Hema Final Flashcards
Hypoadrenocorticism and hypothyroidism cause what, how?
Low cortisol and low thyroxine lead to decreased epo’esis –> non-regen anemia d/t decreased production
Name three types of selective BM failure
non-regen IMHA (targets precursors), hrEpo administration, FeLV induced eryth hypoplasia
Cause of anemia of inflammation
Decreased epo’esis from hepcidin cytokine trapping Fe in macs and decreasing GI absorption; cytokine direct epo’esis inhibition; concurrent fragility from ox damage
Lab findings of anemia of inflammation
normo/normo
How long until regeneration seen in peripheral blood?
3-5 days
Shorter RBC lifespan leads to (faster/slower) onset of anemia; rank dog cat horse cattle via RBC lifespan lifespan
Faster onset; cat (70d) –> dog (100d)–> horse/cow (150d)
Non-regenerative macrocytic anemia falls in what subcategory
Ineffective epo’esis (think FeLV and poodles)
Mechanisms of anemia in CKD; MCV/MCHC findings
Renal lesions = dec. epo’esis, GI hemorrhage from uremic toxins; normo/normo (typically)
FeLV-induced eryth hypoplasia –> subcategorize
non-regen (dec. production)
Cause of anemia of Fe deficiency; MCV/MCHC findings
Ineffective epo’esis- microcytic (extra mitotic divisions when low in Hgb), normo- to hypochromic (decreased Hgb content), increased fragility
3 causes of Fe def’cy anemia
diet, ext. hemorrhage, copper/B6 def’cy
Ddx- microcytosis in non-anemic
cong. PSS, japanese breeds, some chronic inflammation
Lead tox blood smear changes; type of anemia
basophilic stippling (from remnant ribosomes d/t enzyme inhibition), +/- nRBCs from marrow damage, siderocytes (pappenheimer bodies); none to mild non-regen anemia
Causes of macrocytic non-regen anemia
FeLV-induced (from maturation defect), poodles: DNA synth defect
Cause of cobalamine/folate def’cy anemia; MCV/MCHC
DNA synth impaired in precursors –> macrocytosis, hyperseg neuts, normo/normo/non-regen
Which types of blood loss is most likely to progress to Fe def’cy
Chronic external blood loss
External blood loss and PCV/TS changes
initial- unchanged; 6-12h - plasmadilution = decrease HCT/TP values; chronic- anemia persists, TP normalizes
Extravasc hemolysis- mechanisms
RBCs killed by macs in spleen/liver/marrow, Hgb breakdown leads to initial conj bili in urine, excretion/liver conversion overwhelmed –> bilirubinemia –> icterus >2 mg/dL, cholestasis
Intravasc hemolysis- mechanisms
Lysis in vessels = Hgb in plasma –> dimers form complex via haptoglobin with protein to retain in kidney, macs eat and release bili to plasma; Haptoglobin overwhelmed –> Hgb’uria;
CS of intravasc hemolysis
hyperbilirubinemia (d/t mac destruction), Hgb’uria; DIC/Shock/renal compromise can follow
Lab findings of hemolytic anemias
poikiliocytosis, hyper-bili, leukocytosis w/L shift and tox (d/t inflammatory cytokines from RBC destruction), Hgb’emia/’uria (intra), reticulocytosis (Fe quickly recycled to precursors), splenomegaly (from macrophage hyperplasia)
When are hemolytic dz animals icteric, dependent on?
