White blood cell disorders Flashcards
1
Q
List congenital White Blood Cell Disorders
A
- Chediak-Higashi Syndrome
- Pulger Huet Anomaly
- Leukocyte Adhesion Deficiency
- Trapped Neutrophil Syndrome
- Pyruvate Kinase Deficiency
- X-linked Severe Combined Immunodeficiency
- Autosomal Recessive Severe Combined Immunodeficiency
- Cyclic Haematopoiesis
- Common Variable Immunodeficiency
- Lysosomal Storage Disorders
2
Q
Describe Chediak-Higashi Syndrome including breed predisposition and relvant frequency
A
- Persian cats
- Recurrent neutropenia and neutrophil function defects
- Seen in combination with oculocutaneous albinism - blue smoke colour in persian cats
- Neutrophils, eosinophils and other cells contain abnormally fused granules
- Granulocyte colonsy stimulating factor can partially correct the nuetrophil function defects
- Cats are less prone to infection when compared to other species
3
Q
Describe Pelger Huet Anomaly
A
- Autosomal dominant (incomplete penetrance) genetic disorder
- Australian Shepherds are over-represented
- Neutrophils and eosinophils have hyposegmented nuclei with mature chromatin
- No functional defects found in affected neutrophils
- Immunodeficiency does not occur
- Homozygous state likely to cause embryonic death
4
Q
Describe leukocyte Adhesion Deficiency
A
- Various disorders that result from mutations in the leukocyte adhesion proteins.
- Leads to impaired adhesion and transport through the vascular endothelium
- LAD Type 1 seen in Irish Setters - defect in beta-2-subunit (CD18) of the heterodimeric integrins
- Marked peripheral neutrophilia with hypersegmented nuclei is a typical diagnostic finding
- Affected pups typically develop omphalitis, then lymphadenopathy, low body weight and febrile infection
- Most dogs die within 2-3 months of life
5
Q
Describe Trapped Neutrophil Syndrome
A
- Autosomal recessive neutropenia
- Seen in Border Collies (originally described in Aust / NZ)
- Causes a neutropenia with a degenerative left shift and marked monocytosis
- Bone marrow: myeloid hyperplasia with increased mature neutrophils
- May see craniofacial development abnormalities
- Pups generally present for recurrent infection (bacterial or other), adverse vaccination reaction or poor growth.
6
Q
Discuss how pyruvate kinase deficiency can affect the white blood cells
A
- progressive bone marrow myelofibrosis is seen with PKD in dogs
- Osteosclerosis and hepatic changes are also seen
- Myelofibrosis and myelophthisis leads to marrow failure and pancytopenia
- Iron overload may occur due to ongoing haemolytic anaemia together with excessive iron absorption (due to anaemia) and prolonged effects of increased erythropoiesis.
7
Q
Describe X-Linked Severe Combined Immunodeficiency
A
- Mutation in the gene encoding the interleukin 2 receptor gamma chain
- Seen in Cardigan welsh corgi and basset hounds
- Deficient IL-2-R affects developing CD4+ and CD8+ thymocytes.
- Hypoplastic or dysplastic thymus and hypoplastic to absent lymphoid tissue
- Affected pups have rare non-functional peripheral T cells and increased numbers of B cells
- Stunted growth, recurrent infection, rarely survive past 4 months
8
Q
Describe Autosomal recessive Severe Combined Immunodeficiency
A
- Described in Jack Russel Terriers
- Point mutation in the gene encoding the catalytic subunit of DNA-dependent protein kinase
- Affects T and B cells
- Severe lymphopenia
- Decreased serum globulin - agammaglobulinaemia
- Marked lymphoid hypoplasia in spleen, thymus and other lymphoid tissues
- Opportunistic infection and vaccination (MLV) frequent causes of death
9
Q
Describe Cyclic Haematopoiesis in Gray Collies
A
- Autosomal Recessive disorder
- Defect in trafficking of lysosomal membrane proteins
- An insertional mutation in the AP3B1 gene is documented
- cycling of neutrophil (and other blood cell) counts every ~ 2 weeks
- Affected neutrophils are deficient in neutrophil elastase and myeloperoxidase
- Frequent infections occur.
