Clin Path/Transfusion Medicine/Coagulopathies/hemolymphatic Emergencies

Question 1

Hematopoiesis

Answer 1

Production of all blood cells

Regulated by poietins, colony stimuli, interleukins

Question 2

Solid cellular portion of blood components

Answer 2

red blood cells (erythrocytes),
platelets (thrombocytes)
five kinds of white blood cells (leukocytes)
– These cells are suspended within plasma, the fluid portion of blood

Question 3

Erythropoietin

Answer 3

– manufactured in the kidneys
– also facilitates hemoglobin synthesis and stimulates the release of immature RBCs; aka reticulocytes, into the circulation
– increase in production is stimulated by renal hypoxia
– transported to the bone marrow, where it stimulates the proliferation and maturation of erythroid progenitor cell

Question 4

Erythropoiesis

Cell line up
regulated by?
how long does it take?

Answer 4

Production of RBCs
stem cells → erythroblasts → reticulocytes → erythrocytes

Regulated by EPO which is regulated by blood O2 levels in kidneys

*HYPOXIA stimulates EPO
takes 1 week for RBC maturation

Question 5

Thrombopoiesis

How long does it take?

what is the precursor cell?

Answer 5

Production of Platelets
Stem cells → megakaryocyte → pieces of cytoplasm become platelets

normal platelet count in small animal patients is 200 000–800 000/mL

Can take 1 week for produciton

Question 6

Leukopoiesis

types of cells
life span

Answer 6

Production of WBCs
Granulocyte = neutrophils, eosinophils, basophils
Agranulocytes = lymphocytes (T and B), monocytes
– type of cell formed is influenced by cytokines and hormones
– destroyed by lymphatic system

life span ranges from 13-20 days

Question 7

RBC structure

Life span K9/fel

Answer 7

Contains: H2O, Hb, Bi concave disc shape that creates more membrane for O2/CO2 diffusion

Lacks: Nucleus, mitochondria, ribosomes

K9 Lifespan: 120 days
Fel Lifespan: 68 days

Question 8

Oxyhemoglobin

Answer 8

when oxygen is bound to hemoglobin

Question 9

Deoxyhemoglobin

Answer 9

when oxygen is not bound to hemoglobin

Question 10

CBC Values

Answer 10

vHb - Hemoblobin
HCT
MCV: Mean corpuscular vol; RBC avg size
MCH: Mean corpuscular Hb; Avg wt of Hb in RBC
MCHC: MCH concentration; Avg density of Hb in RBC
RDW: Red Cell Distribution width; EBC size variation
Retic %: Calc # can be overestimated w/ anemia
Absolute Retic count: # of immature RBCs; used to characterize anemia regen vs nonregen

Question 11

High MCV and low MCHC means:

Answer 11

Regenerative anemia tends to be macrocytic and hypochromic (high MCV, low MCHC)

Question 12

Normal MCV and Normal MCHC means:

Answer 12

nonregenerative anemias tend to be normocytic and normochromic (normal MCV, normal MCHC).

Question 13

Low MCV and Low MCHC means:

Answer 13

Iron-deficient anemia (e.g., associated with chronic gastrointestinal hemorrhage) is often microcytic and hypochromic (low MCV, low MCHC).

Question 14

Dyserythropoiesis

Answer 14

– defective development of RBCs
– non-regenerative anemia, primary bone marrow dz (neoplasia)
– extra marrow suppression from systemic dz
– some toxins (sulfonamides)
– bone marrow typically required for diagnosis

Question 15

Marrow examination with IMHA

Answer 15

Two major variants are encountered:
1. precursor directed immune-mediated anemia (when reticulocytes are targeted but bone marrow aspirates are still consistent with erythroid hyperplasia)
2. pure red cell aplasia, where earlier precursors are targeted with an absence of these cells on marrow examination.

Question 16

3

Treatment approach to anemia

Answer 16

therapeutics aim to address impaired DO2, support erythropoiesis, or treat underlying primary disease.

Question 17

Treatment that Support erythropoiesis

x3

Answer 17

1. Darbepoietin: support erythropoiesis in situations of endogenous erythropoietin deficiency
2. Iron dextran: support erythropoiesis in iron-deficient patients
3. Cobalamin: support erythropoiesis in hypocobalaminemic patients

Question 18

Senescene

What can exacerbate this?

Answer 18

RBC aging process
1% of old RBCs removed daily via intravascularly or extravasclularly

Oxidative Stress (free radicals) contribute to rapid RBCs aging/destruction
-exacerbated by dz/toxins

Question 19

Intravascular vs Extravascular Hemolysis

where does it occur? what % is destroyed where?

Answer 19

Intravascular: accounts for 10%, Hb released into blood stream → hemglobinemia → excess unconj Hb in plasma → eliminated by kidneys

Extravascular: 90% of RBC destruction via macrophages in spleen and liver into amino acids, iron, and heme (from Hb)
-AA recycled by Liver
-Iron to bone marrow
-Heme broken into free or unconj bilirubin

Question 20

What clin path finding is present in intravascular hemolysis but not extravascular?

Answer 20

Hemoglobinemia and hemoglobinuria are not seen in extravascular hemolysis since the cells are destroyed outside the blood vessels via normal mechanisms

Question 21

Pathophysiology of Icterus

3 types

Answer 21

-Excessive RBC breakdown → excessive unconj bilirubin in plasma
-Unconj bilirubin exceeds Livers ability to conjugate → desposits to tissues (PRE-hepatic)
-Liver dz/dysfunction cannot handle processing unconj. bilirubin → buildup
- Bilirubin obstruction → conj bilirubin backs up into blood stream then tissues (POST- hepatic)

Question 22

Regenerative Anemia

What do the RBCs typically look like?

Answer 22

– bone marrow responds appropriately by increasing red blood cell production and increased reticulocytes release
– occurs either due to hemorrhage or hemolysis → result of internal loss, external loss, destruction by way of hemolysis, or dilution
– polychromasia → more immature RBCs than mature
– can be macrocytic → larger than normal OR anisocytosis → various different sizes
– peripheral metarubricytosis (nucleated red cells)
– hypochromic = low hemoglobin concentration and hence appear a paler color due to the abundance of reticulocytes in circulation

Question 23

Two forms of reticulocytes observed in cats:

Answer 23

1. aggregate → shorter lived and should be used to gauge regeneration in cats
2. punctate

Question 24

Metarubricytes in the face of nonregenerative anemia is:

Answer 24

an inappropriate marrow response, and reasons for bone marrow derangement should be considered (e.g., bone marrow neoplasia, heat related illness, feline leukemia).

Question 25

How long does it take for bone marrow to respond to acute blood loss?

Answer 25

– bone marrow requires time to respond to acute blood loss, and this typically takes 2–3 days in cats and 4–5 days in dogs
– anemia can be “preregenerative”

Question 26

5

Macrocytic, Normocytic Anemia

Answer 26

1. FeLV infections with no reticulocytosis (common)
2. Poodle macrocytosis (not anemic)
3. Hyperthyroid cats (slight macrocytosis without anemia)
4. Spurious with erythrocyte agglutination
5. Spurious in cats and dogs with persistent hypernatremia

Question 27

Regenerative Anemia Absolute retic count #

Answer 27

Absolute reticulocyte/PCM count:
> = 100,000/ul (dog)
> = 60,000/ul (cat)

non regen < than these #s

Question 28

Non-regen, Normocytic, Normochromic anemia

Answer 28

the type of anemia in which circulating RBCs are the same size (normocytic) and have a normal red color (normochromic)
– Pre-Regenerative anemia → not enough time has passed for reticulocyte generation to respond

Question 29

Non‐Regenerative Anemia

2 categories
Describe RBC appearance

Answer 29

– occurs secondary to impaired erythropoiesis associated with primary bone marrow disease or systemic disease leading to secondary extra-marrow suppression.
– Most cases of non‐regenerative anemia have normal red blood indices as they are normocytic and normochromatic
– two categories:
1. hypoproliferative anemia
2. abnormal RBCs are sequestered in the bone marrow
– red blood cells appear microcytic after Hb, iron, and RBC reserves are exhausted

Question 30

Hypoproliferative anemia

Answer 30

– bone marrow RBC production is static or reduced

Question 31

What is the best way to evaluate regeneration response?

Answer 31

the presence or absence of reticulocytes in the peripheral blood

Question 32

7

Potential causes for NNN anemia

Answer 32

1. Chronic inflammation and neoplasia (sometimes slightly microcytic)
2. Chronic renal disease
3. Endocrine deficiencies
4. Selective erythroid aplasia
5. Aplastic and hypoplastic bone marrow
6. Lead toxicity (may not be anemic)
7. Cobalamin deficiency

Question 33

Non Regen Anemia: Primary Bone
Marrow Disorder

Answer 33

1. Pure Red Cell Aplasia (PRCA)
2. Aplastic Anemia
3. Myelodysplastic
4. Syndrome
5. Myeloproliferative
6. Diseases
7. Myelophthisis
8. Myelonecrosis
9. Viral Infection
   * Parvovirus
   * (Dog/Cat)
   * FeLV (Feline)
   * FIV (Feline)
10. Drug-Induced
11. Hematologic Dyscrasia

Question 34

4

Non Regen Anemia: Secondary Suppression
of Bone Marrow From Systemic Disease

Answer 34

1 Chronic Inflammatory Disease
*Infection
*Inflammation
*Neoplasia
2. Chronic Renal Failure
3. Endocrine Disorder
*Hypothyroidism
*Hypoadrenocorticism
*Estrogen toxicity

Question 35

primary failure of erythropoiesis

Answer 35

severe erythroid hypoplasia of the bone marrow occurs and precursor red cells are not produced
– uncommon, but primary failure is typically immune mediated, acquired, and may be associated with many disease conditions

Question 36

Aplastic anemia: Non regen or Regenerative

Answer 36

Non-regenerative: characterized by bone marrow failure
Examples:
Estrogen induced
Drug use : antibiotics
Chemotherapy
Radiation
Infectious disease

Can be primary or secondary to another dz process: thymoma, leukemia, infection, toxicities, or renal disease

Question 37

Marrow infiltration

Answer 37

another form of bone marrow failure associated with
1. neoplasia
1. myelofibrosis: the replacement of bone marrow with fibrous connective tissue
1. osteopetrosis

Question 38

Hemolysis: Non-regen or Regenerative?

Answer 38

Regenerative
Immune mediated
Neonatal isoerythrolysis
Transfusion reaction
Infectious
Heinz body anemia
Zinc toxicity
Copper toxicity
Pyruvate kinase deficiency
Phosphofructokinase deficiency

Question 39

Impaired red cell production: Non-regen or Regenerative

Answer 39

Non-Regenerative
Immune mediated → can be both
Neoplasia → can be both
Drug induced
Inflammatory disease→ Always Non Regen
Chronic renal disease
Endocrine diseases

Question 40

Bone marrow infiltration: Non-regen vs Regenerative

Answer 40

Non‐regenerative
Neoplasia
Myelofibros

Question 41

anemia of chronic inflammatory disease

Type of anemia
suspected mediator

Answer 41

– usually mild to moderate, normocytic, normochromic, and always non‐regenerative
– decreased RBC lifespan
– suspected mediator is hepcidin, a protein produced by the liver in response to the release of IL‐6 as part of host defense against inflammatory stimuli
– Hepcidin is also produced in hypoxic or iron‐deficient states and inhibits iron export from duodenal enterocytes and macrophages, resulting in decreased iron absorption

Question 42

Polycythemia

Definition and consequences

Answer 42

abnormally increased packed cell volume, red blood cell count, and hemoglobin concentration
– induces an increase in blood viscosity, particularly when the packed cell volume rises above 50–60% in dogs
– polycythemia increases cardiac workload and hinders microcirculation.
– potentiates thrombosis, causes tissue hypoxia, and makes neurological complications more likely
Absolute vs Relative

Question 43

Absolute polycythemia

primary vs secondary

Answer 43

caused by an increased total RBC mass, divided into primary or secondary polycythemia
– primary when the increase in red cell mass results from an abnormality of the myeloid stem cells
– secondary when the increase in red cells is in response to increased levels of erythropoietin inappropriately
* ex: PDA, congenital heart defects, renal neoplasia, → local hypoxemia triggers erythropoietin

Question 44

Relative polycythemia

Answer 44

hemoconcentration due to decreased plasma volume
because of the shifting of body fluids from the vascular space into the interstitial space due to dehydration, excessive external loss of body fluids, or overuse of diuretics
– ex: hemorrhagic gastroenteritis, who lose a large volume of fluids rapidly
– Splenic contraction can lead to an increase in circulating red blood cells but not in the total number of red cells in dogs; this normal physiological response should not be interpreted as polycythemia

Question 45

Answer 45

Acanthocytes
spiculated red cells with a few projections
RBCs with blunt finger like projections
Injury via RBC damage traveling thru vasculature or fragile from iron deficiency
Liver dz, DIC, vasculitis

Question 46

3 examples
what do these suggest?