> 2 mg/dL plasma bili concentration (dependent on severity of destruction, rate of clearance)
Erythroparasite MOAs
attach to membrane surface (mycoplasma), invade cell (babesia, anap, plasmodium), hemolytic toxins (clostridium), initiation of Ab-mediated destruction (any epi- or intra- cellular parasite)
IMHA lab findings
Spherocytes, poikiliocytosis, icterus, neutrophilia, leukocytosis, CBC with marked regen, + coombs, RBC autoagglutination, +/- TCP
Dz of fragmentation anemia
Fe deficiency, DIC, HSA/neos, vasculitis, sepsis, caval syndrome, heat stroke, splenic/hepatic dz
Which types of poikilocytosis in fragmentation anemia
Schistocytes (hallmark finding), spherocytes (resealed RBC), acanthocytes (club projection in HSA), pre- and keratocytes
3 sites of oxidative dmg in RBC
Heinz bodies- globin precipitation on membrane; cross-linked cytoskel proteins (eccentrocytes and pyknocytes); Oxidation of Fe2+ –> 3+= metHgb
Effects of MetHgb’emia
reduced oxygen carrying capacity (Fe 3+ cant carry O2)
Who is more susceptible to oxidative damage, why
Cats: more -SH groups, non-sinusoidal spleen for clean-out
Clinical significance of feline Heinz body findings
<10% normal; must compare # HzBd, CS, strength of regen, likelyhood of oxidant exposure
Dz causing Heinz bodies in cats without concurrent anemia
hyperthryroidism, DM, LSA
Toxic oxidants- name several
onion, garlic, copper, tylenol, zinc, skunk spray
MOA - Zn toxicity
Inhibition of RBC metabolic paths (esp protecting from oxidative dmg), direct ox-dmg, Zn as hapten for IMHA RBC binding
Seen in Zn toxicity
Heinz bodies, eccentrocytes, spherocytes; regen anemia, negative Coombs
Hemolysis as sequelae to TPN/tube feeding in lipidotic patient- MOA
decreased phos = dec. ATP in RBC –> fragility, ox dmg susceptibility; refeeding causes increased cell anabolism, intracell shift of P leads to low P in serum
Envenomation changes
echinocytosis (first 48h), spherocytes (hemolytic anemia)
SA anti-coagulant of choice, why
EDTA- better WBC morphology, less platelet clumping than heparin
Underfilled EDTA tube =
crenation (morphology change), lower PCV/MCV, higher MCHC/TP
Changes when EDTA tube sits, timing?
crenation, WBC vacuolization, pyknosis, prepare slide if more than 1-2 hours before processing
Why use NMB; preparation
Confirm Heinz bodies, estimate retics; 1:1 prep sits for 30 min to allow RNA aggregation
Perform manual retic count; dog vs cat differences; perform corrected retic%
retic/ 500 counted RBC= %retic; (dogs- count all, cats- count aggregate) If anemic–> [%retic x (pHCT/normHCT)
Why only count aggregate retic’s in cats
these are the ones that correlate to polychromasia and active regen (punctate circulate longer)
Perform absolute retic concentration; interpret cat and dog
retic % x RBC/uL; cat >50k aggregates = regen; dog >80k total retic = regen
Interpret reticulocytosis in non-anemic patient
hypoxia, neoplasms, toxic/metabolic
Rouleaux- normal in? abnormal indicates? how to test?
normal in cats/horse/pig; abnormal indicates presence of inflammatory proteins; blood:saline 1:0.5 = disperse in rouleaux, stay clumped in agglutination
Leukergy- define; indicates?
Small aggregates of WBC on smear, non-specific finding (inflammatory or neoplasic), indicates automated CBC may have read clumps, lowering WBC count
RDW- define, interpret findings
red cell distribution width; determines anisocytosis but not macro vs micro
MCV- define, determine artifact readings
mean cell volume; increased may be due to clumping, swelling d/t hyperosmolar plasma (hyperGluc/Na) with dilution in isotonic diluent; decreased may be due to hypoosmolar plasma with dilution in isotonic diluent leading to fluid efflux
Benign/artifact poikilocytosis
crenation/echinocytes- low edta ratio, delay in slide prep, normal in cats/pigs; regen anemia retics can have normal stomatocytes and codocytes due to large cell size and abrormal membrane
multiple, irregularly spaced, club shaped projections; name/ddx
Acanthocyte; HSA, RBC membrane canges, liver/spleen dz, fragmentation disorders
hemoglobinized center within central pallor (target cell); name/ddx
Codocyte; retics, hypothy, Fe anemia
irregularly shaped spherical erythrocytes with a small cytoplasmic tag; name/ddx
Pyknocyte; from eccentrocyte loss of fused membrane portion
“opened” blister with 2 pinchers; name/ddx
Keratocyte; fragmentation hemolysis, Fe deficiency
teardrop shaped RBC; name/ddx
Dacrocyte; artifact, fragmentation, glomerulonephritis, myelofibrosis
RBC morphology associated with envenomation, acute Zn tox, burns, hypoP, and others
Spherocyte; also in IMHA!
