Haemolymphatic Flashcards
what disease are associated with non-regenerative anaemia in the cat?
- Pre-regn anaemia
- recent haemorrhage
- reg anaemia where the bone marrow has yet to respond
- frequent sampling in critically ill patients - kidney disease
- CKD
- Acute on chronic kidney disease - Inflammatory disease
- IBD
- Systemic illness/inflammation
- pancreatitis - Infectious disease
- FIV
- FeLV
- FIP
- Cytauxzoon felis
- Haemotrophic mycoplasma
- Leishmania infantum
- E.canis
- Mycobacterium sp. - Bone Marrow disease
- Pure red cell aplasia
- non-regen, IM haemolytic anaemia
- Aplasitc anaemia
- myelodysplastic syndrome
- myelofibrosis
- melopthesis - Neoplasia
- lymphoma - Hepatic lipidosis
- Deficiency
- B12
- Iron - Toxicity
- Drug reactions
- chemo/radiation
- propylthiouracil
- methimazole
- albendazole
- erythropoiesis stimulating agents
- antibiotcs - idiosyncratc, dose/duration dependant anaemia - TMS chloramphenicol
Olson JFMS 2019
What are the main pathogenesis of non-regenerative anaemia in cats?
RBC lifespan =73d.
- Decreased or ineffective erythropoesis
i. reduced EPO production
- CKD/AKI
- neutralizing Abs against EPO secondary to erythropietsis stimulating agents.
ii. Ineffective erythropoiesis
- - nutruent deficiency - iron/B12
- cystokine abnormalitis - systemic inflam aka anaemia of chronic disease
- primary bone marrow disorders: pure red cell aplasia, non-regen, IMHA, aplastic anaemia, myelopthesis etc - Decreased RBC lifespan - usually associated with regen anaemias but can be seen with non-regen too.
i. oxidative damage - higher numbers of oxidizable sulfhydryl groups + lower intrinsic antioxidant capacity + lack N-acetyl transferase 2 => increased risk fo oxidative damage and subsequent removal.
- oxidative stress
- mechanical stress
- complement induced injury
- rearrangement of memberane phosphlipids
- contact with cationic proteisn from activated Neutrophils
- heinz bodies
- haemotrophic parasites
- hereditary RBC defects: membarn protein abnormalities, RBC enx deficiency, haemoglobinopathies, increased ostmotic ragility
ii. Increased activation of the reticuloendothelial system => removal of RBC sooner.
- Immune med disease
- infectious disease
inflam
- paraneoplastic disease
Olson JFMS 2019
What are potential causes of acanthocytes in cats?
- neoplasia
- Bone marrow disorder
- hepatic lipidosis/liver disease
- doxorubicin therapy
Olson JFMS 2019
what are potential causes of elliptocytes/ovalocytes in cats?
- myelofiboris
- iron deficiency
- hepatic lipidosis/liver disease
- doxorubicin therapy
Olson JFMS 2019
what are possible cause of schistocytes in cats?
- neopalsia
- liver disease
- haemophagocytic histocytic disease
- acquired dyserythropoesis
- iron deficiency
- DIC
- doxorubicin
Olson JFMS 2019
what are possible causes of haemophagocytosis in cats?
- histocytic disease
- MCT
- mycoplasma haemofelis
Olson JFMS 2019
What are possible causes of heinz bodies in cats?
- acetaminophen
- onions and similar
- benzocaine
- propofol
- methionine
- methelene blude
- propylene glycol
- phenazopyridine
- DM
- hyperT4
- lymphoma
- liver disease
- other
Olson JFMS 2019
what are possible causes of erythrophagocytosis on cytology of BM, spleen Ln or liver in a cat?
- IMHA
- histocytic disorder
- multiple myeloma
- MCT
lymphoma - acute myeloblastic leukaemia
leishmaniosis.
Olson JFMS 2019
How can you differentiate iron deficiency anaemia from anaemia of chronic disease in cats?
