THE NEW ZEALAND VETERINARY NURSE SEPTEMBER 2015 Evans Syndrome: Breaking down IMHA and ITP

Amy Breton CVT, VTS (ECC), BluePearl-Massachusetts, USA NZVNJ Issue 75 Volume 21 Pages 24-28

Introduction There is an increased rate of extra vascular -associated antibody levels. In ITP Immune-mediated haemolytic anaemia haemolysis within the spleen and liver patients, platelet life span is reduced from (IMHA) is the most common cause of because of the removal of the antibody- the normal four to eight days to usually less haemolytic anaemia in dogs and immune- coated RBCs by the macrophages.3 While than one day.5 In patients with high antibody mediated (ITP) is the generally the antibodies attack the antigens levels may survive less than one most common cause of severe thrombocy- of mature RBCs, in some patients, they may hour.5 Platelets that survive usually function topenia in dogs.1, 2 Both can occur in cats, attack the precursors of RBCs in bone mar- normally. 1 4 but are less common. IMHA and ITP may row. In most IMHA patients regeneration Immune-mediated haemolytic occur simultaneously or separate from each of RBCs is apparent, but if the antibodies anaemia other. When they occur together they are attack the bone marrow the patient may 4 IMHA can affect both dogs and cats, but is known as Evans syndrome, an autoimmune develop a non-regenerative IMHA. 2 typically seen in middle aged dogs. Dogs disease in which an individual’s antibod- ITP, also written with the acronym of IMT, that have secondary IMHA due to disease ies attack their own red blood cells and 3 1 occurs also because of primary (idiopathic) are commonly spayed females. There is platelets. or secondary (drug induced, neoplasia) some evidence of genetic predisposition in Pathophysiology reasons.1 Similarly to IMHA, ITP occurs Cocker Spaniels and Miniature Schnau- IMHA can be primary (idiopathic), or because antibodies are produced against zers, but it is also prevalent in Poodles, Irish secondary (viral, bacterial, parasitic, drug or platelet antigens which ultimately destroy Setters, Dobermans, Lhasa Apsos, English 2 vaccine induced). Approximately 60-75% platelets.3 The major organ of immune- Springer Spaniels and Old English Sheep- of IMHA in dogs is primary IMHA rather mediated platelet destruction is the spleen, dogs. 1, 2, 3 Roughly 60% of dogs with IMHA 2 than secondary. Vaccines and some medica- which is also a major source of anti-platelet will also experience concurrent ITP (Evans tions (cephalosporin’s, trimethoprim-sulfa) antibodies.5 Platelet life span is correlated to Syndrome).6 have been reported as a secondary causes 1 of IMHA. In both primary and second- B cell ary IMHA, the destruction of red blood cells (RBCs) occurs because antibodies are produced against the secretion membrane antigens.2 An antibody is a spe- cialized immune protein which is produced IgG IgM in response to an antigen in the body and works to destroy the antigen. It is unknown Splenic macrophage what triggers this inappropriate antibody production in primary IMHA. Antibody Fcy receptor attachment to cell membranes triggers RBC destruction by a number of different C3b C3b mechanisms. With high levels of antibody C3b attachment the RBC membranes may C3b C3b become damaged so that water leaks into C3 receptor complement fixation agglutination to C3b the cytoplasm.4 This causes swelling and 4 phagocytosis of immunoglobin- rupture of the RBC thus causing hemolysis. and complement (C3b)-coated RBCs Antibodies may bind to two different RBCs, which, in turn, causes the RBCs to clump complement fixation 4 to membrane attack complex together, also known as agglutination. causing intravascular RBC lysis This clumping of RBC will slow down the Above: IMHA RBC destruction passage of other RBCs through the vessels. Image sourced from http://www.eclinpath.com/wp-content/uploads/IMHA-rbc-destruction.jpg 24 THE NEW ZEALAND VETERINARY NURSE SEPTEMBER 2015