multiple, regularly spaced, spikey to blunt projections; name/ddx
Echinocyte; electrolyte depletion, envenomation, renal dz, inherited RBC disorders
Elliptocyte/Ovalocyte ddx; normal in:
liver dz, myelofibrosis, congenital RBC abnormalities: normal in llama, birds, reptiles
Clear vesicle at margin of cell, ddx
Prekeratocyte (aka blister cell); associated with keratocytes
Stomatocyte ddx:
retics, stomatocytosis (inherited), thick blood artifact
Peripheral fusion of opposing membranes;; name/ddx
Eccentrocyte; oxidative damage, rarely inherited
Varied shape RBC fragment ; name/ddx
Shistocyte- mechanical RBC injury in DIC, frag hemolysis, Fe anemia, vasculitis
What does increased polychromasia indicate
Basophilic RBCs from retained RNA are retics on NMB stain, less Hgb per cell volume leads to hypochromasia
Causes of hypochromasia
Les [Hgb] (usually Fe deficiency in mature RBC); may indicate presence of retics; can also be seen in non-regen anemia of inflam dz d/t iron sequestration
Howel-Jolly bodies- mechanism, causes
retained single nuclear fragment; increased in regen anemias, splenectomized, chemo/steroid admin; low normal in cats/horses
Basophilic stippling– mechanism, causes
decreased heme synthesis enzyme that retains ribosomal aggregates; regen anemia (esp hemolytic, bovine), lead poisoning
When is peak reticulocyte response
7-10 days after peracute event
Heinz bodies- - mechanism, causes
dentaured Hgb protruding from membrane; oxidative damage to globin part of Hgb (most in cats)
Pappenhemier body- mechanism, causes
aka Siderotic inclusion; iron granule- lightly basophilic, some clumps; hemolytic anemia, PSS, vitamin/drug deficiencies
Refractile appearance to RBC
watermark artifact of slow drying
Describe canine distemper inclusions; proper stain
Pleiomorphic, eosinophilic or basophilic- stain with diff-quik
nRBC effect on total [leuk]; correct
Increased WBC count due to nRBCs counted; if >5 nRBC/100 WBC:
[WBC/uL x (100/ 100+ nRBC#)]
Describe appropriate release of nRBC-
Released in regen anemia d/t increased epo’esis in BM and extra-med sites, highest in earliest phase of regen or in regen anemia with EMH (extramed hematopoeisis)
Describe inappropriate release of nRBC-
presence does not def. indicate increased epo’esis- injury to blood-BM barrier can release; when >5/100WBC with non-regen, or non anemia could be due to marrow injury, decreased splenic clearance, hypoxia-induced RBC production
List causes of nRBC
lead toxicosis; heatstroke/adderall toxicity; endotoxemia/sepsis; hypoxemia; myelophthisis: marrow neoplasm, myelofibrosis; cobalamin deficiency (Border Collies); certain breeds (e.g. Schnauzer, Dachshund); decreased splenic function; erythroid leukemia (seen most in cats); trauma; inflammatory conditions; hyperadrenocorticism
Plt slide estimate- dog and cat
Dog: #cells/uL = (#cells/100x oil) x 15,000
Cat: #cells/uL = (#cells/100x oil) x 20,000
(lab microscope 60x oil= x6000)
Causes of increased MPV
Younger plt (megaplts) are larger, clumping
Leukocyte slide estimate and differential
Differential: at monolayer 100x oil, coulnt 200 cells in 10 fields= avg #per field x obj^2
Describe neut toxicity
Cytoplasmic changes (only in neuts) from maturation arrest: 1+ dohle or basophilic cytoplasm; 2+ both; 3+ both and foamy cyto vacuolization; 4+ all + gigantism or toxic granulation
How is toxicity different from degenerative change
degen: nuclear changes that occur in peripheral tissues
Causes of neut hypersegmentation
> 5 segments- d/t steroids, dysplastic BM dz, delay in smear prep, heat stroke/adderall
Describe features of lymphocyte reactivity
Basophilic cytoplasm, eccentric nucleus, perinuclear clear zone
Monocyte response to inflammation
very b’philic cytoplasm, vacuolated
Process by which immune system removes self-reactive lymphocytes
Central and peripheral tolerance
3 roles of complement in auto-immune cell destruction
combine with Ab or bind to microbe to trigger 1) release of comp fragments which are chemotactic for inflammatory cells and 2) activation of MAC (membrane attack complex) to lyse cell wall; 3) bound complement can flag an RBC for phagocytsosis
Why are RBC more likely to be target of type II hypersensitivity
Many surface molecules, high concentration of circulating exposed to lymphocytes and Ab, more prone to adsorb drugs/infxn components to their surface
In IMHA, macs recognize Ig’s or complement on RBCs to target for phagocytosis- what type of hemolysis is this associated with
Extravascular (within mononuclear phagocyte system of spleen, liver, BM)
Why/how are spherocytes formed
Often in IMHA; macrophages remove portions of membranes and membrane seals creating smaller surface to area volume ratio
What do ghost RBCs indicate, how do they form in dz process
indicate intravascular hemolysis; in IMHA- complement binds and creates a pore in RBC membrane through which cell is lysed and contents (including Hgb) are leeched out, leaving just the membrane
Pathophysiology of intravascular hemolysis; why is it a poor prognostic indicator?
