Hematology - IMHA

Question 1

What is the pathogenesis of IMHA?

Answer 1

The immune system produces antibodies that bind to the patient’s own RBCs leading to RBC destruction via intravascular and extravascular hemolysis

Question 2

What is the most common form of IMHA (think antibody)?

Answer 2

IgG mediated - where RBCs are destroyed by macrophages in the liver in the spleen (Extravascular)

Question 3

How do spheryocytes form?

Answer 3

When macrophages consume a piece of the RBC membrane and not the entire thing they leave fragments called spherocytes

Question 4

IgM activates complement better than ____ which leads to ______ destruction ultimately resulting in ______ hemolysis.

Answer 4

IgG; intravascular; intravascular

Question 5

What are the three etiologies of icterus?

Answer 5

Pre-hepatic due to hemolysis, hepatic, and post-hepatic due to biliary obstruction

Question 6

How do you differentiate between the etiologies of icterus?

Answer 6

Obtain minimum database of CBC, chemistry panel, and urinalysis

Question 7

Why may a dog with IMHA have a non-regenetative anemia at presentation when it is more commonly associated with regenerative anemia?

Answer 7

Immune attack at the level of the bone marrow OR early disease

Question 8

What test is commonly positive in patients with IMHA?

Answer 8

Saline agglutination test

Question 9

What is agglutination in IMHA patients induced by?

Answer 9

five-armed IgM or large quantities of IgG

Question 10

How do you perform a slide agglutination test?

Answer 10

Mix 4 drops of saline with 1 drop of anticoagulated whole blood on a slide. Gently agitate and then examine for macroagglutination. Look under microscope for microagglutination

Question 11

When evaluating a slide agglutination test, what must you look for that is not agglutination due to IMHA?

Answer 11

Rouleaux formation

Question 12

When should a Coomb’s test be performed?

Answer 12

Only if there is negative autoagglutination

Question 13

In an IMHA patient, why would there not be autoagglutination?

Answer 13

The anti-RBC antibody levels are too low to cause agglutination

Question 14

What does the Coomb’s test detect?

Answer 14

antibodies or complement attached to RBCs

Question 15

What is a common CBC finding in patients with IMHA?

Answer 15

Very high WBC counts

Question 16

What is a leukemoid response?

Answer 16

Neutrophilic leukocytosis with a left shift

Question 17

What can cause a leukemoid response?

Answer 17

Increased marrow release during strong regenerative RBC response or tissue necrosis

Question 18

Leukocytosis in dogs with IMHA is correlated with _______ ______.

Answer 18

tissue necrosis

Question 19

What platelet abnormality is associated with IMHA patients?

Answer 19

thrombocytopenia

Question 20

Why do patients with IMHA often have thrombocytopenia?

Answer 20

Immune-mediated platelet destruction and disseminated intravascular coagulation (DIC)

Question 21

True or false: There are no consistent chemistry abnormalities with IMHA.

Answer 21

TRUE

Question 22

What does a biochemistry often reflect in patients with IMHA?

Answer 22

dehydration (elevated bilirubin) and hypoxic damage (mild to moderate elevations)

Question 23

If there is no red in a urinalysis in a patient with IMHA, what does that indicate?

Answer 23

there is no intravascular hemolysis

Question 24

True or False: There is a single definitive test for IMHA.

Answer 24

FALSE

Question 25

Diagnosis of IMHA is based on a number of findings. Name them.

Answer 25

Anemia with a HCT of < 25-30% Evidence of hemolysis Evidence of antibodies against RBCs Elimination of underlying causes of anemia An appropriate response to immunosuppressive therapy

Question 26

What are some hereditary non-immune causes of hemolysis?

Answer 26

Pyruvate kinase deficiency (PK), Phosphofructokinase deficiency (PFK), and hereditary stomatocytosis

Question 27

What are some acquired non-immune causes of hemolysis?

Answer 27

Toxins - zinc, onions, garlic Hypophosphatemia - diabetic ketoacidosis or refeeding syndrome Microangiopathic hemolytic anemia - DIC or heartworm disease

Question 28

Primary IMHA is what type of hypersensitivity reaction?

Answer 28

type 2 hypersensitivity reaction

Question 29

What breeds are predisposed to primary IMHA?

Answer 29

Cocker spaniels, Old English Sheepdogs, Poodles, and Dachshunds

Question 30

What is secondary IMHA?

Answer 30

An immune response to nonself antigens that have modified or are associated with normal RBC membranes

Question 31

What history/tests are important for secondary IMHA diagnosis?

Answer 31

Vaccination history, travel history, flea/tick exposure and prevention, CBC with clinical pathology evaluation, biochemistry panel, UA, abdominal rads, imaging to screen for cancer, test for infectious agents

Question 32

True or false: Animals with IMHA are often hypercoagulable.