- RBC- microcytosis and hypchromasia are insensitive markers of iron deficiency
- reticulocyte HB content <0.88fmol has 93% sens and 76% spec for iron deficiency in cats.
- serum iron - low in both
- ferritin:
- low in iron deficiency
- increase in anaemia of inflammation - Transferrin, measured indirectly by total iron binding capacity
- normal to increased in iron deficiency
- lower with inflammation and if concurrent inflammation and iron deficiency, this can lower TIBC even if iron deficiency is present. - Iron saturation percentage <20% may be suggestive of iron deficiency
Olson JFMS 2019
what is the difference between:
- pure red cell aplasia
- non-reg IMHA
- Aplastic anaemia
- myelodysplastic sytndrome
- secondary dysmyelopoiesis
- myelofibrosis
- myelopthesis
1. Pure red cell aplasia Blood smear: - normocytic normochromich non-regen anaemia - no other cytopenias Bone marrow: - decreased to absent RBC precursors
- non-reg IMHA
Blood smear:
- normocyti to mactocytic (secondary to agglutination)
+/- neturopenia/thrombocytopenia
+ at least 1 of the following:
- persistent agglutination following saline washing of RBCs
- positive direct antiglobulin test
- ghost cells
Bone marrow
- marked erythroid hyperplasia with low myeloid:erythroid ratio
+/- maturation arrest
+/- erythrophagocytosis
+/- dysplasia, fibrosis, necoriss and inflam
3. Aplastic anaemia Blood smear - bi to pancytopenia Bone marrow - marked reduction or absence of normal haemaotpoetic tissue, replaced with fat.
4. myelodysplastic sytndrome Blood smear - bi to pancytopenia \+/- macrocytosis Bone marrow - normo to hypercellular - blast cells (reubriblast or myeloblasts) < 30% of nucleated cells - dysplastic change in all 3 cell lines
5. secondary dysmyelopoiesis Blood smear - non-regen anaemai without macrocytosis Bone marrow - normal to increased cellularity with dysplastic changes most prominent in the red cell line
- myelofibrosis
Blood smear:
- reflects underlying cause (MDs, acute myelogenous leukaemia, non-regen IMHA, PRCA)
Bone marrow
- req histopath staining for an excess of reticulin fibrosis (usually absent in normal feline bone marrow) - myelopthesis (infiltration and replacement of BM by abnormal cells)
Blood smear:
- non-regen anaemia
+/- circ neoplastic cells
+/- variable cytopenia
Bone marrow:
- infiltration with neopalstic haemopoetic cells.
Olson JFMS 2019
Is the use of eyrthroid stimulating agents expected to be beneficial in pure red cell aplasia?
No as EPO is already increased
Olson JFMS 2019
What proportion of cats receiving Darbopoetin develop antiEPO antibodies? and for epoetin?
Darbopoetin - 8%
Epoetin - 25-45%
Olson JFMS 2019
which patients are most likely to develop hospital acquired anaemia?
- both dogs and cats but cats»_space;dogs
- patients that had more blood samples
- had surgery
- dogs were less likely to survive to discharge.
Lynch JVIM 2016
What are 3 markers of oxidative stress?
Which is altered in anaemia dogs?
- Glutathione peroxidase - decreased in anaemia
- plasma total antioxidant capacity - no change
- urinary F2 isoprostanes. - no change
Kendall JVIM 2017
What are Kai 1 and Kai 2?
Additional canine blood groups not related to DEA 1, 3, 4, 7 and Dal.
Euler JVIM 2016
What combination of Kai 1 and Kai2 are most dogs in the USA?
Kai 1+/Kai 2-
Euler JVIM 2016
What classes of antibodies are antiKai 1 and antiKai2 antibodies?
AntiKai 1 = IgM
AntiKai 2 = IgG
Euler JVIM 2016
do dogs negative for Kai1, Kai2 or both have naturally occuring alloantibodies?
no
Euler JVIM 2016
Which breeds in north america are most likely to be Dal -? What is the significance of this?