Because the animal’s body is destroying its and anticoagulated blood, placing them on a positives can occur, but they are rare. False RBCs, it typically presents with signs of slide and rocking it back/forth for a minute.7 negatives can occur because of a low amount anaemia. Anaemic signs include weakness/ It is not possible to differentiate between of circulating antibodies.9 If the patient collapse, lethargy, dull/depressed mentation, rouleax and autoagglutination using this receives a blood transfusion or if there is pale/white mucous membranes, bounding method. 7 Lastly there are other references a large amount of agglutination a direct 1 1, 9 pulses, heart murmur and tachycardia. Some that recommend one drop of anticoagulated Coombs’ test will not be accurate. patients may present with a fever due to the blood should be mixed with “several” drops Flow cytometry is a newer test for evaluat- immune and/or inflammatory response 10 of 0.9% NaCl on a slide and rocked back/ ing antibodies in dogs. It allows for the while others may be hypothermic due to the 8 forth. It is recommended to look at the detection of red cell surface bound immu- anemia.1, 4 The spleen and, less commonly, slide using a microscope to identify rouleax noglobulin G (IgG) and immunoglobulin the liver may be enlarged since they are 10 versus agglutination. No matter the method M (IgM) antibodies. Anaemic dogs are the major organs where RBC destruction used, a positive agglutination test does not more likely to be positive for antibod- takes place. As large quantities of RBCs are confirm or rule out IMHA, but it does mean ies (IgG, IgM, or both) than nonanaemic broken down, bilirubin is released into the 4 11 the condition is acute and severe. dogs. However, dogs with IMHA have blood stream which may overwhelm the liver significantly higher percentages of the causing some patients to become icteric.5 A CBC should always be submitted to an outside laboratory to check for reticulocytes. antibodies than other dogs that are anaemic Diagnosis of IMHA 11 Reticulocytes are immature red blood cells. for non-IMHA causes. Flow cytometry The diagnosis of IMHA relies heavily on The presence of them indicates a functioning for the detection of IgG on RBCs is highly blood work. On a complete blood count bone marrow and often a better prognosis sensitive and, therefore, very specific for the 11 (CBC) 95% of dogs will have spherocytes for the pet. Reticulocytes will circulate diagnosis of IMHA. (small, spherical RBCs).9 Agglutination, for about a day in the blood stream before In cats it is important to test for feline leu- also known as clumping, of the RBCs usually 1 developing into mature red blood cells. kaemia and Mycoplasma haemofelis as they are occurs. There are several reported methods 3 Reticulocytes are found in approximately often the cause of IMHA. The organism on how to perform a slide agglutination test, 60-70% of IMHA patients and the number will fall off red blood cells in samples that but all involve anticoagulated blood and 0.9% of reticulocytes is relative to the degree of are greater than 24 hours old. Therefore it NaCl. One reference suggests taking one 2 anemia. is best to make a blood smear with a fresh drop of anticoagulated blood (from a purple sample. 12 In an acute infection the organism or capillary tube) and mixing with 10 drops The Coombs’ test, also known as a direct is only visible 50% of the time. 12 In cats the of 0.9% NaCl on a slide.1 Rouleax, which antiglobulin test (DAT), offers a more con- 9 anaemia is often regenerative and therefore causes the RBC’s to look like ‘stacked coins’ clusive diagnosis for IMHA. The Coombs’ offers a better prognosis.3 under the microscope, will disperse while test detects antibodies that are attached to agglutination will clump.1 Another reference the RBCs 9, and consists of running a series Complications of IMHA suggests taking equal parts of 0.9% NaCl of dilutions until agglutination occurs. False The complications of IMHA are vast. These include thrombocytopenia, disseminated intravascular (DIC), thrombo- embolism, gastrointestinal (GI) ulceration, renal failure and refractory anemia.2 Throm- bocytopenia can occur because of ITP (Evans Syndrome) or because of platelet consumption.2 The exact physiology of why ITP occurs concurrently with IMHA is unknown. 13 DIC can be triggered for a variety of reasons including thromboplastic substances released from the RBC membranes or tissue ischemia from hypoxia, 2 Ultimately coagulation times should be checked and patients should be monitored for signs of excessive , petechiae and ecchymoses. Thromboemobolism, particularly pulmonary thromboembolism, can occur in patients with IMHA, but it is unknown how fre- quently this occurs. The exact pathogenesis remains unknown, but the release of throm- Above: Note the stacking appearance of the RBC’s boplastic substances from RBCs, high Image sourced from http://www.myelomapennstate.net/images/DrBayerl/Rouleaux50x.jpg. volume of circulating bilirubin, venipuncture, 25 THE NEW ZEALAND VETERINARY NURSE SEPTEMBER 2015 catheters, and immunosuppressive agents immunoglobulin IgG.3,16 Steroids are not as Lastly both cyclosporine (Atopica™, may be contributing factors. 