Answer 32

TRUE

Question 33

Why is hypercoagulability difficult to diagnose in IMHA patients?

Answer 33

Because they have increased D-dimers, reduced antithrombin, and shortened aPTT and PT times

Question 34

What is the most common complication of IMHA?

Answer 34

pulmonary thromboembolism

Question 35

What plays a role in the formation of pulmonary emboli in IMHA patients?

Answer 35

Stasis of blood, vascular endothelial injury, and hypercoagulability

Question 36

What is the mortality rate in IMHA patients and why?

Answer 36

High mortality rate of 50% is related to pulmonary thromboembolism and DIC

Question 37

What are the five principles of treatment of IMHA?

Answer 37

Provide supportive care, treat tissue hypoxia, treat secondary cause if present, prevent hemolysis with immunosuppressive therapy, and deter formation of thrombi

Question 38

What supportive care is recommended for patients with IMHA?

Answer 38

Maintain hydration and GI protection/support

Question 39

When are IV fluids indicated in IMHA patients?

Answer 39

For patients with hemoglobinuria to prevent pigment nephropathy

Question 40

True or False: Oxygen therapy is recommended in IMHA patients.

Answer 40

False - it does not help with anemia

Question 41

Transfusions are needed in what percentage of IMHA patients?

Answer 41

70-90% of patients

Question 42

What is the mainstay of therapy for IMHA?

Answer 42

glucocorticoids

Question 43

What is the preferred glucocorticoid for IMHA?

Answer 43

Prednisone at immunosuppresive doses - can give dexamethasone initially if oral medications cannot be tolerated

Question 44

How do glucocorticoids work in the face of IMHA?

Answer 44

They decrease macrophage phagocytosis of antibody-coated RBCs and in the long-term mimimize autoantibody production by B ccells

Question 45

How quickly does it take to see a response to glucocorticoids in IMHA patients?

Answer 45

3-7 days

Question 46

What are the side effects associated with glucocorticoid use in IMHA treatment?

Answer 46

PU/PD, polyphagia, secondary infections due to immunosuppression, muscle weakness, diabetes melitus, GI ulceration, and panting

Question 47

When is a second immunosuppressive drug indicated in IMHA patients?

Answer 47

If the PCV is not stabilized or transfusion dependent for greater than 7 days Severe disease Larger dog due to the side effects

Question 48

True or False: you should always use steroids as part of front-line therapy because they are the most rapidly acting drug choice.

Answer 48

TRUE

Question 49

What are some 2nd immunosuppressive drug options?

Answer 49

Azathioprine, Cyclosporine, Mycophenolate mofetil, and Leflunomide

Question 50

How does azathioprine work?

Answer 50

It is converted into 6-mercaptopurine which inhibits purine synthesis. Purines are needed for DNA and RNA synthesis. This suppresses T cell proliferation and function

Question 51

What are the side effects of azathioprine?

Answer 51

bone marrow suppression, hepatopathy, and pancreatitis

Question 52

True or False: You should not use azathioprine in cats.

Answer 52

TRUE

Question 53

What does cyclosporine do?

Answer 53

It inhibits T cell function by preventing T cell IL-2 production, which is necessary for T cell activation

Question 54

What type of IMHA can cyclosporine be used in and why?

Answer 54

nonregenerative IMHA because it is not myelosuppressive

Question 55

What are the side effects of cyclosporine?

Answer 55

Anorexia, diarrhea, gingival hyperplasia, papillomatosis, and hirsutism

Question 56

Aside from glucocorticoids, what immunosuppressive 'agents' could be used in IMHA cases?

Answer 56

Splenectomy and plasmapheresis

Question 57

What is plasmapheresis?

Answer 57

The removal of components of plasma that is thought to cause disease and replace the remainder of the plasma

Question 58

What antithrombotics can be used in IMHA patients?

Answer 58

Aspirin, Clopidogrel, and heparin

Question 59

How does asprin work as an antithrombotic?

Answer 59

Ultralow-dose aspirin inhibits platelet aggregation without inhibiting beneficial effects of prostaglandins

Question 60

How does Clopidogrel work as an antithrombotic?

Answer 60

It inhibits P2Y12 ADP receptor on platelets

Question 61

How does heparin work as an antithrombotic?

Answer 61

It binds to antithrombin allowing it to inhibit FII and Fxa

Question 62

True or False: All heparin doses are the same for dogs with IMHA.

Answer 62

False - you need to do individualized dosing - every dog is different

Question 63

When should you begin to taper glucocorticoids?

Answer 63

when PCV is normal

Question 64

If the CBC is normal, but what percentage should you taper the glucocorticoid dose and how often?

Answer 64

Taper the dose by 25% every 3 weeks if the CBC was normal