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Immune Mediated Hemolytic Anemia (IMHA)(Formerly known as autoimmune hemolytic anemia or AIHA)
The dog's own immune system destroys the red blood cells, the carriers of oxygen, which the body obviously needs in Immune Mediated Hemolytic Anemia (IMHA) (formerly known as autoimmune hemolytic anemia or AIHA)

The symptoms of Immune Mediated Hemolytic Anemia (IMHA)can appear suddenly or gradually. The signs are usually related to the lack of oxygen. The dog becomes usually weak, lethargic with increased heart and respiration rate because the heart has to work the heart has to work harder Pale mucous gums, ears, eyelids may be observed. The dog also may appear to be jaundice. The dog may also show signs of wasting.even with normal eating although there may be vomiting or abdominal pain or/and Owners may blood in the urine or stool. The urine may be dark orange or even brown. There may be a loss of appetite. An increase in temperature may also be observed in some dogs. A Coomb’s test should be performed although sometimes there are false negatives on rare occasions.

There is no consensus for a specific cause for Immune Mediated Hemolytic Anemia (IMHA) although many theories exist such as multivalent modified-live vaccines overstimulating the immune system, environmental pollutants, or food additives such as ethoxyquin. There is strong evidence for a genetic factor in the following breeds: the Basenji, West Highland White terrier, English springer spaniel, Alaskan malamute, poodle, and beagle. Females have a much higher rate than males in having Immune Mediated Hemolytic Anemia (IMHA)

The Immune System and Disease Resistance By W. Jean Dodds, DVM
An overview of the Immune System which will aid you in understanding AIHA better
Immune Mediated Hemolytic Anemia (IMHA)
A Great Overview of Immune Mediate Hemolytic Anemia (IMHA)
"in fact 20% to 80% mortality (depending on the study) have been reported with this disease. "
Immune Mediated Hemolytic Anemia
IMHA - crisis treatments
Immune mediated hemolytic anemia in Giant Schnauzer
Drug treatment options following IMHA
IMHA recovery
Immune mediated hemolytic anemia and Cushing's
Vaccinations and Immune mediated hemolytic anemia
Hemolytic anemia


Diagnosis of Immune-mediated Hemolytic Anemia
Kristin M. Hiers, DVM; Kenneth Latimer, DVM, PhD; Perry J. Bain, DVM, PhD; Paula M. Krimer, DVM, DVSc
Class of 2003 (Hiers) and Department of Pathology (Latimer, Bain, Krimer), College of Veterinary Medicine, The University of Georgia, Athens, GA 30602-7388

"Accurate evaluation of clinical, hematologic, and immunologic data is necessary to establish a diagnosis of IMHA.4,5 Clinicians should remember the importance of blood smear findings (agglutination and spherocytes) and not rely solely on the results of the direct antiglobulin (Coombs’) test to diagnose IMHA.7 It also is important to submit both an EDTA blood sample and an air dried blood film for evaluation. To eliminate the prozone effect, direct antiglobulin testing should use species-specific Coombs' serum that is tested in serial dilutions."

Computer Design Yields Better, More Efficient Therapeutic for Preventing Tissue Damage
" In this study, the researchers modeled a peptide (a chain of amino acids, such as a protein or protein fragment) called Compstatin, which prevents the autoimmune-mediated damage of organs during transplantation, and various inflammatory diseases"

J Am Vet Med Assoc. 2004 Jan 15;224(2):232-5. : Case-control study of blood type, breed, sex, and bacteremia in dogs with immune-mediated hemolytic anemia.

Miller SA, Hohenhaus AE, Hale AS.

The Department of Medicine, The Bobst Hospital, The Animal Medical Center, 510 E 62nd St, New York, NY 10021-8302, USA.

