Exam 2 Flashcards
Iron deficiency anemia (diagnostic characteristics)
- Microcytic
- Hypochromic
- Non-regenerative
- Fragmentation morphologies
- +/- reactive thrombocytosis
IMHA (diagnostic characteristics)
- Severe, very regenerative
- Polychromatophils/aggregate reticulocytes
- Macrocytic
- Hypochromic
- Spherocytes
- +/- inflammatory leukogram
- +/- macro/microagglutination
- +/- ghost cells
IMHA (treatment)
- Prednisone
- Blood transfusion
Anemia of Chronic Inflammatory Disease (diagnostic characteristics)
- Mild, non-regenerative anemia
- Normochromic
- Normocytic
Anemia of Chronic Inflammatory Disease (how it happens)
Body is sequestering iron and storing it because it thinks it should because it thinks you have a bacterial infection and bacteria LOVE iron
Fragmentation Morphologies
- Keratocytes
- Acanthocytes
- Schistocytes
Diseases indicated by fragmentation morphologies
- Hemangiosarcoma
- Iron deficiency anemia
- DIC
- Liver disease
Liver Disease
- Frag morphs - cholesterol metaboism messed up ⇒ can’t make good cell membrane
- Icterus - liver isn’t meeting demand of metabolizing billiburin
- Body is lysing RBCs too fast
- Liver isn’t working well
Intravascular vs. Extravascular Hemolysis
Both can have billirubinemia
Hemoglobinemia indicates intravascular hemolysis
Thrombocytosis (causes)
- Inflammation
- Iron deficiency anemia
- Cushing’s disease
- Steroid therapy
Thrombocytosis & Inflammation
IL-6, TNF-alpha, IL-1 cause increased thrombopoietin production
Thrombocytosis & Cushing’s Disease
Cortisol inhibits marcophages ability to eat senescent platelets
Thrombocytopenia & Hemorrhaging
Very unlikely unless you’ve lost nearly your entire blood volume or are in DIC (bleeding out internally)
Calcium in clotting
Ca is positively charged and mediates the binding of the coagulation factor enzyme complexes via their negatively charged residues to the negatively charged phospholipid surfaces of platelets
- Platelets have Ca
- Allows platelets to act as scaffolds for these reactions to occur
Purple Top Tube
- K/EDTA
- Chelates Ca to prevent clotting
Primary Hemostasis
Formation of platelet plug
- Peripheral vasoconstriction initially
- Blood starts flowing again
- Platelets start degranulating & release Ca ⇒ platelet plug
- Endothelial defect exposing endothelial collagen
Secondary Hemostasis
- stimulation of coagulation system
- Thrombin converts fibrinogen to active fibrin
- Fibrin is incorperated into clos to stabilize it
- Coagulopathy here worse than problem w/ primary hemostasis
Coagulopathy
Excessive bleeding due to abnormal function or lack of coagulation factor
- Problem in secondary hemostasis
- Leads to petechiae, purpura, hemo-…
When shouldn’t you trust a hematology analyzer (platelet count)
- Clot in tube
- Cat blood
King Charles Spaniels
High prevalence of inhereted asymptomatic thrombocytopenia w/ macrocytic platelets
(very few, but very large platelets)
Increased Mean Platelet Volume (MPV)
- Young platelets (tend to be larger)
- Sign of enhanced thrombopoiesis in response to thrombocytopenia)
- Platelet clumps (decr. platelet count, incr. MPV)
Thrombocytopenia
- < 50,000/uL
- Often leads to petechia, purpura, ecchymoses (signs that bleeding is also happening internally)
- Spontanous hemorrhage won’t occur unless platelet counts < 20,000/uL (more like 10,000/uL)
Sample collecting in thrombocytopenia
- Do NOT use jugular or any vessel close to the heart
- Use a peripheral vein (i.e. Cephalic)
- Don’t puncture organs for sample collection (won’t be able to stop bleeding)
Hallmark of tickborne disease
Thrombocytopenia! (& shifting leg lameness)
Evan’s Syndrome
IMHA & immune mediated thrombocytopenia simultaneously
Thrombocytopenia differentials
(NOT specific diseases)
- Incr. platelet desctruction***
- Decr. platelet production
- Incr. platelet consumption
Thrombocytopenia via decr. platelet production
- Bone marrow aspirit to check megakaryocytes (would be low)
- Myelophthisis
- Myeloproliferative disease
- Aplastic anemia**
Myelophtheisis
- Space occupying lesion of bone marrow
- Decr. platelet production
Aplastic Anemia
Bone marrow not making anything
Ex. estrogen knocks out bone marrow in ferrets & dogs
Thrombocytopenia via incr. platelet consumption
- Changes in PT/PTT
- Animal is using up platelets & coagulation factors to make clots
- DIC & thrombosis, vasculitis, hemangiosarcoma
Thrombocytopenia via incr. platelet destruction
- MOST COMMON CAUSE OF THROMBOCYTOPENIA
- Primary immune mediated thrombocytopenia
- Secondary immune mediated thrombocytopenia (drugs, infectious agents, neoplasia, SLE)
Vitamin K dependent clotting factors
2, 7, 9, 10
Thrombin
Converts fibrinogen to fibrin
Stopped by anti-thrombin
Heparin
Keeps thrombin and anti-thrombin together
Low albumin & low globulin
Protein losing enteropathy (PLE)
Low albumin, normal globulin
Protein losing nephropathy (PLN)
Low Anti-thrombin
- Hypercoagulable state
- DIC
- Protein losing enteropathy (PLE)
- Protein losing nephropathy (PLN)
Vascular Phase (of clotting)
Exposure of subendothelial matrix and exposure of tissue factor (TF)
Platelet Phase (of clotting)
Adhesion, activation, shape change, secretion (degranulation), aggregation of platelets
Platelet Adhesion
von Willebrand’s factor allows platelets to adhere to each other and the vasculature
Desmopressin
Stimulates transient release of von Willebrand’s factor from endothelial cells
von Willebrand’s Factor
- Helps platelets adhere to each other and vasculature
- Synthesized & released from endothelial cells and platelets
- Deficiency is a platelet function disorder
- Seen in Dobermans!