Requires complement cascade activation to form MAC and lyse cell= Hgb’emia/uria, ghost cells; worse bc breakdown products (Fe, heme) cause oxidative damage once hapten transport systems are overwhelmed
Describe intravasc hemolysis oxidative damage MOAs
NO in blood maintains homeostasis, free Hgb oxidizes NO and prevents it from maintaining vasodilation and stop plt agg’gn. Also release of phospholipid pieces of RBC allow coagulation factor pathways to propagate, creating conditions for DIC
Differences between intra- and extra-vascular hemolysis
extra-: within MPS, conserves Iron/AAs; intra-: outside of MPS (loss of Fe/AAs), greater DIC/shock risk
Causes of secondary IMHA
Infectin ( ana, FeLV, FIV, etc), ITP, LSA, HSA, drugs acting as haptens
Evan’s syndrome
IMHA and ITP concurrent
Warm agglutinin dz- describe, CS
CS and agglutination occurs at body temp; non-specific generalized CS, more common PTE/DIC
Cold agglutinin dz- describe, CS
Occurs at temps below body temp, often armless, more likely in peripheral sites; CS- cyanosis, necrosis, extremity gangrene
Dx IMHA
At least one of: marked spherocytes (dog), positive direct coombs, autoagglutination
Other causes of spherocytes
fragmentation hemolysis, Zn tox, envenomation, hypoP, burns, transfused RBC
Clin Path findings of IMHA
Low: RBC, PCV, Hgb
Increased: MCV, anisocytosis
+/- Retics , L-shift toxic neutrophilia, monocytosis
Why run direct Coombs?
Only way to test for anti-RBC-Ab’s when concentration too low to auto-agglutinate; not useful in patients who already auto-agglutinate; cannot tell difference between primary and secondary IMHA
Reasons for false negative coombs
Lab error, low qty bound Ab
Poor prognostic indicator in IMHA dog
Bili >10 mg/dL; intravasc hemolysis
Cat IMHA signalment trends
Younger more likely to be primary and have good outcome
Cat primary IMHA: negative and positive prognostic indicators
Neg: older age, higher bili; Pos: lymphocytosis or hyperGlobulinemia
Most common cause of cat 2* IMHA
Neoplasia (> mycoplasma, FeLV, FIP, inflammation)
Pathophys of primary ITP; signalment
IgG binds to plt surface to mark for destruction by spleen/liver; middle aged cockers, dogs»_space;> cats
Pathophys of secondary ITP; causes
Ag binds to surface of plt and Ab then targets cell
Non-pathologic low plt count on machine- causes
Plt clumping, breed variation (larger, fewer), greyhounds/shiba inu - normal size but decreased number; may-hegglin anomaly
Causes of 2* ITP
Infectious dz (ricketsiosis, FIV, FeLV, histo, HWD, babesia), neoplasms (MCT, HSA, nasal adeno, fibrosarc, LSA); drugs (heparin novel exposure, previous exposure, Abx, aspirin/anti-inflammatories); 3-5 days post modified live vaccines (distemper, parvo, panleuk)
Clin path findings of ITP
low plt, +/- increased MPV, increased BM megakaryocytes
ITP signalment
Middle age (wide range); Cocker, mini poo, sheepdog;
IMHA signalment
COCKERS! Young-mid age; mini schnauz, collie, springer, OE Sheepdog
Why should cats be cross-matched when typing is not available
Cats have pre-formed anti-RBC Ab’s, so transfusion reactions can be very dangerous
Which cats could be killed by the wrong transfusion
Type B cats given type A blood- 95% have preformed anti-RBC-Ab
How can Mik incompatibility be tested? What will results show?
Cross matching- ____________
What cats have high type B prevalance?
exotic shorthairs, rexes, abyssinians, persians
What cats have low type B prevalance?