OBJECTIVE: To determine whether blood type, breed, or sex were risk factors for immune-mediated hemolytic anemia (IMHA) in dogs and whether bacteremia was common in dogs with IMHA. DESIGN: Case-control study. ANIMALS: 33 dogs with IMHA, 1,014 dogs without IMHA for which blood type (dog erythrocyte antigens 1.1, 1.2, 3, 4, 5, and 7) was known, 15,668 dogs without IMHA for which breed was known, and 15,589 dogs without IMHA for which sex was known. PROCEDURE: Blood type, breed, and sex distribution of dogs with IMHA were compared with data for control dogs with Fisher exact tests and by calculating odds ratios (ORs). Results of bacterial culture of blood samples were documented for dogs with IMHA, when available. RESULTS: Dog erythrocyte antigen 7 was associated with a significant protective effect (OR, 0.1) in Cocker Spaniels with IMHA (n = 10), compared with control dogs. Cocker Spaniels, Bichon Frise, Miniature Pinschers, Rough-coated Collies, and Finnish Spitz had a significantly increased risk of IMHA, as did female dogs (OR, 2.1). Blood samples from 12 dogs with IMHA were submitted for bacterial culture, and none had bacteremia. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that blood type, breed, and sex may play a role in IMHA in dogs.

J Small Anim Pract. 2004 Jan;45(1):21-4. : Immune-mediated haemolytic anaemia associated with a sarcoma in a flat-coated retriever.
Mellanby RJ, Holloway A, Chantrey J, Herrtage ME, Dobson JM.
Queen's Veterinary School Hospital, University of Cambridge, CB3 0ES.

A seven-year-old flat-coated retriever presented with a history of lethargy, dyspnoea and inappetence of several days' duration. Clinical examination revealed pale mucous membranes and tachypnoea, and haematology demonstrated marked autoagglutination. Thoracic radiographs revealed an increased opacity in the perihilar region. The owners declined further evaluation and the dog was treated symptomatically with immunosuppressive doses of prednisolone and azathioprine. The dog's demeanour improved, although it was eventually euthanased seven weeks later because of dysphagia and worsening dyspnoea. Postmortem examination revealed a widespread, poorly differentiated sarcoma involving the lungs, pericardium, thoracic lymph nodes and spleen. Immune-mediated haemolytic anaemia is a well recognised condition in dogs and is occasionally associated with neoplastic conditions. This is the first case report to describe immune-mediated haemolytic anaemia associated with a diffuse, poorly differentiated sarcoma.

1: Vet Clin North Am Small Anim Pract. 2003 Nov;33(6):1295-315. : Immune-mediated hemolytic anemia: understanding the nemesis.
McCullough S.
College of Veterinary Medicine, University of Illinois, 1008 West Hazelwood Drive, Urbana, IL 61801, USA.

IMHA is one of the most common causes of anemia in small animals. Although treatment may be rewarding, many patients do not respond adequately to glucocorticoids alone and require additional immunosuppressive therapy. Some patients may succumb to acute severe anemia and die within the first few weeks of treatment; even if they survive, relapses may occur. IMHA is the nemesis; as our understanding of this disease increases and treatment options expand, it is hoped that survival rates will finally improve.

Influence of drug treatment on survival of dogs with immune-mediated hemolytic anemia: 88 cases (1989-1999).
Grundy SA, Barton C
Dept of Small An Med and Surg, College of Vet Med, Texas A&M Univ, College Station 77843-4474, USA.
J Am Vet Med Assoc 2001 Feb 15;218(4):543-6 OBJECTIVE: To evaluate association of various treatments for immune-mediated hemolytic anemia with survival to discharge in dogs.
DESIGN: Retrospective cross-sectional analysis. ANIMALS: 88 dogs with idiopathic immune-mediated hemolytic anemia. PROCEDURE: Medical records of dogs with immune-mediated hemolytic anemia treated between August 1989 and August 1999 were examined. Survival to discharge, PCV at referral, autoagglutination, and drug treatment and dosage were recorded. RESULTS: Treatments included administration of prednisone, dexamethasone, azathioprine, danazol, cyclosporine, cyclophosphamide, bovine hemoglobin solution, and human immunoglobulin. Overall mortality rate was 50.5%. Significant associations with death were not detected for use of azathioprine, cyclosporine, danazol, or human immunoglobulin. A significant difference in mortality rate was not detected between use of multiple immunosuppressive drug treatments and use of single immunosuppressive drugs. Use of cyclophosphamide and bovine hemoglobin solution were associated with significant increases in relative risk of death
CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that use of cyclophosphamide and bovine hemoglobin solution in treatment of idiopathic immune-mediated hemolytic anemia may be associated with increased risk of death.

