Harvey Chapter 4 Evaluation of Erythrocytes PART II AKG Flashcards
Erythrocyte and Iron Assays Ddx of anemia and erythrocytosis
What causes splenic contraction in cats, dogs, hot-blooded horses, and some marine diving mammals (e.g., seals)?
- Exercise
- Hypoxia
- Hemorrhage
- Excitement
HCT in the spleen (about 80-90%) is much higher than that of peripheral blood. T/F
True
That is why splenic contraction increases HCT 1.3-1.5x above resting levels
What causes splenic enlargement and subsequent decrease in HCT?
Anesthesia (especially with barbiturates)
Why are manual reticulocyte counts recommended to be performed in cats compared to dogs?
Cats have more punctate reticulocytes than aggregate reticulocytes. In dogs, aggregate reticulocytes are present in blood for a few days and mature into punctate reticulocytes for only a very short period of time (hours?) before they become mature RBCs. In cats, punctate reticulocytes circulate in blood for up to a week before they mature. Additionally, punctate reticulocytes continue to be released from BM after HCT begins to increase and aggregate reticulcoyte release has ceased in cats. Most analyzers do not detect punctate reticulocytes because of the very small amount of ribosomal DNA present, and manual counts are required to count both aggregate and punctate reticulocytes.
What is the corrected reticulocyte count equation?
(patient’s HCT/mean normal HCT) x raw reticulocyte count%
How long does it take to reach a maximal aggregate reticulocyte response to anemia?
4 days
What are these larger cells?
Macroreticulocytes (aka ‘stress’ reticulocytes) - thought to occur during severe regenerative anemia - thought that one less mitotic division occurs during production and that large immature reticulocytes are released
The MCV is larger in the fetus or adult?
What it is compared to adults at the time of birth in dogs and cats vs horses and cattle?
Fetus
Horses and catte at birth: MCV is within adult RI
Cats and dogs at birth: MCV is higher than adult RI
Copper and pyridoxine are important in iron metabolism and heme synthesis. Deficiencies in these nutrients may result in _____ anemia.
microcytic
Which drugs interfere with heme synthesis and have the potential for causing the formation of microcytic RBCs with siderotic inclusions?
- chloramphenicol
- lead
- hydroxyzine in dogs
Which dog breeds normally have MCV values below the reference interfals established for other breeds of dogs, but they are not anemic?
Japanese breeds: akita and shiba
MCVs may be spuriously ______ in dogs with persistent hyponatremia.
MCVs may be spuriously ____ and MCHC may be spuriously ______ in dogs with persistent hypernatremia.
MCVs may be spuriously decreased in dogs with persistent hyponatremia because RBCs shrink when they are diluted in vitro with counting fluid. MCVs may be spuriously increased and MCHC may be spuriously decreased in dogs with persistent hypernatremia because RBCs swell when they are diluted in vitro.
What causes high MCHC values?
- Artifactual increases in hemoglobin: lipemia, protein precipitation (cryoprotins and paraproteins), Heinz bodies
- Artifactual decreases in HCT (via analyzer): in vitro or in vivo hemolysis, RBC agglutination
*remember MCHC = Hgb/HCT x 100
In iron deficiency, which value decreaes first:
MCV or MCHC?
MCV first, then MCHC
What would cause two separate populations like this on the histogram?
Blood transfusion of a donor that has a substantially different MCV.
May also see two populations if there is substantial fragmentation of RBCs
You have normal or increased PaO2 but arterial blood is dark-colored. What should you suspect?
Methemoglobinemia
Significant methemoglobinemia (oxidative damage) has been associated with clinical cases of which toxins (that serve as oxidants)?
- Benzocaine
- Acetominophen
- Phenazopyridine in cats
- Skunk musk in dogs
- Chlorate toxicity in cattle
- Copper toxicity in sheep and goats
- Red maple toxicity in horses and alpacas
- Nitrite (cattle eating nitrate-accumulating plants and nitrate is reduced to nitrite by ruminal microbes) - also sodium nitrite preservative
- Onions/garlic
- Naphthalene (moth repellent) in dogs
- Methylene blue in cats
- Propofol and propylene glycol in cats
- Brassica sp. (kale) in cows
Persistent methemoglobinemia resulting from RBC ______ deficiency has been recognized in many dog breeds, DSH cats, and horses.