- Shih tzu (57.1%)
- Doberman (42%)
- Dalmations (11.7%)
this increases their risk of being sensitized by a blood transfusion from the common Dal + donor => extended Dal testing should be consideded in these breeds and in dgs with incompatibly blood after initial transfusions.
Goulet JVIM 2017
What is the prevalence of major cross match reactions in cats that were:
- transfusion naive
- previously cross matched
tansfusion anive - 15%
Previously transfused 27%
McClosky JVIM 2018
With what frequency do febrile transfusion reactions occur in cats which were:
- cross match prior
- not cross matched
Cross matached - 2.5%
not cross matched - 10%
McClosky JVIM 2018
When is a cross match recommended for cats? Why?
Before each transfusion - including the first due to the risk of non-AB/Mik alloantibodies resulting in transfusion reactions.
McCloskly JVIm 2018
What changes are expected to be seen in feline whole blood stored for 35 days?
- reduced WBC
- reduced PLT
- reduced normal RBC
- increased echinocytes
- increased lysed RBC
Spada JFMS 2019
What factors regarding RBC indices may change in dogs donating blood more than 6 times annually? What is this likely secondary to?
- lower PCV, HCT and retic count
- Retic indices: lower retic MCV, and retic Hb
- normal serum iron and ferritin but lower TIBC
Suggests iron deficiency erythropoiesis.
Foy JVIM 2015
Does Leukoreduction prior to storage of canine pRBC cause any changes?
All resolve during storage but initially:
- increased thromboxane B2 and prostaglanin T2alpha
doesn’t decrease the accumulation of 6-keto-PGF1alpha
Muro JVIM 2017
what percentage of DEA-1 matched recieviers become incompatible against other RBC antigens after matched transfusion in dogs?
44%
Goy-Thollot JVIM 2017
Does major cross matching transfusion naive cats prior to blood transfusion improve transfusion PCV stabilization?
no
Didn’t change efficacy or decreased adverse events assocaited with RBC transfusion in AB blood typed transfusion naive cats.
Sylvane JVIM 2017.
Can blood be collected from cats via a closed system?
yes - TEC 724 kit, Futurlab Srl)
1/8 at day 35 did have bacterial growth
Crestani JVIM 2017
Can weakly DEA 1+ blood be transferred to a DEA 1- recipient?
It should not be as this will cause alloimmunization in the DEA 1- recipient.
Guidetta JVIM 2019
When should dogs be blood typed?
When should it be cross matched?
Typed
- prior to any transfusion for DEA 1 to ensure appropriate matching
Cross match:
- after receiving any RBC products > 4 days before the next transfusion.
Give an example of when an autologus blood transfusion can be used in cats?
haemoperitoneum
Cole JFMS 2019
how frequently do dogs and cats receiving haemodialysis for AKI or CKD require blood transfusions?
Cat - 87%
dog 32%
Langston JVIM 2017
What factor is associated with increased need for blood transfusions in cats receiving intermittent haemodialysis?
number of dialysis treatments
Langston JVIM 2017
What does cryoprecipitate contain high concentrations of? how does this correlate to CRYO factor content
it is plasma with
- Factor VIII
- vWF
- fibrinogen
Positive correlation betweee donor plasma Factor VIII, vWF and fibrinohgen concentration and CRYO factor content.
Drinkhouse JVIM 2018
What components of cryoprecipitate are lower in which breed?
Greyhounds - lower vWF and fibrinogen.
Still acceptable for use
Drinkhouse JVIM 2018
what component of cryoprecipitate can be variably low? and what disease may this impact the treatment of?
Factor VIII
haemophillia A
Drinkhouse JVIm 2018
What factors do mesenchymal stem cells produce?