Answer 46

Spherocyte; more disc shape than biconcave, smaller, more dense lacking central pallor
IMHA; regenerative
Oxidative injury
Coral snake
– suggest immune mediate destruction

Question 47

Causes x4

Answer 47

Schitocytes; RBC fragments
mechanical injury to erythrocytes, turbulent blood flow
-Vascular abnormalities; DIC, vasculitis, PSS, hemangioma

Question 48

Causes x4

Answer 48

Echinocytes “Spur cells” (tiny sun)
Drugs; chemo agents, furosemide
Renal dz; glomerulonephritis
Snake envenomation

Question 49

Answer 49

Reticulocytes; immature RBCs. Lg amounts of RNA form dark blue clumps/strands
Bone marrow respone to anemia

Question 50

Answer 50

Ghost Cells; pale RBCs due to loss of hemoglobin thru intravascular hemolysis
-IMHA
-Oxidant injury
-Snake envenomation

Question 51

Answer 51

Basophilic stippling; numerous small blue punctuate stippling in RBCs
-Regenerative Anemia
-Lead poisoning

Question 52

caused by;
examples x6

Answer 52

Heinz bodies; dense granuel on the edge of RBC caused by oxidative injury = hemoglobin to precipitate
Propofol; acetaminophen in cats
toxins; Onion, zinc in dogs
anticoagulant rodenticide
Skunk musk

Question 53

Answer 53

Howell- Jolly bodies; small round dark purple dots (nucleus remnants) within RBCs
Regenerative anemia
impaired splenic function (corticosteroids/splenectomy)

Question 54

Answer 54

Nucleated RBC - most mature nucleated RBC
present in strongly regenerative anemias

Question 55

Answer 55

Band Neutrophil; immature neutrophils
↑ bands present = left shift with acute or severe inflammation

Question 56

Answer 56

Toxic neutophilic change

Question 57

Neutrophils

how much of count do they make up?
how do they migrate to tissues?

Answer 57

– phagocytes aka “clean up crew” that engulf micor-organisms and tissue debris
–Circulates for few hours then migrates into tissues
– most numerous circulating leukocyte in the dog and cat
– become attracted to site of potential infection or inflammation through a chemical signaling process known as chemotaxis that employs endogenous inflammatory mediators.

Question 58

Eosinophils

what % of count do they make up?
how long do they stay active?

Answer 58

Respond to histamines → allergies, anaphylaxis, parasitic infx, sometimes cancer
– ≤5% of the total WBC count
– do not stay in the circulating pool for very long and migrate into tissues within hours
– granules contain anti-inflammatory subtances
– effective against protozoas an parasitic infections

Question 59

Basophils

what do they initiate? what do they release and in reponse to what?

Answer 59

Initiate immune/allergic responses
Release histamines in response to chemicals from mast cells
– rarest WBCs in circulation
– granules contain histamine and heparin, making these cells effective at initiating inflammation by working in conjunction with eosinophils
– Eosinophils are attracted to the site of allergic reaction by chemotactic factors released from basophilic granule
– Basophilia is most commonly associated with an allergic or hypersensitivity reaction

Question 60

Monocytes

how do they enter tissue site?
make up % of circulating WBCs

Answer 60

• Mono-nuclear
• Phagocytosis, process antigens
• become macrophages → most of their phagocytosis occurs in the tissues
• monocytes enter tissues by the process of chemotaxis.
  – after entering tissues = tissue macrophages
  – make up 5–6% of the circulating WBCs
  – mature much faster than neutrophils,
  – stay in peripheral blood longer
  – largest WBC in circulation

Question 61

Tissue macrophages

Where are they mostly found? #4

Answer 61

most prevalent in filter organs such as the liver, spleen, lungs, and lymph nodes

Question 62

Mononuclear phagocyte system (MPS)

Answer 62

Monocytes and tissue macrophages
responsible for the clean‐up of variety of microscopic debris in the body:
* cellular debris left over from inflammation and infection,
* specific antigens that have been destroyed by lymphocytes,
* other foreign substances.

Question 63

Lymphocytes

2 types

Answer 63

only WBC type w/o phagocytic capability
Memory cells of immune system
– B cells = divide into plasma cells to create antibodies, Humoral immunity (lymphoid tissues)
– T cells= Cytokine production, cell-mediated immunity (killing/activation/regulation) lymphoid and other tissues

Question 64

T cells

what % do they make up?
how long do they survive?
Role

Answer 64

– predominant circulating lymphocyte, accounting for up to 80% of peripheral blood lymphocytes
– very long‐lived, surviving on average from 6 months to 10 years.
– there are two subtypes:
* killer T cells and helper T cells

Question 65

B cells

Answer 65

• After B lymphocytes recognizes an antigen, → transforms into a plasma cell that can release antibodies in a process called humoral immunity.
• Plasma cells derived from B lymphocytes produce, store, and release antibodies that are known as immunoglobulins
• Plasma cells are found in all tissue in the body, but are most common in the lymph nodes and spleen.

Question 66

Leukocytosis / Neutrophilia mechanisms

#4

Answer 66

1. ↑ production due to inflammation (appropriate)
2. ↑ production due to neoplasia (inappropriate)
3. Demargination
4. ↓ egress from circulation

Question 67

Clin path findings with Increase in production of leukocytes/neutrophils due to inflammation

Answer 67

–Degenerative Left shift: absolute #s of band/immature neutrophils are > than mature ones
–Leukemoid response: strong inflammatory stimulus that can mimic neoplastic response (can be seen with infx)

Question 68

Demargination

Answer 68

Corticosteriod response = stress leukogram from endongenous or exogenous steriods
–15 - 20K cells/uL
–Steriods usually clear w/i 24hrs but may take longer with prolonged use
– Epinephrine response: excitement (puppies/kittens)

Question 69

Decreased neutrophil transit time into tissues

caused by

Answer 69

Corticosteriods ↓ neutrophil transit time

Question 70

Left Shift

Answer 70

↑ immature neutrophils (bands)
– sign of inflammation or infection as the body increases neutrophil release in response to injury
Immune system responsible for causing WBCs to be released early
↑ # of monocytes
– degree of left shift corresponds with the severity of the inflammation or infection

Degenerative vs Regenerative

Question 71

Regenerative Left Shift

Answer 71

mix of adult and immature cells
– neutrophilic leukocytosis with an increase in immature neutrophils but a larger population of mature neutrophils

Question 72

Degenerative left shifts

Answer 72

Condition where a neutrophilic leukocytosis is present but there are more immature neutrophils than segmented neutrophils in the blood
– associated with severe disease and typically indicate a poor prognosis

Question 73

Toxic neutrophils

what is it in response to?

Answer 73

produces in response to bacterial infx tissue necrosis
Lg # = poorprognostic indicator
– very granular appearance

Question 74

Affect of Addisons on WBCs

Answer 74

Will not see stress leukogram
–body unable to respond phisologically to stress

Question 75

Leukopenia

Answer 75

– abnormally low white blood cell count, usually due to a decreased neutrophil count known as neutropenia (most abundant WBC)

Question 76

Leukopenia causes

x7

Answer 76

Decrease production in bone marrow
–Viral: Parvo/Panleuk/FIV/FeLV
–Neoplasia, radiation
–Necrosis
–Drug Toxin; chemo/chloramphenicol/TMZ
–Increased utilization; fulminant inflammation, bacterial sepsis, endotoxemia
-Destruction; immune mediated
–2nd to lymphopenia

Question 77

Leukocytosis

Answer 77

elevated white blood cell count and is common in a variety of inflammatory states
– historical or clinical evidence of inflammatory disease such as pyrexia, weight loss, loss of appetite, infected wounds, and specific organ system involvement

Question 78

Infectious Agents/Parasites that cause Leukopenia

#7

Answer 78

Histoplama
Hepatozoon
Ehrlichia
Anaplasma
Babesia
Mycoplasma
Distemper

Question 79

Thrombocytopenia

4 mechanisms

Answer 79

N = > 200,000 (8-15 phpf)
4 mechanisms of thrombocytopenia:
1. Sequestration; rare in animals
2. Consumption; DIC, Parvo, heatstroke, MODS
3. Destruction; ITP
4. Hypoproliferation; Bone marrow dysfunction/Liver dz = decrease thrombopoeitin production

*CKCS have abnormally low platelets due to them being oversized - idiopathetic asymptomatic thrombocytopenia

Question 80

Immune‐Mediated Thrombocytopenia results from:

x4

Answer 80

Can be due to:
1. decreased production, → myelosuppression (chemo/drugs)
1. increased consumption (e.g. a large blood clot), DIC
1. increased sequestration, → splenomegaly
1. increased destruction = ITP/DIC

Question 81

ITP definition

Answer 81

increased platelet destruction results due to an inappropriate immune response
– either primary or secondary
– Regardless of cause ITP is a type II hypersensitivity reaction that results in destruction of circulating platelets when antiplatelet antibodies attach to the surface of the cells and are removed by the monocyte macrophage phagocytic system in the spleen

< 30,000/mL

Question 82

Secondary ITP

Answer 82

or acquired ITP can occur due to infectious, inflammatory, neoplastic, or toxic processes

Question 83

Primary ITP

Answer 83

diagnosed based on exclusion of other causes; in cases of acquired ITP, the underlying cause must be determined in order for treatment to be effective.

Question 84

Blood smear platelet count

Answer 84

Each 100× field should contain 8–15 platelets, with each platelet visualized representing approximately 15 000/μL

Question 85

Why is vincristine used for ITP treatment?

Answer 85

– vinca alkaloid and immunomodulating antitubular agent
– works by inducing release of platelets from megakaryocytes through premature fragmentation and by impairing the consumption of platelets by macrophages

Question 86

Veterinary blood products and components that contain platelets

Answer 86

fresh whole blood,
fresh platelet concentrate,
cryopreserved platelets,
lyophilized platelets, and
platelet‐rich plasma

Question 87

Effusions

Answer 87

Pure Transudate: < 2.5g/dl
–PLE, PLN, portal hypertension, PSS
Modified transudate: 2.5-5.0 g/dl
–blood, neoplasia, CHF, Liver dz
Exudate: > 5 g/dl
–purulent, pyothorax

Question 88

Lactate forms found in the body

where is it metabolized?