Cytochrome B5 reductase
*animals with this deficiency, in contrast to thsoe with methemoglobinemia produced by oxidant drugs, usually exhibit few or no clinical signs of illness
Which anticoagulant causes erroneuously low iron concentrations when measuring serum/plasma iron concentrations?
EDTA
so use heparin or serum
Serum iron concentration is generally increased (hyperferremia) in animals with….
- Hemolytic anemia
- Dyserythropoiesis
- Hypoplastic or aplastic anemia
- Iron overload
- Acute iron toxicity
- Chronic hepatopathy (dogs)/acute hepatocellular necrosis
- Experimental pyridoxine deficiency (pigs)
- Administration of glucocorticoids (dogs and horses)
- Opposite effect in cattle and goats
Serum iron concentration is low in….
- Iron deficiency anemia
- Inflammation
- ~50% of dogs with PSS
- Demand for iron > iron stores: EPO administration or acute hemorrhage
- GC administration in cattle and goats (opposite in dogs and horses)
How can serum ferritin concentrations help differentiate true iron deficiency from anemia of inflammatory disease?
Because both conditions will have decreased circulating serum iron levels, but only true iron deficiency will have decreased serum ferritin. Serum ferritin will be normal to high in anemia of inflammation.
What increases serum ferritin concentrations?
- Hemolytic anemia
- Inflammation (ferritin is an APP)
- Liver damage: toxic, hepatitis
- Malignancy: HS, LSA in dogs
- Iron overload
- Transiently increased in horses after moderate to severe exercise and in foals following consumption of colostrum
Stainable iron is assessed int he bonw marrow with which stain?
Prussian blue
Identify which parameters will increase and which will decrease to aid detecting early iron deficiency in dogs.
- CHr
- MCVr
- CHCMr
- %LowCHr
- %Hypo-r
- CHr ↓
- MCVr ↓
- CHCMr ↓
- %LowCHr ↑
- %Hypo-r ↑
*%LowCHr = percentage of all reticulocytes with low hemoglobin (a preset value)
*CHr = mean hemoglobin concentration in reticulocytes
*These changes are not specific for iron deficiency, but should raise supsicion for iron deficiency
____ is considered as an indirect measure of transferrin concentration in serum or plasma.
total iron binding capacity (TIBC)
What causes a decrease in TIBC?
- Decreased production:
- Increased hepatocyte iron content
- Inflammation (transferrin is a negative acute phase protein)
- Hepatic insufficiency or PSS
- Decreased protein intake
- Loss
- Lost with albumin in PLN or PLE or exudative disorders
- Catabolism during negative energy balance
What causes increases in TIBC?
- Iron deficiency (woodchucks, pigs, horses, and cattle; not so much in dogs, cats or camelids)
- Artifact: high serum iron (e.g., iron overload), and possibly severe lipemia
- Necrotizing hepatitis in dogs (mechanisms unclear)
How is TIBC measured?
- Add a known amount of iron – some of these iron molecules will bind to unsaturated transferrin, and the rest will remain free
- Measure excess free iron in alkaline pH
- Total Fe added – excess free Fe = UIBC (amount of unbound iron sites on transferrin)
- UIBC + serum Fe = TIBC
How is iron measured?
Approximately ____ of the circulating iron binding sites on transferrin are occupied in healthy patients.
33%
Calculate the % saturation (Tf)
% saturation of Tf = [iron/TIBC] x 100
Interpret:
Iron ↓
TIBC normal
% saturation ↓
Any cause of low iron. Most common causes are transient variation and inflammatory disease. May be seen with or without anemia. If there is a concurrent anemia, these results do not indicate an iron deficiency anemia (would expect low TIBC), unless there is evidence of chronic external blood loss and concurrent expected changes in hemogram results (microcytic hypochromic RBC indices).
Interpret:
Iron ↓
TIBC ↓
% saturation N
ferritin - N to ↑
This pattern is typical of inflammation of >24-48 hours duration. Both iron (inflammatory cytokines, hepcidin) and TIBC (negative acute phase protein) decrease, resulting in a normal % saturation.
