When to suspect bone marrow disease

Question 1

Bone marrow

Answer 1

Haematopoiesis, a lot of fat, stromal tissue (connective tissue- structured), bone marrow composition changes as we get older (red in young when haematopoeisis dominates and yellow in old when adipose tissue dominates)

Question 2

When do we take a bone marrow aspirate for a cytologic evaluation?

Answer 2

haematological abnormalities are present, persistent and not readily explained.

Question 3

Haematological abnormalities include

Answer 3

Decrease or increase in a blood cell line (severe), atypical or immature cells, marked hyperproteinemia, hypercalcinaemia. ** KEY IS PERSISTENT AND UNEXPLAINED**

Question 4

Decrease in Cell number

Answer 4

Most common indications for bone marrow evaluations. Red cell line, white cell line, or platelet line. Can be one, two, or all three cell lines involved. Bicytopenia (two decreased)- Pancytopenia (three decreased). The more cell lines that are involved… increases the suspicion for bone marrow involvement! Neutropenia would happen first!! Red cell lines- anemia isn’t seen for quite a while!

Question 5

Examples of a decrease in cell numbers

Answer 5

Persistent nonregenerative anemia (no polychromasia/ reticulocytosis), persistent neutropaenia (no left shift or toxic change), Thrombocytopaenia (no large or giant platelets, run coag panel to rule out DIC first)

Question 6

Pancytopaenia- at risk of?

Answer 6

Bleeding, infection, etc.

Question 7

Causes of decreased cell numbers

Answer 7

Infection e.g. Parvovirus, FeLV; toxins- e.g. estrogen, bracken fern, chemotherapy; immune mediated disease (IMHA); endocrine disease (hypothyroidism, hypoadrenocorticism); neoplasia

Question 8

Severe increase in cell numbers

Answer 8

Unexplained elevations in blood cell numbers should suggest bone marrow evaluation. Examples include: erythrocytosis (commonly seen from dehydration), rubricytosis but no evidence of splenic contraction, dehyrdation, hypoxia renal disease.
Leukocytosis- no evidence of infection
Thrombocytosis- no evidence of Fe deficiency, inflammation

Question 9

Marked increase in cell numbers suggest possible malignancy: Leukaemia vs. Lymphoma

Answer 9

Leukaemia- neoplastic haematopoeitic cells originate in bone marrow but often seen in circulation. - acute v. chronic - lymphoid v. myeloid (all cells except lymphoid)

Lymphoma- neoplastic lymphocytes originate in solid tissue- lymphoid tissue outside the bone marrow e.g. lymph node, spleen, liver, intestine, skin

Question 10

Lymphoma can circulate peripheral blood and also metastasis in the bone marrow (stage V lymphoma) how can we distinguish this from acute lymphoblastic leukaemia?

Answer 10

One off blood sample- huge lymph nodes often. Imaging to look at the spleen and the liver to see if either are enlarged. Bottom line, it doesn’t matter- treatment is similar and prognosis is the same. Being able to identify the neoplastic lymphocytes in the blood is the important thing.

Question 11

Atypical cells present in the blood

Answer 11

Abnormal cell morphology often warrants bone marrow evaluation. Such as immature cells (in absence of regenerative response), abnormal cells- bone marrow may help determine if the changes are due to a stimulus (infection, toxin) or neoplasia

Question 12

Marked hyperproteinaemia (could mean two things- when what marks the hyperproteinaemia? What are those two possibilities?)

Answer 12

When hyperproteinaemia is characterized and marked by hyperglobulinaemia (especially with no evidence of haemoconcentration or dehydration). Marked hyperglobulinaemia supports bone marrow evaluation for:

• lymphoid neoplasia
• systemic fungal and protozoal infections (histoplasmosis or leishmaniasis)

Question 13

Hypercalcaemia

Answer 13

Of unexplained eitiogoly may warrant bone marrow eval. Neoplastic infiltration of bone marrow: lymphoid neoplasms, multiple myeloma (localized osteolysis caused by this tumour may result in hypercalcaemia), metastatic neoplasia

Question 14

Cytology

Answer 14

Looks at cells- super fast- aspirates

Question 15

Histology

Answer 15

Looks cells- sliced thinly- core biopsy

Question 16

Bone marrow collection

Answer 16

Simulataneous eval of bone marrow cytology and histology is recommended (aspirates and core biopsies). Maximizes info. Aspirates are great for cell morphology.
Core biopsies evaluate architecture- cellularity, focal inflamm., metastatic neoplasia myelofibrosis, necrosis, osteolysis, essential if repeated “dry taps” on aspiration (especially when the animal is already sedated)

