Canine IMHA Treatment and Management Quiz

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Questions and Answers

What is a significant risk factor for dogs with immune-mediated hemolytic anemia (IMHA) during the first one to two weeks of the disease?

Decreased respiratory rate

Low blood pressure

Thromboembolic complications (correct)

Increased appetite

Which of the following treatments is NOT typically used for acute stabilization in IMHA?

Immunosuppressive drugs

Anti-thrombotic drugs

Thrombolytics (correct)

Corticosteroids

How long should anti-thrombotic drugs be administered to dogs with IMHA before reevaluating treatment?

4 weeks

Until the dog recovers

1 week

2 weeks (correct)

Which anti-thrombotic drug is considered an anti-platelet medication?

Aspirin Signup and view all the answers

What common clinical signs should be monitored for during a blood transfusion?

Fever, facial swelling, tachypnea Signup and view all the answers

What is the typical initial dosage reduction rate for tapering immunosuppressive drugs?

25-50% every 2-4 weeks Signup and view all the answers

What should be reassessed before tapering immunosuppressive drugs?

PCV/Hct levels Signup and view all the answers

When tapering adjunctive drugs, what should be the next step once prednisone reaches around 0.5 mg/kg/d?

Taper the adjunctive drug Signup and view all the answers

If a disease relapses during tapering of steroids, what is the recommended action?

Add a second immunosuppressive drug if only on steroids Signup and view all the answers

What approach should be taken if using a second immunosuppressive drug along with prednisone?

Taper prednisone more rapidly than if on monotherapy Signup and view all the answers

In the tapering schedule for a 20 kg dog, what is the dosage of prednisone at week 6?

20 mg Signup and view all the answers

What is a consideration when compounding medications for immunosuppressive therapy?

Ensure dosing efficacy Signup and view all the answers

Which immunosuppressive drug is typically tapered first due to its side effects?

Prednisone Signup and view all the answers

What is a common type of coagulopathy that can be acquired?

Rodenticide toxicosis Signup and view all the answers

Which body cavity is NOT typically associated with internal blood loss?

Cranial cavity Signup and view all the answers

What triggers extravascular hemolysis?

Antibody attachment Signup and view all the answers

What is the primary cause of immune-mediated hemolytic anemia (IMHA)?

Loss of immunological tolerance Signup and view all the answers

Which of the following conditions is associated with microangiopathic hemolytic anemia?

Hemangiosarcoma Signup and view all the answers

What is a key step in diagnosing immune-mediated hemolytic anemia?

Confirming regenerative and/or hemolytic anemia Signup and view all the answers

What is one of the exceptions in diagnosing anemia of immune-mediated origin in felines?

Absence of regenerative response Signup and view all the answers

What is typically NOT included in the approach for diagnosing immune-mediated hemolytic anemia?

Imposing immediate blood transfusion Signup and view all the answers

What is known as a pre-hepatic cause of hyperbilirubinemia in cases of IMHA?

Excessive heme metabolism Signup and view all the answers

Which of the following is a common outcome of intravascular hemolysis?

Hemoglobinuria Signup and view all the answers

What condition does bilirubinuria indicate in healthy cats?

Pathological condition Signup and view all the answers

Which drug is associated with the hapten effect in IMHA?

Methimazole Signup and view all the answers

What is the primary role of performing titers after vaccinations in dogs suspected of developing IMHA?

Assess immune response to vaccinations Signup and view all the answers

Which treatment option is NOT commonly included in the management of IMHA?

Dietary changes to remove onion Signup and view all the answers

Regarding the correlation between vaccination and ITP, what was a significant finding of the underpowered study?

Correlation did not imply causation Signup and view all the answers

In distinguishing primary from secondary IMHA, what element is crucial in the diagnosis?

Presence of autoreactive antibodies Signup and view all the answers

Which of the following is NOT a type of pigmenturia?

Neoplasia Signup and view all the answers

Which diagnostic method is used to rule out infectious diseases?

Blood smear Signup and view all the answers

What is the primary treatment for acute stabilization in IMHA?

Anti-thrombotic and immunosuppressive drugs Signup and view all the answers

Which condition is NOT typically associated with IMHA?

