemorrhage

34
Q

What clin path finding may suggest GI bleeding?

A

Raised urea concentrations relative to creatinine

35
Q

When may you see severe hypophosphataemia?

A

diabetes mellitus, hepatic lipidosis, re-feeding syndrome and the oral administration of phosphate-binding antacids.

36
Q

When can you get a false positive on a coombs test?

A

hyperglobulinaemia, pancreatitis and myelodysplastic syndromes.

37
Q

What is the coombs test?

A

detects the presence, and can describe the nature of, erythrocyte-bound antibodies