2,14 Pulmonary beneficial when dealing with intravascular Novartis) and (Danocrine, Win- thromboembolism should be suspected in haemolysis that is mediated by IgM, so throp Pharmaceuticals) have both been used patients that suddenly develop respiratory in those cases other immunosuppressive to treat IMHA as secondary line medica- distress.4 agents (cyclosporine, cyclophosphamide) tions.17 Cyclosporine has been widely used can be used.3 Unfortunately, the studies in people for IMHA as well as for trans- Gastrointestinal ulceration and bleeding involving other immunosuppressive agents plantation surgery to help decrease factors can occur secondary to DIC, the use of are limited and have shown they are not any that stimulate an inappropriate autoimmune glucorticosterioids, ischemic injury to the 16 17 2 more effective then . The response. Cyclosporine is generally well GI mucosa and thrombocytopenia. GI pro- most common corticosteroids are prednisone tolerated in dogs, but rare gastrointestinal tectants are frequently used in these patients or prednisolone.16 The difference between signs can occur as a side effect which resolve for these reasons. Renal injury can occur 17 after the drug is discontinued. The efficacy because of hypoperfusion, vasoconstriction, prednisolone and prednisone is how they are of danazol is not supported by any published ischemia and dehydration.2 Patients may metabolized. Prednisone is metabolized by the liver while prednisolone is not. Therefore reports and is rarely used perhaps because it experience refractory anaemia because of a 17 can be hepatotoxic in dogs. direct immune injury to erythroid precursors, prednisolone is generally considered easier bleeding from GI tract or suppressed eryth- in patients with liver disease. Response to A can be performed, but is rec- ropoiesis by immunosuppressive agents.2 corticosteroids includes rising haematocrit, ommended as a last attempt in treatment due adequate reticulocytes, reduced spherocytes, to the numerous risk factors of putting the Treatment of IMHA 2 and reduced agglutination of the RBCs. pet under a general anaesthesia who is ane- Treatment first involves dealing with the 17 Azathioprine is a purine (mimics DNA mic. A splenectomy may help to decrease anaemia. This may include oxygen supple- 16 and RNA) analogue immunosuppressive RBC destruction in patients with IMHA. mentation and/or red blood cell transfusion. It is not recommended if the pet also has ITP There are valid concerns that transfusing a drug that is commonly combined with prednisone therapy.16 Since it is commonly as the pet will likely bleed from the surgery patient may worsen the IMHA, thus the and die as a result of its inability to clot. In recommendation that patients should not be used with prednisone, its efficacy alone is unknown. Reports and studies are variable humans where a splenectomy was performed transfused until they have a packed cell vol- on patients with Evans sydrome, the patient’s 4 when it comes to its effectiveness when ume (PCV) less than 20–22%. If patients response was poorer than those just receiv- used with prednisone. It is thought to have with a PCV greater than 22% are transfused ing medical management. For patients who there is an increased risk of thromboembo- a synergistic effect which allows for a faster 6 experience reoccurrences of Evans syndromes 4 reduction of prednisone. Azathioprine is lism. Haemoglobin based oxygen carriers a splenectomy may be an option. are no longer available, but should they be low-cost and well tolerated in dogs which is Prognosis available they offer greater oxygen carrying why it’s an attractive choice as an additional 17 capacity then red blood cell transfusion and line of defense. Unfortunately it can take Prognosis depends on numerous things, but is quickly alleviate signs of hypoxia.4 up to six weeks for the medication to take more favourable in the cat than the dog. The full effect so it is used in conjunction with number of blood transfusions required is a 4 Fluid therapy is important. Stabilization other medication. 17 negative prognostic factor for IMHA. This of patients is usually achieved through the could be because of the severity of the disease In humans intravenous immunoglobulin use of crystalloids. Maintenance of tis- or because of the transfusion complications (IVIG) is considered a first line treatment sue perfusion is equally important, even themselves. Dogs with Evans syndrome when it results in further lowering of the and is used in cases where prednisone doses 13 have a worse prognosis than those that have 14 are dangerously high or are ineffective. 