- G-CSF eliminated neutropenia but did not correct functional defects in one report.
10
Q
What breeds have been report to be affected by Common Variable Immunodeficiency, and what is the clinical relevance?
A
- Described in both miniature dachshund and CKCS
- Described in dogs diagnosed with pneumocystis carinii pneumonia.
- Lymphocyte function deficit
- hypogammaglobulinaemia
- Absence of B cells in lymph nodes
11
Q
Discuss the diagnosis of immune mediated neutropenia with respect to both potential triggers and need to exclude other causes of neutropenia
A
- Neutropenia can be cause by
- infection / inflammatory demand
- decreased production - myelophthisis / hemic neoplasia
- Marrow injury - drug induced or infection
- Sequestration - spleen primarily
- IMN can be triggered by
- Infection - especially tick borne disease
- drug administration - cephalosporins, phenobarbital
- IMN generally has the lowest neutrophil counts
- Flow cytometric methods can be used to identify anti-neutrophil antibodies - sensitive and specific for diagnosis
- Bone marrow aspiration can define maturation arrest, myeloid hyperplasia or myeloid hypoplasia
- Rapid response to corticosteroids is expected unless severe myeloid hypoplasia is present
12
Q
Describe the pathogenesis of primary myelodysplastic syndrome (MDS)
A
- Clonal disorder resulting from mutations within the haematopoietic stem cells.
- Non-regenerative anaemia is a consistent feature
- FeLV can cause MDS and dysmyelopoiesis
- FeLV associated clonal MDS and AML has been proven
- Clonal origin not proven in canine MDS
- Suggestions of primary MDS in marrow aspirates include
- increased blasts
- increased % of dysplastic cells
- megaloblastic precursors
- Lack of exposure to drugs/toxins or infection
- Suggestions of primary MDS in marrow aspirates include
- Similar signs to CML except for lack of increased mature leukocytes in circulation.
13
Q
List the 3 sub-categories of primary MDS - as differentiated by bone marrow cytology/histopathology. Briefly discuss the cytological appearance and clinical implications of each.
A
- MDS-excess blasts
- peripheral pancytopenia
- >20% blasts and dysplasia of all cell lines (neutropenia, thrombocytopenia, anaemia)
- Prognosis in dogs is poor with this form
- 6/13 cats with MDS-EB were positive for FeLV
- MDS-refractory cytopenia
- Older dogs and typically an insidious onset
- Non-regenerative anaemia - other cytopenias are rare
- marrow can be normocellular or hypercellular and erythroid dysplasia with excessive rubriblasts is typical
- MDS - Refractory cytopenia with multi-lineage dysplasia
- Dysplasia in at least 2 cell lines without excessive blasts (<5% myeloblasts)
14
Q
List known causes of secondary dysmyelopoiesis
A
- IMT and IMHA
- Myelofibrosis
- Pure Red Cell Aplasia
- Lymphoma
- Drug exposure
- chemotherapeutic agents
- chloramphenicol
- phenobarbital
- oestrogens (endogenous and exogenous)
- Heavy metal toxicosis
- Iron deficiency
- Adenocarcinoma
- Leishmaniasis
- Glomerulonephritis (cats)
- FIP and FIV infection (cats)
15
Q
Define myelophthisis and describe known causes in dogs and cats
A
- Myelophthisis is defined as replacement of normal haemtopoietic tissue in the bone marrow by abnormal cells or tissue.
- Myelofibrosis - primary (neoplastic) or secondary (due to PKD) is the most common non-neoplastic cause.
- other causes include:
- high dose EPO
- FeLV infection
- bone marrow necrosis
- infections
- drugs/toxicoses
- Haemic neoplasia is a common cause of myelophthisis in dogs
