Erythrocytes & Leukocytes Chs 1, 2 D&P Flashcards
What does hemoglobin consist of?
Heme and globin, a tetramer, each heme has a iron and there is four hemes connected to four globin chains as dimers with alpha and beta chains.
What is the action of lead on erythropoesis?
Lead inhibits most steps in heme synthesis.
What are porphyrins?
Intermediates in heme synthesis and certain enzyme defeciencies lead to excessive accumulation of porpphyrins > porphyria; these compounds may escape the RBC and accumulate in tissues (like skin etc) and lost in urine etc. (I think also in photosensitization type II)
What is hepcidin?
produced in liver and plays a role in iron metabolism, increased hepcidin means decrease in iron availability and its a component of acute phase response with IL-6 to control plasma iron conc by inhibiting iron export by ferroportin (it induces internalization and degradation of ferroportin) from enterocytes and macrophages. Main regulator of iron homeostasis
How is iron transported in the blood?
Bound to transferrin, a gamma globulin I think
Five conditions where you might have decreased serum Iron
Iron defeciency Acute and chronic inflammation Hypoproteinemia Hypothyroidism Renal dz
Conditions with increased serum iron
Hemolytic anemia
accidental lysis or RBCs
Glucocorticoid excess
Iron overload - acquired or hereditary like in some birds like Mynahs and Toucans, and Salers cattle where you will see hemochromatosis which is a good gross image.
How is iron stored in macrophages?
As ferritin and hemosiderin.
What is ferritin? When is it increased and decreased?
Iron protein storage complex thats water soluble and a more labile form (hemosiderin is more stable and less available and comprised of denatured ferritin and protein), and small amounts can circulate in serum; serum amounts are decreased in iron deficiency and
increased with hemolytic anemia, iron overload, acute and chronic inflammation, liver dz and some neoplastic disorders, and malnutrition in cattle.
Abnormalities in serum iron are related to what?
Absorbtive failures, nutritional defs, loss via hemorrahge, aberrant metabolism with diversion to macs at the expense of hematopoesis (ie chronic dz or inflammation).
How does erythrocyte metabolism take place and why?
Embden-Meyerhof pathway (RBCs don’t have mitochondria); its an anaerobic pathway and glycolysis generates ATP and NADH (used to reduce methemoglobin).
Important enzymes in the Embden-Meyerhof pathway? What happens with their deficiencies?
Pyruvate kinase (PK) and phosphofructosokinase (PFK) > defeciences >> hemolytic anemia (PK def = macrocytic hypochromic anemia; reported in several dog breeds and abyssian and somali cats. (PFK def = hematocrit is WNL or decreased and there is persistent reticulocytosis and alkalemia leading to hemolysis, also reported in dogs)
Three other 3 pathways involved in RBC metabolism besides Emden Meyerhof?
Pentose phosphate pathway (ie Hexose monophosphate pathway) > produces NADPH via Glc -6-phosphate dehydrogenase and defeciency = hemolytic anemia when there is oxidative stress.
Methemoglobin reductase pathway (enzyme def = methemoglobin accumulation = cyanosis and brown mm and blood).
Rapoport-Leubering pathway. > formation of 2,3 diphosphoglycerate that plays a role in oxygen transport and release. Amount varies with spp. p7
What is the name of the earliest RBC precursor cell?
Rubliblast, and the last stage before erythrocyte is reticulocytes (rubricyte and metarubricyte are in between)
When is the nucleus extruded from the RBC during development?
At the metarubricyte stage (forming a reticulocyte). IN birds avian retics retain their nuclei.
Where do retics mature?
IN cattle and horses its in the bone marrow and mature RBCs are released, in most other animals retics are released into blood and mature in the periph blood or spleen.
Once stimulatino occurs how long before retics are released?
5 days. p9
Where is EPO produced? Two factors that work with Epo to stim RBC production.
Peritubular interstital cells in the kidney and a little in the liver. (Ito cells and specific hepatocytes).
IL-3 from T lymphocytes and GM-CSF from T lymphocytes.
Whats the average RBC lifespan in dogs and who has the longest and shortest of the different species?
Dogs is 110 days; cow is longest at 160 days and birds are only 35 days; cats are 70 days.
What happens to heme when RBCs and hemoglobin are broken down in Macs?