Leptospira infection Signup and view all the answers

What is a poor prognostic factor indicated by increased BUN levels?

Acute renal failure Signup and view all the answers

What should be done prior to the first transfusion in canines?

Type donor and recipient Signup and view all the answers

Which of the following is true for feline blood typing?

Typing is unnecessary for emergency transfusions Signup and view all the answers

What indicates the severity of hemolysis in a patient?

Icterus Signup and view all the answers

Which clinical sign indicates a regenerative response in anemia?

Increased reticulocyte count Signup and view all the answers

What is a common clinical sign of hypoxemia in anemic patients?

Increased lethargy Signup and view all the answers

In cases of chronic external blood loss, what type of red blood cell change is typically observed?

Microcytic, hypochromic Signup and view all the answers

Which laboratory finding would indicate hemolysis in an anemic patient?

Increased bilirubin levels Signup and view all the answers

What is the typical time frame for a regenerative response after an episode of hemorrhage?

3-5 days Signup and view all the answers

Which condition is commonly associated with external blood loss through the gastrointestinal tract?

Melena Signup and view all the answers

What is the effect of iron loss on erythropoiesis in chronic blood loss situations?

Decreased RBC production Signup and view all the answers

Which specific hemolytic response is characterized by nucleated red blood cells in circulation?

Regenerative anemia Signup and view all the answers

What might be indicated by pale mucous membranes in an anemic patient?

Low concentration of red blood cells Signup and view all the answers

Which of the following is not a mechanism of anemia?

Increased platelet production Signup and view all the answers

Study Notes

Immune-mediated Hemolytic Anemia (IMHA) - Part 1

IMHA is a common cause of anemia in dogs and cats, affecting young adults and middle-aged animals.
It can be primary (no known cause) or secondary (caused by an underlying condition).
While a cause for secondary IMHA may be suspected, proving it is usually impossible. Primary IMHA is more common in dogs, while secondary IMHA is more frequent in cats.
Secondary IMHA has connections with RBC-infecting organisms (e.g., Babesia in dogs, Mycoplasma in cats) and less concrete links to feline leukemia virus, certain medications, recent vaccinations, or neoplasia.
Causation hasn't been definitively proven for most potential triggers.

Learning Objectives

Recognize clinical signs of anemia.
Use clinical signs and diagnostic algorithms to differentiate anemia mechanisms (loss/hemorrhage, destruction/hemolysis, decreased production).
Diagnose and treat IMHA.

Outline

Algorithms for pallor and anemia.
Clinical signs.
Complete Blood Count (CBC) changes for different types of anemia, including regenerative, hemorrhage, and hemolysis.
Immune-mediated hemolytic anemia (IMHA).

Anemia Classification

Regenerative Anemia: This type of anemia shows specific indicators: PCV and CRT value are less than 2 seconds.
Hemorrhage: PCV and total solids is low.
Hemolysis: PCV is normal, but total solids is normal.

Clinical Signs of Anemia

Degree and chronicity of anemia.
Changes in circulating volume.
Concurrent disorders.
Extent of physical activity.
Hypoxemia: Lethargy, weakness/collapse, increased heart rate, mild-moderate heart murmur (grade I-III, hemic, altered blood viscosity), weak pulses, hypotension.

Regenerative Anemia (Hemorrhage)

Initially, normocytic and normochromic, non-regenerative.
Erythropoietin concentrations increase within 3-5 days, peaking at 4-7 days.
Leukocytosis with left shift occurs.
Anemia, panhypoproteinemia (low albumin and globulin), reticulocytosis.
Interpretation of reticulocytosis depends on anemia severity.

External Blood Loss

Gastrointestinal (GI) tract: Melena (dark tarry stool) if upper GI bleeding. Underlying causes may include endoparasites, NSAIDs, Addison's disease, IBD, or neoplasia.
Urinary tract: Trauma, neoplasia, idiopathic renal hematuria.
Respiratory tract: Epistaxis (nosebleed) that can be swallowed or hemoptysis (coughing up blood).
Skin: Ectoparasites.
Young animals are sometimes misclassified as anemic due to developmental factors, milk diets, and/or endoparasites.