2 types

Answer 88

D-Lactate = non-physiological (short bowel syndrome)
L-Lactate = main form of lactate in body
–produced in skeletal muscle, brain tissue, adipose tissue and circulating blood cells
–Metabolized in Liver (60%) and Kidney (30%)
– <3 uses lactate for ATP production

Question 89

Normal energy Metabolism

Answer 89

Glucose → glycolysis → pyruvate + 2 moles of ATP per mole of glucose
→ pyruvate enters mitochondria → 36 moles of ATP/glucose mole

Question 90

Energy metabolism under Anaerobic conditions

Answer 90

Abnormal anaerobic conditions → inadequate O2 supple
–glycolysis rate too high for mitochondria metabolism to keep up → accumulation of pyruvate and NADH = becomes main source of energy production for ATP

Question 91

Glycolysis role in producing lactate

Answer 91

Glycolysis → glucose = pyruvate → lactate → NADH
–Lactate dehydrogenase activity ↑ = ↑ lactate to pyruvate ratio

Question 92

Measured Lactate

Answer 92

– Indirect measure of tissue O2 balance
Liver cannot eliminate amount of lactate produced by hypoxic tissue = level of lactate we measure

Question 93

Cori Cycle

Answer 93

Reverses lactate metabolism when aerobic metabolism restored

Question 94

Type A Lactate examples

Answer 94

Oxygen Related
↑ O2 demand:
–exercise, shivering, tremors, sz
↓ O2 availability:
– shock, LV failure, CPA, Pulmonary dz
↓ Arterial O2 content:
Acute Anemia, hypoxemia, CO poisoning

Question 95

Type B Lactate

Answer 95

Not directly O2 related → metabolic
B1= Systemic dz → inflammatory process affecting cells ability to proccess O2
B2 = Drugs or Toxins → medication related to metabolic hyperlactemia, acetaminophen, corticosteriods, Catecholamines
B3 = Hereditary dz → congenital hyperlacemia (GSP), enzyme deficiencies, pyruvate dehydrogenase

Question 96

FFP

Answer 96

– plasma that has been separated from red blood cells and frozen within 8 hours
– contains all of the coagulation factors, anticoagulants, alpha macroglobulins, albumin, fibrinogen, and fibronectin

Question 97

Frozen Plasma

Answer 97

fresh plasma is frozen for more than a year (frozen plasma) or kept at room temperature for more than 8 hours, it loses its labile clotting factors (factors V and VIII).
– Frozen plasma contains clotting factors II, VII, IX, X and plasma proteins

Question 98

Cryoprecip

Answer 98

created by slowly thawing and centrifuging FFP
– centrifuged supernatant is discarded, and the remaining solution (CRYO) contains vWF, factor VIII, fibrinogen, and fibronectin

Question 99

Cryopoor Plasma (CPP)

Answer 99

CPP is the supernatant removed after FFP has been centrifuged
– contains albumin, globulin, antithrombin, protein C, protein S, and factors II, VII, IX, and X
– albumin concentration and COP were highest in CPP compared with CRYO or FFP
– CPP is a reasonable alternative to FFP for albumin replacement and oncotic support

Question 100

Albumin

6 important functions

Answer 100

Albumin makes up 70%–80% of COP within the body
– plays an important role in wound healing; as an antioxidant, free-radical scavenger, and transport agent; and in preserving normal platelet function

Question 101

Causes of hypoAlb

Answer 101

protein-losing nephropathy, protein-losing enteropathy, end-stage liver failure, malnutrition, and systemic inflammatory states

Question 102

Alb deficit equation

Answer 102

albumin deficit (g) = 10 × 0.3 × BW (kg) × (desired albumin – patient albumin

Question 103

HSA administration dose

Answer 103

2ml/kg 25% HSA is administered IV over 2 hours followed by 0.1 to 0.2 ml/kg/hr for 10 hours, for a total dose of up to 2 g/kg

Question 104

Marked leukocytosis and polycythemia with hypoglycemia

Answer 104

because of increased cell utilization of glucose

Question 105

Pathologic hemolysis

Answer 105

– occurs when the rate of destruction is increased, and the life span of RBCs is shortened

Question 106

Hemolytic anemia (HA)

Answer 106

results when regeneration of RBCs from precursor cells is inadequate to replenish the destroyed cells
– caused by several immunologically and nonimmunologically mediated mechanisms

Question 107

9

Causes of Hemolysis

Answer 107

1. Fragmentation hemolysis
2. Toxicant-induced hemolysis
3. Foodstuffs and additives
4. Drugs
5. Chemicals
6. Immune-mediated hemolysis
7. Heritable hemolysis
8. Infection-related hemolysis
9. Miscellaneous

Question 108

Fragmentation hemolysis

How does it occur?
What type of cell is typically seen?

Answer 108

– mechanical process, most commonly the result of shearing of the RBC membrane in the small vessels (microangiopathic hemolysis) or from altered rheologic forces
– Because shearing occurs inside the vascular space, hemoglobinemia and hemoglobinuria commonly result
– observation of schistocytosis on a peripheral blood smear provides supportive evidence of fragmentation; keratocytes and acanthocytes also are seen
– Assays of coagulation to check for DIC

Question 109

Toxicant-induced hemolysis

Answer 109

– often related to oxidative injury
– Oxidation of hemoglobin iron results in the formation of methemoglobin, which, although unable to bind oxygen, does not shorten RBC life span
– Cats are more susceptible to chemical oxidant injury than dogs

Question 110

What causes Heinz-bodies?

Answer 110

Oxidation of hemoglobin causes Heinz body formation
– ultimately resulting in RBC removal

Propofol use in cats

Question 111

Substances that can cause toxicant-induced hemolysis

5 examples

Answer 111

1. Onion/Garlic
2. Propylene glycol → propofol
3. Zinc/Copper
4. Skunk Musk
5. Acetaminophen
6. Benzocaine

Question 112

Heritable hemolysis

Answer 112

– relatively uncommon
– all hereditary erythrocyte defects lead to HA
– Osmotic fragility, Phosphofructokinase deficiency, Pyruvate kinase deficiency

Question 113

Infection-related hemolysis

Answer 113

result of direct cell damage, through initiation of an immunologically mediated response to infection, or both
– Systemic infections also can lead to microangiopathic hemolysis

Question 114

Infection of red blood cells causes in US:

Answer 114

1. hemotropic Mycoplasma spp.
2. protozoan parasites → Cytauxzoon felis and Babesia spp

Question 115

Mycoplasma haemofelis

Answer 115

causative agent of feline infectious anemia
– Presumably transmitted by fleas, the resulting hemolysis is variable in severity, cyclic in nature, and often Coombs positive

Question 116

Babesia most likely to cause HA in the United States

Answer 116

*B. gibsoni *
any breed can be infected, but infection in North America is most common in pit bull terriers.

Question 117

Cytauxzoon felis

transmitted by
CS seen

Answer 117

causes a tick-transmitted infection endemic to the southeastern, midwestern, and mid-Atlantic regions of the United States
– Cats typically become sick in the warm weather months with an acute febrile illness often accompanied by icterus and pancytopenia.

Question 118

Systemic infections that may cause HA

Answer 118

– hemolysis may be due to hemotropic mycoplasmosis
– Feline leukemia
– feline immunodeficiency virus

Question 119

Immune-mediated hemolysis

secondary vs primary

Answer 119

– destruction of RBCs is mediated by antibody or complement-triggered events
– i.e., secondary IMHA
→ infection, drugs, cancer, procedure
– occurs more commonly in dogs than cats (rare) → cocker spaniels overrepresented
– primary IMHA is idiopathetic

Question 120

7

Drugs that might trigger Secondary IMHA

Answer 120

1. acetaminophen,
2. cephalosporins,
3. NSAIDs,
4. penicillins,
5. phenylbutazone,
6. tetracyclines,
7. trimethoprim‐sulfa

Question 121

What is the most common form of IMHA?

Answer 121

immunoglobulin-mediated type II hypersensitivity reaction causing extravascular hemolysis

Question 122

3

IMHA autoantibodies invovled

Answer 122

IgG, IgM, and IgA
– produced against the animal’s own red blood cell membrane antigens regardless of the age or health of the cells
– in normal scenarios, these autoantibodies regulated by suppresor T cells
– animals with IMHA have poor T cell

Question 123

Microangiopathic hemolytic anemia

what do they result in?

Answer 123

condition in which RBCs are physically damaged during circulation due to vessel occlusion, abnormal vascular morphology, or fibrin shearing.
– Ex: splenic torsion, HWD, DIC, IVCs, hemangiosarcoma

result in Schitocytes

Question 124

5

Complete blood count findings in IMHA

Answer 124

1. regenerative anemia,
2. leukocytosis with left shift,
3. lymphocytosis,
4. thrombocytopenia,
5. elevated reticulocyte percentage

Question 125

Agglutination

Answer 125

– can be seen grossly and microscopically but must be differentiated from rouleaux formation

Question 126

How to differentiate between Agglutination and Rouleaux?

Answer 126

Rouleaux disperses with saline washing
True agglutination does not

Question 127

Treatment for IMHA: Immune suppression

Answer 127

Glucocorticoids mainstay of treatment for IMHA
– positive response may still take 3-5 days
– adjunctive immunosuppressive drugs include azathioprine and the less myelotoxic/hepatotoxic but similarly acting agent mycophenolate mofetil
– cyclosporine

Question 128

Treatment for IMHA: supportive care

Answer 128

provision of adequate oxygen-carrying capacity via transfusion of RBCs
– need for transfusion based on clinical signs
– however reaching a certain level of anemia despite CS can still warrant transfusion due to likely hypoxia (< 12%)

Question 129

Anti-thrombotics for IMHA

Answer 129

– dogs with IMHA commonly euthanized due to complications from IMHA such as PTE or DIC
– anticoagulants = rivaroxiban, UF heparin
– antiplatelet therapy = clopidogrel, aspirin

Question 130

Other possible complications with IMHA

x3

Answer 130

– Gastric ulceration and erosion
– both as a result of poor oxygenation of GI tissues and due to the use of high-dose glucocorticoids
– use of proton pump inhibitors as gastric protectants is only recommended routinely when ulcers are suspected

Question 131

Other causes of immune-mediated hemolytic anemia

Answer 131

transfusion reactions and
neonatal isoerythrolysis result from immunologically mediated but normal attack against RBCs.
– in dogs subsequent transfusions may result in hemolysis

Question 132

Feline neonatal isoerythrolysis

Answer 132

Type A or type AB kittens born to type B queens can develop hemolytic anemia after absorption of alloantibodies via colostrum.

Question 133

Hemophagocytic histiocytic sarcoma syndromes

Clin path findings

Answer 133

– severe regen anemia with thrombocytopenia
– result in a rapidly progressive severe extravascular HA that can be confused with IMHA
– Despite HA, the spherocytosis or autoagglutination typical of IMHA is absent and affected dogs are Coombs negative
– hyperbilirubinemia with hypoalbuminemia and hypocholesterolemia are commonly identified.

Question 134

Platelet aggregation

what does it need to occur?

Answer 134

In the presence of thrombin, platelets change shape and develop pseudopods that allow them to intertwine with each other.
– platelets squeeze together to form a primary hemostatic plug

Question 135

Thrombin Definition

Answer 135

an enzyme in blood plasma which causes the clotting of blood by converting fibrinogen to fibrin
– essential product of secondary hemostasis
– end‐result is a stable fibrin clot

Question 136

Thrombin actions

Answer 136

– stimulates platelets and endothelial cells to enhance clot formation

– affects the natural inhibitors of coagulation, causing consumption of antithrombin (AT) and protein C

Question 137

Fibrinogen

what does it become and how?

Answer 137

a soluble plasma protein present in blood
– from which fibrin is produced by the action of the enzyme thrombin.

Question 138

Fibrin

Answer 138

an insoluble protein formed from fibrinogen during the clotting of blood.
– It forms a fibrous mesh that impedes the flow of blood by keeping platelets in place

Question 139

Primary hemostasis definition

Answer 139

activated platelets form a platelet plug in minutes

Question 140

Secondary hemostasis definition

what initiates it?

Answer 140

reinforcement of the frail platelet plug with fibrin strands occurs within hours
– Factor VII and tissue factor (factor III) are considered the main initiator of secondary hemostasis.

Question 141

Fibrinolysis definition

Answer 141

the enzymatic breakdown of the fibrin in blood clots

Question 142

Primary hemostasis pathway

where does it take place?
how is a clot formed?
what actions do platelets have?

Answer 142

Takes place between the injured vessel wall and platelets.
→ results in the formation of a platelet plug at the site of a vascular injury; activated platelets, along with endothelial cells = form an unstable fibrin clot.
→ This platelet plug fulfills multiple purposes:
* provides a physical barrier to inhibit loss of blood
* provides membrane surfaces as binding sites for procoagulant enzymes that aid the formation of thrombin in secondary hemostasis.
→ In primary hemostasis, following platelet adherence, platelets undergo conformational changes and release substances that stimulate platelet aggregation.
→ Aggregated platelets constitute the primary hemostatic plug.