Interpret:
Iron - N
TIBC - ↓
% saturation - N, ↑
Loss or decreased production of transferrin, e.g. protein-losing enteropathy
Interpret:
Iron - ↑
TIBC - N
% saturation - ↑
ferritin - ↑
- Hemolytic anemia
- Non-regenerative IMHA (PIMA) or pure red cell aplasia
Hereditary stomatocytosis
Breeds
Clinicopathologic findings
Where is the defect
- Breeds: dwarf Alaskan Malamute dogs, Drentsche Patrijshond, standard and mini schnauzers
- C/S: Macrocytic, hypochromic RBCs; HCTs are often within normal range due to larger RBC size; ↓ RBC life span (EVH - osmotically and mechanically fragile); reticulocytosis
- Defect: Membrane defect involving increased Na and water influx - abnormal phospholipid composition in RBC membrane (increased sphingomyelin and decreased cholesterol and phosphatidylcholine)
Which animals can normally have stomatocytes?
Woodchucks
Manatees
Dolphins
Hemolytic anemia can be caused by decreases in this analyte, which can commonly decrease secondary to postparturient hemoglobinuria (cattle), ketoacidotic diabetic animals following insulin therapy (cats and dogs), hepatic lipidosis (cats)
Hypophosphatemia
*can be lost in milk in cattle; insuline promotes movement of glucose and phosphate into cells other than RBCs (remember glucose transport into RBCs is NOT insulin dependent)
*bilirubin interference can cause artifactual hyposphatemia
List ddx for macrotyic hypochromic anemia
- Regenerative anemia with marked reticulocytosis
- Hereditary stomatocytosis in dogs
- Abyssinian and Somali cats with increased erythrocyte osmotic fragility
- Spurious with prolonged storage of blood sample
List ddx for macrocytic normochromic erythrocyte indices (usually anemic)
- Regeneratie anemia (MCHC is not awlays present)
- FeLV infections with no reticulocytosis (common)
- AML-M6 (erythroid leukemia) and MDS
- Nonregenerative immune-mediated anemia and/or myelofibrosis in dogs
- Poodle macrocytosis (no anemia)
- Hyperthyroid cats (no anemia)
- Folate deficiency (rare)
- Congenital dyserythropoiesis of Hereford calves
- Spurious with erythrocyte agglutination
- Spurious in cats and dogs with persistent hypernatremia (may be hypochromic)
PSS may cause ____ _____ anemia.
mirocytic normochromic/hypochromic
Akita and shiba dogs normally have ↑ or ↓ MCV?
↓ - mirocytic
Neonatal isoerythrolysis can occur in kittns with blood type ___ born to queens with blood type ___ who have had no prior exposure to blood type___ antigens, becuase all adult cats with type __ blood naturally have high anti-__ antibody titers.
Neonatal isoerythrolysis can occur in kittens with blood type A born to queens with blood type B who have had no prior expsoure to blood type A antigens, becuase all adult cats with type B blood naturally have high anti-A antibody titers.
*transfusion of type A blood into a type B cat can result in life-threatening IVH reaction the first time such a transfusion is given
Both these protozoal organisms have a tissue phase and a erythrocyte phase.
How are they different based on where the stages of their lifecycle are?
Theileria and Cytauxzoon
Schizonts in Theileria develop in macrophage and lymphocytes.
Schizonts of Cytauxzoon develop exclusively in macrophages.
Which species are affected by Babesia?
- Dogs: B. canis canis, B. canis vogeli, B. canis rossi; B. gibsoni
- Cats: B. felis
- Cattle: B. bigemina, B. bovis
- Horse: B. caballi, B. equi
Which species are affected by Mycoplasma?
- Dog: Mycoplasma haemocanis
- Cat: Mycoplasma haemofelis
- Pig: Mycoplasma suis
- Sheep: Mycoplasma ovis
- Cattle: Mycoplasma wenyoni
- Llamas and alpacas: Mycoplasma haemolamae
**pretty much all, except the horse**
Equine infectious anemia (EIA) is a viral infection that causes anemia. What are the mechanisms of hte anemia?
Immune-mediated destruction or RBCs and bone marrow suppression
This enzyme _____ in venoms appears to be important in causing RBC injury.
Phospholipase A2
In cattle, consuming which plants results in heinz body hemolytic anemia?
- Cattle grazing on St. Augustine grass pastures due to selenium deficiency
- Perennial ryegrass (post partum in New Zealand)
- Lush winter rye
- Kale and other Brassica species
Why can hypophosphatemia result in secondary hemolytic anemia?