- IDO (indoleamine 2,3-dioxygenase)
- IL-10
- IL-6
- HGF (hepatic growth factor)
- PGE2
- TGF-beta
- PD-L1 (programed death ligand 1)
- FASL
- HMOX1 (heam-oxygenase 1)
Parys JVIM 2016
What are Mesenchymal stem cells used for?
immunomodulation
- capable of inducing T-reg
Parys JVIM 2016
By what routes can mesenchymal stem cells be given in cats?
- IV - however exposure to plasma complement reduces cell survival + PTE + instant blood mediaded inflammatory reaction.
- Intraperitoneal - mild- self limiting side ffects including lethargy, decreased activity, enlarged jejunal Ln and hyperechoic renal cortical lesion.
- Other:
- intra-articular
- intracardiac
- intrahepatic
- intranasal
Parys JVIM 2016
What does the CYB5R3 gene missense variant result in? in what breed?
- Methemoglobinaemia in pomeranians
Shino JVIM 2018
How does the CYB5R3 gene variant cause Methemoglobinaemima?
Amino acid substitution that results in replacement of isoleucine by leucine
=> located in the proximal region of the NADH-binding motif
=> affects the function of methemoglobin b5 reductase => methemoglobin b5 reductase deficiency
=> increased methemoglobin.
Shino JVIM 2018
What does changes in the CYB5R3 gene cause in cats?
Missense variant:- disruption of the NADH binding domain
Splcing error - affected downstreman translation of the protein.
=> higher RBC methemoglobin concentration and reduced cytochrom b5 reductase activities in RBCs.
Jaffey JVIM 2019
What are the indications for BMB aspirate?
- persistent neutropenia without evidence of regen
- unexplaned thrombocytopenai
- non/poorly regen anaemia
- bi/pancytopenia
- persistent thrombocytosis
- persistent leukocytosis esp lymphocytosis with circ atypical lymphocytes
- abnormal blood cell morphology or abnormal cells in circ
- unexplaeined immautre cells in blood
- staging lymphoma or MCT
- assessment of body iron stores
- suspicion of osteomyelitis or infiltrative bone marrow disease
- unexplained hypercalcaemia
- unexplained hyperproteinaemia
- monoclonal hyperglobulinaremia
- PUO/unexplained weight loss/malaise etc.
Stacey VCNA 2017
what are “erythroid islands”?
Erythroid islands:
the precursoes of the erythroid cell line that surround macrophages that provide growth factors needed for RBC production in the bone marrow.
Stacey VCNA 2017
Describe the systematic approach to evaluation of bone marrow aspirates?
- Overall cellularity, cell distribution and cellularity of bone marrow particles
- frequency of cells
- orderly, synchronous and complete maturation?
- morphology normal/abnormal
- myeloid to erythoid ratio
- morphology of erythroid cell line
- morphology of granulocytic cell line
- morphology of megakaryocytic cell line
- morphology of monocytic cell line
- Morphology of lymphocytes and plasma cells
- Osteoblasts and osteoclasts
- Misc cells and mitotic ficures
- free nuclei of lysed cells.
- adipocytes
- stromal cell
- capillary
- MCT
- mitotic figures - normal in up to 2% of nucleated cells.
Stacey VCNA 2017
What are possible interpretations of a normal myeloid to erythroid ratio?
- normal myeloid and erythroid porduction
- both myeloid and erythroid hyperplasia
- increased bone marrow cellularity
Possible CBC findings
- neutrophilia (effective granulopoiesis)
- neutropenia (ineffective granulopoiesis),
- regen anaemia (effective erythroipoiesis - iron deficiency, IMHA),
- non- regen anaemia (ineffective erythroipoiesis) - Both myeloid and erythroid hypoplasia
- Decreased Bm cellularity
Possible CBC findings
- non-regen anaemia
- neutropenia
- thrombocytopenia
- pancytopenia
Stacey VCNA 2017
What are possible interpretations of a high myeloid to erythroid ratio?