3 phases: 1 Initiation, 2 Extension, Stabilization

Question 143

Main mechanism for primary hemostasis

Answer 143

platelets

Question 144

Primary Hemostasis

1 Initiation

Answer 144

binding of platelets to collagen and vWF triggers platelet activation

Question 145

Primary Hemostasis

2 Extension

Answer 145

Extension of the adhered platelet monolayer on injured vessels undergoes further activation resulting in secretion, shape change, formation of the procoagulant membrane, and integrin activation.

Question 146

Primary Hemostasis

Stabilization

Answer 146

forces generated by contraction of actin/myosin filaments in platelet further strengthen platelet-to-platelet interactions by narrowing the gap between platelets and preventing the diffusion of activators away from the platelets, hence fostering a local procoagulant microenvironment

Question 147

Secondary hemostasis pathway

Answer 147

→ formation of fibrin in and around the primary plug, stabilization of the platelet clot through the generation of thrombin (factor II), and activation of the fibrinolytic system.
→ known as the coagulation cascade.
two pathways for the activation of the coagulation cascade: intrinsic and extrinsic.

Question 148

main initiator of secondary hemostasis

Answer 148

Factor VII and tissue factor (TF; Factor III)
– Factor VII synthesized in liver

Question 149

Intrinsic pathway

What does it work on?
What factors does it involve?

Answer 149

surface activated, operating strictly with components present in the blood
Factors XII, XI, IX, VIII

12-11 = 1, 9-8 = 1

Question 150

Extrinsic pathway

What does it work on?
What factors does it involve?

Answer 150

requires tissue factor for activation
Factors: III (TF), VII

Question 151

Where are clotting factors produced?

Answer 151

All coagulation factors are produced in the liver, with the exception of factor VIII

Question 152

What is factor IV?

Answer 152

Calcium
– required for most reactions and is the reason why calcium chelators such as citrate and ethylenediaminetetra‐acetic acid (EDTA) are used for blood collection
– Binding agent for Vit K dependent factors

Question 153

Which factors require Vit K?

Answer 153

Factors: II, VII, IX, X

2+7 = 9 then 10

Question 154

What initiates the coag cascade?

Answer 154

exposure of tissue factor (TF) which is also known as factor III

Question 155

Coag Cascade pathway

Answer 155

– TF is exposed from vascular endothelial cell damaged but also contributed by activated monocytes and inflammatory mediators.
– After being exposed, TF binds to factor VII → forms a thrombin complex that initiates the extrinsic cascade.
→ small amount of thrombin produced activates clotting factor XI to factor XIa,
→ which activates factors V, VIII, and XIII.
– Through processes, thrombin formation is maintained.

Question 156

Fibrinolytic system

Answer 156

consists of plasminogen and many other substances that convert plasminogen to its active form, plasmin

Question 157

Plasmin

Answer 157

Plasmin is ultimately responsible for dissolution of the fibrin clot.
– exists in circulation as the proenzyme plasminogen.
– Plasmin’s cleavage of fibrin releases fibrin degradation products (FDPs) and D‐dimers that are used to monitor fibrinolytic activity and are clinical markers for DIC
– converted from Plasminogen + t-PA/u-PA

Question 158

Plasminogen

Answer 158

– produced in Liver
– present in tissues in kidney and brain
– important role in Fibrinolysis
Plasminogen is activated and convert to plasmin primarily by tissue‐type plasminogen activator (t‐PA) and urokinase‐type plasminogen activator (u‐PA)

Question 159

tissue‐type plasminogen activator (t‐PA)

Answer 159

produced by endothelial cells and is essential to intravascular fibrinolysis
– used as Thrombolytic agent, second generation agent

Question 160

α2 anti-plasmin

Answer 160

– inhibits plasmin and therefore fibrinolysis
– produced by liver
– binds plasminogen and interferes with the fibrin–plasminogen interaction because both involve the same lysine binding site

Question 161

plasminogen activator inhibitor 1 (PAI-1)

Answer 161

– important inhibitor of fibrinolysis
– main source for PAI-1 is platelets

Question 162

urokinase

Answer 162

– urinary-type plasminogen activator
– released upon activation of injury with t-PA
– converts plasminogen to plasmin
– also commercially made for treatments as Thrombolytic agent, first generation

Question 163

Thrombin-activatable fibrinolysis inhibitor (TAFI)

Answer 163

TAFI,
– produced by the liver
– activated by the thrombin/thrombomodulin complex and by plasmin
– removes the C-terminal lysine residues and therefore inhibits fibrinolysis.

Question 164

Inhibitors of Fibrinolysis

x3

Answer 164

– A2- antiplasmin
– plasminogen activator inhibitor 1 (PAI-1)
– Thrombin-activatable fibrinolysis inhibitor (TAFI)

Question 165

Thrombolytic agents

Streptokinase

Answer 165

– Streptokinase is considered a first-generation thrombolytic
– readily binds circulating plasminogen, potentially inducing a systemic lytic state
– Streptokinase has a longer half-life compared to t-PA
– extracellular protein produced by streptococci that binds plasminogen in a 1:1 complex promoting the conversion to plasmin

Question 166

Indications for thrombolytic agents

Answer 166

–acute PTE
– deep vein thrombosis (DVT), acute myocardial infarction (AMI), and acute ischemic stroke (AIS) in people

Question 167

Where is Fibrin degradation?

Answer 167

products are ultimately removed from circulation by the liver

Question 168

Relationship between Thrombin and plasmin?

Answer 168

– thrombin affects numerous phases of hemostasis, and plasmin opposes these actions.
– Thrombin “coagulates” and plasmin then “derogates.”

Question 169

immunothrombosis

Answer 169

– active initiator of thrombosis through the activation of neutrophils, monocytes, and dendritic cells to propagate clot formation and activate platelets
– can become dysregulated in diseases resulting in excessive clot formation or consumptive coagulopathy

Question 170

Effect of thrombin on platelets

Answer 170

1. release of platelet granule contents,
2. irreversible platelet aggregation,
3. platelet consumption (which can result in thrombocytopenia)

Question 171

How is Plasmin activated?

Answer 171

Thrombin activates its opposing enzyme plasmin through activation of plasminogen

Question 172

Buccal Mucosal Bleeding Time

what does it assess?
what is normal for dog vs cat?
what does an abnormal result reflect?

Answer 172

used to assess primary hemostasis and platelet function
– normal time for a dog to form a visible clot in the incision is < 4 minutes.
– normal time for a cat to form a visible clot in the incision is < 2–2.5 minutes
– prolonged BMBT could reflect thrombocytopenia, von Willebrand’s disease, or thrombocytopathy

Question 173

Activated Clotting Time

What does this assess? which pathways and how?
What does an abnormal result mean?

Answer 173

– used to assess secondary hemostasis and specifically screen for abnormalities in the intrinsic and common pathways by measuring the time for a fibrin clot to form
– A prolonged ACT can be due to deficiencies in intrinsic or common pathway factors or severe thrombocytopenia (e.g. < 10 000/μL)

Question 174

Prothrombin Time

Answer 174

used to assess secondary hemostasis and specifically measures the extrinsic and common pathway factors.
– does not require a normal platelet count.
– Only a significantly prolonged PT is a relevant clinical finding → require elevations of 1.25–1.5 times the high end of normal before considering a PT truly prolonged.

Question 175

4

A prolonged PT but normal activated partial thromboplastin time (aPTT) may occur with

Answer 175

1. factor VII deficiency from warfarin therapy,
2. inherited factor deficiency,
3. early vitamin K deficiency or antagonism,
4. DIC.

Question 176

Which coagulation test becomes prolonged first with anticoag-based rodenticide toxicity?

Answer 176

due to short half‐life of factor VII (~6 hours in the dog), the PT is the first test to become elevated in patients with anticoagulant‐based rodenticide toxicity

Question 177

What may cause spurious prologed PT results?

Answer 177

Overdilution of plasma with citrate will spuriously prolong PT (and aPTT) test results.
– may also occur in severely anemic animals

Question 178

Activated Partial Thromboplastin Time (aPTT)

Answer 178

– used to assess secondary hemostasis and specifically measures the intrinsic and common pathway factors
– similar to but more specific than the ACT test.
– does not require a normal platelet count
– elevations of 1.25–1.5 times the high end of normal before considering an aPTT truly prolonged

Question 179

A prolonged aPTT with a normal PT suggests:

Answer 179

defect in the intrinsic pathway (e.g. factors XII, XI, IX, VIII)

Question 180

prolonged PT and aPTT together can occur with:

Answer 180

multiple factor deficiencies; affecting both factor VII, extrinsic, intrinsic or common pathway factor deficiencies.
– including:
* inherited factor X deficiency or
* acquired defects such as vitamin K deficiency or antagonism,
* DIC
* liver failure
* hypofibrinogenemia

Question 181

What drug will cause aPTT to be prolonged without affecting PT?

Answer 181

Treatment with unfractionated heparin will prolong the aPTT without affecting the PT

Question 182

What diseases will cause prolonged aPTT without affecting PT in dogs?

Answer 182

1. Hemophilia A (factor VIII deficiency)
2. Hemophilia B (factor IX deficiency)

Question 183

Protein Induced by Vitamin K Antagonism Test (PIVKA)

Answer 183

rare test used to assess vitamin K‐dependent coagulation factors (i.e. II, VII, IX, X)
– factors are produced in the liver initially as non‐functional precursors and then become active in the presence of vitamin K
– w/o Vit K there is an abundance of inactive precursors that can be measured

Question 184

Thromboelastography (TEG) and Thromboelastometry (ROTEM) tests

Answer 184

used to provide global assessment of the dynamics of clot development, stabilization, and dissolution
– these tests evaluate clot initiation, amplification, propagation, and fibrinolysis, including the interaction of platelets with proteins of the coagulation cascade

Question 185

What does each value mean?

Answer 185

1. Reaction time (R): The time to onset of fibrin formation (or when the curve deviates by more than 2 mm from midline).
2. K: The time it takes for the curve to deviate 20 mm from the centerline (rate of fibrin formation).
3. α: The angle between the time point K and the centerline (rate of fibrin formation).
4. Maximum amplitude (MA): Strength of the clot.

Question 186

Fibrin Degradation Product (FDP)

Answer 186

occasionally used in dogs and cats to assess a patient’s fibrinolytic activity
– FDP, specifically fragment D and E, are end‐products of cleavages from fibrinogen and fibrin
– rise in many conditions, including DIC, thrombosis, hemorrhage, or any condition causing decreased clearance of FDPs by the liver and monocyte‐macrophage system (e.g. liver failure)

Question 187

D‐Dimer Test

Answer 187

used in dogs and cats to assess fibrinolytic activity
– specific plasmin‐mediated breakdown product of cross‐linked fibrin.
– more specific than FDP
– increases whenever there is activation of thrombin to form cross‐linked fibrin and fibrinolysis.
– Ex: thrombosis, DIC, surgical wound healing, neoplasia, hemorrhagic effusions, and fibrinolysis

Question 188

Disseminated Intravascular Coagulation definition

Answer 188

– acquired syndrome characterized by intravascular activation of coagulation leading to generalized coagulopathy.
– can originate from damage to the microvasculature which, if sufficiently severe, can lead to thrombosis and organ dysfunction.
– endothelial damage, platelet activation, or a release of tissue procoagulants

Question 189

DIC Pathophysiology

Answer 189

initial activation from proinflammatory cytokines → intravascular fibrin formation, microvascular thrombi and organ dysfunction, consumptive intravascular coagulopathy and thrombocytopenia
→ ultimately widespread hemorrhage

Question 190

10

Disease processes that can lead to DIC

Answer 190

1. sepsis, shock,
2. immune‐mediated disease,
3. envenomation,
4. burns,
5. heat stroke,
6. trauma,
7. pancreatitis,
8. malignancy,
9. severe hepatic failure,
10. major surgery

typically acute

Question 191

What can cause “chronic DIC”?