The heme is cleaved by heme oxygenase forming Carbon monoxide and biliverdin . Biliverdin > Bilirubin (unconjugated) > excreted from Mac into blood > binds albumin and txported to liver where it would be conjugated in hepatocytes and secreted in the bile (I think). The Iron is released and probably goes into Ferritin or Hemosiderin
What happens to hemoglobin in intravascular hemolysis? Whats the relationship between plasma hemoglobin and hemoglobinuria?
Its released into plasma and binds haptoglobin which prevents it from being lost in the urine, and then it is cleared from the blood by liver. Enough haptoglobin is present to bind 150mg/dl of hemoglobin and the plasma appears pink at 50-100mg/dl of hemoglobin so the plasma is pink before hemoglobinuria occurs.
If haptoglobin is saturated, hemoglobin saturated its lost in the urine freely. Over time its oxidized to methemoglobin > dissociates to free ferriheme > complexes with hemopexin.
What happens to hemoglobin that passes into the glomerular filtrate?
Absorbed by the proximal tubules, catabolized to iron, bilirubin and globin. Hemoglobin not absorbed will end up in the urine. Tubular cells with hemosiderin may slough into urine and cause hemosiderinuria, so you can see renal cells with hemosiderin in them if there was intravascular hemolysis.
Whats the difference between HCT and PCV
HCT is calculated using MCV and RBC level (RBC/ul), by multiplying them, and PCV is determined by centrifuge so there is less potential for error with PCV.
What does a measure of hemoglobin concentration tell you?
Its the most direct indication of oxygen transport capacity of the blood and should be approximately one-third the HCT if erythrocytes are of normal size.
What factors will affect Hct, Hgb conc and RBC count all three togather?
Low values for all occur in anemia and overhydration. All will be increased in dehydration.
How is MCV (mean corpuscular volume determined and what factors will affect it?
(PCVX10) / RBC count = MCV
Reticulocytosis causes macrocytosis (increased MCV)
Iron deficiency causes microcytosis, dec. MCV, and it also occurs in portosystemic shunts.
Interference with nucleic acid synthesis prevents cell division so there is macrocytosis.
FeLV cats have macrocytosis.
RBC agglutination can cause a false increase in MCV.
What is MCH?
What is MCHC?
MCH is mean corpuscular hemoglobin, how much Hb is present within an average RBC in picograms (PG)
MCHC is the average Hb concentration per average erythrocyte (g/dl), ie its a concentration. Note an increased MCHC will never occur, it cannot be produced inside the cells. But MCHC may be reduced in reticulocytes; hypochromia is low MCHC and may occur in Fe defeciency.
Best stain for Reticulocytes?
New methylene blue (RNA, DNA stain blue). Romanowsky stains like Diff-Quik are polychromic.
Comparison of canine and feline RBCs. Bovine, Equine, Porcine?
Felines lack the central pallor of canine RBCs and are a little smaller.
Bovine anisocytosis is common,
Equine lack central pallor also (like cats) and rouleaux formation is common.
Porcine show poikilocytosis (remember P for P).
Agglutination versus Rouleaux?
Agglutination is present if the erythrocytes remain clumped when blood is diluted 50:50 to 10:90 with physiologic saline. (ie as occurs in immune med dz.)
Two conditions where you see microcytosis?
Iron deficiency and Portosystemic shunts and some asian dog breeds.
When are spherocytes seen?
Immune med anemia and decreased MCV due to decreased membrane surface area, they are globoid cause the smaller cell must enclose a normal amount of Hemoblobin (I think these are basically smaller RBCs without central pallor, see pg 17)
What does polychromasia refer to
Blue gray RBCs with residual RNA, usually macrocytic. Polychromatophilic RBCs seen wtih Romanowsky stains are synonymous with reticulocytes seen with NMB stain. These indicate a regenerative response to anemia.
What is hypochromia? Name two causes.
Decreased ctyoplasmic staining and increased central pallor of the RBC caused by insufficient Hb, Iron def is the most common cause but it also occurs with lead toxicosis via inhibition of Hb synthesis (esp in birds).
What does poikilocyte refer to?
Generic term for abnormally shaped RBC. Specific types include Echinocytes, Keratocytes, Schistocytes, Acanthocytes, Fusocytes, Ellipotcytes, Dacrocytes, Leptocytes, Target cells / Codocytes, Stomatocytes and Spheroctyes.
Whats an echinocyte?