18 hematocrit. Fluids are also important in IMHA or ITP alone. Patients who experi- maintaining renal perfusion and helping to There are several studies showing evidence ence DIC have a worse prognosis.14 that IVIG competitively inhibits the bind- deal with the high levels of circulating bili- Immune-mediated rubin.10 Patients experiencing DIC should ing of canine IgG making it effective for 17 thrombocytopenia receive fresh frozen plasma. IMHA. The mechanism of action of IVIG is not completely understood, but it may While not as common as IMHA, ITP occurs 19 Treatment may involve dealing with any work on the cytokine network and help to in dogs and less commonly in cats. There underlying diseases that may have caused neutralize autoantibodies.16 There have been are numerous similarities between IMHA the IMHA (rickettsia, Mycoplasma, etc.). no studies with regards to only IVIG being and ITP. It is more common in middle If the pet is experiencing primary IMHA, 19 used by itself, so it is recommended that it is aged females. Breeds that are predisposed immunosuppressive drugs are given along include Airedales, Dobermans, Old English used in conjunction with prednisone or after 3 with GI protectants to prevent GI bleeding. 13 an attempt with prednisone has occurred. Sheepdogs, Cocker Spaniels and Poodles. Corticosteroids (prednisone, prednisolone) Unfortunately due to expense, periodic lim- Clinical Signs of ITP are the primary drugs used for helping to ited availability, potential increased risk of Clinical signs include petechial haemorrhage, suppress the .13 High doses thromboembolic disease and the concern of ecchymoses, melena, haematuria, retinal of corticosteroids help to reduce phago- the pet building a hypersensitivity reaction to haemorrhage and epistaxis. A worsening cytosis of RBCs, decrease production of the human product it is usually not the first of the signs occurs in patients with severe cytokines and decrease the production of choice of treatment.16 thrombocytopenia (<10,000 platelets/µL).6 26 THE NEW ZEALAND VETERINARY NURSE SEPTEMBER 2015

Diagnosis of ITP the therapy because it interferes with some Blood transfusions may be needed and will A diagnosis is performed by obtaining a immune system effects on the platelets and require diligent monitoring. Patients should platelet count. An in-house count can be also helps to mature megakaryocytes into be monitored for any signs of a blood trans- performed by counting 10 high power fields, functional platelets faster.20 Several studies fusion reaction including urticaria, vomiting, 1 and divide by 10 to get the average per field. have shown that the addition of vincristine collapse, fever, shaking or panting. Then multiple by 15,000 to obtain the total along with prednisone helped dogs reach Patients will also need to be monitored for estimated platelet count. 1 A normal patient 40,000 cells/µL faster than prednisone blood transfusion illness, which can take up should have between 200,000-800,000 cell/ alone.20 1, 20 to five days to occur. µL. While a low in-house platelet test Nursing care may suggest ITP, it is best to send a CBC for Physical exams should occur minimally a manual platelet count to be read. A platelet Patients with Evans syndrome often require every eight hours and include a heart rate, count of less than 30,000 in addition to a intensive veterinary nursing care which is pulse rate, respiratory rate and effort, mucous low mean platelet volume (MPV) is highly dependent on their degree of illness. Upon membrane colour, capillary refill time, rectal suggestive of ITP.1 MPV (the average size initial presentation these patients may temperature and neurological status. If there of platelets) is increased when bone marrow require oxygen supplementation. Oxygen is any change from normal parameters, the has an active response to an insult (like an should be provided initially by the least- veterinarian should be notified. Besides a 22 immune response). The bone marrow will stressful route. Oxygen hoods made from stethoscope and thermometer to monitor release a high number of immature platelets elizabethan collars tend to be well tolerated. vitals there are a couple other tools which which will increase the average size of the Oxygen hoods tend to provide quick relief can be utilized to improve patient moni- platelets, thus increasing MPV. Conversely and FiO2 levels can get up to 60% oxygen toring: blood pressure, lactate and central the number of megakaryocytes in the bone very quickly. 