- Myeloid hyperplasia
Bone marros cellularyity normal or increased
Possible CBC findings
- neutrophilia with a left shift
- neutropenia
- non-regen anaemia
- thrombocytosis secondary to chronic inflam
- if abnormal cells, consider acute or chronic myeloid leukaemia - Erythroid hypoplasia
- bone marrow cellularity normal or decreased
Possible CBC - non-regen anaemia - combination of both
Stacey VCNA 2017
What are possible interpretations of a low myeloid to erythroid ratio?
- erythroid hyperplasia
- bone marrow celulary normal or increased
Possible CBC findigns
- regen anaemia
- non-regen anaemia
- variable leukocyte counds
- if abnormal RBC in circ, consider MDS-erythroid (<20% blasts) or erythroleukaemia (> or = 20% blasts) - Myeloid hypoplasia
- Bone marrow cellularity normal or decreased
POssible CBC - neutropenia - Combination of both.
Stacey VCNA 2017
What is a normal myeloid to erythroid ratio in:
- dogs
- cats?
Dogs: 0.75-2.53
Cats:1.21-2.16
Stacey VCNA 2017
Do cats have stainable iron in their bone marrow?
No
Stacey VCNA 2017
What colour does haemosiderin stores in the bone marrow appear in dogs?
in cats?
Haemosiderin in dogs:
Wright-Giemsa: blue-grey to black
Prussian blue: blue to blue-green
often in macrophages or extracellularly
Haemosidering/iron stores in cats not stainable.
Stacey VCNA 2017
What are the normal proportions of the following in the bone marrow:
- Cellularity
- megakaryocytes per particle:
- Mature megakaryocytes:
- Rubriblasts and prorubricutes:
- Eosinophils:
- Basophils
- Lymphocytes
- Plasma cells
- Mononuclear phagocytes:
- Mitotic figures
- Cellularity 1/3-2/3 cells. >75% cell = hypercellular. >75% fat = hypocellular
- megakaryocytes per particle: 5-15 per particle
- Mature megakaryocytes: >80-90% mature
- Rubriblasts and prorubricutes: < or = 5% of all nucleated cells
- Eosinophils: <6%
- Basophils < or = 1%
- Lymphocytes generaly <10% but can be up to 14% in dogs or 20% in cats
- Plasma cells < or = 2%
- Mononuclear phagocytes: < or = 2% (generally <1%)
- Mitotic figures: < or = 2%
Stacey VCNA 2017
Is TEG in cats affected by needle size?
or difficulty of venipuncture?
No
no
Shin JFMS 2019
What measures of coagulation does the use of tetrastartch bolus (colloid) affect?
Summary: transient hypocoagulability
- prolonged aPTT
- decrease clot formation, speed and clot strength
- acquired type 1 vWF disease
Detailed.
- decreased R
- increased aPTT
- increase CL305
- increased K
- decreased platelet coung
- decreased alpha
- decreased MA
- decreased vWF
- decreased collagen binding activity.
Gauthier JVIM 2015
Does the use of tetrastarch impair primary hemostasis?
no
Diniz JVIM 2018
In regards to rotational thromboelastography what are the following correlated to:
- Fibrinogen
- PT
- aPTT
- Fibrinogen = MCF (FIBTEM)
- PT = CT (EXTEM)
- aPTT = CT (INTEM)
Enk JVIM 2018
What targets for PT and R via TEG are requred to achieve therapeutic anti-Xa concentration of rivaroxaban in dogs?
1.5-1.9 x delay in PT and R value of TEG 3 hours after rivaroxaban.
Bae JVIM 2018
Which procoagulant factors are produced by the liver?
Fibrinogen Prothrombin Factor V factors VII to XIII Thrombopoietin
Webster VCNA 2017
Which anticoagulant factors are produced by the liver?
Protien C
Protein S
Tissue factor pathway inhibitor
Antithrombin
Webster VCNA 2017
Which profibrinolysis factors are produced by the liver?