Chronic External Blood Loss

Microcytic, hypochromic, with reduced iron and Hb in red blood cell precursors.
Erythrocytes undergo extra division. Eventually becomes non-regenerative.
Treat underlying cause.
Iron supplementation (oral or IM).

Internal Blood Loss

Body cavities: Thoracic, abdominal, pericardium, joints, cerebral spinal fluid (CSF), subcutis.
Coagulopathies: Congenital (e.g., hemophilia) or acquired (e.g., rodenticide toxicosis, trauma, neoplasia).
Iron is recycled, not depleted.

Extravascular Hemolysis

Normal destruction of old red blood cells by the spleen, bone marrow, and liver.
Triggered by antibody or parasite attachment, oxidative damage, intrinsic defects, or membrane fragility.

Non-immunologic Hemolytic Anemia

Microangiopathic HA (e.g., heartworm disease, hemangiosarcoma, schistocytes).
Phospholipases (e.g., snake venom, spider bites, bee stings).
Oxidative stress (e.g., onion/garlic, zinc from pennies, sunscreen).
RBC intrinsic defects/fragility (e.g., enzyme deficiencies, osmotic fragility, hypophosphatemia, refeeding syndrome, DKA).

IMHA: Pathophysiology, Diagnosis, Differentiation, Treatment

Pathophysiology.
Diagnosis.
Differentiating between primary and secondary IMHA.
Treatment: Acute stabilization, anti-thrombotic and immunosuppressive drugs, splenectomy/therapeutic plasma exchange.
Precursor-targeted IMHA.

Diagnostic Approach to IMHA

Diagnose anemia.
Confirm regenerative and/or hemolytic (exceptions exist for precursor immune-mediated anemia or feline anemia of immune-mediated origin).
Rule out secondary/associative causes.
Conclusion: IMHA is a diagnosis of exclusion.

Pathogenesis of IMHA (Summary)

Predisposing factors: genetics, age, environment.
Neoplasia, infections, vaccines, drugs.
Immune dysregulation (primary vs secondary, non-associative vs associative).
Autoreactive antibodies targeting RBCs.

Drugs Associated With IMHA

Hapten effect: Penicillins (e.g., Clavamox), cephalosporins (e.g., Cephalexin), trimethoprim sulfa, methimazole, or vaccines.

Vaccine-Associated IMHA

Temporal relationship between vaccination and IMHA exists; however, correlation does not equal causation..
Studies have not consistently established that vaccination causes IMHA, although a temporal association may exist.

Pathogenesis of IMHA (Cellular Activity)

Extravascular hemolysis: FcR+ cells in fixed mononuclear phagocytic system phagocytose and destroy RBCs.
Intravascular hemolysis: Complement activation with intravascular hemolysis and RBC destruction through lysis.

Extravascular Hemolysis (Details)

Opsonization of erythrocytes leads to spherocytes.
Heme metabolism and excretion in canine kidneys.
Kidneys can secrete conjugated bilirubin, urine bilirubin levels are normally present in healthy canine patients.
Bilirubinuria (presence of bilirubin in urine) is not typical for healthy cats.
IMHA causes excess hemoglobin and enters the bilirubin pathway causing pre-hepatic hyperbilirubinemia, jaundice, bilirubin levels > 1.5-2.0 mg/dl.

Intravascular Hemolysis

Complement activation and intravascular hemolysis leads to lysis of RBCs and further destruction.
Hemolyzed erythrocytes result in hemoglobinemia and hemoglobinuria, which often have a poorer prognosis.

Clinical Signs (More Details)

Degree of anemia, chronicity, changes in circulating volume, concurrent disorders, and extent of activity.
Hypoxemia: Lethargy, weakness, collapse, increased heart rate, mild-moderate heart murmurs, weak pulses, hypotension (grade I-III, hemic, altered blood viscosity).
Regenerative anemia can manifest as macrocytosis or anisocytosis, polychromasia/hypochromasia, and nucleated red blood cells (nRBCs).
Hemorrhage shows lower PCV and total solids.

Diagnostic Tests (Patient Side)

Physical examination: Mucous membrane color, capillary refill time (CRT), pulse quality, blood pressure, and PCV/total solids.
Blood smear: Polychromasia, spherocytes, nRBCs, hemoparasites (evaluate WBCs and platelets).
Saline agglutination test: Assess for antibodies that make RBCs clump together.

