Anaemia has three broad causes (Mills, 2012): haemorrhage (blood loss due to bleeding), dyserythropoiesis (the inadequate production of red blood cells by the bone marrow) and haemolysis (the destruction of red blood cells in the body). This article will discuss immune-mediated haemolytic anaemia (IMHA), which is a common form of anaemia caused by haemolysis, and how veterinary nurses can care for small animal patients suffering from this disease.
What is immune-mediated haemolytic anaemia?
Anti-erythrocyte antibodies are produced by the immune system of animals with IMHA. These antibodies attach to red blood cells (RBCs), flagging them for removal. They are subsequently destroyed. This haemolysis can take place intra- or extravascularly, but the intravascular pathway has been associated with a worse prognosis.
Intravascular haemolysis happens within the blood vessels, causing haemoglobin to be released from the RBCs. A common clinical sign of intravascular haemolysis is port-red-coloured urine. Although a patient’s urine can appear red for a few reasons, the presence of RBCs is a common cause of this discoloration. Spinning a urine sample in a centrifuge is a good way to determine the cause of red-coloured urine. If the discoloration is a result of the presence of haemoglobin (haemoglobinuria), the sample will retain the port-red colour. Alternatively, if the urine contains RBCs, the sample will be layered after centrifugation with the RBCs present at the bottom of the spun sample and the urine, a normal yellow in appearance, on top.
If RBCs are destroyed extravascularly, haemolysis occurs mainly in the spleen and liver – organs that are normally involved in the destruction of RBCs at the end of their lifespan. This process produces bilirubin, which is excreted mainly via faeces. However, due to the excessive amount produced because of IMHA, the excretion system is overwhelmed. In the latter case, the patient could become jaundiced.
What causes immune-mediated haemolytic anaemia?
IMHA can be non-associative (without known cause) or associative, secondary to other conditions, such as infectious diseases (Mycoplasma spp, Ehrlichia spp), neoplasia (lymphoma/leukaemia) and medications (cephalosporin, carbimazole).
Non-associative IMHA is treated with immunosuppressants, whereas associative IMHA should resolve once the underlying disease is treated. This difference in source is why it is important to check for secondary causes before initiating immunosuppressive treatment. Therefore, a good clinical history should be taken and diagnostic tests carried out to check for underlying causes. Diagnostic testing usually involves various blood tests, diagnostic imaging and occasionally bone marrow biopsies.
Non-associative IMHA is treated with immunosuppressants, whereas associative IMHA should resolve once the underlying disease is treated. This difference in source is why it is important to check for secondary causes before initiating immunosuppressive treatment
IMHA is a disease commonly diagnosed in dogs and less commonly in cats. Certain breeds of dogs, such as Poodles, Collies, Miniature Schnauzers and Spaniels, are overrepresented, although any breed can be affected. Middle-aged female dogs are also overrepresented.
What are the clinical signs?
Patients with IMHA typically present with weakness, tachypnoea and lethargy. On physical examination, they usually have pale mucous membranes, bounding pulses and tachycardia, and may be jaundiced and/or have haemoglobinuria.
Patients can have concurrent immune-mediated thrombocytopenia (IMTP); 30 percent of patients that present with IMTP also have IMHA. Both conditions together are referred to as “Evans syndrome”. These patients may have petechiae or bruising (Apps, 2023).
How can veterinary nurses help diagnose immune-mediated haemolytic anaemia?
To assist the veterinary surgeon with a diagnosis, veterinary nurses can analyse blood smears. Blood smears of patients with IMHA will likely show spherocytes – small RBCs with a lack of central pallor – as 80 percent of patients with IMHA have spherocytes. Reticulocytes (immature RBCs) can also be seen, and their presence indicates that the anaemia is regenerative. If reticulocytes are not seen, it may suggest either that the anaemia has developed acutely and the bone marrow has not had time to start regeneration, or that the reticulocytes are also being destroyed.