Spiculate RBC with uniform projections. Crenated RBCs that are in in vitro artifact of drying. May also be observed in uremia, electrolyte depletion, lymphoma, doxorubicin tox and glomerulonephritis.
What are keratocytes?
Helmet cells. RBCs with one or two projections that form a ruptured vesicle, these abnormalities often result from oxidative damage to the RBC membrane as seen with Heinz body formation.
What are schistocytes?
Irregular RBC fragments from shearing by fibrin or turbulent blood flow. DIC, HSA, glomerulonephritis, congestive heart failure, myelofibrosis, vasculitis.
What are acanthocytes?
Spiculated RBCs with two or more irregular, often blunted projections (in contrast with echinocytes that have regular uniform projections all over), thought to form as a result of altered lipid:cholesterol ratios in the RBC membrane. Seen in HSA (esp in the liver), glomerulonephritis, lymphoma, LIVER DZ.
What are dacryocytes?
Teardrop-shaped RBCs that may result from the inability of the RBC to return to its pre-existing shape after deforming in the vessels, not sure why this happens - cytoskeletal protein alterations. May be an artifact if all tails are in the same direction. Seen in llamas with Fe deficiency anemia.
Leptocytes.
Thin cells with an increased membrane:volume ration. Appear folded due to excess membrane. Have been associated with portosystemic shunts;
They are also called target cells or Mexican Hat cells, they are clear in the middle the a thick outer rim of membrane and may also have a spot in the middle like a hat.
What are target cells / codocytes?
A type of leptocytes that is bell shaped and resembles a target cause the Hb is at the periphery and in the middle of the cell. Associated with liver dz, Fe def anemia and reticulocytosis.
What are stomatocytes?
A type of leptocyte that is bowl shaped with oval areas of central pallor; due to expansion of the inner cell membrane and observed in hereditary stomatocytosis of Alaskan malamutes etc and may also be artifact of thick area of blood smear.
What are spherocytes?
Small dark microcytes that lack central pallor with reduced amount of membrane per unit volume. Readily detected only in the dog because of the normal abundance of central pallor. Seen with IMHA; result from partial phagocytic removal or Ab coated membrane or pitting of Heinz bodies. They get removed by splenic Macs d/t their reduced ability to deform/loss of flexibility.
Basophilic stippling.
Punctate aggregation fo residular RNA with Diff Quick stain. Anemic sheepa nd cattle. Same significance as polychromasia (ie reticulocytes) (regen anemia) and may be appropriate response in anemia. May also be seen in lead toxicosis where there would be metarubricytes (nucleated reds) with minimal polychromasia (ie inappropriate response - dyserythropoeisis) in an animal with normal RBC values.
What are Howell Jolly bodies?
Basophilic nuclear remnants in the cytolasm of RBCs, seen most often in accelerated erythropoiesis or post splenectomy.
Whats a Heinz body and when is it seen?
Round structure that protrudes from the membrane of a RBC, like a blister of membrane. Its denatured precipitated Hb due to oxidation and they appear as dark basophilic bodies with NMB stain. Cats are most susceptible due to a larger number of sulfhydral groups that increase susceptibility to oxidation, and the feline spleen is inefficient at removing these structures. Up to 10% of feline RBCs may have these in health.
Eccentrocytes.
RBCs with Hb condensed to one side of hte cell leaving a clear or bilster line area in the remaining portion of the cells. The result of oxidative injury with lipid peroxidation and cross linking of the cell membrane. p20
What is the meaning of nucleated reds in the bood smear and what is it called?
Metarubricytosis (can occur with rubricytes or earlier stages as well). It can be appropriate (with strongly regen anemias where you would also see reticulocytes) or inappropriate (ie with lead toxicosis, iron deficiency, copper deficiency, HSA, EMH, myelophthisis, endotoxemia, bone marrow dz, FeLV infection, myelodysplastic syndrome, leukemia, erythremic myelosis in cats.)
What are the three possible locations of RBC parasites and what are some specific parasites that occur in these locations?
Intracellular: (Hemoproteus, Leukocytozoon and Plasmodium of birds); (Cytauxzoon felis and Babesia felis of cats); (Anaplasm marginale, Babesia bovis, & bigemia of cattle); Babesia canis & gibsoni of dogs), (Babesia equi and caballi of horses).
