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Acanthocyte



DEFINITION


Erythrocyte morphologic abnormality characterized by irregular, usually blunt projections from the normally smooth round cell membrane (from the Greek akantha, meaning “thorn”).



SYNONYMS


Burr cell, spur cell, echinoacanthocyte



TYPICAL NORMAL RANGE


Not reported unless seen on blood film. Healthy dogs and cats should not have appreciable numbers of circulating acanthocytes on properly prepared, fresh blood films.



PHYSIOLOGY


Mechanism for membrane shape abnormality is not known. Associated with abnormalities in red blood cell membrane lipids.



CLINICAL APPLICATIONS


CAUSES OF ABNORMALLY HIGH LEVELS: Hemangiosarcoma; liver, splenic or renal disease; artifact of blood film preparation


NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: Repeat CBC to confirm; if consistent finding, evaluate for liver, splenic, or renal disease and metabolic abnormalities as suggested by clinical signs.



SPECIMEN AND PROCESSING CONSIDERATIONS


LAB ARTIFACTS THAT MAY INTERFERE: Specimen age artifact (delay in preparing blood film, sample not refrigerated); artifact of blood film preparation SPECIMEN: Whole blood in EDTA (lavender-top tube) or heparin (green-top tube); include a blood film prepared when specimen was collected to help rule out specimen age artifact.


RELATIVE COST: Reported if present on blood film; $/$$ (depending on reflex testing included in CBC panel)



PEARLS


Considered nonspecific and a common artifact; should be evaluated in a second, fresh specimen prior to drawing diagnostic conclusions


AUTHOR: LOIS ROTH-JOHNSON



Acetylcholine Receptor Antibody Test



DEFINITION


Test for detection of antiacetylcholinereceptor (AChR) antibodies, which cause acquired myasthenia gravis



SYNONYMS


ARAT, myasthenia gravis tit er



TYPICAL NORMAL RANGE


0 to 0.6 nmol/L (dogs), 0 to 0.3 nmol/L (cats)



PHYSIOLOGY


Acetylcholine is released from a neuron’s presynaptic membrane at the neuromuscular junction. In myasthenia gravis patients, the acetylcholine fails to adequately bind to muscle-based receptors in the postsynaptic membrane (sarcolemma) because the receptors are inactivated by autoantibodies. This test detects the autoantibodies in the serum.



CLINICAL APPLICATIONS


CAUSES OF ABNORMALLY HIGH LEVELS: Myasthenia gravis


NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: The ARAT is the confirmatory diagnostic test for myasthenia gravis; assessment of the response to immunosuppressive and/or oral pyridostigmine treatment may further support the diagnosis but is variable (some cases may be refractory to treatment). Intravenous edrophonium (Tensilon) is occasionally used for immediate relief of signs, but response rate is low even in confirmed cases.



SPECIMEN AND PROCESSING CONSIDERATIONS


DRUG EFFECTS ON LEVELS: False negative: corticosteroid or other immunosuppressive therapy. If clinically feasible, treatment should be stopped at least 4 weeks prior to testing.


LAB ARTIFACTS THAT MAY INTERFERE: False negative: failure to keep specimen chilled


SPECIMEN: Serum (red-top tube), 2 mL minimum; separate from clot as soon as possible. Should be frozen and sent on dry ice (preferable) or cold pack to reference lab immediately (courier/overnight express delivery). RELATIVE COST: $$$



PEARLS


Some dogs with myasthenia gravis are negative for AChR antibodies but have immune complexes associated with other antigens at the neuromuscular junction that interfere with neurotransmission. Nerve stimulation studies may be needed in these patients (see p. 1255).


AUTHOR: LOIS ROTH-JOHNSON



Acetylcholinesterase Level



DEFINITION


Blood level of the enzyme that catabolizes acetylcholine



SYNONYM


Cholinesterase level



TYPICAL NORMAL RANGE


500 to 1500 U/L for dogs. A positive diagnosis of low level means the patient’s level is at least 25% less than the lower limit of normal range.