Facto XIIa
Plasminogen
Webster VCNA 2017
Which antifibrinolysis factors are produced by the liver?
Plasminogen activator inhibitor-1
Alpha -antiplasmin
Tissue activatable fibinolysis inhibitor
Webster VCNA 2017
what is the MYPBC3 gene and what mutation is seen there?
Mutation A31P seen in the myosin-binding protein C (MYBPc) => HCM in main coons.
+ increased platelet activation secondary to:
- increased expression of P-selectin, platelet-derived microvesicles and platelet endothelial cell adhesion molecule-1.
LI JVIM 2016
Does clopidogrel work for all cats? Does it work in cats with the MYBPC3 gene mutation?
No - some may be pharmacologically resistant
Yes works in cats with the MYBPC3 mutation.
Li JVIm 2016
Does the concurrent use of cyclosporine and aspirin impact the anti-platelet effects of Aspirin?
no
low dose aspirin inhibits the cyclosporine induced thromboxane synthesis.
Thomason JVIM 2016
What is Glanzmann thrombasthenia?
- autosomal recessive
- quantitative or qualitative defect the platelet GP complex IIb-IIIa (aka fibrinogen factor or integrin alpha(IIb)beta(3)).
- causes impaied platelet aggregation and abent clot formation
=> failure of primary hemostasis
Haysom JVIM 2016
What abnormalities in coagulation are seen with Glanzmann thrombasthenia? What breed is it seen in?
- prlonged BMBT
- Failure of platelet aggregation
- Failure of clot retraction
Seen in great pyrenees, otterhounds and mixed breed dogs.
Haysom JVIM 2016
What 3 variables are positively associated with higher final platelet counts in platelet concentrated blood products?
- pre-donation CBC platelet vlaues
- lipaemia
- phosphorous.
Raleigh JVIM 2017
What diseases is secondary thrombocytosis most commonly identified with including percentage of thrombocytosis cases?
- Neoplasia exp carcinoma (55%)
- Inflammatory disease 46% including Immune med disease with glucocorticoids -22%
- Endocrine disease 125
Woolcock JVIM 2017
What electrolyte abnormality is frequently seen with secondary thrombocytosis?
- hyperkalemia
Woolcock JVIM 2017
which platelet function test was able to detect all the effects of both aspirin and clopidogrel?
- Plateletworks for arachadonic acid
Saati JVIM 2018
What differences in eicosanoid metabolities of arachadonic acid are seen in greyhounds?
Why is this important?
- higher isomers of HETE and DHET
- Albuminuria correlated with DHET
- Systolic blood pressure correlated with 11,12EET and 20(S)HETE
Thus plasma eicosanoud profile in greyhounds is consistent with the activation of metabolic pathways known to promote vascular dysfunction and may contribute to increase systolic BP and albuminuria.
Martinez JVIM 2016
What s therapeutic plasma exchange and what is it used for?
Extracorporeal blood purification that removes circulating large molecular products such as antibodies, pathogenic proteins and protein bound toxins.
Francey JVIM 2018
What is the prefered replacement fluid when used therapeutic plasma exchange?
What other fluids can be used?
- FFP
- human albumin
- colloid
- saline
Francey JVIM 2018
What are the common relevant laboratory changes associated with therepeutic plasma exchange in dogs?
- 25% reduction in total proteins
- 53% reduction in fibrinogen
- 36% reduction in bilirubin
- 4.5% reduction in creatinine
Francey JVIM 2018
What are the options for anticoagulation as part of thereapeutic plasma exchange? what are the complications or contraindications?
- Systemic heparinization:
- contraindicated with systemic bleeding including
- thrombocytopenia
- DIC
- pulmonary haemorrhage
- CNS bleeding - Regional citrate anticoagulation:
- risk of citrate toxicosis => ionised hypocalcaemia, total hypercalcaemia and metabolic alkalosis
Francey JVIM 2018
How frequently are complications observed in therapeutic plasma exchange?
34%
Francey JVIM 2018