Siamese, burmese, russian blue- 0% prevalance
What is the most clinically significant DEA type in dogs
1- 60% are DEA-1 positive, so 40% can have severe reaction
What is the universal dog blood donor
DEA 4; a DEA 1 negative dog can be used in emergencies
Components of major crossmatch
Recipient serum with donor RBCs
Components of minor crossmatch
Recipient RBC with donor serum
What does + crossmatch indicate
Hemolytic reaction likely to occur
Interpret autocontrol in cross-match
Minor results will not be interpretable bc agglutination already present in DONOR before minor reaction, cant determine if reaction occurs
Cytauxzoonosis- which domestic species
Cats
How is cytauxzoonosis different in bobcats/panthers compared to domestic cats
Mild to subclinical manifestation of dz in reservoir hosts
Describe cytauxzoonosis in exotic felids (lions/tigers)
can be fatal but asymptomatic with + PCR has been seen
How has cytauxzoonosis changed in domestic cats over time
previously almost completely fatal, increasing recovery from initial stage to move to carrier status (d/t organism genetic variation, awareness, improved tx)
T/F chronic carrier cats with cytauxzoonosis cannot act as reservoir hosts
False
Diagnosis of cytauxzoonosis
blood smear: piroplasm organisms in RBC that stain light blue with purple nuc
CS of cytauxzoonosis, source of CS
depression/anorexia –> fever (in first 3-4 days) –> +/- dyspnea/organomegaly –> end-organ damage of liver and BM by schizonts (CS not from piroplasm form)
Clin path findings of cytauxzoonosis
non-regen anemia, icteric plasma, +/- pancytopenia and/or thrombocytopenia (d/t BM infiltration and DIC)
cytauxzoonosis- infected cells/organism life stages
Sexual repro in tick (amblyomma americanum), sporozoites infect macs/monos in MPS system; Piroplasms in RBC replicate via binary fission
cytauxzoonosis- cause of severe/fatal manifestations of dz
Schizogony within macs- end organ damage
Tx/prevention cytauxzoonosis
atovaquone and azithromycin; tick prevention and indoor housing prevents
What is limitation of PCR for cytauxzoonosis
Slow turnaround time
Babesiosis- species in US (*= most clinically relevant)
B. vogeli; B. coco B. gibsoni, B. conradae, B. microti
Describe the differences in morphology between the two most clinically relevant babesia species
B. vogeli: larger, pear shaped; B. gibsoni: smaller, signet ring shape
What cell is infected in mammals with babesia
Erythrocytes
Mode of transmission, signalment- babesia
Large: puppies, immunocompromised, greyhounds; Small: dog bites, staffordshire terriers
Dx- babesia
PCR most sensitive to speciate, light micro may not be definitive ID
CS and severity- babesia
Range from inapparent dz to chronic to severe: thrombocytopenia (immune mediated destruction and consumption) +/- hemolytic anemia, splenomegaly + non-specific CS; less commonly hepatopathy, renal failure, CNS signs
hepatozoon: species in dogs, clinically relevant species, geographical area
Dogs: H. canis; H. americanum- SE and S. central US
How is hepatozoon transmitted
INGESTION of tick (not tick bite like babesia, cytaux)
Mechanism of disease- H. canis vs H. americanum
merozoites invade monos and neuts where gamonts are formed in both; H. canis- mild/inapparent, rarely severe (typically immunocompromised) meronts develops in hemolymphatic and other organs; H. americanum- severe dz, meronts develop in skel and cardiac mm.
Labs/imaging findings- H. americanum
Neutrophilic leukocytosis, long bone periosteal reaction, cysts within muscle from inflammatory rxn
Dx hepatozoon
Dx: gamonts in leukocytes (more readily found in h. canis), buffy coat concentration may help find. PCR avail, but may get flase negative in H. am.
Tx hepatozoon
H. am: TMS, clinda, primethamine, decoquinate; H. canis: imidocarb
Where does rangeliosis occur
Southern Brazil
What cell types will rangeliosis be found in
Piroplasms in RBC, neut, monos
CS- rangeliosis
icterus, organomegaly, GI hemorrhage, regenerative anemia
Infective species of cats and dogs in mycoplasmosis
Cats: m. haemofelis, m. haemominutum, m. turicensis; Dog: m. canis, h.