Platelet Activating Factor (APF)
- Made by cells of immune system
*
DIC (secondary to what primary diseases?)
- Pancreatitis
- IMHA (especially intravascular - schist everywhere)
- Neoplasia
- Extreme enteritis
- Vasculitis
- …
Intrinsic Clotting Casade
12, 11, 9, 8 (PTT) + common pathway
Brad PiTT goes to store to buy a PeT. A pet is normally $12 but it’s on sale for $11.98. Finds common ground wth manager and makes a deal for $10.50 (then remember 2, 1)
Extrinsic Clotting Cascade
7a, TF (PT) + common pathway
Brad PiTT goes to store to buy a PeT. A pet is normally $12 but it’s on sale for $11.98. Finds common ground wth manager and makes a deal for $10.50 (then remember 2, 1)
Common Pathway (clotting cascade)
10, 5, 2, 1 (PT & PTT)
Brad PiTT goes to store to buy a PeT. A pet is normally $12 but it’s on sale for $11.98. Finds common ground wth manager and makes a deal for $10.50 (then remember 2, 1)
Clotting cascade (PT, PTT) test sensitivity
Not very sensitive. Must have decr. in 70% of factors to see prolongation in clotting time
TEST QUESTION:
How do you evaluate platelet function
Buccal mucosal bleeding test (BMBT)
Factor VIIa
- Shortest half life (expect to see prolonged PT before prolonged PTT)
- Part of extrinsic pathway (use PT)
- Needs vitamin K
Blue Top Tube
Citrated plasma
Test for PT & PTT
Factor XIIIa
- Part of common pathway
- Cross links fibrin
Eastern Diamondback rattlesnake venom
- Crotalase induces fibrinogenolysis (degrades fibrinogen)
- Causes incr. in fibrin degradation products, but NOT incr. D dimers
- Spheroechinocytes
Cryoprecipitate
- Form when fresh frozen plasma is thawed
- Contains von Willebrand factor, fibrinogen, factors 8, 13
Cat Platelets
Cats have largest, most activated platelets of any species
Thrombocytosis
Incr. platelets
- Inflammation (most common cause)
- Iron deficiency anemia
- Cushing’s, prednisone
- incr. cortisol
- Rebound response to thrombocytopenia
- Within 1 wk of splenectomy
Hypercoagulable State
More likely to have a clot
- Initial reactions that lead to thrombosis & DIC
- Anti-thrombin deficiency
Incr. FDPs
- Rattlesnake venom
- Breakdown of fibrin monomers by plasmin before fibrin has been crosslinked by factor 13a
- These FDPs usually removed by liver
- Does NOT necessarily mean activation of clotting cascade w/ active lysis of cross-linked fibrin clot
Presence of D-dimers
Indicates active breakdown of covalently crosslinked fibrin
Incr. D-dimers
Indicates active coagulation and breakdown of clots
Only occurs when soluble fibrin has been crosslinked by factor 13a & plasmin has cleaved this stable fibrin
- Thrombus
Mast cells in circulation (dog)
- IMHA
- Inflammation
- Parvo virus**
- NOT likely from a mast cell tumor
Mast cells in circulation (cat)
Likely mast cell tumor in spleen, liver or intestines
Purple top vs. Blue top for PT/PTT
EDTA (purple top) is too strong of a Ca chelator. Ca is needed to start the clotting cascade
Fibrinogen
- Positive acute phase protein
- Incr. w/ inflammation (may be only sign you see in large animal)
- Decr. w/ liver failure
- Decr. w/ conversion to fibrin (throwing clots)
DIC (indices)
- Low fibrinogen
- Incr. D-dimers AND incr. FDPs
- Thrombocytopenia
- Fragmentation morphologies
WHEN YOU SEE THIS, THE ANIMAL NEEDS PLASMA STAT!