Question 17

Locations of bone marrow collection

Answer 17

Pelvis (ileac crest- esp med and large dogs), proximal femur (trochanteric fossa- cats and small dogs), proximal humerus (common site esp. in obese animals), sternum (common in horses)

Question 18

Bone marrow collection**

Answer 18

• Smears are made immediately after collection- haematopoietic cells rapidly degenerate, clot formation results in cell lysis (happens fast!)
• submit several unstained smears
• smears must be submitted with a blood sample (with EDTA) or data from within 24 hours of taking the bone marrow aspirate- WHY? We want to know, is the bone marrow effectively producing cells or not?

Question 19

Normocellular marrow

Answer 19

Cells make up 25-75% of marrow particles

Question 20

hypercellular marrow

Answer 20

abundance of cells and rare fat (>75% haemopoietic cells)

Question 21

Hypocellular marrow

Answer 21

Abundant fat, visible stromal cells, rare cells (less than 25%)

Question 22

Myeloid to erythroid ratio

Answer 22

500 cell differential. Tells us if it is hyperplastic. Is it responding appropriately to inflamm?

Question 23

Ex) Horse with platelets and red cells- anisocytosis. No RBCs- anaemic. Horses don’t release polychromatophils. Only see macrocytes- so possibly regenerative. Had to take a bone marrow. Is the marrow responding? Or were the stem cells insulting and not proliferating?

Blood marrow- polychromatophils, metarubricytes, rubricytes, prorubricytes, and rubriblasts. No abnormalities at all.

Answer 23

Should expect PCB to increase in the next day or so. Regenerative anaemia

Question 24

Aplastic Anaemia. What is it ? Causes?

Answer 24

Generalized bone marrow aplasia. Pancytopaenia of all three cell lines. Immune mediated, toxicity, infectious, genetic

Question 25

Erythroid aplasia (pure red cell aplasia). What is it? Causes?

Answer 25

Erythroid line only. Causes: primary: immune mediated, secondary: infectious i.e. parvo

Question 26

10 yo cat- depressed, off food, losing weight, not cleaning, normal limits on clinical findings. DDx? Plan?

Low Red cell count, low white cell, low neutrophils, low lymphocytes, low platelets, REALLY high total solids (much higher than just dehydration- which means we need a serum sample). Reticulocytes- low. Anaemia- non-regenerative OR pre-regenerative. 5 days later should see regeneration.

Serum sample- high globulin- what are they doing? Stim. by inflammation or is there a proliferation of one type of globulin from neoplasia. Neoplasia most likely.

Bone marrow aspirate- sampled because of pancytopenia and high globulin. You see lots of plasma cells (specialized B lymphocyte)- way more than usual. Consistent with multiple myleoma.

Answer 26

DDx: oral disease, anorexic, decreased energy intake, protein losing enteropathy, inflamm. bowel disease, disease with increased energy requirements- hyperthyroidism for example.

CBC, biochem, urinanalsysis.

Pancytopaenia (low platelets because we also checked for clotting- blood smear, leukopenia, anemia). Non-regenerative anaemia.

Question 27

Multiple Myleoma

Answer 27

AKA Plasma cell myeloma. Bone marrow tumour of Plasma cells (specialized B lymphocyte),

• Diagnostic criteria
• neoplastic plasma cells in bone marrow- aspirate plus core biopsy ideal
• hyperglobulinaemia
• osteolytic lesions- common in dogs- axial or proximal long bones
• light chain- proteinuria- dipstick does not detect these- not found in routine biochemistry dipstick for protein. Urine protein electrophoresis (UPE) or urine protein sulfosalicylic acid test (SSA) can be used to confirm presence of paraproteins

Question 28

Flame cells

Answer 28

plasma cells where you can see the protein like a tutu around them. Hyperglobunaemia.

Question 29

What are some other uses of bone marrow to evaluate a patient?

Answer 29

Evaluate Fe stores and determine Fe sequestration. (unless it is a cat or neonate due to normal lack of discernible storage levels). Clinical stages for malignancies, such as lymphoma or mast cell tumour.

Question 30

Aplasia

Answer 30

Lack of a cell line (in a core biopsy this is typically less than 5% of cells)