Becuase hypophosphatemia decreases the erythrocyte glycolytic rate, which results in a decreased ATP concentration and potentially decreased RBC 2,3-DPG concentration (making it more alkaline fragile)
Describe the signalment and clinical hallmarks of pyruvate kinase (PK) deficiency
- Young age: macrocytic, hypochromic regenerative anemia; pale mucous membranes, decreased exercise tolerance, tachycardia and splenomegaly
- As dogs age: hemochromatosis and cirrhosis –> myelofibrosis and liver failure –> death within 1-5 years
- Signalment: high prevalence in basenji and beagles; cats get it, but do not develop myelofibrosis and liver failure
Which way does the oxygen-hemoglobin dissociation curve shift in dogs with PK deficiency?
To the right
PK deficiency –> build up of 2,3-DPG upstream of the Kreb’s cycle –> decreases oxygen binding affinity
Describe the clinicopathologic features of phosphofructokinase (PFK)-deficiency.
- Dogs
- Persistent compensated hemolytic anemia and sporadic episodes of IVH (‘hemolytic crisis) that often occur when dog develops alkalemia secondary to hyperventilation
- RBCs become alkaline fragile becuase intracellular 2,3-DPG is decreased –> results in higher intracellular pH
Which way does the oxygen-hemoglobin dissociation curve shift in PFK-deficient dogs?
To the left
PFK deficiency is upstream of 2,3-DPG synthesis, so 2,3-DPG decreaes –> increasing oxygen binding affinity
Describe the signalment and clincopathologic features of increased erythrocyte osmotic fragility in cats?
Abyssinian and Somali cats
Regenerative anemia, splenomegaly, polyclonal hyperglobulinemia
RBC membrane defect is suspected (but RBCs appear morphologically normal)
Very suspceptible to hemolysis with sampel storage (marked in vitro hemolysis within 24 hours)
Cattle with band 3 deficiency have which clinical hallmark upon blood smear review?
Marked spherocytosis
Hemolytic anemia - non-regenerative
Hereditary elliptocytosis has been documented in dogs due to a deficiency in which cytoskeletal RBC protein?
Name which breed was foudn to have a hereditary condition.
Spectrin deficiency
Goldens have hereditary spectrin deficiency - had a quantitative issue and coudl not make spectrin at all.
There is a case report in a dog that has a qualitative issue - meaning the dog could make spectrin but it was mutated and number of spectrin tetramers were decreased (spectrin was mostly in the form of dimers in this dog).
Describe the signlament and clinicopathologic hallmarks of hereditary stomatocytosis
- Dogs - schnauzers, Drentse partrijshond hounds, dwarf malamutes
- One or more membrane defects lead to RBCs taking up too much sodium –> RBCs swell and stomatocyte shape –> increased osmotic fragility + shorted RBC survival
- Macrocytic and hypochromic RBCs
- Usually not anemic to very mildly anemic
There is a case report of a dog that lacked erythrocyte membrane protein 4.1. This resulted in persistent ______ and _____ in RBCs, which ultimately shorted RBC life span and resulted in reticulocytosis (although animal was non-anemic).
elliptocytosis and microcytosis
*remember that elliptocytes form with horizontal issues (with spectrin and P4.1). Vertical interactions (what tacks spectrin to the membrane - band 3/ankryn) lead to spherocytosis
Postparturient hemoglobinuria in dairy cattle has been associated with _________.
hypophosphatemia (leads to decreased ATP concentrations)
Describe the changes that you would expect with anemia of inflammation to the following:
HCT
MCV
Serum iron
Serum TIBC
Serum ferritin
Marrow hemosiderin
HCT - slight to moderate decrease
MCV - normal to slight decrease
Serum iron - slight to moderate decrease
Serum TIBC - normal to decreased
Serum ferritin - normal to increased
Marrow hemosiderin - normal to increased
Why do disorders such as hypopituitarism, hypoadrenocorticism, and hypothryoidism result in mild non-regenerative anemia?
Because these hormones enhance the growth of RBC progenitor cells in the presence of EPO.
Also, thyroid hormones may promote the synthesis of EPO in the kidney.
Deficiencies in which two nutrients leads to anemia from disorders of nuclei acid synthesis.