Answer 191

hemangiosarcoma in dogs

Question 192

DIC diagnosis

x5 clin path findings

Answer 192

no single test for diagnosing DIC and several hematological findings must be used in conjunction to support a presumptive diagnosis
1. regenerative hemolytic anemia,
1. hemoglobinemia,
1. red cell fragmentation (schistocytosis),
1. neutrophilia with a left shift,
1. and thrombocytopenia

Question 193

7

Other laboratory abnormalities associated with DIC:

Answer 193

1. decreased fibrinogen,
2. prolonged thrombin time,
3. prolonged PT,
4. prolongation of aPTT,
5. production of FDPs,
6. elevated D‐dimers,
7. decreased concentrations of AT

Question 194

DIC treatment

x4

Answer 194

1. fresh frozen plasma
2. cryoprecipitate therapy for fibrinogen supplementation
3. Unfractionated or low molecular weight heparins can also be considered in patients that are not actively bleeding
4. Platelet transfusion for thrombocytopenia and factor IIa administration

Question 195

Acquired Coagulopathy causes

Answer 195

caused by production defect:
liver failure,
vitamin K deficiency as an activation defect

Question 196

Acquired Coagulopathy: Liver Failure

Answer 196

liver is the primary site of coagulation factor synthesis
→ diseases that cause liver insufficiency or failure,
→ acute liver failure, portosystemic shunt, or cholestasis, will subsequently cause factor deficiency or dysfunction

Question 197

Acquired Coagulopathy: Vit K deficincies

Answer 197

Vitamin K is essential to coagulation and liver disease is associated with vitamin K deficiency due to impaired intrahepatic recycling
– conditions such as infiltrative bowel disease, biliary obstruction, or pancreatic insufficiency cause decreased vitamin K absorption in the intestinal tract.
– rodenticide toxicity induces severe coagulopathy caused by vitamin K deficiency.

Question 198

Von Willebrand’s Disease

Answer 198

most common inherited bleeding disorder of dogs
– result of a deficiency in von Willebrand’s factor (vWF) a large, multimeric glycoprotein found in plasma, platelet granules, endothelial cells, and subendothelial connective tissue.

Question 199

Where is vWF made?

Answer 199

synthesized by the vascular endothelium and megakaryocytes, and is necessary for normal platelet function.
– vWF needed for platelet adhesion

Question 200

vWF mechanisms

3

Answer 200

1. mediates platelet adhesion to exposed endothelium after vascular injury,
2. promotes platelet aggregation under high shear conditions,
3. serves as a carrier for coagulation factor VIII.

Question 201

vWF deficiency effects

Answer 201

– experience a range of hemorrhagic states ranging from mild bleeding to life‐threatening hemorrhage following injury or surgery
– since vWD is a platelet function defect, all coagulation tests, including the platelet count, will be normal except those that assess primary hemostasis and require functional platelets, such as the BMBT.

Question 202

most common form of vWD

Answer 202

type 1 in which vWF levels are notably decreased
– autosomal dominant and is common in certain breeds such as the doberman
– Dogs are usually non‐clinical until a surgical or trauma event, in which they may experience prolonged bleeding

Question 203

What may exacerbate bleeding tendencies in dogs with vWD?

Answer 203

Hypothyroidism

Question 204

3 examples

vWF deficiency treatment

which one is preferred?

Answer 204

– In emergencies: transfusions with fresh whole blood or fresh frozen plasma may stabilize a bleeding patient with vWD
– cryoprecipitate contains factor VIII, vWF, fibrinogen, and fibronectin, is preferred for the management of patients with vWD
– desmopressin (DDAVP) is a synthetic vasopressin analogue that through the V2 receptor results in the release of body vWF stores

Question 205

Epistaxis

common causes #10

Answer 205

hemorrhage originating from the nose can result from intranasal or extranasal systemic causes
Common causes of epistaxis include:
1. coagulopathy,
1. platelet disorder such as ITP,
1. systemic hypertension,
1. nasal tumor,
1. nasal foreign body,
1. nasal trauma,
1. oronasal fistula,
1. immune‐mediated rhinitis,
1. fungal infection of the nose,
1. DIC.

Question 206

Acute Traumatic Coagulopathy

Answer 206

occurs in patients with severe trauma, known as acute traumatic coagulopathy (ATC)
– condition of hypocoagulation and hyperfibrinolysis that occurs in the absence of clotting factor consumption

Question 207

Acute Traumatic Coagulopathy

ATC: Pathophysiology

What is the key component?

Answer 207

– Trauma induces endothelial injury and hypoperfusion, leading to fibrin formation.
– Enhanced fibrinolysis then occurs, leading to a hypocoagulable state
– consumption of fibrinogen and fibrinolysis by the action of plasmin is a key component of ATC

Question 208

Acute Traumatic Coagulopathy

ATC coagulopathy tests

Answer 208

expected to have a prolonged PT, aPTT,
and decreased maximum amplitude (MA) on thromboelastography (TEG)

Question 209

Lymphatic System Disorders

Answer 209

divided into those of internal organs and those of the peripheral lymphatics
– lymphangitis and lymphadenitis and are typically secondary to local inflammation, involving the skin, mucous membranes, or the subcutaneous tissues.

Question 210

Lymphangitis causes and effects:

Answer 210

result from bacterial, fungal, inflammatory, or adjacent neoplasia
– lymphatics become affected and potentially occluded as they drain inflammatory by‐products from the tissues.
– Pyrexia, anorexia, and leukocytosis may be present with acute lymphangitis

Question 211

Lymphadenitis

Answer 211

–lymph nodes, micro‐organisms are phagocytized, destroyed, or inactivated, which may cause the node to become enlarged or obstructed.

Question 212

Lymphedema

Answer 212

result of accumulation of fluid in the interstitial space secondary to abnormal lymphatic drainage.
– categorized as either primary or secondary

Question 213

Primary lymphedema

Answer 213

– capillary filtration exceeds resorption capacity; the protein‐rich fluid causes a high osmotic gradient and exacerbates fluid accumulation.
– refers to an abnormality of the lymphatic vessels or lymph node

Question 214

Secondary lymphedema

Answer 214

– refers to conditions caused by a disease in the lymphatic vessel or lymph node that actually began in a different tissue.
– more common than primary lymphedema, occurring as a result of neoplasia, trauma, parasites, or infection.

Question 215

Hypercoagulability or thrombophilia definition

Answer 215

propensity for inappropriate thrombus formation
– balance has been tipped in favor of coagulation, which may arise due to a variety of derangements
–result of inherited or acquired causes

Question 216

Mechanisms of thrombophilia

Glycocalyx review

Answer 216

endothelial barrier is composed of vascular endothelial cells (ECs) and a thin carbohydrate-rich luminal glycocalyx that localizes many key anticoagulant elements.

Question 217

Glycocalyx is composed of

x3

Answer 217

1. network of negatively charged glycosaminoglycans (GAGs)
2. proteoglycans
3. glycoproteins.

Question 218

Proteoglycans:

Answer 218

– facilitates the binding of antithrombin (AT)
– 50-90% made up of Heparan sulfate
– increased thrombin inhibition

Question 219

Other mechanisms of glycocalyx

Answer 219

serves as a mechanoreceptor, sensing altered blood flow and releasing nitric oxide (NO) during conditions of increased shear stress to maintain appropriate organ perfusion.

Question 220

Nitric Oxide role in the inflammatory response

x2

Answer 220

1. leukocyte adhesion to the endothelium
2. inhibition of platelet aggregation.

Question 221

Glycocalyx mechanisms with inflammation

Answer 221

inflammation decreased synthesis of the GAGs that comprise the glycocalyx,
→ decreasing the function of the anticoagulants that rely on the glycocalyx (e.g., TM and protein C, TFPI)
→ glycocalyx also buffers ECs by preventing the binding of inflammatory cytokines to cell surface receptors.

Question 222

5

Endothelial Cells can be activated by

Answer 222

1. TNF-α,
2. bradykinin,
3. thrombin,
4. histamine,
5. vascular endothelial growth factor

Question 223

Endothelial disruption exposes

Answer 223

procoagulant substances such as tissue factor [(TF) fIII] to the circulating blood.

Question 224

coagulation in vivo is initiated through

Answer 224

interaction of Tissue Factor (TF) fIII with activated factor VII (fVIIa)

Extrinsic pathway

Question 225

Role of platelets as a pro-coagulant element

Answer 225

– serve as a source of procoagulant membrane.
–platelets undergo a shape change and shuffle negatively charged phospholipids
– These provide the catalytic surface essential for the tenase and prothrombinase complexes for the propagation phase of clot formation

Question 226

Reltionship between vWF and Endothelial Cells

Answer 226

when ECs become injured, they release ultra-large multimers of vWF (UL-vWF) from the Weibel-Palade bodies
– needed for platelets to attach to subendothelium collagen

Question 227

Microparticles (MPs)

Answer 227

– circulating small vesicles (membrane blebs) released from activated or apoptotic cells
– derived from platelets, ECs, leukocytes, erythrocytes, and neoplastic cells.
– can express TF on their surface,

Question 228

neutrophil extracellular traps (NETs)

Answer 228

released from activated neutrophils
– consist of nuclear contents, including DNA, histones, and some extranuclear proteins
– their role is to immobilization and sequestration of microbial elements as a response to septicemia;
– also released by PAMPs interaction
– can be procoagulant

Question 229

Endogenous anticoagulants role

x3 examples

Answer 229

essential to localizing coagulation to the site of vascular insult
– simultaneous activation of anticoagulant factors, even during clot propagation, helps to prevent a procoagulant state or the dissemination of coagulation
– examples: Antithrombin, protein C, and Tissue factor pathway inhibitor (TFPI)

Question 230

Antithrombin (AT)

Answer 230

– primarily acts to inhibit thrombin and factor Xa
– typically decreased in systemic inflammation or critical illness via 3 pathways:
1. consumption (due to thrombin generation),
1. decreased production (negative acute phase protein), or
1. degradation by NE.

Question 231

protein C system

Answer 231

important inhibitor of factors Va and VIIIa
– less functional during systemic inflammation due to decreased hepatic synthesis of proteins C and S

Question 232

Tissue factor pathway inhibitor (TFPI)

Answer 232

released primarily from ECs and acts to inhibit fVIIa-TF complexes and factor Xa (fXa);
– or all components of the TF- or extrinsic pathway
– Other sources of TFPI include platelets, mononuclear cells, vascular smooth muscle and cardiac myocytes, fibroblasts, and megakaryocytes

Question 233

Fibrinolysis

Answer 233

– final protective step to prevent vascular occlusion → fibrin clot must be dissolved to allow the reestablishment of blood flow
– Thrombi remaining in the macro- or microvasculature can impair organ perfusion and oxygen delivery, and may provide a second insult that leads to MODS

Question 234

Basic Diagnostics for Hypercoagulability

Answer 234

– Prolongations of aPTT/PT and decreased platelet count
– due to consumption of platelets and coagulation factors following unregulated thrombin generation

Question 235

Platelet count changes with consumptive coagulopathy

Answer 235

drop in circulating platelet count accompanied by a ≥20% prolongation in baseline aPTT in an at-risk patient should raise concern of a consumptive coagulopathy

Question 236

Advanced Diagnostics for hypercoagulopathy

Answer 236

1. rise in procoagulant elements (e.g., MPs, fV or VIII activities, or fibrinogen),
2. decrease in endogenous anticoagulants (e.g., AT, protein S and C, or TFPI),
3. decrease in fibrinolysis (e.g., decreased tPA; increased α2-antiplasmin, PAI-1, TAFI).

Question 237

SIRS

coagulopathy associated with systemic inflammation

Answer 237

involves:
1. increased expression of TF,
1. activation of ECs and disruption of the glycocalyx,
1. impairment of anticoagulant systems,
1. reduction of fibrinolysis.

Question 238

SIRS

glycocalyx shedding and EC activation in the face of inflammation:

Answer 238

– leads to compromised production of local regulators (e.g., NO)
– increased expression of procoagulant molecules (e.g., UL-vWF or TF)
– and adhesion molecules (e.g., P-selectin) with derangement of anticoagulant defenses.

Question 239

SIRS

thrombomodulin [TM] dysfunction from inflammation

Answer 239

may be damaged by multiple mechanisms (leading to decreased activation of protein C),

Question 240

SIRS

Antithrombin dysfunction from inflammation

Answer 240

– Antithrombin is less effective due to both decreased concentrations and impaired interactions with an endothelium that has been layered of GAGs.

