Differential Diagnosis of Clinicopathological Abnormalities Flashcards
1
Q
Anaemia and erythrocytosis
A
2
Q
Define anaemia.
A
Reduced RBC indices:
- RBC
- PCV
- HCT
- Haemoglobin
3
Q
Define erythrocytosis.
A
Increased RBC mass/indices including:
- RBC
- PCV
- HCT
- Haemoglobin
4
Q
What can cause erythrocytosis?
A
- Relative e.g. dehydration or splenic contraction
- Absolute e.g. polycythaemia vera
5
Q
What is polycythaemia vera?
A
Refers to chronic myeloproliferative disease specifically erythroid leukaemia
6
Q
What can cause hyperviscosity of blood?
A
- Relative erythrocytosis e.g dehydration
- Absolute e.g. polycynthaemia vera e.g. chronic myeloproliferative disease such erythroid leukaemia
- Hyperproteinaemia
7
Q
What is the difference between PCV and HCT?
A
PCV is a measure value from haematocrit tubes whereas HCT is a calculated values, HCT = MCV x RBC, thus is more prone to artifactual or real changes in MCV which are less likely to affect the PCV.
8
Q
What is the first step in interpretation of HCT or PCV?
A
Determining whether it is physiological or true.
9
Q
What is important about interpreting HCT or PCV in Greyhounds?
A
Given they have a higher HCTs than other breed a HCT <45% would be considered anaemia in this breed.
10
Q
What are the three main pathophysiologic mechanisms for anaemia?
A
- Loss
- Destruction/decrease life span
- Lack of production
11
Q
How can we determine between loss and destruction vs lack of production?
A
Determining if there is evidence of regeneration. If regeneration is present than the underlying mechanism is loss or destruction.
12
Q
What are the differentials for haemorrhage?
A
- Internal e.g. into a body cavity
- External e.g. skin, respiratory, genitourinary, gastrointestinal tract.
- Chronic blood loss which can results in iron deficiency anaemia
13
Q
What other cbc and biochemistry parameters could support haemorrhage?
A
Hypoproteinaemia e.g. low albumin and globulins
14
Q
What are some features of iron deficiency anaemia?
A
Hypochromasia and RBC fragmentation. Will see microcytic hypochromic non or pre-regenerative anaemia.
Low reticulocyte-haemoglobin concentration - not definitive but supports a diagnosis.
15
Q
What are the differential for low reticulolcyte haemoglobin concentration?
A
- Iron deficiency
- Inflammatory disease
- PSS
- Breed associated microcytosis.
16
Q
What are the types of haemolysis?
A
- Extravascular - premature phagocytosis by macrophages in spleen, liver and bone marrow
- Extravascular with a component of intravascular - extravascular haemolysis is occuring in all cases of haemolysis but in some cases there will be a component on intravascular haemolysis where RBCs are destroyed in circulation liberating haemoglobin.
17
Q
How do were determined if there is a component of intravascular haemolysis?
A
- Haemoglobinaemia
- Haemoglobinuria
- Ghost RBCs , heinz bodies or infectious organisms may also be seen by not relied upon.
18
Q
What other CBC and biochemistry changes can support haemolysis?
A
- Normal or high TP
- Elevated TBIL
19
Q
What are clues to indicate decreased production or a bone marrow problem?
A
- Severity of anaemia - often a mild to moderate normocytic, normochromic anaemia
- Concurrent cytopaenia particularly neutropaenia and thrombocytopaenia
20
Q
What are the differentials for haemolysis?
A
- Immune-mediated which can be associative or non-associative
- Infectious organisms e.g. Babesia, theileria, mycoplasma haemocanis and haemofelis, leptospira
- Oxidant-induced: zinc, onion, acetominophen
- Fragmentation injury (microangioppathic haemolytic anaemia: vasculitis, DIC
- Aberrant macrophage activity: reactive or neoplastic histiocytic disorders
- Inherited defects in the RBC membrane or metabolic pathways
- Severe hypophosphataemia, envenomation
21
Q
What are the differentials for decreased production Rbcs?