Hemophilia A
Factor 8 deficiency
Hemophilia B
Factor 9 deficiency
Factor 12 deficiency
- Commonly seen in cats
- Does NOT cause bleeding disorder b/c it’s not necessary for seconday hemostasis in vivo
- Will cause incr. PTT since that assesses factors 12, 11, 9, 8, 10, 5, 2, 1 (intrinsic & common pathway)
Normal PT, prolonged PTT
Only intrinsic pathway is affected
- commonly seen in cats (some don’t have factor 12)
Prolonged PT & PTT
Likely problem with common pathway
Alpha Granules in platelets
- Adhesion proteins (von Willebrand’s factor)
- Growth factors
- Coagulation proteins
Snake thrombocytes
Very large platelets which are actually cells (not fragments)
Platelet estimate
Count # of platelets in ten 100x oil immersion fields & find average.
Multiply average by one of the following factors to get estimate
dogs: 15,000/uL
cats: 20,000/uL
Anti-coagulant proteins
- Anti-thrombin
- Alpha 2 macroglobulin
Vitamin K antagonists
- Inhibits vitamin K epoxide reductase in the liver
- Makes vitamin K dependent clotting factors hypofunctional
- Prolonged PT
- Ex. rodenticide
Leukemoid response
- ~50,000 leukocytes/uL
- Indicates serious acute inflammation
- Looks like leukemia
Diseases/Processes causing leukemoid response
- Infectious processes: pyothorax, pyelonephritis, septic peritonitis, pyometra, abscess, pneumonia
- Immune-mediated disorders: IMHA, glomerulonephritis, polyarthritis, vasculitis
- Will see mostly in dogs b/c they have huge neutrophil reserves in bone marrow
Metarubricytes in blood machines
Will be counted as leukocytes
Normal neutrophil storage pool in bone marrow in different species
Dogs > Cats > Horses > Cows & sheep
Ability to mount an inflammatory response
Leukocyte count
Must look at absolute numbers and not percentages (50% of nothing is nothing!)
Hypersegmentation of Neutrophils
- 5 or more distinct nuclear lobes
- Glucocorticoids - older neutrohils staying in circulation because macrophages aren’t eating them
- Old blood samples
- Normal in horses
Chediak-Higashi
Neutrophil function problem - cannot form phagolysosome
Neutrophilic granules
- Normal in siamese cats & healthy foals
- Indicates toxicty in neutrophils (immature neutrophils released from bone marrow w/ basophilic RNA)
Left Shift of neutrophils
More immature forms of neutrophils are coming out of the bone marrow
- Sign inflammation is occurring
Band neutrophils
Normal: 0-300 band/uL
Inflammatory leukogram: >300 bands/uL
Neutrophilic toxicity
- Accelerated release of immature neutrophils
- Indicates inflammation is only evident in neutrophil lineage
- Does NOT refer to presence of toxins
House is on fire and the neutrophils are running out of bone marrow and haven’t had time to clean up basophilic RNA in their cytoplasm
1+ Neutrophilic Toxicity
Döhle bodies OR basophilic cytoplasm
2+ Neutrophilic Toxicity
Döhle bodes AND basophilic cytoplasm
3+ Neutrophilic Toxicity
- Foamy cytoplasm (vacuolization)
- Döhle bodies and basophilic cytoplasm
4+ Neutrophilic Toxicity
Granulation band (“band neutrophil”)
Segmented neutrophil
= mature neutrophil
Regenerative Left Shift
Mature (segmented) > Immature (bands, metamyelocytes, myelocytes)
Better prognosis
Degenerative Left Shift
Immature (bands, metamyelocytes, myelocytes) > Mature (segmented)
Worse prognosis, bone marrow is not keeping up with demand
Pelger-Huet Anatomy
Cannot segment neutrophils, eosinophils, basophils but they are still functional
- Common in Australian Shepherds
Inflammatory Leukogram
- More bands than the reference interval (>300/uL)
- Usually accompanied by some neutrophil toxicity
Physiologic Leukogram
- Caused by stress (but NOT a stress leukogram)
- more like “excitement”
- Caused by vasoconstriction & splenic contraction
- Mature neutrophilia w/ lymphocytosis
Lymphocytosis in cats
Think physiological leukogram (excitement)
Super contracting spleens
Can see up to 20,000/uL
Stress Leukogram
- Mature neutrophilia, lymphopenia, eosinopenia, monocytosis
- Only really trust lymphopenia because you could have underlying inflam. leukogram
Neutropenia
- Incr. utilization of destruction
- Acute infection before granulocytic hyperplasia
- Overwhelming sepsis of endotoxemia
- Infection
- Decr. marrow production
- Estrogen toxicity in dogs/ferrets
- Severe, chronic ehrlichiosis
Eosinophilia
Observed in some cancers
- Eosinophilic leukemia
- Mast cell tumors
- T cell lymphomas
Low total protein in baby animal
Indicates failure of passive transfer ( no maternal antibodies to protect them)
Order of type of leukemia you’d rather have
Chronic lymphocytic (sometimes not even treated) > Chronic myelogenous > Acute lymphocytic > Acute myelogenous
Chronic leukemias
Cells are well differentiated
Acute leukemias
Have a lot of blasts & immature forms in circulation
Lymphocytosis in dogs (mod-severe)
- Suspect chronic lymphocytic leukemia
- Make diagnoses w/ bone marrow aspirit or advanced diagnostics