Most pathogenic cat mycoplasmosis
H. haemofelis
Which mycoplasmas can be seen on blood smears
haemofelis and haemominutum
Transmission of mycoplasmas
blood sucking arthropods like fleas; queen to kitten (m. haemofelis), iatrogenic via transfusion
CS/Lab findings- m. haemofelis
weakness/depression/etc, splenomegaly; parasites in peripheral blood, mild to moderate anemia that may be regenerative, +/- bilirubinemia/uria
Risk factors for m. haemofelis
bite abscess, FeLV/retroviral +, outdoors, < 3y old, male, (dogs: splenectomized)
How is dz of m. haemofelis different from cytauxzoon
Cats less sick in m. haemofelis, m. h. has more male predisposition; attach to surface and destruction is immune mediated in m. haemo
Dx mycoplasma
light microscopy or PCR
How should mycoplasma samples be shipped
fresh smears right away so EDTA doesnt remove orgs within tube in transport
Tx- mycoplasma
tetracylines in dogs; doxy or enro in cats +/- supportive care
Species of monocytic erlichiosis and SA species affected
E. canis and e. chaffiensis are both found in dogs
CS- monocytic erlichiosis; unique features of E. canis
Asymptomatic to fever, thrombocytopenia, nasal/ocular discharge, non-specific; E. canis: chronic infxn at 40-80d- bone marrow hypo/aplasia (myelosuppression), hyperglobulinemia, plasmacytosis, lymphocytosis, bleeding, uveitis, CNS, organomegaly
Dx- monocytic erlichiosis
Morula sometimes seen within monocytes in smear or splenic aspirates. Speciate via splenic PCR ( blood PCR may give false negative). IFA can diagnose but cannot speciate due to cross rxn
Tx- monocytic erlichiosis
Tetracyclines
What agents are responsible for granulocytic rickettsial infection
E. ewingii, Anaplasma phagocytophilum
CS- granulocytic rickettsial infection
E. ewingii: non-specific, nero, swollen joints (neutrophilic polyarthropathy); Anaplasma: fever, lethargy, anorexia
Lab findings of - granulocytic rickettsial infection
Thrombocytopenia, non-regen anemia, leuko and lymphopenia, morulae in neutrophils
Dx - granulocytic rickettsial infection
4DX differentiates ana from erl; Morulae in neutrophils, speciate via PCR, 16SrRNA
What agent causes thrombocytic anaplasmosis
A. platys
CS- thrombocytic anaplasmosis
Typically subclinical, mild fever, minor hemorrhage/ecchy/petech of MM possible
Dx- thrombocytic anaplasmosis
Dx- org in platelet (not often seen), PCR, 16SrRNA. 4DX and IFA cross-react with other species
Tx- thrombocytic anaplasmosis
tetracyclines
Indications for bone marrow eval
Unexplained cytopenias/persistent cytoses (except neuts), /clinical chemistry findings, FUA, suspicion of systemic infection in marrow, dx/stage marrow neoplasms
Marrow collection sites- dog/cat
iliac crest, trochanteric fosa of the femur, prox humerus (in skeletally immature)
Supplies needed for marrow aspirates
Illinois or rosenthal needle with stylet, analgesia (lidocaine), scalpel, sterile prep supplies, saline/EDTA lined 6-12cc syringe for suction, sterile gloves, slides, petri dish
How is M:E ratio quantified
Count 500 nucleated cells total. M= ALL stages of granulocytes (eos, neuts, basos); E= nucleated RBC precursors
Interpret M:E > 2 with hypercellular marrow
Granulocytic hyperplasia
Interpret M:E < 1 with hypercellular marrow
Erythroid hyperplasia
Interpret M:E > 2 with hypocellular marrow
Erythroid hypoplasia
Interpret M:E < 1 with hypocellular marrow
myeloid hypoplasia
Erythroid hyperplasia- ddx
Matur’n WNL (effective): strong regen anemia (hemolysis, blood loss);
Matur’n arrest (ineffective): immune mediated attack on later RBC precursors, MDS, iron deficiency
Erythroid hypoplasia- ddx
(decreased production) inflamm dz, ckd, endocrine dz, endocrinopathies (less common), myelofibrosis, MDS, etc (other cells taking over bone marrow)
Myeloid hyperplasia- ddx
(Usually in response to neut demand) Effective: hemolysis, blood loss, polycythemia vera; Ineffective: IMHA against later precursor, MDS, low Fe, low cobalamine, congenital dyserythropoiesis
Dog and cat- BM cellularity normal range
25-75% (older = lower)
Dog and cat - %small lymphocytes normal range
Dog- <5-10%; Cat- <15-25%
Dog and cat BM normals: % immature erythroid, % immature myeloid, % plasma cells, %macs/monos
eryth/myeloid each <5%; plasma/macs/monos each <3%
megas/particle- dog and cat
1-3
T/F - stainable iron is present in dog bone marrow but not in cats
T
What are the most common causes of megakaryocytic hyperplasia
Consumption/destruction/loss, inflammation response, iron deficiency
What are the cuases of megakaryocytic hypoplasia
ITP directed at megakaryocytes, generalized marrow hypoplasia
Describe general marrow hypoplasia/aplasia
hypocellular at <25%, aplastic if all cell types are severely reduced/absent
Ddx- generalized marrow hypo-/aplasia
Drug induced (TMS, alben/fenben, azathioprine, chemo), estrogen tox, parvo/panleuk, chronic erlichia, imm-med/idiopathic
What is myelofibrosis
Deposition of connective tissue in marrow secondary to injury which releases TGF-B cytokine.
