When to suspect bone marrow disease Flashcards
Bone marrow
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)
When do we take a bone marrow aspirate for a cytologic evaluation?
haematological abnormalities are present, persistent and not readily explained.
Haematological abnormalities include
Decrease or increase in a blood cell line (severe), atypical or immature cells, marked hyperproteinemia, hypercalcinaemia. ** KEY IS PERSISTENT AND UNEXPLAINED**
Decrease in Cell number
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!
Examples of a decrease in cell numbers
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)
Pancytopaenia- at risk of?
Bleeding, infection, etc.
Causes of decreased cell numbers
Infection e.g. Parvovirus, FeLV; toxins- e.g. estrogen, bracken fern, chemotherapy; immune mediated disease (IMHA); endocrine disease (hypothyroidism, hypoadrenocorticism); neoplasia
Severe increase in cell numbers
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
Marked increase in cell numbers suggest possible malignancy: Leukaemia vs. Lymphoma
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
Lymphoma can circulate peripheral blood and also metastasis in the bone marrow (stage V lymphoma) how can we distinguish this from acute lymphoblastic leukaemia?
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.
Atypical cells present in the blood
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
Marked hyperproteinaemia (could mean two things- when what marks the hyperproteinaemia? What are those two possibilities?)
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)
Hypercalcaemia
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
Cytology
Looks at cells- super fast- aspirates
Histology
Looks cells- sliced thinly- core biopsy
Bone marrow collection
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)
Locations of bone marrow collection
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)
Bone marrow collection**
- 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?
Normocellular marrow
Cells make up 25-75% of marrow particles
hypercellular marrow
abundance of cells and rare fat (>75% haemopoietic cells)
Hypocellular marrow
Abundant fat, visible stromal cells, rare cells (less than 25%)
Myeloid to erythroid ratio
500 cell differential. Tells us if it is hyperplastic. Is it responding appropriately to inflamm?
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.
Should expect PCB to increase in the next day or so. Regenerative anaemia
Aplastic Anaemia. What is it ? Causes?
Generalized bone marrow aplasia. Pancytopaenia of all three cell lines. Immune mediated, toxicity, infectious, genetic
Erythroid aplasia (pure red cell aplasia). What is it? Causes?
Erythroid line only. Causes: primary: immune mediated, secondary: infectious i.e. parvo
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.
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.
Multiple Myleoma
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
Flame cells
plasma cells where you can see the protein like a tutu around them. Hyperglobunaemia.
What are some other uses of bone marrow to evaluate a patient?
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.
Aplasia
Lack of a cell line (in a core biopsy this is typically less than 5% of cells)