PHYSIOLOGY


Acetylcholine is the main neurotransmitter at the neuromuscular junction, and the enzyme responsible for catabolism of acetylcholine is acetylcholinesterase. When acetylcholinesterase levels are low, there is decreased catabolism of acetylcholine, resulting in poorly controlled or uncontrolled neuromuscular activation. Muscle tremors and smooth-muscle activation (gastrointestinal and other autonomic signs) occur. Organophosphates antagonize acetylcholinesterase, leading to these clinical signs. Organophosphate intoxication is the most common cause of low blood levels of this enzyme. Measurement of red blood cell acetylcholinesterase concentration helps diagnose intoxication with organophosphate-containing insecticides.



CLINICAL APPLICATIONS


CAUSES OF ABNORMALLY LOW LEVELS: Organophosphate intoxication, carbamate intoxication


NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS LOW: Response to treatment


IMPORTANT INTERSPECIES DIFFERENCES: Cats naturally have lower cholinesterase levels, making the test less reliable in this species (false-positive results).



SPECIMEN AND PROCESSING CONSIDERATIONS


SPECIMEN: Whole blood in EDTA (lavender-top tube) or heparin (green top); 20 grams of brain tissue may be used for postmortem diagnosis.


RELATIVE COST: $$



PEARLS


Turnaround time is usually longer than clinical condition allows, so the test is often confirmatory (retrospective). Treatment decisions must be based on physical exam findings +/− known history of intoxication before results are available. See Organophosphate Intoxication, p. 792.


AUTHOR: LOIS ROTH-JOHNSON



ACTH (Adrenocorticotropic Hormone), Endogenous/Baseline



DEFINITION


Peptide hormone secreted by anterior pituitary in response to corticotrophin releasing hormone (CRH) secreted by hypothalamus



SYNONYM


Corticotropin



TYPICAL NORMAL RANGE


Dogs: 10 to 110 pg/mL; cats: 0 to 110 pg/ml. To convert pg/mL to pmol/L, multiply pg/mL by 0.22.



PHYSIOLOGY


Stress causes hypothalamic release of CRH. CRH stimulates anterior pituitary release of a large precursor hormone, proopiomelanocortin (POMC), which undergoes proteolytic cleavage to yield ACTH, β-endorphin, melanocyte-stimulating hormone, and other hormones. ACTH stimulates cortisol and aldosterone release from the adrenal cortex. High circulating levels of cortisol inhibit release of CRH (feedback inhibition). High baseline ACTH concentrations help differentiate pituitary-dependent hyperadrenocorticism from functional adrenal cortical tumors, in which serum ACTH is subnormal.



CLINICAL APPLICATIONS


CAUSES OF ABNORMALLY HIGH LEVELS: Hypocortisolism, either natural (primary Addison’s disease) or iatrogenic (after sudden cessation of chronic glucocorticoid administration); pituitary-dependent hyperadrenocorticism due to pituitary neoplasia. Additionally, there are rare instances of nonendocrine neoplasms producing high concentrations of ACTH (ectopic ACTH syndrome).


NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH:


• Determine treatment (glucocorticoid, including topical medications) history.

• ACTH stimulation test if no history of glucocorticoid administration

• Evaluation for occult nonendocrine neoplasm (rare)

CAUSES OF ABNORMALLY LOW LEVELS: High endogenous cortisol levels, either spontaneously (hyperadrenocorticism/Cushing’s disease) or iatrogenic (during administration of glucocorticoids); panhypopituitarism


NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS LOW: Rule out sampling error (see below). Evaluate for hyperadrenocorticism. If history, physical examination, and diagnostic tests support hyperadrenocorticism, and ACTH level is below the normal range, a diagnosis of adrenal cortical neoplasia is suspected, and further testing (e.g., abdominal ultrasonography) is warranted.