Folate (macrocytic anemia) - very rare in animals
Cobalamin (vitamin B12)
Describe the clinicopathologic features found in blood of cobalamin deficiency in dogs
- Occurs secondary to inherited malabsorption of coabalamin
- Normocytic, nonregenerative anemia
- Neutropenia with hypersegmeneted neutrophils
- Giant platelets
In iron deficiency anemia, which drops first, MCV or MCHC?
MCV
Copper and pyridoxine (B6) deficiency can lead to ____ _____ anemia.
iron deficiency
Selective erythroid aplasia occurs in cats infected with which FeLV subgroup?
FeLV subgroup C - binds to a heme exporter on BM CFU-E cells - may inhibit heme export from these cells
(NOT in subgroup A or B)
High doses of _____ cause reversible erythroid hypoplasia in some dogs and erythroid aplasia in cats.
Chloramphenicol
What is another differential for pancytopenia other than bone marrowhypoplasia/aplasia and myelophthisis?
Hisitocytic inflammatory conditions: terminal stage of cytauxzoonosis in cats, histoplasmosis, leishmaniasis, mycobacteriosis
Hemophagocytic syndrome in dogs (BM has > 2% hemophagocytic macrophages)
Hypersplenism - increased phagocytosis of blood cells
Hemophagocytic histiocytic sarcoma
Drug-induced causes of aplastic anemia or generalized marrow hypoplasia in animals include:
- Estrogen toxicity in dogs and ferrets
- Phenylbutazone toxicity in dogs
- TMS in dogs
- Bracken fern poisoning in cattle and hseep
- Trichloroethylene-extracted soybean meal in cattle
- Albendazole toxicity in dogs, cats, and alpacas
- Griseofulvin toxicity in cats
- Methimazole toxicity in cats
- Chemo, radiation, immunosuprresive durgs (azathioprine)
What are endogneous tumors that secrete excess estrogen?
Sertoli cell tumor
Interstitial cell tumor
Granulosa cell tumor
Adrenocortical tumors in ferrets
Describe the hemoglobin content in the first 4 months of life
At birth, hemoglobin values reach near those of adult animals
Following birth, rapid decrease in hemoglobin and HCT for few weeks
After few weeks of age, HCT and HGB increase slowly and reach adult values at about 4 months.
Primary erythrocytosis (aka ______) is considered to be a myeloproliferative neoplasm that results from an autonomous (EPO-independent) proliferation of erythroid precursor cells, resulting in high numbers of mature erythrocytes in blood.
polycythemia vera
Please list disorders that lead to secondary erythrocytosis
- Chronic hypoxemia: heart defects with R-L shunting, diffuse lung disease, persistent methemoglobinemia
- Renal disorders causing local tissue hypoxia (renal tumors and localized inflammation)
- TUmors that secrete EPO, EPO-like proteins, or other hormones such as androgens that might enhance the effects of EPO
Which of the following tests is not useful in determining the cause of absolute erythrocytosis:
- Arterial blood gas measurements
- Diagnostic imaging
- BM cytology
- Methemoglobin screening test
- Validated EPO test
- Arterial blood gas measurements: low PaO2 suggests heart defect or chronic lung disease
- Diagnostic imaging: differentiate heart from lung dz and look for renal tumors
- BM cytology - NOT useful
- Methemoglobin screening test
- Validated EPO test: primary vs secondary erythrocytosis
Serum iron concentration is only measured as iron bound to transferrin by a colorometric procedure (formation and quantitation of iron-chromagen complex). Which two chelating agents are used to prevent copper from complexing with chromagen and interfering with iron measurement?
Thiourea and thioglycolic acid
Serum iron concentration is only measured as iron bound to transferrin by a colorometric procedure (formation and quantitation of iron-chromagen complex). What can cause sepctrail interferences?
Hemoglobin - avoid hemolyzed samples!
Why are cats very susceptible to acetominophen toxicity?
They lack glucuronyl transferase that is used by most animals to conjugate acetominophen.
Why do healthy cats have circulating Heinz bodies?