23 Small oxygen cages can be venous pressure (CVP). Because patients are marrow will be reduced. A 2008 study utilized for cats and FiO2 levels can get up at risk for DIC it is important to look for showed MPV to be almost 100% reliable to 40%, but take anywhere from 25 minutes early signs, which include excessive bleeding when differentiating ITP from other causes for the FiO2 to reach a level greater than after venipuncture and/or petechiae on the 21 of thrombocytopenia. An ELISA test for 40%.23 You also cannot work with your gums, pinna or abdomen. the presence of antiplatelet antibodies can be patient if they are in a cage. Flow-by oxygen It is important that IMHA patients have performed though it is not very specific to efficacy is still debated since it is unknown their blood pressure monitored minimally ITP.10 A negative results will rule out ITP, how much of the oxygen the animal actually every eight to twelve hours. If the mean but a positive result just indicates thromo- inhales. The oxygen tubing must be inches arterial pressure (MAP) falls below 60 cytopenia.10 ITP is ultimately a disease of away from the animal’s nose in order for it mmHg, the kidneys and other organs are not rule-outs. 23 to be effective. Long term oxygen therapy appropriately perfused putting the patient at Complications of ITP can include the use of oxygen cages or nasal risk for organ failure. Normalization of blood The biggest complication of ITP is DIC. oxygen lines. Patients may need arterial pressure, defined by a of MAP of 80-120 Coagulation times should be checked blood gas or pulse oximetry performed to mmHg or systolic between 110-160 mmHg, and patients should be monitored for monitor overall oxygenation ability. is the goal in any Evans syndrome patient.25 signs of excessive bleeding, petechiae and ecchymoses. Treatment of ITP Treatment is similar to that of IMHA. While transfusing with red blood cells is done to prevent life threatening anaemia in IMHA patients, the transfusion of platelet rich plasma or whole blood is not as common. Unfortunately platelets are extremely fragile and, if transfused, the patient’s immune sys- tem will often destroy new platelets within hours.10 One application of transfusing is for those patients where a splenectomy has been chosen as a method of treatment.10 Trans- fusing patients with whole blood right before surgery may decrease the rate of bleeding. Patients with ITP will be put on corticos- teroids (prednisone, prednisolone) and other adjunctive therapies may also be added (azathioprine, cyclophosphamide, danazol, Above: Note the petechial haemorrhage on the gums cyclosporine).20 Vincristine may be added to Image sourced from http://www.hazeldeananimalhospital.ca/happy-tails/ 27 THE NEW ZEALAND VETERINARY NURSE SEPTEMBER 2015

Lactate accumulates in the tissues and blood References: 15. Silverstein D., Hopper K., “Small Animal as a result of inadequate oxygen availability, 1. Norkus C., “Veterinary Technician’s Critical Care Medicine”, Chapter 121: caused by tissue hypoperfusion, and can Manual for Small Animal Emergency and Acute Hemolytic Disorders, Ed. Cohn L., occur in Evans syndrome patients. Lactate Critical Care”, Chapter 11: Specific Organ St. Louis, MI, Saunders Elsevier, 2009, pp: can be measured using a simple hand-held System Disorders, ed. Campbell M., Ames, 518-522. device similar to a blood glucose machine. It Iowa, Wiley-Blackwell, 2012, pp. 243-252 15. Lunn K., “Innovative Therapies for is important to normalize lactate concentra- 2. Wingfield W., Raffe M., “Veterinary ICU Immune-Mediated Hemolysis in Dogs”, tions through fluid therapy, blood pressure Book”, Chapter 46: Immune-Mediated ACVIM Proceedings 2009 normalization, and providing adequate Hemolytic Anemia, ed. Faudskar L., Jack- 17. Whitley N., Day M., “Immunomodula- oxygen delivery to the tissues. son, WY: Teton New Media, 2002, pp: tory drugs and their application to the 710-720. management of canine immune-mediated Since IMHA patients often require frequent 3. Tizard I, “Veterinary Immunology”, Chap- disease”, J Small Anim Pract. 