Blood smears of patients with IMHA will likely show spherocytes – small RBCs with a lack of central pallor – as 80 percent of patients with IMHA have spherocyte
Nurses can also perform a saline agglutination test (SAGT) by placing a drop of fresh blood on a slide with four drops of saline and gently mixing them to assess for agglutination using the microscope. Agglutination occurs when the antibodies, which have several receptors, cause the RBCs to stick together in a form that is described as a “bunch of grapes”. Blood cells may also stack on top of each other in rouleaux formation – a normal finding described as a “stack of coins”. If the blood agglutinates, IMHA is highly likely, as 45 to 89 percent of IMHA patients have a positive SAGT(Archer and Mackin, 2013).
Another test that may be ordered is a Coombs test, which demonstrates the presence of the antibodies themselves, supporting a definitive diagnosis. However, concurrent anaemia, spherocytosis and a positive SAGT would be enough to reach a presumptive diagnosis and start treatment sooner. Packed cell volume (PCV) and total protein (TP) should also be checked, as monitoring PCV will tell us how well the patient is responding to treatment.
How do we treat immune-mediated haemolytic anaemia?
Non-associative IMHA is treated by suppressing the immune system, thus stopping RBCs from being destroyed.
Depending on the patient’s PCV and cardiovascular status, they may need a blood transfusion until their body can replenish its RBCs. Although the PCV value is an important factor, the whole clinical picture must be taken into consideration before deciding whether the transfusion of blood products is required. This is because transfusion reactions can be severe and, therefore, the benefit of the transfusion must greatly outweigh the risks involved. If the patient is tachycardic and tachypnoeic, and therefore cardiovascularly unstable, transfusion with blood products is indicated. However, some animals with a more chronic disease process cope well with a low PCV, so blood transfusion may be unnecessary.
Patients may present with a normal total blood volume (normovolaemic), just with low red blood cells. This can occur when the body compensates for the lack of circulating RBCs by upregulating the renin–angiotensin–aldosterone system, which is involved in regulating blood pressure and retaining water. For veterinary patients presenting this way, the provision of any form of fluids (unless they are hypovolaemic) can easily cause fluid overload. Therefore, we need to be careful when giving these patients crystalloids as, commonly, the only products they need are blood products (Swann et al., 2019).
Medications
The drug most commonly used to treat non-associative IMHA in unstable hospitalised patients is intravenous dexamethasone, but oral prednisolone is given to stable patients. If patients do not respond to steroids alone, or they develop significant adverse effects to these drugs, second-line drugs include cyclosporine and mycophenolate mofetil.
Patients with IMHA may be prescribed the anticoagulant rivaroxaban. This is because immune system dysregulation can cause them to have a reduced clot breakdown function. This hypercoagulable state increases the risk of thromboembolism. Studies have found that giving rivaroxaban can reduce the risk of thromboembolism, therefore, in certain cases, this is given pre-emptively (Uchida et al., 2020).
Surgical options
Less common forms of treatment from IMHA include splenectomy and therapeutic plasma exchange.
Although splenectomies have been linked with good outcomes (Bestwick et al., 2022), they are only suggested in patients that show a lack of response to several attempts at treatment.
Therapeutic plasma exchange replaces the patient’s plasma with donor plasma, removing the IMHA antibodies. It has been shown to be effective, but it is only available in a few places in the UK (RVC, n.d.).
What is the role of the nurse in treating immune-mediated haemolytic anaemia?
Most of the nursing interventions associated with looking after IMHA patients involve supportive care. This often involves making sure they receive adequate nutrition, preventing fluid overload and ensuring they have the opportunity to urinate/defaecate as and when needed.
As these patients are on immunosuppressants, good hygiene is very important. Therefore, nurses must ensure that all intravenous catheters:
- Are placed in a sterile manner
- Are redressed at least twice a day
- Do not become infected
Checking heart rate, respiratory rate and pulse quality is crucial, as the results will indicate whether patients are becoming transfusion-dependent.
Conclusion
The prognosis of IMHA is guarded, with mortality rates varying from 30 to 70 percent between studies, although newer studies are reporting better survival rates. Mortality usually occurs in these patients due to a lack of response to treatment, owner decision or euthanasia due to complications such as thromboembolic events (Archer and Mackin, 2013). Complications most commonly occur within the first two weeks after diagnosis.