Diagnostic Tests (More Details)

CBC: RBC indices, reticulocytosis, WBC, platelets.
Chemistry: Albumin/globulin (hemolysis vs hemorrhage), renal parameters (chronic kidney disease), liver enzymes (hepatic and post-hepatic hyperbilirubinemia), electrolytes (e.g., Na, K, phosphorus).
Urinalysis: Urine specific gravity (renal failure), bilirubinuria, pigmenturia, hemoglobinuria, hematuria (spin down), myoglobinuria, and sediment exam.
Neoplasia screening (thoracic and abdominal radiographs, ultrasound, or CT)
Infectious disease testing: Blood smear for organisms, serology (e.g., Mycoplasma hemocanis, Babesia, Leptospira), SNAP tests (Feline Leukemia Virus [FeLV] antigen/FIV antibody, and Mycoplasma hemofelis), PCR testing, fresh bone marrow for occult infection like Feline Leukemia Virus (FeLV).

IMHA - Primary vs Secondary

Screen for neoplasia (thoracic and abdominal radiographs, abdominal ultrasound, or CT, ECG, and echocardiogram.)
Rule out infectious causes (antibodies/titers/serology, PCR, antigen within cells/plasma).

Poor Prognostic Factors in IMHA

Increased blood urea nitrogen (BUN) levels (pigment nephropathy, GI bleed).
Icterus (indicates severity of hemolysis).
Band neutrophils and petechiae (severity of systemic inflammatory response).
Association with other immune-mediated diseases (e.g., Evans disease, systemic lupus erythematosus [SLE]).

Treatment Summary

Acute stabilization.
Anti-thrombotic and immunosuppressive drugs.
Splenectomy/therapeutic plasma exchange.
Precursor IMHA is a challenging diagnosis to manage.

Volume Support for Anemia

Crystalloids: Deficiency replacement + ongoing losses + maintenance (60 ml/kg/day for dogs, 45 for cats to reflect the disease timeline.
Aids kidneys with pigment nephropathy (bilirubin/Hb).

Blood Products

Only transfusion if clinically indicated.
Use clinical signs (Heart Rate [HR], Respiratory Rate [RR]), not only PCV%.
Ideal: Type donor and recipient for first transfusion.
Crossmatch for subsequent transfusions.
Feline patients require donor and recipient typing for all transfusions.

Canine Transfusion Considerations

Incompatible first transfusion can lead to sensitization, potentially resulting in hemolysis during subsequent transfusions. The use of DEA 1.1+ antibodies is relevant in this process.

Small Animal Blood Typing

Visible hemagglutination: Patient RBC surface antigen.
Known monoclonal or polyclonal antisera.
Methods: Card and ELISA (to identify the different blood types).

Autoagglutination

Macroagglutination (visible on blood tubes using saline agglutination tests).
Microagglutination (seen with microscopic slide examination; differentiate from rouleaux).

Direct/Serum Antiglobulin Test (DAT/SAT or Coombs' Test)

Patient RBCs with attached autoantibodies.
Agglutination occurs due to the presence of anti-canine immunoglobulin antibodies.
This test confirms IMHA.

Flow Cytometry

Diagnose the presence or absence of anti-canine globulin antibodies.
Differentiate between negative and positive signals (using forward and side scatter, gating, and fluorescence).

Diagnostic Testing - Patient Side

Evaluate mucous membrane color, capillary refill time (CRT), pulse quality, blood pressure. - PCV/total solids is crucial.
Blood smear to evaluate for polychromasia, spherocytosis in dogs; and nRBCs; hemoparasites, and to assess for WBCs and platelets.
Saline agglutination test.

Additional Diagnostic Tests

CBC (red blood cell indices, reticulocytosis, white blood cell [WBC], platelets)
Chemistry panel (albumin/globulin, renal parameters, liver enzymes, electrolytes).
Complete urinalysis (urine specific gravity, bilirubinuria, pigmenturia/hemaglobinuria, hematuria-spin down, myoglobinuria, sediment exam).
Neoplasia screening (thoracic and abdominal radiographs, abdominal ultrasound or CT, ECG and echocardiogram).