A
- Inflammatory disease
- Chronic kidney disease e.g. decreased EPO mostly - GI ulceration, haemolysis or inflammation can all contribute
- Endocrine disease e.g. hypoT or hypoadrenocorticism
- Bone marrow disease
- Increased intramedullary cell death e.g. precursor-directed immune-mediated anaemia (PIMA), drugs or hormone e.g. oestrogen, toxins or infectious organisms (erlichia) or histiocytic disorders
- Abnormal production with intramedually cell death e.g. myelodysplastic syndrome or primary myelodysplasia in cats often secondary to FELV
- Destruction or damage to erythroid progenitor cells e.g. PIMA, infectious (parvo or erhlichia), drugs
- Decreased HGB production e.g. iroon deficiency, PSS, lead toxicosis
- Decreased or abnormal DNA production e.g. vit b12 or folate deficiency FeLV
- Cancer e.g. primary such as acute myeloid leukaemia, or infiltrative such as histiocytic sarcoma, multiple myeloma in cats, lymphoma in dogs.
22
Q
Name the inherited defects in RBCs membrane.
A
- Stomacytosis in alaskan malamutes
- Spherocytosis in golden retrievers
23
Q
Name the inherited defects in RBCs metabolic pathways.
A
- Phosphofructokinase deficiency in dogs
- Pyruvate kinase deficiency in dogs and cats
24
Q
Describe the pathogenesis of inflammatory disease causing non-regenerative anaemias? Give some differentials.
A
Inflammatory cytokines supress erythropoiesis , EPO release and response to EPO. It also stimulated hepcidin release, inhibiting iron absorption causes iron sequestration.
DDx include sepsis, IBD, inflammatory liver disease, cancer.
25
26
What are some features on a blood smear that can indicate an immune-mediated haemolytic anaemia?
1. Spherocytes
2. Agglutinaemia
3. Ghost cells
27
What are some features on a blood smear that can indicate an infectious process?
Identifying organisms on a blood smear
28
What are some features on a blood smear that can indicate an oxidant induced process?
1. Heinz bodies
2. Eccentrocytes
3. Pyknocytes
4. Ghost cells - often with heinz bodies
29
What are the four main questions to ask when working up an anaemia?
1. How acute is the anaemia?
2. Is the anaemia regenerative?
3. Is the cause identifable from a smear?
4. Which additional tests are indicated?
30
What is the first question in the algorithm for evaluating the anaemic patient?
Is the anaemia adequately regenerative?
31
What is the algorithm for when the anaemia is not adequately regenerative?
Ask is this an acute onset?
NO --> to non-regenerative algorithm
YES --> Re-evaluate in 3 to 5 days if stable.
32
What is the algorithm for when the anaemia is regenerative?
Determine if there is evidence of internal or external haemorrhage e.g. faecal occult blood, supportive data e.g. low TP
YES --> is it acute or chronic. If chronic --> Is there evidence of iron deficiency?
NO --> Is there evidence of haemoylsis e.g. RBC abnormalitis or Elevated TBIL or IRON -->
No --> unknown mechanism additional test as indicated e.g. coombs. Yes --> haemolytic anaemia --> is there haemoglobinaemia and haemoglobinuria? No--> extravascular haemolysis. Yes --> intravascular and extravascular haemolysis is present.
33
What is the algorithm for a macrocytic normochromic non-regenerative anaemia?
First need to rule out breed associated e.g. miniature and toy poodles.
FELV postive cat?
Yes --> FELV induced dysplasia or leukaemia.
No --> Evaluate history (drugs, toxins) Additional diagnostic tests as indicated e.g. BM aspiration.
34
What is the algorithm for a microcytic normochromic non-regenerative anaemia?
First rule-out breed associated e.g. shar-pei or siberian husky
Evidence or iron deficiency or PSS? Yes --> iron deficiency anaemia or function iron deficiency secondary to shunts.