IMPORTANT INTERSPECIES DIFFERENCES: Adrenal disease is uncommon in cats; test is infrequently done in this species.


DRUG EFFECTS ON LEVELS:


• Increase: insulin

• Decrease: glucocorticoid administration


SPECIMEN AND PROCESSING CONSIDERATIONS


LAB ARTIFACTS THAT MAY INTERFERE: Decrease: thawing of specimen; collection or storage in glass tubes SPECIMEN: Morning sample preferred. Collect in cold, heparinized plastic syringe; centrifuge; collect plasma immediately; freeze in plastic tubes. Samples must be shipped frozen and remain frozen until analysis to avoid degradation of ACTH. Aprotinin-containing tubes may help prevent degradation in unfrozen samples.


RELATIVE COST: $$



PEARLS


Useful for differentiating pituitary-dependent Cushing’s disease from adrenal cortical tumor. The hormone is very labile, however; inappropriate specimen handling yields false-negative results.


AUTHOR: BRUCE LEROY



Activated Coagulation Time (ACT)



DEFINITION


The time interval from contact of blood with diatomaceous earth pellets to formation of a visible clot. ACT evaluates the intrinsic and common pathways but is less sensitive than activated partial thromboplastin time (APTT).



TYPICAL NORMAL RANGE


Dogs: <120 seconds. Cats: <165 seconds.



PHYSIOLOGY


Contact activation occurs when whole blood is drawn into a warmed (37○C) tube containing diatomaceous earth pellets. After multiple inversions for mixing, the tube is kept in a heating block or tucked in the clinician’s axilla and checked for clot formation every 5-10 seconds.



CLINICAL APPLICATIONS


CAUSES OF ABNORMALLY HIGH LEVELS: Decreased concentration of any of coagulation factors of the intrinsic or common coagulation pathways (all factors except VII) to less than 5% of normal; severe thrombocytopenia (< 10,000 platelets/μL); uremia. In the absence of coagulopathy, critically ill dogs may have prolongation of ACT due to inflammatory disease.


NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: Confirm with tests that are more sensitive (activated partial thromboplastin time); platelet count.


DRUG EFFECTS ON LEVELS: Prolonged by heparin or aspirin therapy, some antibiotics (newer lipoglycopeptide antibiotics may interfere with factor Xa), and barbiturates (contribute to splenic sequestration of platelets).



SPECIMEN AND PROCESSING CONSIDERATIONS


LAB ARTIFACTS THAT MAY INTERFERE: Considered an in-office test. Any variation in test protocol may alter results. Endpoint (visual clot detection) is subject to observer variability. Difficult venipuncture causing platelet activation may falsely shorten ACT.


SPECIMEN: Whole blood into siliceous (gray top, with large granules) tube, prewarmed to 37○C. Mix by inversion, incubate at 37○C (purpose-made heating block, water bath, or human axilla), and check for clot formation every 5-10 seconds. Do not incubate in a closed palm, as it does not provide a consistent 37○C environment.



PEARLS


Considered an insensitive test but may be useful for suspected warfarin-intoxicated dogs if APTT unavailable. Carriers of hemophilia (coagulation factors are 40%-60% of normal) and beagles with hereditary factor VII deficiency will not be detected by the ACT.


AUTHOR: BRUCE LEROY



Activated Partial Thromboplastin Time (APTT)



DEFINITION


Screening test for disorders of the intrinsic and common coagulation pathways



SYNONYM


Partial thromboplastin time (PTT)



TYPICAL NORMAL RANGE


Reported in seconds. Approximate ranges for normal animals are 8.6-12.9 seconds (canine) and 13.7-30.2 seconds (feline), but laboratory-, instrument-, and species-specific reference ranges must be used. Prolonged when at least one coagulation factor is <70% of normal.