2011 Feb; blood draws, a central line should be placed. ter 35: Organ-Specific Autoimmune Diseases, 52(2):70-85 While the internal and external jugular veins St. Louis, MI: Elsevier Saunders, 2013, pp: 18. Orcutt E, Lee J, Bianco D., “ Immune- are usually used for central catheter place- 417-421. mediated hemolytic anemia and severe ment, it is not recommended for patients 4. Mackin, A., “Immune-Mediated Hemo- thrombocytopenia in dogs: 12 cases at risk of . The lateral saphenous lytic Anemia: Pathophysiology and (2001-2008)”, J Vet Emerg Crit Care (San vein is an alternative for use in dogs. While Diagnosis”, Atlantic Coast Veterinary Antonio), 2010 Jun; 20(3):338-45. this can be used in cats also, the medial Conference Proceedings 2010 19. McGavin M., Zachary J., “Pathologic saphenous is more commonly used. If the 5. Mackin, A., “Immune-Mediated Throm- Basis of Veterinary Disease 4th Edition”, patient is experiencing Evans syndrome then bocytopenia: Pathophysiology and venipuncture should be avoided on large ves- Section II, Chapter 13: Bone Marrow, Blood Diagnosis”, Atlantic Coast Veterinary Cells, and Lymphatic System, eds. Fry, M., sels unless the veterinarian feels the patient Conference Proceedings 2010 1 McGavin M., St. Louis, MI: Mosby Else- has adequate platelets. If a central line is 6. Kahn C., “The Merck Veterinary Manual vier, pp: 781-195 placed, CVP can be performed. CVP is gen- Tenth Edition”, Immune System, Rahway, 20. Silverstein D., Hopper K., “Small Animal erally monitored when a patient is prone to NJ: Merck Publishing Group, 2010, pp. Critical Care Medicine”, Chapter 119: changes in blood pressure or when aggressive 750-751. Thrombocytopenia, Ed. Cohn L., St. fluid therapy is being utilized. 7. Abrams-Ogg A., “Immune-Mediated Louis, MI, Saunders Elsevier, 2009, pp: Hemolytic Anemia and/or Thrombocy- Urine output should be monitored and 515-517. topenia in the Dog: Is There Anything recorded. Quantifying urine output is key 21. Ntaios G, Papadopoulos A, Chatz- More I Can Do?” Western Veterinary in monitoring fluid therapy as well as in inikolaou A, Saouli Z, Karalazou P, Kaiafa Conference Proceedings 2011 patients with renal disease. In both dogs and 8. G, Girtovitis F, Kontoninas Z, Savopoulos Jutkowitz L., “Clinical Approach to the cats, one to two ml/kg/hr of urine should C, Hatzitolios A, Alexiou-Daniel S., “ Anemic Patient”, Western Veterinary be produced (if the patient is not on fluids) Increased values of mean platelet volume Conference Proceedings 2009 or the volume out should equal the volume 9. and platelet size deviation width may 24 Ruderman C., “Diagnosis, Treatment, given. provide a safe positive diagnosis of idi- & Long Term Management of Canine Lastly, nutritional support must be consid- IMHA”, ACVIM Proceedings 2010 opathic thrombocytopenic ”, Acta ered in Evans syndrome patients that are 10. Haematol. 2008; 119(3):173-7. Kahn C., “The Merck Veterinary Manual 22. hospitalized. Providing nutritional support Tenth Edition”, Circulatory System, Rah- Biddinger B., Assessment and Monitoring to these patients early is essential in order way, NJ: Merck Publishing Group, 2010, of Pleural Diseases, ACVIM Conference to minimize weight loss and to provide pp. 12-13. Proceedings 2007 26 23. adequate energy for metabolic support. 11. Morley P, Mathes M, Guth A, Dow S., “ Crowe T., Oxygen Therapy: Techniques In both human and veterinary patients a Anti-erythrocyte antibodies and disease and Monitoring, IVECCS Symposium better outcome is seen in those that receive associations in anemic and nonanemic Proceedings 2004 24. nutritional support earlier. dogs”, J Vet Intern Med. 2008 Jul-Aug; Wingfield W. Raffe M. “Veterinary ICU 22(4):886-92. Book”, Chapter 13: Fluid and Electrolyte Since some of these patients may present 12. Ettinger S, Feldman E, “Textbook of Vet- Therapy,Jackson, WY: Teton New Media, collapsed and unable to walk at all, it is erinary Internal Medicine”, Chapter 209: 2002, pp 166-188 important to ensure the patient is kept clean, 25. Infectious Diseases, Saunders Elsevier, 2010, Bryant S., “Blood Pressure: Physiology dry and on adequate bedding. Patients who pp: 923-925. and Troubleshooting Hypotension Under do not turn themselves should be turned to 13. Norton A., Roberts I., “Management of Anesthesia”, International Veterinary prevent atelectasis of lung lobes. Evans syndrome”, British Journal Haema- Emergency and Critical Care Symposium Ultimately the patient’s condition may tology, 2006 Jan; 132(2):125-37 Proceedings 2009 change quickly depending on the progres- 14. Giger U., “Treatment of Immune-Medi- 26. Battaglia A., “Small Animal Emergency sion of the disease. It is imperative that ated Hemolytic Anemia”, World Small and Critical Care, 2nd Ed.” Nutritional appropriate veterinary nursing care is pro- Animal Veterinary Association World Support of the Critically Ill Patient, 2007, vided to them to allow for the best outcome. Congress Proceedings, 2010 St. Louis, Missouri: Elsevier: pp. 85-108 28