Primary conditions associated with myelofibrosis
leukemias, marrow neos, IMHA, marrow necrosis, drugs, PK deficiency
What is myelophthisis
Crowding out of bone marrow
What are the causes of dysplastic features in hematopoietic cell lines
MDS, lead tox, low Fe, low cobal/folate, FeLV, drugs (chemo, anti-convulsants, sulfa), IMHA/ITP, Leukemia, LSA
Supplies for core bx
Jamshidi needle with stylet, scalpel, sterile prep supplies, saline/EDTA lined 6-12cc syringe for suction, sterile gloves, 10% formalin, slides
Where is EPO made
interstitial fibroblasts within the kidney
What is the function of EPO
Increases survival of RBC by diminishing normally high apoptosis
Where is CSF made, what is it
Produced by various cells in response to inflammation, colony stimulating factor stimulates proliferation of neut and/or mono stem cells by inhibiting apoptosis of precursors and helping survival
What is the function of CSF-GM?
enhances function of mature neuts and maxs
Where is TPO made?
Constantly synthesized by hepatocytes
Fxn of TPO
Stimulates platelet production- increased concentration (less platelets to bind to) increases megakaryocyte differentiation and fragmentation
What cytokine is responsible for eosinopoiesis
IL-5
what is the progression of the erythroid lineage?
rubriblast –> prorubricyte –> rubricyte –> metarubricyte –> reticulocyte –> erythrocyte
what is the progression of the granulocyte lineage?
myeloblast –> promyelocyte –> myelocyte –> metamyelocyte –> band –> segmented neut
Marrow transit time for erythrocytes, granulocytes, platelets
erythrocytes 5 days, granulocytes 7 days, platelets 5 days
What cell line will begin increasing first in bone marrow recovery and why
Monocytes, 3 day transit time
Causes of increased and decreased iron stores in BM
Inc: anemia of inflammation, hemolytic anemia, previous transfusions; Dec: cats (none present normally), iron deficiency
Define leukemia
Neoplasm of one or more lines of hematopoeitic cells
Differentiate acute and chronic leukemia via lab findings and diagnosis (cbc/bone marrow results)
Acute: typically with peripheral cytopenias (esp. anemia), abnormal blast cells, >20-30% blasts in marrow; Chronic: marked cytopenia of affected line in periphery, <20-30% blasts, neoplastic cells appear more mature
T/F- chronic leukemias have poorer prognosis than acute
F
Besides acute leukemia, why else could >20-30% blasts be found in marrow aspirate
Rebound toxicity- New recovery from toxic insult to marrow which caused hypoplasia
How can rebound toxicity be differentiated from leukemia?
rebound tox animals wont have CIRCULATING blasts
Chronic leukemias must be differentiated from what process? How?
Reactive cytosis; presence of dysplastic change in blood or BM indicates leukemia
Why wont bone marrow eval help diagnose chronic leukemias
Cells may look well-differentiated, so may be hard to determine if they are neoplastic
What makes chronic lymphocytic leukemia different from all other discussed leukemias
May not arise from BM (check spleen- T cell can arise here)
What is primary MDS
Primary myelodysplastic syndrome (neoplastic) is from abnormalities in early precursor cells in marrow +/- changes to microenvironment; hypercellular marrow, peripheral cytopenias, >10% dysplastic features in one or more cell lines, blast count <20%; may progress to leukemia
Ddx for marrow dysplasias
MDS, acute leukemia, lead tox, low Fe, drugs, 2* to immune/neoplastic
What is the prognosis for MDS
Varies depending on form
Define multiple myeloma
malignant tumor from plasma cells in BM
Dx multiple myeloma
2 of 4: monoclonal gamopathy, Bence Jones proteinuria, >20% plasma cells in marrow, osteolytic bone lesions
Differences in K9/fel MCT (marrow involvement, prognosis)
cat»_space;> dog marrow involvement, poorer px in dogs, good px in cats with splenectomy
What is histiocytic sarcoma? What forms can be present in marrow?