PHYSIOLOGY


Citrated plasma is incubated at 37○C with excess procoagulant phospholipid. Contact activator is added to activate the intrinsic pathway via factors XII and XI. Citrate in the specimen chelates Ca2+, limiting activation beyond factor XIa. After additional incubation, CaCl2 is added to saturate the citrate and allow the reaction to continue to clot formation. The APTT is the time from addition of CaCl2 to clot formation.



CLINICAL APPLICATIONS


CAUSES OF ABNORMALLY HIGH LEVELS: Liver disease (decreased factor production), vitamin K inactivation (anticoagulant rodenticides, coumarin therapy), decreased vitamin K absorption (biliary obstruction), increased factor inactivation or consumption (disseminated intravascular coagulation [DIC]), factor dilution (massive blood loss, with colloid or crystalloid fluid replacement), hereditary factor defects, heparin therapy NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: Assess history for exposure to toxic substances or treatment. Measurement of individual factors if hereditary disease is suspected.


IMPORTANT INTERSPECIES DIFFERENCES: Prolonged APTT is reported in cats without evidence of clinical hemostatic disease, leading to increased false-positive results in this species.


DRUG EFFECTS ON LEVELS: Increased: heparin, aspirin. Polymerized bovine hemoglobin (Oxyglobin) administration interferes with ability to detect clot.



SPECIMEN AND PROCESSING CONSIDERATIONS


LAB ARTIFACTS THAT MAY INTERFERE:


• Decrease: contamination with tissue factor when specimen obtained; overfilling citrate tube

• Increase: underfilling of citrate tube; old/improperly stored samples

SPECIMEN:


• Citrated whole blood (blue-top tube). Fill completely. Refrigerate and submit to reference lab. If time interval between sampling and testing is >6 hours, mix thoroughly, centrifuge, collect plasma, freeze. Samples stored at −20○C may show significant false increases in APTT.

• Minimally traumatic phlebotomy is required to prevent tissue factor from falsely shortening the result. Ideally, collect a sufficient volume of blood to place first aliquot in red-top tube and discard (or use for serologic tests). Acceptable samples for APTT may be collected from an indwelling venous catheter.

RELATIVE COST: $$



PEARLS


APTT values generally increase before PT values with heparin therapy, but not with warfarin/anticoagulant rodenticide toxicosis or coagulopathy of liver disease.


AUTHOR: BRUCE LEROY



Alanine Aminotransferase (ALT)



DEFINITION


Enzyme located in hepatocyte cytoplasm



SYNONYM(S)


Serum glutamic pyruvate transaminase (SGPT)



TYPICAL NORMAL RANGE


Dogs: 0 to 30 U/L; cats: 10 to 25 U/L



PHYSIOLOGY


ALT is released from the cytoplasm following injury to the hepatocyte cell membrane. Low concentrations in erythrocytes or skeletal muscle may cause minor (usually clinically insignificant) increases in hemolytic diseases or with muscle injury, respectively.



CLINICAL APPLICATIONS


CAUSES OF ABNORMALLY HIGH LEVELS: Hepatocellular injury from any cause. Liver injury may be primary (e.g., hepatitis, neoplasia, blunt trauma) or secondary (e.g., translocation of enteric bacteria due to intestinal disease). Dystrophin-deficient muscular dystrophy causes slight to moderate increases in dogs and slight to marked increases in cats.


NEXT DIAGNOSTIC STEP TO CONSIDER IF LEVELS HIGH: If elevations >2 times the upper limit of reference range persist, assess history for exposure to hepatotoxins (including medications). If none, assess hepatic structure (e.g., abdominal radiographs, ultrasound) and function (preprandial and postprandial serum bile acids; alkaline phosphatase, bilirubin). Consider biopsy if values remain elevated or increase or if aforementioned tests reveal abnormalities.

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Jul 24, 2016 | Posted by in SMALL ANIMAL | Comments Off on A

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