No --> Evaluated history for drugs, toxins. Additional diagnostics as indicated e.g. bone marrow biopsies
35
What is the algorithm for a normocytic normochromic non-regenerative anaemia?
Assess severity
Mild to moderate --> evdience of extra-medullary disease. Yes --> Anaemia of endocrine disease vs anaemia of inflammatory disease or neoplasia vs anaemia of chronic disease. No --> is there evidence of other abnormal cells or cytopaenia? No --> BM aspiration if persistant anaemia and no other cause (likely cause is PIMA). Yes --> BM aspiration likely aplasia or neoplasia.
Severe --> is there evidence of other abnormal cells or cytopaenia? No --> BM aspiration if persistant anaemia and no other cause (likely cause is PIMA). Yes --> BM aspiration likely aplasia or neoplasia.
36
Which breeds commonly have an increased HCT normally?
Greyhounds. Jack russell terriers. German shephard dogs.
37
What can causes a relative erythrocytosis?
- Dehydration
- Splenic contraction
38
What are the causes of an absolute erythrocytosis?
1. Primary e.g. polycythaemia vera
2. Secondary e.g. appropriate increased EPO or inappropriately increased EPO
39
What can cause an appropriate increase in EPO?
Caused by hypoxic conditions e.g. respiratory or cardiac results in secondary erythrocytosis.
40
What can causes an inappropriate increase in EPO?
- renal disease
- paraneoplastic response
41
Describe the algorithm of evaluating an animal with HCT.
First step , is there a high TP? Evdience of dehydration?
YES there is high TP or dehydration --> Correction after rehydration? or transient? Yes --> likely relative change. No --> Erythrocytosis pathway
No, normal TP, euhydrated --> likely erythrocytosis --> Evidence of hypoxia? (Measure pO2 on blood gas), Evidence of cardiovascular or respiratory disease? Yes --> likely secondary appropriate EPO. No --> Evidence of renal disease Yes --> likely secondary inappropriate erythrocytosis. No --> Evidence off extra-medually neoplasia --> yes --> likely secondary inappropriate EPO. No --> Possible primary neoplastic erythrocytosis.
42
Leukopaneia and Leukocytosis
43
What are the two main cells line commonly responsible for a leukocytosis? Why?
Neutrophils and to a lesser extent lymphocytes.
Because there are the most numerous and dynamic.
44
What broadly can cause a neutrophilia?
1. Physiologic
2. Inflammation
3. Infection
4. Neoplasia
45
What can causes a physiologic neutrophilia?
Left shift marginating to circulationg neutrophil pools causes by exercise, adrenaline and cortisol.
46
What factors can help rule out a physiologic neutrophilia?
1. A neutrophil count > twice its upper limit should not be physiologic in origin
2. Will not produce a left shift
47
Describe left shift.
A the inflammatory process continues and there is increased demand for neutrophils which results in early release of neutrophils from the maturation pools results int he left shift to producing immature forms of neutrophils.
48
What is a degenerative left shift?
It's when the demand for neutrophilic exceeds the capacity of the bone marrow and there are increasing ratios of immature neutrophils are release.
49
What is the most common cause of a degenerative left shift?
Infection
50
What is toxic change?
Morphologic changes of neutrophils caused by accelerated maturation.
51
What are the types of toxic changes of neutrophils?
1. Cytoplasmic basophilia
2. Dohle bodies
3. Increased vacuolization
4. Decrease nuclear condensation
5. Increased granules
52
If you have a leukocytosis characterised by a neutrophilia with left shift, what are you most concerned about?
Infection e.g. peritonitis, pleuritis and pneumonia; neoplasia etc.
Severe inflammation e.g. pancreatitis, haemolytic anaemia
53
What are some causes of a monocytosis?
1. Chronic granulomatous disease
2. Chronic infections
3. Myelomonocytic leukaemia
54
What is classed as a severe leukocytosis?
> 35,000 cell/mcl
55
What are some causes of a leukocytosis?