Malignant tumor of histiocytes; disseminated dendritic cell form and hemophagocytic macrophage cell form; both rapidly fatal
What marrow disorders can cause peripheral pancytopenias
Double check this: acute leukemia, myelodysplasia, myeloid hypoplasia
Species and breeds- LAD
Dogs and cattle; GSD, irish setters, mixed breeds
CS- LAD
recurrent unexplained bacterial infections of skin, lung, GI in young dogs; GSD may have bleeding d/t plt affects
Tx/Px- LAD
Symptomatic support and Abx, poor Px
Blood film and lab findings- LAD
bacteria and inflam cells (usually macs) with little to no neuts; labs: marked neutrophilia +/- non-regen anemia, “pus-poor” infections
Species and breeds- defective neutrophil function
Weimaraner, dobie
CS- defective neutrophil function
chronic recurrent respiratory tract infections
Tx/Px- defective neutrophil function
Symptomatic support and Abx, poor Px
Species and breeds- Cyclic Hematopoiesis
Grey collies
CS - Cyclic Hematopoiesis
non-specific
Blood work findings- Cyclic Hematopoiesis
cyclic neutropenia q 12-14d; thrombocytosis, reticulocytosis, monocytosis when in neutropenic episode
Tx/Px- Cyclic Hematopoiesis
Abx, bone marrow transplant; poor px
Species/breed- trapped neutrophil syndrome
border collies (ferrets?)
CS/bloodwork- trapped neutrophil syndrome
persistent neutropenia despite myeloid hyperplasia within BM, recurrent infections, +/- born narrow skull and extremities
Species/breed- Pelger-huet
dogs (es.p australian shep) > cats
Dx- Pelger-huet
Microscopy- bilobed, dense chromatin clumping, non-toxic mature neutrophils (functionally normal with normal cytoplasm)
PE/CS- - Pelger-huet
None! great Px
Tx- Pelger-huet
None needed
Rule outs- Pelger-huet
left shift, pseudo-PH (drugs, leukemia, MDS)
Species/breed- Chediak-Higashi
Persian cat
Dx- Chediak-Higashi
Blood film with enlarged abnormal granules/inclusions in neutrophils in “smoke blue” Persian
PE/CS- Chediak-Higashi
photophobia, bleeding (plt defect), hypopigmentation, +/- increased infxn risk
Reasons for leukocyte inclusions
organelles, toxic change granules, genetically-abnormal cell components, phagocytized material, infectious agents
What might reddish granules in neutrophils of Birman cat indicate?
Nothing- genetic variation. Also seen in himalayan and siamese
Species/breeds- macrothrombocytopenia
CKCS, norforlk, cairn terriers
Clinical significance- macrothrombocytopenia
no increased bleeding bc plt size makes up for lower numbers, 30-50% CKCS affected, genetic testing available
Species/breeds- hereditary stomatocytosis
Mini and standard schnauzers, poms, malamutes, Drentse patrijshonds
Of hereditary stomatocytosis breeds, in which breeds are other conditions associated
Malamutes also have chondrodysplasia; Drentse dogs have polysytemic dz (growth retardation, D, pu/pd, weakness, somnolence (NO CS in schnauz, pom)
Px - hereditary stomatocytosis
Not life threatening in malamutes, Drentse usually euthanized young due to progressive deterioration
Non-hereditary causes of stomatocytosis
regenerative anemias, liver dz, lead poisoning
Why does hereditary elliptocytosis occur? What is the clinical significance
abnormalities in RBC skeletal membrane proteins that maintain normal shape; No clinical signs
Important differences between acquired and inherited methemoglobinemia; name similarities
Acquired d/t toxicity, so CS= V, D, anorexia, anemia, etc; no other oxidative damage, signs of toxicity in hereditary. All forms have brown blood, + spot test, and cyanotic MM
What enzyme is deficient in hereditary methemoglobinemia
methemoglobin reductase (cytochrome B5 reductase)
Species/breed- PK deficiency
Dog/cat: Basenji and beagle, Abyssinian, Somali, DSH
Compare dog/cat differences in PK deficiency
Dogs: young, more severe regen. anemia, fatal in 1-5 y d/t sequelae of osteosclerosis and myelofibrosis;
Cats: older at dx, more mild anemia, less CS, good Px
Testing options- PK deficiency
Measure low total RBC PK acitvity or basenji or cat genetic test- no test works all the time in dogs
Species/breed- PFK deficiency
Springers, Cockers, whippets, Wachtelhund
CS/lab findings- PFK deficiency
Persistent hemolytic anemia +/- occasional intravasc hemolysis w/ Hgb’uria, also general non-specific illness signs, mild hepato-splenomegaly, muscle wasting (less myopathy than in people)
Testing options- PFK
Measure RBC PFK activity in homozygous >3m old; PCR DNA test for heterozygous carriers and normal animals (but doesnt work in wachtelhunds)
Px/Tx for PFK
Normal life if managed well: avoid stress, excitement, high temps; tx with aspirin for fever in hemolytic episodes