Immune-mediated hemolytic anemia: 70 cases (1988-1996).
Reimer ME, Troy GC, Warnick LD
Dept of Small Animal Clin Sci, Vet Teaching Hosp, Virginia-Maryland,Regional College of Veterinary Medicine, Blacksburg 24061-0442, USA.
J Am Anim Hosp Assoc 1999 Sep-Oct;35(5):384-91
Survival times and mortality rates in dogs with idiopathic immune-mediated hemolytic anemia (IMHA) have been infrequently reported in the literature. This study evaluates survival and mortality in a large group of dogs with IMHA. The association of age, sex, and breed with IMHA was evaluated by comparing affected dogs to control dogs admitted to the hospital during the same time period. Treatment regimens were reviewed to determine the effects of different agents upon survival of dogs with IMHA during hospitalization and after discharge. Median survival times for each treatment group were 57 days (prednisone), 28 days (prednisone, cyclophosphamide), 974 days (prednisone, azathioprine), 15 days (prednisone, cyclophosphamide, azathioprine), and one day (no treatment). Overall mortality rate in the population of dogs studied was 70%. Twenty-nine (41.4%) dogs either died or were euthanized while hospitalized. Forty-one (59%) dogs were discharged from the hospital. Of the dogs discharged, 10 died within the first month, another five died within three months, and another five died within a year of discharge due to assumed complications of therapy or relapses of IMHA.

Hemostatic abnormalities in dogs with primary immune-mediated hemolytic anemia.
Scott-Moncrieff JC, Treadwell NG, McCullough SM, Brooks MB.
Dep of Vet Clin Sci, School of Vet Med, Purdue University, West Lafayette, Indiana 47907, USA. J Am Anim Hosp Assoc 2001 May-Jun;37(3):220-7
Hemostatic parameters were prospectively measured in 20 dogs with primary immune-mediated hemolytic anemia. Eight of 20 dogs had received prior treatment with prednisone. Activated partial thromboplastin time was increased in nine dogs; one-stage prothrombin time was increased in two dogs; fibrinogen concentration was increased in 17 dogs; and antithrombin activity was decreased in 10 dogs. Fibrin(ogen) degradation products concentration was increased in 12 dogs, and D-dimer concentration was increased in 16 dogs. Four or more laboratory criteria of disseminated intravascular coagulation (DIC) were present in nine dogs, and three criteria of DIC were found in four additional dogs. Thromboembolism was the most common finding in the dogs that died. In this study population, mortality was not significantly associated with any clinical finding or laboratory variable.

Correlation between leukocytosis and necropsy findings in dogs with immune-mediated hemolytic anemia: 34 cases (1994-1999).
McManus PM, Craig LE.
Dept of Pathobiol, School of Vet Med, Univ of Pennsylvania, Philadelphia 19104, USA.
J Am Vet Med Assoc 2001 Apr 15;218(8):1308-13
OBJECTIVE: To determine whether severity of leukocytosis correlates with severity of postmortem lesions in dogs with immune-mediated hemolytic anemia (IMHA). DESIGN: Retrospective study. ANIMALS: 34 dogs with IMHA that had CBC performed within 48 hours prior to death and complete necropsy examinations. PROCEDURE: Dogs were independently assigned to 4 leukocytosis groups (within reference range; mild leukocytosis, moderate leukocytosis, marked leukocytosis) and 3 lesion severity groups (mild lesions, moderate lesions, severe lesions).RESULTS: Moderate to marked leukocytosis correlated with moderate to severe postmortem lesions. Ischemic necrosis within liver, kidney, heart, lung, and spleen attributable to thromboembolic disease or anemic hypoxia were the most common important lesions found at necropsy. None of the dogs with mild lesions had moderate or marked leukocytosis. Four of 14 severely affected dogs had WBC counts within reference range, but all 4 had neutrophilic left shifts. Three of these 4 dogs had toxic change in neutrophils. CONCLUSION AND CLINICAL RELEVANCE: Moderate to marked leukocytosis, neutrophilic left shift, and toxic change in neutrophils in dogs with IMHA should alert clinicians to the potential for moderate to severe tissue injury, which could complicate treatment and worsen prognosis. Lesions appear to be secondary to anemic hypoxia, thromboembolic disease, or both; therefore, treatment objectives should focus on improving blood oxygen-carrying capacity and monitoring for thromboembolic disease.

Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.
Burgess K, Moore A, Rand W, Cotter SM
Tufts Univ School of Vet Med, Harrington Onc Prog,North Grafton, MA 01536, USA.
J Vet Intern Med 2000 Jul-Aug;14(4):456-62
A review of 60 cases of immune-mediated hemolytic anemia (IMHA) in the dog was performed in order to characterize the disease and to identify potential prognostic indicators. Dogs ranged in age from 1 to 13 years, with a mean age of 6.5 years. The 2 most commonly affected breeds were Cocker Spaniels and Labrador Retrievers. Fifty-two of the 60 dogs tested (87%) were autoagglutination positive and spherocytes were present in 45 (75%). Forty-one (89%) of 46 patients tested positive for the presence of immunoglobulin on the red blood cell surface (Coombs assay). The most common clinical signs at presentation were lethargy, weakness, pale mucous membranes, icterus, hemoglobinuria, and anorexia. PCV less than 25% was present in 59 (98%) dogs. At the time of presentation, 35 dogs (58%) had a nonregenerative anemia, whereas 25 patients (42%) had a regenerative response. Thrombocytopenia was seen in 41 (68%) dogs. Nine of 34 dogs (26%) had a prolonged prothrombin time, 19 of 34 (56%) had a prolonged activated partial thromboplastin clotting time, and 12 of 34 (35%) had abnormal fibrinogen concentrations. All dogs received prednisone at immunosuppressive doses (2.2-4.4 mg/kg PO as a single or divided dose every 24 hours) and cyclophosphamide as primary therapy. Forty-one dogs (63%) received cyclophosphamide at 50 mg/m2 q24h for 4 days, whereas 9 dogs (15%)received an initial high dose (200 mg/m2) followed by 3 days of a lower dose (50 mg/m2 q24h). No statistical difference in survival times was found for either protocol. Thirteen dogs were treated with azathioprine in addition to cyclophosphamide and prednisone. The median survival time of dogs that received all 3 drugs was 370 days as compared to 9 days for those dogs that were treated with cyclophosphamide and prednisone alone. Thirty-one (52%) dogs died from the disease, 13 (22%) dogs were alive, and 15 (25%) dogs were lost to follow-up. The median length of survival for all dogs was 21 days. Eight dogs that were discharged from the hospital suffered a relapse (PCV < 25%).

Cyclophosphamide exerts no beneficial effect over prednisone alone in the initial treatment of acute immune-mediated hemolytic N anemia in dogs: A randomized controlled clinical trial
Mason, D Duval, FS Shofer, U Giger
Univ Penn,Sch Vet Med,Dept Clin Studies,3850 Spruce St,Philadelphia,PA 19104 USA
Journal of Veterinary Internal Medicine, 2003, Vol 17, Iss 2, pp 206-212
Cyclophosphamide is commonly used with prednisone in the initial treatment of severe idiopathic immune-mediated hemolytic anemia (IMHA) in dogs because retrospective reports suggest its benefit. This randomized controlled prospective clinical trial evaluated whether combined cyclophosphamide and prednisone therapy is more efficacious than prednisone therapy alone in the initial treatment of IMHA. Eighteen dogs with acute, severe idiopathic IMHA were randomly assigned to I of 2 treatment groups. The P group received prednisone therapy alone (1-2 mg/kg PO q12h), and the PC group received prednisone (1-2 mg/kg PO q12h) and cyclophosphamide (50 mg/m(2) PO q24h for 4 consecutive days a week) for 4 weeks. The mortality rate in the P group was 20% (2 of 10), and in the PC group, the mortality rate was 38% (3 of 8). There was no difference in sequential CBC evaluations between the 2 groups. However, whereas dogs in the P group showed increases in reticulocyte count, reticulocytosis was suppressed in dogs in the PC group during the 1st week of therapy. Spherocytosis resolved more quickly in the P group (day 21) than in the PC group (day 28), but the time taken to achieve a negative Coombs' test result was comparable between groups. No difference was observed in the volume of packed red blood cells (pRBCs) given per transfusion between treatment groups, but more dogs in the PC group required a 2nd transfusion. The results of this limited study suggest that cyclophosphamide plus prednisone has no benefit over prednisone alone in the initial treatment of acute, severe idiopathic IMHA in dogs.