Question 241

Potential Lab findings in dogs with sepsis

Answer 241

– significantly prolonged aPTT and/or PT, along with higher FDP and D-dimer
– lower protein C and AT activities → consumptive
– TAFI is increased

Question 242

Hypercoagulopathy

thrombophilia associated with PLN

Answer 242

– increases in fVIII activity and fibrinogen concentration
– Platelets are hyperaggregable and exhibit increased markers of activation
– AT activity was lower in PLN

Question 243

Hypercoagulability with IMHA

Answer 243

– low AT activity, elevated fibrin[ogen] degradation product [FDP], and D-dimer, and markedly elevated fibrinogen concentration
– TEGs increased MA (clot strength)
– increased concentrations of circulating cfDNA due to NET formation from neutrophil response to hypoxia/inflammation/free heme exposed
– Circulating TF contributes to procoagulant state

Question 244

Hypercortisolemia (hyperadrenocorticism) risk of hypercoagulopathy

Answer 244

– no consistent cause or definable procoagulant state has been identified
– pts can present with thrombic conditions
– study found increased activities of factors V, XI, AT, and elevated plasminogen
– TEG changes consistent with procoagulant state

Question 245

Cardiomyopathies risk for hypercoagulopathy

Answer 245

– Arterial thromboembolism (ATE) in cats
– Left atrial (LA) and LA appendage enlargement associated withprocoagulant phenotypes; increased TF and vWF
– 50% of cardiomyopathic cats with spontaneous echocardiographic contrast (or “smoke”) with or without a LA thrombus
– cats with thyrotoxic cardiomyopathy, platelets were less responsive to ADP and more responsive to collagen for aggregation

Question 246

Coagulopathies with Neoplasia

3 examples

Answer 246

– dogs with hemangiosarcoma, mammary carcinoma, and adenocarcinoma of the lung
– TF has been identified on malignant cells and in the tumor vasculature, and these cells have the ability to shed TF-bearing MPs
– distant metastasis commonly have higher fibrinogen and D-dimer levels than locally invasive or noninvasive disease
– canine patients with carcinomas, thrombocytosis and hyperfibrinogenemia were more common
– dogs with untreated mammary carcinoma included hyperfibrinogenemia, elevated fV, and decreased fVIII activities

Question 247

2 types and their examples

Antithrombotic therapy definition

Answer 247

consist of drugs that inhibit platelet function (e.g., aspirin or clopidogrel) or drugs that facilitate the inhibition of thrombin (e.g., unfractionated heparin (UFH) or low molecular weight heparin [LMWH])

Question 248

Hypercoagulopathy definiton

Answer 248

two or more of the following:
1. coagulation factor excess (i.e., high fibrinogen concentration or factor VIII coagulant activity),
1. inhibitor deficiency (i.e., low antithrombin activity),
1. thrombin generation (i.e., high thrombin-antithrombin complex and d-dimer concentrations)

Question 249

complications following thrombolysis

Answer 249

hyperkalemia, acute kidney injury, clinical bleeding, and coagulation abnormalities.

Question 250

commonly prescribed antiplatelet medications

Answer 250

Aspirin and clopidogrel

Question 251

Aspirin MOA

Answer 251

acts on the arachidonic acid pathway and irreversibly inhibits the cyclooxygenase pathways

Question 252

Clopidogrel MOA

Answer 252

– is a thienopyridine that selectively inhibits ADP-induced platelet aggregation but has no direct effects on arachidonic acid metabolism
– requires hepatic biotransformation to produce the active metabolite.

Question 253

Commonly used anticoagulants

Answer 253

warfarin,
unfractionated heparin (UFH),
low-molecular weight heparin (LMWH)

Question 254

unfractionated heparin (UFH)

Answer 254

– pharmacokinetics of UFH are quite variable and depend on the proportion of heparin molecules large enough to bind thrombin
– therapy must be monitored closely and titrated to effect to avoid under treatment or bleeding complications
–

Question 255

Target value when using UFH

Answer 255

use the aPTT, with an accepted therapeutic target range of 1.5 to 2.5 times the normal control aPTT value.

Question 256

low-molecular weight heparin (LMWH)

Answer 256

– LMWH has reduced anti-IIa activity relative to anti-Xa activity and also has better predictable pharmacokinetic properties.
– standard doses has a minimal effect on aPTT
– One potential benefits is its reduced affinity for binding to plasma proteins or cells compared with UFH, leading to a more predictable dose response relationship and longer half-life
– 100% bioavailability after subcutaneous administration

Question 257

thrombocytopenia

Answer 257

– common hematologic abnormality can be caused by:
decreased production, increased consumption, increased destruction, and sequestration.
– can be acquired or congenital

Question 258

Thrombocytopenia

Examples of Increased consumption

Answer 258

1. Disseminated intravascular coagulation
2. Acute/severe blood loss
3. Platelet activation/aggregation
4. Sepsis
5. Thrombotic microangiopathies
6. Massive thrombosis

Question 259

Acquired intrinsic platelet dysfunction

Answer 259

• Platelet inhibitors
• Uremia
• Synthetic colloids
• Myeloproliferative disease
• Pit viper envenomation
• Disseminated intravascular coagulation
• Trauma-induced coagulopathy

Question 260

Thrombocytopenia

spontaneous hemorrhage can occur when

Answer 260

– platelet count is < 30 × 109/ml
– fatal = platelet is < 10 × 109/ml

Question 261

Thrombocytopenia

Examples of Iatrogenic causes

Answer 261

1. Hemodialysis
2. Postcardiopulmonary bypass
3. Hemodilution including massive transfusion
4. EDTA-mediated

Question 262

Thrombocytopenia

Examples of Increased destruction causes

Answer 262

Primary immune mediated thrombocytopenia
Secondary immune mediated thrombocytopenia
* Anaplasmosis
* Babesiosis
* Ehrlichiosis
* Neoplasia
* RMSF
* Dirofilariasis
* Vaccination
* Drug reaction

Question 263

Thrombocytopenia

Examples of Decreased production causes

Answer 263

• Bone marrow disease
• Chemotherapy/Radiation
• Immune Mediated

Question 264

Thrombocytopenia

Examples of Increased sequestration causes

Answer 264

• Splenic torsion
• SIRS
• Hypersplenism
• Severe hypothermia

Question 265

sepsis-mediated thrombocytopenia

Answer 265

result of:
1. increased platelet consumption due to direct microbial–platelet interactions,
1. platelet–leukocyte aggregate formation,
1. and increased platelet sequestration secondary to microvascular thrombosis.

Question 266

Which bacteria cause platelet aggregation?

Answer 266

– Escherichia coli and Streptococcus can directly interact with platelets through a variety of molecular interactions leading to platelet activation and aggregation.

Question 267

Platelet interactions with neutrophils

Answer 267

Once activated, platelets interact with circulating neutrophils to form platelet-neutrophil aggregates and neutrophil extracellular traps (NETs),

Question 268

Uremia-associated platelet dysfunction

Answer 268

– due to defects in platelet adhesion, secretion, and aggregation
– uremia may directly alter the function of vWF producing a phenotypic resemblance of type II von Willebrand disease (vWD) in humans
– defects in vWF may manifest more profoundly in the microcirculation, where shear forces are high

Question 269

Liver disease associated thrombocytopenia and platelet dysfunction.

Answer 269

– Decreased platelet aggregation in response to collagen and arachidonic acid has previously been documented in dogs with liver disease, but its underlying mechanism is unknown

Question 270

Drug-associated platelet dysfunction: Nonsteroidal Antiinflammatory Drugs

Answer 270

Conflicting data in the literature. May exacerbate platelet dysfunction in animals with increased thrombopoiesis.

Question 271

Drug-associated platelet dysfunction: Selective phosphodiesterase (PDE) inhibitors:

Answer 271

Pimobendan: vitro antiplatelet effects seen at 1000x fold higher than clinically achievable concentration
Sildenafil: Potentiation of platelet inhibition with concurrent use of nitric oxide donors

Question 272

Drug-associated platelet dysfunction: Nitric Oxide Donors

Answer 272

Sodium nitroprusside (T)
Nitroglycerin (T)

Question 273

Drug-associated platelet dysfunction: Antithrombotics

Answer 273

Heparin
Factor X inhibitors:
Rivaroxaban
Apixaban
– synergistic inhibitions of tissue factor-mediated platelet aggregation and platelet-dependent thrombin generation occur when given with antiplatelet drugs

Question 274

Drug-associated platelet dysfunction: Antimicrobials

Answer 274

Beta-lactams: Dose- and time-dependent effects on platelet function
Cephalosporins

Question 275

Which COX enzyme do platelets express?

Answer 275

Platelets express mainly the isoform, COX-1, which is irreversibly inhibited by acetyl salicylic acid, thereby modulating the biosynthesis of thromboxane A2 (TXA2) and prostaglandin.

Question 276

platelet dysfunction secondary to hydroxyethyl starch (HES) administration

Answer 276

1. binding of colloidal molecules on the extracellular domains of integrin αIIbβ3 or glycoprotein 1b inhibits their conformational changes and, subsequently, platelet aggregation and adhesion.
2. Second, binding of colloidal molecules also interferes with factor VIII/vWF complex formation causing their accelerated elimination.
3. slowly degradable HES may further exert its inhibitory effects in platelets by interfering with intracellular signaling function.

Question 277

Congenital platelet disorders

Answer 277

– commonly result from inherited mutations in one or more genes causing platelet dysfunction or hyperactivity

Question 278

Congenital von Willebrand disease

Answer 278

– is not an intrinsic platelet disorder
– deficiency or dysfunction in vWF, which is primarily produced by endothelial cells, results in abnormal platelet adhesion and aggregation in high shear environment
– Type 1 vs Type 2

Question 279

Type 1Congenital von Willebrand disease

Answer 279

– autosomal recessive disorder caused by mutations in the vWF gene
– commonly reported in Doberman Pinschers,

Tx ; Cryoprecipitate, Desmopressin

Question 280

Type 2 vWD

Answer 280

– qualitative abnormalities in vWF and is further divided into types 2A, 2B, 2M and 2N based on the mutation involved.
– can cause more severe bleeding diatheses such as spontaneous mucocutaneous bleeding

Tx : Cryoprecipitate, Desmopressin

Question 281

Type 3 vWD

Answer 281

– most severe form of vWD, has been reported in cats and select dog breeds including Chesapeake Bay Retrievers, Shetland Sheepdogs, Scottish Terriers, and Dutch Kooiker dogs.
– characterized by the complete absence of vWF, causing spontaneous mucosal bleeding and life-threatening hemorrhage following trauma or invasive procedures.

Tx : Cryoprecipitate

Question 282

Glanzmann thrombasthenia (GT)

Answer 282

– Defect in platelet receptors
– Animals with GT have prolonged buccal mucosal bleeding times, prolonged platelet closure time
– associated with a pathogenic variant in the ITAGA2B gene

Question 283

Bernard–Soulier syndrome

Answer 283

– rare disorder characterized by macrothrombocytopenia and a decrease in platelet survival.
– reported in Cocker Spaniels with a mutation or variants in the GP9 gene,

Question 284

Chediak–Higashi syndrome (CHS)

Answer 284

– autosomal recessive disease that manifests as prolonged bleeding times in the presence of normal platelet concentrations
– smoke-blue Persian cats and is classified as an intrinsic platelet storage pool defect in the platelet dense granules causing impaired platelet aggregation in response to collagen

Question 285

Procoagulant phospholipids: Canine Scott syndrome (CSS)

Answer 285

– rare intrinsic platelet disorder found in related and unrelated German Shepherd dogs (GSD)
– homozygous for a mutation in the TMEM16F gene
– Affected dogs also have decreased budding of platelet microvesicles compared with nonaffected GSD
– unpredictable and severe, ranging from prolonged epistaxis and postoperative hemorrhage to spontaneous cavitary hemorrhage

Question 286

DDAVP to reduce bleeding

Answer 286

– can be given in animals with milder hemorrhage.
– most commonly used in bleeding patients to release von Willebrand factor and factor VIII from Weibel–Palade bodies in the endothelial cells
– enhances the density of platelet surface glycoprotein receptors, thereby increasing their adhesion potential

Question 287

Endothelium mechanisms in normal hemostasis

Answer 287

– antithrombotic tendency usually predominates in order for blood to circulate as a liquid → achieved by endothelium separating the cellular and plasmatic components of circulating blood from the prothrombotic substances
– also produces several antithrombotic substances, with either antiplatelet (e.g., prostacyclin, nitric oxide) or anticoagulant (e.g., antithrombin, thrombomodulin) activity

Question 288

prothrombotic tendency

Answer 288

supports blood clot formation at the site of vessel injury, thereby preventing excessive blood loss.

