Hematology - IMHA Flashcards
What is the pathogenesis of IMHA?
The immune system produces antibodies that bind to the patient’s own RBCs leading to RBC destruction via intravascular and extravascular hemolysis
What is the most common form of IMHA (think antibody)?
IgG mediated - where RBCs are destroyed by macrophages in the liver in the spleen (Extravascular)
How do spheryocytes form?
When macrophages consume a piece of the RBC membrane and not the entire thing they leave fragments called spherocytes
IgM activates complement better than ____ which leads to ______ destruction ultimately resulting in ______ hemolysis.
IgG; intravascular; intravascular
What are the three etiologies of icterus?
Pre-hepatic due to hemolysis, hepatic, and post-hepatic due to biliary obstruction
How do you differentiate between the etiologies of icterus?
Obtain minimum database of CBC, chemistry panel, and urinalysis
Why may a dog with IMHA have a non-regenetative anemia at presentation when it is more commonly associated with regenerative anemia?
Immune attack at the level of the bone marrow OR early disease
What test is commonly positive in patients with IMHA?
Saline agglutination test
What is agglutination in IMHA patients induced by?
five-armed IgM or large quantities of IgG
How do you perform a slide agglutination test?
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
When evaluating a slide agglutination test, what must you look for that is not agglutination due to IMHA?
Rouleaux formation
When should a Coomb’s test be performed?
Only if there is negative autoagglutination
In an IMHA patient, why would there not be autoagglutination?
The anti-RBC antibody levels are too low to cause agglutination
What does the Coomb’s test detect?
antibodies or complement attached to RBCs
What is a common CBC finding in patients with IMHA?
Very high WBC counts
What is a leukemoid response?
Neutrophilic leukocytosis with a left shift
What can cause a leukemoid response?
Increased marrow release during strong regenerative RBC response or tissue necrosis
Leukocytosis in dogs with IMHA is correlated with _______ ______.
tissue necrosis
What platelet abnormality is associated with IMHA patients?
thrombocytopenia
Why do patients with IMHA often have thrombocytopenia?
Immune-mediated platelet destruction and disseminated intravascular coagulation (DIC)
True or false: There are no consistent chemistry abnormalities with IMHA.
TRUE
What does a biochemistry often reflect in patients with IMHA?
dehydration (elevated bilirubin) and hypoxic damage (mild to moderate elevations)
If there is no red in a urinalysis in a patient with IMHA, what does that indicate?
there is no intravascular hemolysis
True or False: There is a single definitive test for IMHA.
FALSE
Diagnosis of IMHA is based on a number of findings. Name them.
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
What are some hereditary non-immune causes of hemolysis?
Pyruvate kinase deficiency (PK), Phosphofructokinase deficiency (PFK), and hereditary stomatocytosis
What are some acquired non-immune causes of hemolysis?
Toxins - zinc, onions, garlic
Hypophosphatemia - diabetic ketoacidosis or refeeding syndrome
Microangiopathic hemolytic anemia - DIC or heartworm disease
Primary IMHA is what type of hypersensitivity reaction?
type 2 hypersensitivity reaction
What breeds are predisposed to primary IMHA?
Cocker spaniels, Old English Sheepdogs, Poodles, and Dachshunds
What is secondary IMHA?
An immune response to nonself antigens that have modified or are associated with normal RBC membranes
What history/tests are important for secondary IMHA diagnosis?
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
True or false: Animals with IMHA are often hypercoagulable.
TRUE
Why is hypercoagulability difficult to diagnose in IMHA patients?
Because they have increased D-dimers, reduced antithrombin, and shortened aPTT and PT times
What is the most common complication of IMHA?
pulmonary thromboembolism
What plays a role in the formation of pulmonary emboli in IMHA patients?
Stasis of blood, vascular endothelial injury, and hypercoagulability
What is the mortality rate in IMHA patients and why?
High mortality rate of 50% is related to pulmonary thromboembolism and DIC
What are the five principles of treatment of IMHA?
Provide supportive care, treat tissue hypoxia, treat secondary cause if present, prevent hemolysis with immunosuppressive therapy, and deter formation of thrombi
What supportive care is recommended for patients with IMHA?
Maintain hydration and GI protection/support
When are IV fluids indicated in IMHA patients?
For patients with hemoglobinuria to prevent pigment nephropathy
True or False: Oxygen therapy is recommended in IMHA patients.
False - it does not help with anemia
Transfusions are needed in what percentage of IMHA patients?
70-90% of patients
What is the mainstay of therapy for IMHA?
glucocorticoids
What is the preferred glucocorticoid for IMHA?
Prednisone at immunosuppresive doses - can give dexamethasone initially if oral medications cannot be tolerated
How do glucocorticoids work in the face of IMHA?
They decrease macrophage phagocytosis of antibody-coated RBCs and in the long-term mimimize autoantibody production by B ccells
How quickly does it take to see a response to glucocorticoids in IMHA patients?
3-7 days
What are the side effects associated with glucocorticoid use in IMHA treatment?
PU/PD, polyphagia, secondary infections due to immunosuppression, muscle weakness, diabetes melitus, GI ulceration, and panting
When is a second immunosuppressive drug indicated in IMHA patients?
If the PCV is not stabilized or transfusion dependent for greater than 7 days
Severe disease
Larger dog due to the side effects
True or False: you should always use steroids as part of front-line therapy because they are the most rapidly acting drug choice.
TRUE
What are some 2nd immunosuppressive drug options?
Azathioprine, Cyclosporine, Mycophenolate mofetil, and Leflunomide
How does azathioprine work?
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
What are the side effects of azathioprine?
bone marrow suppression, hepatopathy, and pancreatitis
True or False: You should not use azathioprine in cats.
TRUE
What does cyclosporine do?
It inhibits T cell function by preventing T cell IL-2 production, which is necessary for T cell activation
What type of IMHA can cyclosporine be used in and why?
nonregenerative IMHA because it is not myelosuppressive
What are the side effects of cyclosporine?
Anorexia, diarrhea, gingival hyperplasia, papillomatosis, and hirsutism
Aside from glucocorticoids, what immunosuppressive ‘agents’ could be used in IMHA cases?
Splenectomy and plasmapheresis
What is plasmapheresis?
The removal of components of plasma that is thought to cause disease and replace the remainder of the plasma
What antithrombotics can be used in IMHA patients?
Aspirin, Clopidogrel, and heparin
How does asprin work as an antithrombotic?
Ultralow-dose aspirin inhibits platelet aggregation without inhibiting beneficial effects of prostaglandins
How does Clopidogrel work as an antithrombotic?
It inhibits P2Y12 ADP receptor on platelets
How does heparin work as an antithrombotic?
It binds to antithrombin allowing it to inhibit FII and Fxa
True or False: All heparin doses are the same for dogs with IMHA.
False - you need to do individualized dosing - every dog is different
When should you begin to taper glucocorticoids?
when PCV is normal
If the CBC is normal, but what percentage should you taper the glucocorticoid dose and how often?
Taper the dose by 25% every 3 weeks if the CBC was normal