Infectious Disease Testing

Blood smear (organisms not always apparent).
Serology (Mycoplasma hemocanis, Babesia).
SNAP testing for tick-borne infections (e.g., Babesia, Mycoplasma hemocanis, certain Rickettsias).
Leptospira tests.
Snap tests (FeLV antigen/FIV antibody).
Mycoplasma hemofelis.
PCR assay (Mycoplasma hemofelis/canis, Babesia, Leptospira).

History (Patient Information)

Dietary concerns: Onion or garlic-containing foods?
Medication use: Flea and tick preventatives, other medications.
Phospholipases: Bee stings, spider bites, snake venom exposure.

Criteria for IMHA

PCV < 25%.
Presence of spherocytes (dogs only), autoagglutination, or a positive Coombs' test.

Immunosuppressive Drugs (Review)

Start with prednisone (1 mg/kg PO q12h, 2mg/kg PO q24h for cats).
Consider adjunctive therapy in certain situations (large dogs, cats with intravascular IMHA, and those at high risk of diabetes mellitus).
Utilize cyclosporin, mycophenolate mofetil, or azathioprine as adjunctive immunosuppressive agents.

Using Immunosuppressive Drugs

To spare prednisone effects: Start with careful tapering.
Concurrent diseases may influence drug handling (e.g., renal or hepatic).

Corticosteroids: Adverse Effects

Iatrogenic hypercortisolemia/Cushing's disease.
Acceptable adverse effects: Polyuria, polydipsia, polyphagia, alopecia, muscle wasting, hepatomegaly, panting.
Unacceptable adverse effects: GI bleeding, do not combine steroids with NSAIDs.

CBC changes with IMHA and corticosteroids

IMHA + high dose steroids often causes a leukemoid response (extreme leukocytosis) - Monitor CBC.
Prednisone use can cause hypercortisolemia, expect a stress leukogram, expect left shift to decrease with time. Monitor CBC for toxic changes.

Chemistry Changes with Corticosteroids

ALKP increases in dogs due to hepatic changes (glycogen accumulation) - do not expect increased ALKP in cats.
Hyperlipemia, hypercholesterolemia, and hyperglycemia.

Urinalysis Changes with Corticosteroids

Decreased urine specific gravity.
Increased frequency of urination.
Urinary tract infection (UTI) with bacteria, pyuria, or hematuria; these signs suggest an inflammatory response.

Corticosteroids: Long-Term Adverse Effects

Short-term side effects: Infections, soft tissue catabolism, decreased wound healing, ligament rupture, aggression, sodium retention issues (cardiac or diabetic patients).
Long-term side effects: Uroliths (e.g., calcium oxalate), gall bladder mucoceles, and calcinois cutis.

Tapering Immunosuppressive Drugs

Reassess PCV/Hct before tapering.
Taper one drug at a time, unless a fulminant infection is suspected.
Consider adjusting tapering rates based on disease progression and side effects. (25-50% every 2-4 weeks).

Tapering Schedule Examples

Specific schedules for tapering dosages of prednisone and mycophenolate for a 20 kg dog are provided.

Alternative Therapies

Splenectomy: Salvage option for unresponsive cases. Screen for tick-borne diseases, especially Babesia. Modify anti-platelet doses peri-operatively.
Therapeutic plasma exchange: Removes antibodies. Specialized equipment, with cost implications.

Precursor-targeted Immune-mediated Anemia

Immune response is targeted at RBC precursors, resulting in non-regenerative anemia.
Spherocytes and agglutination are less common.
Bone marrow aspirate/biopsy may be needed for diagnosis.
Anemia can be chronic (stable but severe anemia).

Optional Reading

List of veterinary journal articles and review articles on IMHA from various professional organizations. These resources are provided for additional in-depth exploration of the subject.

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Description

This quiz assesses your knowledge on the management and treatment protocols for immune-mediated hemolytic anemia (IMHA) in dogs. The questions cover risk factors, drug treatments, monitoring during blood transfusions, and tapering of medications. Test your understanding of best practices in canine healthcare related to IMHA.