Idiopathic pure red cell aplasia and nonregenerative immune-mediated anemia in dogs: 43 cases (1988-1999).
Stokol T, Blue JT, French TW
Dept of Biomed Sci, College of Vet Med, Cornell Univ, Ithaca, NY 14853-6401, USA.
J Am Vet Med Assoc 2000 May 1;216(9):1429-36
OBJECTIVE: To examine clinical features, laboratory test results,treatment, and outcome of dogs with pure red cell aplasia (PRCA) and idiopathic nonregenerative immune-mediated anemia (NRIMA). DESIGN: Retrospective study. ANIMALS: 43 dogs with severe nonregenerative anemia. PROCEDURE: Medical records of dogs determined to have PRCA, NRIMA, or ineffective erythropoiesis on the basis of bone marrow analysis between 1988 and 1999 were reviewed. Criteria for inclusion were > or = 5-day history of severe nonregenerative anemia (Hct < 20%; < 60.0 x 10(3) reticulocytes/microliter) with no underlying diseases. Information was retrieved on signalment, clinical signs, laboratory test results, treatment, and outcome. RESULTS: Median age of the dogs was 6.5 years. Spayed females and Labrador Retrievers were significantly overrepresented. Median Hct was 11% with no evidence of regeneration (median, 1.5 x 10(3) reticulocytes/microliter). Direct Coombs' test results were positive in 57% of dogs. Biochemical abnormalities included hyperferremia and high percentage saturation of transferrin. Bone marrow findings ranged from PRCA (5%) to erythroid hyperplasia (55%). Myelofibrosis was common. Dogs were treated with immunosuppressive drugs and the response was complete, partial, and poor in 55, 18, and 27% of the dogs, respectively. Mortality rate was 28%. CONCLUSIONS AND CLINICAL RELEVANCE: An immune-mediated pathogenesis should be considered in dogs with severe, nonregenerative anemia, normal WBC and platelet counts, hyperferremia, mild clinical signs, and no evidence of underlying disease. Bone marrow findings range from the rare PRCA to erythroid hyperplasia. Myelofibrosis is often detected in affected dogs and may prevent bone marrow aspiration

Clinical signs, clinicopathological findings, etiology, and outcome associated with hemoptysis in dogs: 36 cases (1990-1999).
Bailiff NL, Norris CR.
Vet Med Teaching Hosp, School of Vet Med, Univ of California, Davis 95616, USA.
J Am Anim Hosp Assoc 2002 Mar-Apr;38(2):125-33
Hemoptysis, the expectoration of blood or bloody mucus from the respiratory tract at or below the larynx, was retrospectively evaluated in 36 dogs. Cough, tachypnea, and dyspnea were common historical and physical examination signs. Anemia was documented in 11 dogs, but was severe in only one dog. Other clinicopathological findings reflected the underlying diseases. All thoracic radiographs obtained were abnormal; alveolar and interstitial patterns were most common. Diseases predisposing to hemoptysis included bacterial bronchopneumonia (n=7), neoplasia (n=5), trauma (n=5), immune-mediated thrombocytopenia (n=4), heartworm disease (n=4), rodenticide poisoning (n=3), lung-lobe torsion (n=1), left-sided congestive heart failure (n=1), pulmonary hypertension (n=1), and foreign-body pneumonia (n=1). Four additional dogs had more than one underlying disease process. Nine dogs were either euthanized or died in the hospital during the initial visit. While at least half of the 27 dogs discharged went on to completely recover, five dogs discharged were known to have either died or been euthanized as a result of their disease in <6 months.