1. Physiologic - usually mild
2. Reactive lymphocytosis in response to inflammation - usually in cats
3. Chronic infectious disease e.g. FeLV, FIV, toxoplasma or erhlichia
4. Endocrine e.g. hypoadrenocorticism
5. neoplasia e.g. lymphoma, chronic, lymphocytic leukaemia, acute lymphocytic leukaemia (often associated with with a severe leukocytosis).
56
What is needed to distinguish chronic lymphocytic leukaemia (CLL) and reactive lymphocytosis? Why?
Because the cells in CLL are mature often need immunophenotyping, PARR (PCR for antigen receptor rearrangements) to distinguish from a reactive lymphocytosis
57
What can cause and eosinophilia?
1. Parasitism
2. Hypersensitivity reactions
3. Mastocytic disease
4. hypoadrenocortisim
5. Hypereosinophilic syndrome
6. Lymphoid neoplasia
58
What can cause a monocytosis?
1. Chronic granulomatous disease
2. Chronic infections
3. Myelomonocytic leukaemia (rare) - is often associated with neutropaenia and thrombocytopaenia
59
What is the most common cause of a leukopaenia?
Neutropaenia
60
What defines a neutropaenia?
<3000/mcl or < 3 x 10^9/L
61
What defines a mild neutropaenia?
<1500 - 3000 cells/mcl
62
What defines a moderate neutropaenia?
500 - 1500 cells/mcl
63
What defines a severe neutropaenia?
<500 cells/mcl
64
What is a severe neutropaenia often associated with?
Fever and opportunistic infection
65
What are the mechanisms of a neutropaenia?
1. Decrease BM production
2. Consumption
3. Vascular sequestrion e.g. sepsis of anaphylaxis
4. Immune mediated production either in periphery, in marrow reserves or immature precursors
5. Chronic idiopathic or mild neutrophilia in cats - often mild to moderature neutropaenia but can be < 1000 cells/mcl but should not be associated with left shift or toxic change
66
What are the causes of neutrophil consumption?
Anything that can causes of a severe neutrophilia resulting in demand exceeding production or neutrophils.
67
What can cause decrease BM production of neutrophils?
Drugs e.g. chloramphenicol, azathioprine, phenobarbitol, phenylbutazone, methimazole, sulfa derivatives
Chemotherapy
Neoplastic infiltration of BM
68
What are the most common causes of a lymphopaenia?
1. Viral
2. Glucocorticoids
69
Thrombocytopaenia and thrombocytosis
70
What are platelets? Where are platelet produced?
Platelets are small anucleate cell fragments procuded by bone marrow megakaryocytes
71
How long do platelets circulate for?
5 to 9 days
72
What is the major regulator of platelet maturation?
Thrombopoietin (TPO), additional growth factors also act synergistically
73
Where is TPO produced?
The liver is the primary site of TPO synthesis.
74
Where is majority of the platelet mass sequestered?
Approx. one third of circulating platelet mass is sequestered in the spleen.
75
What are the reference intervals of platelets in cats and dogs?
1. Dogs: 186 to 545 x 10^3/mcl
2. Cats: 195 to 624 x 10^3/mcl
OR approx 200,000 - 500,000/mcl
76
What are the clinical signs of thrombocytopaenia?
1. Petechiae
2. Ecchymoses
3. Mucosal haemorrhage e.g. epistaxis, haematemesis, haematuria or melena
4. Prolonged bleeding after injury
77
What can signs of a thnrombocytopaenia overlap with?
- acquired or hereditary plt diorders
- coagulopathies
- von willebrand disease
- vasculopathies
- vascular injury
78
In a dog that is bleeding with a plt count of 30,000/mcl is thrombocytopaenia the sole cause?
Unlikely, it is rare the sole causes of severe or spontaenous bleeding at counts above 30,000/mcl
79
What is the first step in evaluating a thrombocytopaenia in dogs and cats?
Confirmation with a blood smear, recommended to be confirmed by a pathologist.
80
How do you estimate a platelet count?
Count number plt in 10 high power fields then average and times by 15,000