Epicellular: (Mycoplasma haemofelis of cats and M. haemocanis of dogs and M. haemosuis of pigs); (Eperythrozoon wenyoni of cattle).
Extracellular: Filarids and Trypanosomes.
Microfilaria > (Dipetalonema reconditum and D. immitis of dogs); Setaria of horses).
Trypanosomes > (T. theileri, congolense and vivax of cattle); (T. cruzi of dogs); and (T. evansi of horses)
You see irregular to round to ring shaped magenta bodies in the RBCs and also may see them in the leukocytes in a blood smear, what are they?
Distemper inclusions. Stain pink with diff quick or other Romanowsky stain.
In what species will you not see reticulocytes?
HORSES; you will not see retics in the blood of horses in either health or regen anemia. IN ruminants you will only see retics in the blood with anemia cause of their long RBC lifespan but you may see a few normally in dogs and cats.
How do you calculate absolute reticulocyte count and what are the values indicating a regenerative response in dogs and cats?
Multipley the reticuolcyte percentage by the Total RBC count in uL so youhave absolute retic count in uL.
Dog: > 80,000 retics/uL = Regenerative response
Cat: > 60,000 retics/uL = Regenerative response
p22
In what type of anemia does the most severe reticulocytosis occur? When does it become evident in the blood and when is it at its max?
What about reticulocytosis in cattle and horses?
Most intense reticulocytosis occur in hemolytic anemia > external hemorrhagic anemias. (the iron is more readily available)
Not evident until 48-72 hrs and max at 7 days.
Doesn’t occur in cattle until HCT is very low and DOES NOT ever occur in horses.
What does the lack of reticulocytes following anemia tell you?
The bone marrow is no responding. NONregen anemia.
Parts to assess on a bone marrow smear?
Proportion of adipocytes (approx 50%);
proportion of hematopoietic progenitor cells (approx 50%);
Megakaryocytes;
M:E ratio;
Maturation stages of myeloid & erythroid stages - percents of the different stages simply as mature or immature;
Iron in macrophages.
In health in a marrow smear what should the percentages of mature versus immature cells be for the myeloid and erythroid lines?
Myeloid: 80% should be mature (metamyelocytes, bands and segs.)
Erythroid: 90% should be mature (rubricytes and metarubricytes)
A high percent of immature (ie blasts) suggests hyperplasia, neoplasia, maturation abnormality; in the myeloid series you can have depletion of the mature series with shift toward immaturity.
How do you interpret the M:E in the bone marrow smear? (ie if its high or low)
First you need to have the CBC for the WBC counta nd RBC count.
If the WBC count is normal, any change in M:E is due to the erythroid series.
High M:E, normal WBC count = erythroid hypoplasia.
High M:E, anemic animal, increased WBC count = may be myeloid hyperplasia OR erythroid hypoplasia.
Low M:E in an anemic animal with a WBC count within or above the ref interval = RBC regen (or possibly ineffective erythropoesis).
What type of iron does Perls or Prussian stain detect? What about in cats? What will you see in Anemia of chronic dz when staining the marrow for iron?
Perl’s or Prussian blue detects hemosiderin (insoluble iron) but NOT ferritin (soluble iron because its removed during staining). In anemia of chronic dz you see increased iron staining in the marrow. Hemosiderin is NOT seen in the feline marrow.
Which blood types in the dog have the greatest potential for txfusion reactions?
DEA 1.1, 1.2, 1.3 (DEA 1.1 and 1.2 form due to previous txfusion, ie not naturally occuring).
Anti DEA 3, 5 and 7 also occur naturally > RBC removal.
In the horse, Abs to what blood types are most frequently involved in neonatal isoerythrolysis?
Aa and Qa
What type of Abs occur in the cat to blood groups?
Type A and B blood types (Abs to the opposite type occur naturally in the cat without prior txfusion).
Type B cat with anti A abs > life threateninig hemolytic reaction with txfused with type A blood.
Type A cat with anti B abs > erythrocyte removal when txfused with type B blood. p25
For blood cross matching, whats a major versus minor cross match.
Major = RBCs of the donor against serum of the recipient. Detects Abs in the recipient that will react and destroy donor cells; a txfusion reaction will cause massive lysis of donated cells. Minor = tests serum of donor against RBCs of recipient, ie trying to detect Ab in donor blood that would damage host RBC, less significant due to dilution in the recipient and probably only an issue for whole blood txfusions, not an issue if only packed RBCs txfused. p25
What does an incompatible blood cross match indicate?