Question 289

Primary hemostasis components

Answer 289

Platelet number
Platelet function
vWF

Temporary Platelet Plug

Question 290

Secondary hemostasis components

Answer 290

Clotting factors
Cofactors (e.g., calcium, vitamin K)

Coag Cascade

Question 291

A prolonged PT with normal aPTT indicates

Answer 291

an issue within the extrinsic and/or common pathways (e.g., factor VII deficiency),

Question 292

aPTT prolongation with a normal PT suggests

Answer 292

issues within the intrinsic and/or common pathways (e.g., factor VIII deficiency in hemophilia A, synthetic colloid administration).

Question 293

Vitamin K-dependent factor deficiency (factors II, VII, IX, X) will result in

Answer 293

PT prolongation in excess of aPTT

Question 294

Cats with severe thrombocytopenia

Answer 294

are more likely to have bone marrow pathology
– ITP is rare in cats

Question 295

Inherited platelet dysfunction

Answer 295

– inherited instrinsic platelet dysfunction is uncommon
– inherited extrinsic platelet dysfunction = vWF

Question 296

Platelet Factor 3 (PF3)

Answer 296

pro-coagulant activity
– converts Fibinogen to Fibrin to form permanent thrombis

Question 297

Primary hemostasis; Coagulation

pro-constriction substances

x4

Answer 297

1. Serotonin (comes from plts)
2. Thromboxane (TXA2) (comes from plts)
3. Epinephrine (SANS response)
4. Fibrinopeptide B (comes from fibrinogen)

Question 298

Acquired platelet dysfunction

Answer 298

– clopidogrel or aspirin use
– NSAIDs are unlikely to induce clinically relevant platelet dysfunction at normal therapeutic doses, but platelet dysfunction may occur in animals with NSAID toxicity

Question 299

Inherited clotting factor deficiency

Question 300

Acquired clotting factor dysfunction

Answer 300

– Acquired secondary hemostatic disorders are associated with a reduced number or activity of clotting factors
– Hypoperfusion and massive transfusion of citrate phosphate dextrose adenine (CPDA)-containing blood products have been associated with severe acidemia that may impair clotting factor activity
– Vitamin K absence or antagonism
– Acute hypocalcemia

Question 301

Hemostatic dysfunction with Liver dysfunction

Answer 301

– clotting factors, endogenous anticoagulants (e.g., protein C), and fibrinolytic proteins are synthesized in the liver
– Hemostatic dysfunction typically occurs with more advanced liver disease
– Hypercoagulability has also been identified in some animals with liver disease (e.g., congenital portosystemic shunts) and could lead to serious adverse effects (e.g., portal vein thrombosis)

Question 302

Hyperfibrinolysis

Answer 302

– hyperfibrinolytic tendency can be Acute traumatic coagulopathy, liver disease, neoplasia, also purported to occur in Greyhound breeds
– Dogs with more severe hemodynamic compromise, assessed by higher plasma lactate concentrations and greater volume of plasma administered, were more likely to demonstrate a hyperfibrinolytic tendency

Question 303

Antifibrinolytic drugs

Answer 303

– Aminocaproic acid and tranexamic acid
– competitively inhibiting the lysine-binding sites on plasminogen, which prevents the conversion of plasminogen to plasmin in addition to direct inhibition of plasmin action

Question 304

Hemoglobin molecule structure

Answer 304

– composed of four subunits containing an iron atom bound to a heme group.
– enables the transport of up to four oxygen molecules at a time.
– Oxygen binds to the central iron molecule in the ferrous (Fe++) form

Question 305

Hepcidin

relationship to EPO

Answer 305

– liver produces hepcidin, a hormone that decreases the concentration of iron in the plasma.
– inverse relationship between erythropoiesis and hepcidin function

Question 306

Heinz bodies

Answer 306

– aggregates of denatured, precipitated Hb molecules within erythrocytes that form as Hb with oxidative damage is metabolized
– Aggregates of denatured globin and metabolized metHb clump into HzBs and continue to coalesce until visible, pale structures can be seen within the red blood cell cytoplasm
– Formation of metHb is thought to be necessary for the development of HzBs

Question 307

Heinz bodies and Ghost cells

Answer 307

Numerous HzBs can disrupt the membrane sufficiently to result in “ghost” cells; these are empty red blood cells with just a cell membrane and HzB remaining and are associated with oxidation-induced intravascular hemolysis

Question 308

Heinz bodies in cats

Answer 308

– normally spleen can perform pitting functions and remove the HzBs from the erythrocyte
– However, feline spleens have an ultrastructural variation and impaired ability to catch and remove oxidized RBCs
– healthy cats can have notable Heinz bodies in circulation with no clinical symptoms

Question 309

8

Causes of Heinz bodies

Answer 309

1. Allium plants (onions and garlic),
2. propylene glycol,
3. zinc,
4. methylene blue,
5. crude oils,
6. naphthalene (ingredient in moth balls)
7. repeated use of propofol in cats
8. copper storage dz in dogs

Question 310

Thrombosis

What causes this?

Answer 310

Thrombosis is usually defined as the pathological hemostasis leading to the occlusion of blood supply and subsequent ischemia.
– Thromboxane = results in thrombosis

Question 311

Thromboxane

Answer 311

Pro-constriction substance for vasoconstriction at injury site
– comes from Platelets
– promotes platelet aggregation

Question 312

Thrombus

Answer 312

Thrombus has been defined as an aggregation of platelets and fibrin with entrapped blood cells, and a thromboembolism is the migration of a thrombus.

Question 313

5

DDAVP use as Hemostatic agent

Answer 313

– endothelial release of vWF can enhance platelet aggregation and supplement vWF deficiencies
– DDAVP is indicated for patients with hemophilia A and von Willebrand disease (vWD) type I
– may be used to stop spontaneous hemorrhage or in the perioperative period to reduce the risk of hemorrhage during a surgical procedure
– may shorten bleeding times with congenital platelet disorders, although is unpredictable and dependent on the specific disorder
– shown to support hemostasis in patients with coagulopathy caused by chronic uremia and hepatic cirrhosis
– may also be beneficial with prolonged bleeding times caused by antiplatelet drug use, such as aspirin or clopidogrel.

Question 314

Yunnan baiyao

Answer 314

– Chinese herb developed in the early 1900s as a hemostatic agent for trauma
– proposed mechanism of action is that the drug stimulates platelet activation and alpha granule release based on an in vitro experiment
– also possesses antiinflammatory properties through modulation of the lipoxygenase and cyclooxygenase pathways of arachidonic acid metabolism

Question 315

Cryoprecipitate

Answer 315

– made from fresh frozen plasma
– high concentrations of vWF, factors V and VIII, and fibrinogen, and is a good option for treating patients with hemorrhage due to vWD or hypofibrinogenemia
– is not type-specific but treated with care as transfusion product

Question 316

buccal mucosal bleeding time (BMBT)

Answer 316

– screening test that appears to be sensitive for congenital thrombocytopathias and vWD
– normal is 3 to 4 minutes in dogs, < 2 min in cats

Question 317

activated clotting time (ACT)

Answer 317

– measured on whole blood (not anticoagulated)
– assesses the intrinsic and final common pathway of the traditional coagulation cascade; however, it is less sensitive to reductions in clotting factor activity

Question 318

TEG: Reaction time

Answer 318

Clot Time
– Initial fibrin formation (to amplitude of 2 mm)

Question 319

TEG: Kinetics

Answer 319

– Clot formation time
– assess Rate of clot formation (to 20 mm amplitude)
– Fibrinogen, FXIII, platelets

Question 320

TEG: Alpha angle

Answer 320

– measured in degrees
– assess Rate of clot formation and fibrin crosslinking
– FXIII, platelets, fibrinogen

Question 321

TEG: Maximum amplitude

Answer 321

– Maximum clot firmness
–assess clot strength
– Platelets, fibrinogen

Question 322

TEG: Lysis (LY30, LY60)

Answer 322

– Clot lysis
– assess Fibrinolysis
– plasmin

Question 323

Answer 323

1. hypocoagulable (A), prolonged CT/R and CFT/K and decreased α angle and MCF/MA.
2. normal (B), four standard parameters are within the reference intervals defined at our center.
3. hypercoagulable (C) shortened CT/R and CFT/K, and increased α angle and MCF/MA.
   profiles obtained by the viscoelastic tests.

Question 324

Answer 324

hyperfibrinolytic profiles
1. (A) Note that the beginning of the tracing is also in favor of hypocoagulability. Fibrinolysis occurs 18 minutes after the initiation of the test.
2. (B) Fibrinolysis occurs 27 minutes after the initiation of the test
3. (C) cat with aortic thromboembolism 10 minutes after the administration of intravenous alteplase. Fibrinolysis occurs 5 minutes after the initiation of the test with lysis indices equal to 0% and the maximum lysis equal to 100%

Question 325

Blood types

Antibodies in the body

Answer 325

an either be naturally occurring within the body or formed after sensitization to a foreign antigen
– severity of an antibody/antigen reaction depends on the titer level and affinity of the antibody in the recipient’s body
– higher the level and affinity of antibodies, the more severe the reaction

Question 326

Blood types

antibody reactions mediated by

Answer 326

immunoglobulin M (IgM) are more severe than immunoglobulin G‐mediated reactions (IgG)

Question 327

Blood types

Canine Blood Types

Answer 327

– classified using the Dog Erythrocyte Antigen (DEA) system
– currently seven recognized antigen types within the DEA system defined by the availability of international standardized antisera

Question 328

Blood types

Canine antigen sites are known as

Answer 328

– DEA 1, 3, 4, 5, 6, 7, and 8

Question 329

Blood types

DEA 1 group

Answer 329

– considered the most antigenic group.
– antigen can be classified as “weak,” “moderate” or “intermediate,” and “strong,” or negative
– vast majority of dogs lack naturally occurring alloantibodies to the DEA 1 site
– acute antigenic reaction is unlikely to occur with the patient’s first transfusion

Question 330

Blood types

mismatches always result in

Answer 330

delayed hemolytic reactions and prime recipients for severe acute reactions upon second exposure.