- Not removed from circulation as well since cat’s spleens have a closed circulation - RBCs do nto flow through the red pulp in which pitting of Heinz bodies
- Feline hemoglobin has more sulfhydryl groups than other species - may be prone to form more disulfide bridges and thus more denatured Hgb
glucose transport into RBCs is insulin dependent. T/F
False - it is NOT insulin dependent, and uses an insulin-independent glucose transporter (pig RBCs lack this transporter and use inosine for energy instead)
Cattle and horses may develop porphyria and the resulting photosensitization when severe liver disease decreases excretion of ________ (a porphyrin derived from the breakdown of chlorophyll).
phylloerythrin
Bovine congenital erythropoietic porphyria is caused by a hereditary deficiency in _______, which is an enzyme that catalyzes one of the first porphyrin reactions. The cows have reddish brown discoloration of teeth and bones, photosensitivity, and anemia of varying severity. Found primarily in Holsteins.
uroporphyrinogen III cosynthase
Hereditary methemoglobinemia is a condition associated with ____ deficiency in dogs and cats, and _____ defcieicny in a horse.
Erythrocyte band 3 is a membrane protein that has two major functions:
- Serves as an ion-exchange protein for the rapid exchange of chloride and bicarbonate to allow the transport of CO2 from tissues to lungs
- It contributes to the RBC cytoskeleton by anchoring the cytoskeleton to the membrane
A defect in erythrocyte membrane protein 4.1 causes hereditary ______ in dogs.
elliptocytosis
______ anemia has the concurrent findings of anemia and megaloblastic erythroid percursors in the blood. The causes are varibale, and may be the result of neoplastic transformation of RBC precursors, defective nucleic acid metabolism caused by _____ or ______ deficiency, or defective metabolism.
In cats, there is a high clinical association with FeLV subtype ____.
Megaloblastic anemia
folate or B12
subtype C
A diagnosis of sideroblastic anemia was based on the concurrent presence of > ____ % sideroblasts in marrow and of _____ sideroblasts. It can be caused by ______…..
15%; ringed sideroblasts
- Vit B6 deficiency - required in first step of heme synthesis
- Chloramphenicol
- Hydroxyzine
- Zinc
- Lead
- Inflammatory disease
Clinical significance of echinocytes
Hyponatremic dehydration
Doxorubicin toxicosis
Anionic drugs
Significance of ovalocyte/elliptocyte in dog
protein band 4.1 deficiency
mutant spectrin deficiency
myelofirbosis
idiopathic in cats
iron deficiency
List ddx for immune hemolytic disorders
- Idiopathic
- Druge induced
- Vaccine associated
- Alloimmunization
- Neonatal isoerythrolysis
- Blood transfusion reactions
List ddx for hemolysis induced by bacterial and viral infections
- Mycoplasma
- Anaplasma
- Leptospira
- Clostridium spp. - causes erythrocyte membrane damage by phospholipases
- Bacillary hemoglobinuria (C. haemolyticum or C. novyii)
- Yellow lamb disease (C. perfringens, type A)
- Clostridial infections in horses
- EIAV
- FeLV
Why can infection with Clostridium spp. result in hemotlyic anemia?
Clostridium spp. contain phospholipases than can damage RBC membrane
Ddx for hemolysis caused by erythrocytic metabolic defects
- Oxidative damage (heinz body hemolytic anemia, eccentrocytic hemolysis)
- Inherited: FAD deficiency or G6PD deficiency
- Defects in ATP generation
- PK deficiecny
- PFK deficiency
- Hypophosphatemia
- L-sorbose intoxication (fake sugar)
Ddx for hemolysis caused by defects in heme synthesis that result in porphyria
- BOvine congenital erythropoietic porphyria
- Feline erythropoietic porphyria
Ddx for hemolysis caused by RBC fragmentation in blood
- Intravascular coagulation (localized or DIC)
- Vasculitis
- Hemangiosarcoma
- Rheologic processes
- Caval syndrome of dirofillariasis
- Cardiac vulvar disease
Secondary causes for copper deficiency include ruminants with a diet that is too high in _____ or ____.
molybdenum or sulfate
Copper deficiency can relult in low MCV and MCHC and results in a functional iron deficiency because it is involved in which two proteins responsible for iron oxidation and transport?
Ceruloplasmin and hephaestin
What are the major differences between bovine congenital erythropoietic porphyria (CEP) and bovine erythropoietic protoporphyria (EPP)?
- CEP is more clinically significance and involves hemolysis; EEP just causes mild photosensitivity
- CEP is from a genetic defect in UroGenIII-Cosyn; EEP is froma genetic defect in ferrochelatase
- Cattle with CEP only have COPRO I in bile and feces, but RBCs have high levels of PROTO IX
- Cattle with EEP have high levels of PROTO IX in both feces and RBCs