Prior sensitization. Naturally occurring Abs are not usually present in enough numbers to cause transfusion reactions EXCEPT in A negative Type B cats that have naturally occurring anti-A Abs.
What are the indicators of an incompatible cross match?
Agglutination in most spp;
hemodilution predominates in horse and cow.
What is the Antiglobulin / Coomb’s tests? Direct versus indirect.
Coombs > used to confirm immune mediated hemolysis of RBCs.
The Direct Antiglobulin test (DAT) > detects Ab or complement attached to the membrane of patients washed RBCs
Indirect test > detects Anti RBC Abs in the serum of the patient (ie Abs to a potential donors, sires, offsprings RBCs). You can also test colostrum this way in cows and mares to see if it has Abs against other’s RBCs.
What is the easiest and most accurate way to detect anemia?
Hct. (interpret in light of patients hydration status) (remember though this is a calculated value > multiple the volume of one RBC ie. MCV, by the number of RBCs in one ul of blood, aka the RBC level, and this tells you the volume or space in the ul of blood that is being taken up by the RBCs, and the remainder of the space in the ul of blood is serum proteins and fluid, so this calculated HCT will be affected by variations in MCV).
What are the three ways to classify an anemia?
- According to MCV and MCHC. ie. normocytic, macrocytic or microcytic AND normochromic, hypochromic or hyperchromic; remember RBCs never overproduce Hb so hyperchromasia is due to hemolysis.
- According to Marrow response. (ie. regen via polychromasia, retics with anisocytosis and increased RDW, macrocytosis and hypochromasia, decreased M:E in the marrow, regen suggests an extramarrow etiology like lysis or loss); (non regen suggests inadequate time so its acute still or chronic inflammation, renal dz, endocrine disorders, marrow dz, iron def, and all horses appear nonregen due to no reticulocytes).
- According to Major pathophysiologic mechanism like hemorrhage anemia, destruction anemia like with hemolysis, or reduced / defective erythropoiesis.
Common lab findings in cases of acute Blood loss and when does it normalize?
HCT is initially WNL cause all blood components are lost.
As fluid from the interstitium restores blood volume within 48 to 72 hours HCT, RBC count and Hb concentration are reduced and hyoporoteinemia is observed.
Platelet numbers increase.
Neutrophilic leukocytosis.
Signs of regen like polychromasia, reticulocytosis by 48 to 72 hours, max out at 7 days.
Plasma protein levels normalize before HCT (within 2-3 days).
The entire hemogram should normalized within 1-2 weeks.
If marrow is broke you will see Thrombocytopenia and subsequent hemorrhage and the anemia looks non regen.
Lab findings in chronic hemorrhage?
Regen response that is weaker than with acute loss.
Hypoproteinemia. (UNLESS the hemorrhage is internal)
Persistent thrombocytosis
Iron def anemia may develop as iron stores are depleted (microcytosis, hypochromasia) (AGAIN UNLESS the hemorrhage is INTERNAL, the Fe is then recycled like the protein).
Common findings in hemolytic anemia.
Icterus if severe and acute.
Hemoglobinuria and hemoglobinemia if intravascular.
(note extravascular more common that intra)
HIgher retic counts than with hemorrhage due to iron recycling.
Normal or increased plasma protein concentration.
INtravascular hemolysis cause hyperproteinemia, hemoglombinemia and hyperchromasia (inc MCH and MCHC).
Neutrophilic leukocytosis and monocytosis
Hyperbilirubinemia, hemoglobinuria (hemoglobin degradation)
Abnormal RBC morphology like (Heinz bodies, RBC parasites, spherocytes, poikilocytes)
IN cases of extravascular hemolysis that are Antibody or complement mediated, what the the three most common membrane antigens recognized by Abs?
Glycophorins, band 3, and Spectrin.
What are the mechs by which extravascular hemolysis occurs?
- Immune mediates stuff: Antibody or completement C3b binds the RBC and targets it for descruction by macrophages.
Macrophage phagocytosis may result in spherocytes formation as bites of RBC membrane are taken resulting in smaller RBC cell membrane with the same amount of cell contents.