Question 331

Blood types

DEA 3 and 5

Answer 331

– have naturally occurring alloantibodies, and an immune response could be seen on the first transfusion

Question 332

Blood types

DEA 4

Answer 332

– unique in that approximately 99% of dogs are positive for DEA 4
– vast majority of dog transfusions are compatible for DEA 4 and do not show immune reactions
– universal donors can be DEA 4 positive or negative and still referred to as “universal” negative donors

Question 333

Blood types

neonatal isoerythrolysis

Answer 333

– a DEA 1‐negative female that has been sensitized to DEA 1 is bred to a DEA 1‐positive male. The pups that are born DEA 1 positive will likely experience a hemolytic reaction when nursing from the bitch as her colostrum contains anti‐DEA 1 antibodies
– hemolytic reaction begins as general lethargy and failure to thrive soon followed by death, and may be a component of fading puppy syndrome

Question 334

Blood types

Feline Blood Types

Answer 334

– type A, type B, or type AB
– type A is most common blood type

Question 335

Blood types

Type A cats

Answer 335

– have naturally occurring anti‐B antibodies
– anti‐B alloantibodies are fairly weak in affinity and low in titer level, causing a mild or delayed hemolytic reaction

Question 336

Blood types

Type B cats

Answer 336

– have very strong anti‐A alloantibodies and type B cats transfused with type A blood will have an acute and severe hemolytic reaction, often leading to death of the recipient

Question 337

Blood types

Type AB cats

Answer 337

– do not have any alloantibodies as they have both the A and B antigens present on their red cells, and are able to receive type A and type B red blood cell transfusions without consequence

Question 338

Blood types

Mik antigen

Answer 338

— another feline blood group described in 2007 when incompatible cross‐match results were seen between AB type‐matched blood
– Cats lacking expression of the Mik antigen can have naturally occurring antibodies against it, leading to acute hemolytic transfusion reaction upon mismatch

Question 339

Blood types

cross‐matching should always be performed in the following circumstances:

Answer 339

1. patient had a previous transfusion more than four days before
2. patient is a cat. Cats have naturally occurring antibodies against the AB group antigens they do not express.
3. patient is a breeding animal; reduce the risk of neonatal isoerythrolysis
4. patient’s transfusion history is unknown

Question 340

Blood types

Canine Blood Donors

Answer 340

– ages of one and eight years of age
– 25kg or more
– free of parasites and infectious disease
– HW free
– 11–19 mL/kg of blood can be safely taken from dogs with minimal signs of hypovolemia
– A donation frequency of every 8–12 weeks is therefore recommended to minimize detrimental effects and donation fatigue

Question 341

Blood types

Feline Blood Donors

Answer 341

– ages of one and eight years old
– be at least 5 kg in weight
– safely donate 10–15 mL/kg in a single donation
– often taken every 6–8 weeks
– cats more susceptible to hypotension and routine subcutaneous fluids at a volume of 2–3 times the blood volume removed are given

Question 342

Handling of Fresh Whole blood

Answer 342

– FWB may be held at room temperature (20°C−22°C) for up to 24 hours with no deleterious effects on RBC or PLT recovery and survival and plasma functionality

Question 343

Blood components

Cryoprecipitate vs Cryo‐poor plasma

Answer 343

Cyroprecip: contains Factor VIII, fibrinogen, vWF, no plasma protiens or non-liable factors
Cryo-poor: All Liable factors, vitamin K‐dependent clotting factors, EXCEPT VIII, XIII, and fibrinogen, contains non-liable factors and plasma protiens; LACKS vWF

Question 344

Storage duration for Cryoprecip/ Cryopoor

Answer 344

12 months

Question 345

Blood components

FFP vs Frozen Plasma

Answer 345

FFP: plasma portion of whole blood that has been separated from the RBCs via centrifugation and subsequently frozen twithin eight hours of collection
– contains Liable and Non-Liable factors, and Plasma proteins
Frozen Plasma: Plasma separated from whole blood and frozen within 24 hours
– ONLY contains Non-Liable factors and plasma proteins

Question 346

Storage duration for FFP

Answer 346

1yr, then is considered FP which can last up to 5 years

Question 347

Blood components

Platelet viability

Answer 347

– almost immediately begin to lose viability and function when refrigerated, with a 50% decrease occurring within the first 12–18 hours.
– after 72 hours, platelets are no longer present

Question 348

Blood components

Labile clotting factors

Answer 348

– factors V, VIII, and von Willebrand factor (vWf)

Question 349

blood components

non‐labile clotting factors

Answer 349

– factors II, VII, and X

Question 350

Blood components

Storage time for pRBCs

Answer 350

– can vary from 35 to 42 days, depending on the type of anticoagulant and nutrient solution used

Question 351

Blood components

Plasma proteins in FFP

Answer 351

plasma proteins = albumin and globulin

Question 352

Blood components

Platelet Products

Answer 352

– transfusions as fresh platelets in platelet‐rich plasma (PRP) or platelet concentrate (PC), cryopreserved platelets, or lyophilized platelets
– Fresh platelets have a shelf‐life of five days at room temperature
– Cryopreserved platelets can be stored up to six months at –20 °C but have low recovery (49% in dogs)
– Lyophilized platelets can be stored up to two years at 4 °C but their lifespan is observed to be only minutes

Question 353

Blood components

Ideal filter for blood transfusions

Answer 353

– gravity drip with a 170–260 µm filter

Question 354

Transfusion medicine

acute hemolytic transfusion reaction (AHTR)

Answer 354

– can be immunological vs non-immunological
– occurs within the first 30–60 minutes of the transfusion but can occur up to 24 hours after administration
– reaction is severe in felines
– retreatment with antihistamines and/or corticosteroids will not prevent a hemolytic reaction as they do not acutely suppress the production of IgG or IgM antibodies or prevent binding of IgE to mast cells

Question 355

Nonimmunologic HTRs

Answer 355

– occur due to thermal, osmotic, mechanical, or chemical factors that damage transfused RBCs, causing acute or delayed hemolysis
– Ex vivo cellular damage may occur prior to transfusion with improper or prolonged storage or bacterial contamination

Question 356

Immunologic transfusion reactions

Answer 356

– involve antigen–antibody reactions. The quantity and ability of an RBC antigen to provoke an immune response and the anti-RBC alloantibody response determine the consequences of potential RBC incompatibilities
– type II hypersensitivity reactions that occur due to major or minor RBC incompatibility

Question 357

Transfusion medicine

Delayed hemolytic transfusion reactions (DHTRs)

Answer 357

– occur more than 24 hours after the transfusion and commonly 3–5 days post transfusion
– antibody production within the recipient as a result of the presence of foreign antigens in the donor cells
– steady decrease in posttransfusion PCV over a period of 3–5 days, development of jaundice, fever, and anorexia

this is a non-infectious, immunological vs non-immunological reaction

Question 358

Tranfusion Medicine

Immune Complex Formation; Type III hypersensitivity

Answer 358

– formation and depositing of immune complexes in areas such as the glomeruli, endothelial cells, lymph nodes, and synovium,
– can lead to neutrophil migration, activation, and inflammation resulting in glomerulonephritis, vasculitis, lymphadenitis, and immune‐mediated arthritis within hours to weeks of exposure
– use of protein concentrates such as human serum albumin is suspected to cause type III hypersensitivity

Question 359

Transfusion Medicine

transfusion‐related acute lung injury (TRALI)

Answer 359

– Non‐cardiogenic pulmonary edema unrelated to circulatory overload during or hours after a transfusion
– caused by activation of neutrophils in pulmonary capillaries leading to vascular damage and pulmonary edema
– Clinical signs include respiratory distress, fever, tachycardia, and hypotension accompanied by pulmonary infiltrates

Type I and Type II

Question 360

What is TRALI most commonly associated with?

Answer 360

most commonly associated with high-plasma-volume transfusion products, although all transfusion products carry a risk

Question 361

Type 1 TRALI

Answer 361

– patients who have no concomitant risk factors for acute respiratory distress syndrome

Question 362

type II TRALI

Answer 362

reserved for those with acute respiratory distress syndrome (ARDS) risk factors or those that have existing mild ARDS and their respiratory status deteriorates in association with transfusion

Question 363

Tranfucsion Medicine

Transfusion‐associated circulatory overload (TACO)

Answer 363

– common non‐immunological transfusion complication.
– acute respiratory distress secondary to increased circulatory volume from transfusion product administration and consequent hydrostatic pulmonary edema
– Volume overload (hypervolemia) can occur from transfusing too much product or transfusing it too rapidly
– can occur within 6 hours of transfusion

Question 364

Transfusion Medicine

Citrate Toxicity

Answer 364

– Citrate is normally metabolized by the liver but in large‐volume infusions of blood products, the metabolic pathway can be overwhelmed, leading to increased plasma citrate concentration and subsequent hypocalcemia
– Pts with liver failure at higher risk

Question 365

Tranfusion Medicine

Hyperammonemia

Answer 365

– When RBCs within the unit become inactive and die, they are broken down and release potassium and ammonia as a byproduct
– As units approach their expiry date, the bag contains a higher amount of ammonia and inactive RBCs than fresher units
– hyperammonemia can possibly develop in animals with underlying hepatic disease as they are unable to fully filter out ammonia

Question 366

Tranfusion Medicine

Transfusion‐related immunomodulation (TRIM)

Answer 366

– refers to the proinflammatory and immunosuppressive effects that blood transfusions can have on a patient incited by transfused mediators, proteins, and cells involved in the immune system

Question 367

thrombopoietin

Answer 367

– produce by the liver
– regulates the number of platelets circulating in the body

Question 368

What is the life span of platelets?

Answer 368

5-7 days

Question 369

Clotting Factor I

Which pathway?

Answer 369

Fibrinogen
– Common pathway

Question 370

Clotting Factor II

Which Pathway?

Answer 370

Prothrombin
– Common Pathway
– Vit K dependent

Question 371

Clotting Factor III

Which pathway?

Answer 371

Tissue factor
– Extrinsic pathway

Question 372

Clotting Factor IV

Answer 372

Calcium
– acts as binding agent for Vit K dependent factors

Question 373

Clotting Factor V

Which pathway?

Answer 373

Proaccelerin
– Common pathway

Question 374

Clotting Factor VI

Answer 374

Accelerin

Question 375

Clotting Factor VII

Which pathway?

Answer 375

Proconvertin
– Intrinsic/Extrinsic pathway
– Vit K dependent

Question 376

Clotting Factor VIII

Which pathway?

Answer 376

Antihemophilic factor A
– Intrinsic pathway

Question 377

Clotting Factor IX

Which Pathway?

Answer 377

Christmas factor, antihemophilic factor B
– Intrinsic pathway
– Vit K dependent

Question 378

Clotting Factor X

Answer 378

Stuart–Prower factor
– Start of Common pathway
– Vit k dependent

Question 379

Clotting Factor XI

Which pathway?

Answer 379

Plasma thromboplastin antecedent
– Intrinsic pathway

Question 380

Clotting Factor XII

Which pathway?

Answer 380

Hageman factor
– Intrinsic pathway

Question 381

Clotting Factor XIII

Answer 381

Fibrin stabilizing factor
– Result is fibrin clot
end of clotting cascade

Question 382

What intiates the Extrinsic Pathway?

Answer 382

– TF becomes exposed after tissue injury
– Once exposed it binds to Factor VII
– Ultimately forms Thrombin that intiates Extrinsic pathway

Question 383

Tissue Factor (TF)

Which pathway?

Answer 383

Factor III
– Extrinsic pathway
– transmembrane glycoprotein

Question 384

Major crossmatches evaluate:

Answer 384

major crossmatch is designed to test the compatibility between donor RBCs and recipient plasma.

Question 385

Minor Crossmatches evaluate:

Answer 385

minor crossmatch is designed to test compatibility between donor plasma with recipient RBCs.

Question 386

febrile nonhemolytic transfusion reaction (FNHTR)

Answer 386

– characterized by a temperature over (102.5°F) with an increase in temperature > (1.8°F) from the pretransfusion temperature that occurs during or within 4 hours of the completion of a transfusion.
– other etiologies of hyperthermia must be ruled out such as external warming, underlying patient condition or infection, or other transfusion reactions
– most common transfusion reaction in veterinary medicine.
– classically mild and self-limiting

Question 387

TRALI mechanisms

Answer 387

– antibodies (i.e., antibodies to human leukocyte antigen class I and II),
various neutrophil antigens,
lipids,
soluble CD40 ligand

have all been associated with the development of TRALI

– patients that already have primed neutrophils and endothelium from their underlying condition (“first hit”),
– and the transfusion becomes the “second hit” activating those neutrophils

Question 388

Transfusion medicine

Storage lesion

Answer 388

– During the storage of RBCs, biomechanical, biochemical, and immunologic changes occur that may adversely affect the RBCs and the recipient
– may affect the viability, deformability, and oxygen carrying capacity of transfused RBCs as well as the microcirculatory flow and immune response in the recipient
–In veterinary medicine, there is evidence of increased in vivo hemolysis with transfusion of stored versus fresher RBCs in multiple canine studies

Question 389

Mechanisms of Endothelium that prevents clotting under normal conditions:

x7

Answer 389

1. smooth, non-thrombogenic surface
2. Vasodilation - harder for plts to aggregate
3. Endothelial derived vasodilators - N.O.
4. PGI2 = Prostacyclin “keeps blood cyclin”
5. Secretes heparin like molecules
6. Expresses Thrombomodulin - modulates thrombin
7. t-PA - plminogen to plasmin to destroy clots