Type II HS: IMHA/autoimmune dz; infectious agents like FeLV, EIA, Ehrlichia, M. haemofelis (alter rbc membrane or form immune complexes that fixes complement); haptens like penicillin; immune system dysregulation (ie in T cell function); paraneoplastic
IgM or IgG on the surface with complement fixation, even C9 and the MAC in some cases. - Defects or changes in RBC membrane reducing deformability. (ie forming schistocytes, or spherocytes in IMHA or parasitized RBCs or eccentrocytes and RBCs with Heinz bodies.)
- Reduced glycolysis and ATP content of the RBC (dec glycolysis as in pyruvate kinase def and PFK def in animals).
- INcreased macrophage phagocytic activity.
What are the clinical and lab findings with extravascular hemolysis? (4)
Chronic with insidious onset.
Hyperbilirubinemia (if the liver is overwhelmed - unconjugated early and the conjugated later on).
Neutrophilic, monocytosis and thrombocytosis.
Splenomegaly
What things may aid in determining the cause of extravascular hemolysis? (3)
- Dog breed like Cockers and springer spaniels get PFK def and Basengis and Beagles and others like Westies get PK deficiency and some just have a predist to hemolytic anemia like the Cocker etc.
- Positive Coombs test / direct antiglobulin test (test for Ig or C3 on patients RBCs)
- Abnormal RBC morphology like RBC parasites, spherocytes, schistocytes, keratocytes suggest the potential for phagocytosis.
What are the different mechanisms of intravascular hemolysis?
Note with this the hgb is released into plasma and then removed by the liver or excreted by the kidneys.
Also note that in most of these cases the RBC itself and its membrane are initially normal.
What are the five mechanisms of intravascular hemolysis?
- Complement mediated lysis via C9 and Mac (not via C3, that would cause phago and extravasc hemolysis).(comlement fixation / mediated lysis usually mediated by IgM usually like in neonatal isoerythrolysis in foals and in transfusion reactions).
- Physical injury (shearing via fibrin, ie microangiopathic anemia > schistocytes)
- Oxidative injury (> denature Hb and heinz body formation, methemoglobin formation from Hb iron, and cross linking of membrane proteins with eccentrocyte formation)
- Osmotic lysis
- Alterations via other mechanisms (ie snake venom, castor beans, bacterial toxins like from C. novyi, Babesia sp.)
How is the RBC protected from oxidation?
Reduced glutathione neutralizes oxidants, its produced via the pentose phosphate pathway (deficiency of enzymes in the pathway leads to problems (ie glc 6 phosphate dehydrogenase def.).
Iron is maintained in the reduced state via methemoglobin reductase so accum of methemoglobin is minimized.
The main two RBC changes that suggest oxidative damage?
Heinz bodies or eccentrocytes.
What things can result in osmotic lysis of RBCs?
HYPOPHOSPHATEMIA (esp in diabetic patients)
Hypotonic IV fluids
Cold hemoglobinuria of cattle
What are some of the clinical and lab characteristics of intravascular hemolysis?
Acute or peracute onset
Regen response that may take 2 or 3 days to show up
*Hemoglobinemia (red plasma, inc MCHC or MCH)
*Hemoglobinuria (occurs when hemopexin and haptoglobin are saturated and renal tubule cells can’t absorb and metab all the hemoglobinuria)
Hemosiderinuria (formed in renal tubule epi cells)
Hyperbilirubinemia (unconj early and conj later on)
Schistocytes, keratocytes, Heinz bodies, eccentrocytes, RBC parasites, Pos coombs test.
What is conjugated hyperbilirubinemia accompanied by?
Bilirubinuria
If bilirubin is elevated what must have happened - concise but comprehensive answer.
The amount of bilirubin present in the blood has exceeded the livers ability to absorb/uptake it, conjugate it and secrete it into the bile.
Categories of causes of reduced erythropoiesis?
Anemia of chronic disorders like neoplasia and inflammation Cytotoxic bone marrow damage EPO lack Immune med dz Infections Myelophthisis Abnormal maturation Disorders of heme synthesis Disorders of nucleic acid synthesis pg36
Three compounds toxic to bone marrrow.
Estrogen, Bracken Fern, Phenylbutazone.
Three things that can decrease EPO production.
Chronic renal dz
Cushings
Hypothyroidism (also hypoituitarism)
Infections that can zap the bone marrow and dec erythropoesis (4)
Parvo/Pan leuk
FeLV
Anaplasma spp
Trichostrongyles (non blood sucking)
