Everything you need to know about… IMHA

Immune-mediated haemolytic anaemia is one of the most common haematological diseases we see in practice. It can be a really horrible condition, but ultimately a very rewarding one for us as nurses. Today we’re looking at IMHA in more detail – why it happens, how it is diagnosed, and how we as nurses can best support these patients.

If you’ve not seen them already, my previous posts on haematology may be helpful reading alongside this post – so be sure to check those out.

Ready to jump in? Let’s go…

Pathophysiology

IMHA can occur as a primary (or idiopathic) disease, or secondary to other specific causes and conditions. These include infectious disease (such as Mycoplasma haemofelis infection in cats), neoplasia and the administration of certain medications (trimethoprim-sulfa and cephalosporin antibiotics, for example).

In cats, secondary IMHA is the most common form, unlike dogs who typically present with primary or idiopathic IMHA. A genetic link is hypothesised given that spaniel breeds (Cocker and English Springer Spaniels) are over-represented, as are female dogs.

So what happens within the body? Well, the immune system recognises proteins or glycoproteins normally present with the red cell membrane as antigens (known as autoantigens, as they are from the patient’s own body) and ‘marks’ these red blood cells as foreign, which leads to antibodies (IgG or IgM) attaching to the cells. This antibody attachment causes the cell to be removed (fully or partially) from the bloodstream via monocytes and macrophages. This results in extravascular haemolysis. The antibody attachment also causes ‘complement’ (part of the immune system, which functions to enhance the ability of antibodies and macrophages) to attack red cell membranes. The damaged red blood cell membranes allow water and ions to enter the cells, causing them to swell and eventually rupture. This results in intravascular haemolysis. Intravascular haemolysis usually happens on a massive scale, leading to the massive release of free haemoglobin into the bloodstream. This haemoglobin is broken down into bilirubin, leading to the classic jaundice we see in IMHA.

Clinical signs

There are two clinical presentations of IMHA in general, each with different clinical signs. Most commonly, patients present with a gradual onset of signs including:

• Progressive hyporexia or anorexia

• Increasing lethargy

• Exercise intolerance

• Pale mucous membranes

• Petechiation if concurrent thrombocytopenia is present (the combination of immune-mediated thrombocytopenia and anaemia is known as Evan’s syndrome, and is seen relatively frequently in dogs)

• Tachycardia and tachypnoea (compensatory, due to anaemia)

• Cardiac murmur (due to chronic anaemia)

• Splenomegaly +/- hepatomegaly (due to extramedullary haematopoiesis, where the spleen is releasing red blood cells)

Alternatively, patients may present in a haemolytic crisis. This is the IMHA presentation we all classically think of, and signs include:

• Acute collapse

• Severe jaundice

• Haemoglobinuria

• Signs of cardiovascular instability (tachycardia, weak pulses, hypotension, dull mentation)

• Pyrexia

• Tachypnoea (due to reduced oxygen-carrying capacity and tissue hypoxia)

In cats, pica (the eating of abnormal non-food items) may also be seen in cases of chronic anaemia (one of my IMHA patients always used to lick the patio when her IMHA was relapsing!). It is also important to consider that cats have a better ability to cope with chronic anaemia than dogs, so may have much more severe anaemia when they present to the clinic unwell.

Diagnostics

Diagnosis is made through a number of tests, in combination with evaluating the patient’s clinical history and their physical examination findings. Diagnostics tests commonly performed in the IMHA patient include:

• Haematology: A complete blood count is the first step in IMHA diagnosis. Including a reticulocyte count is important here – we need to assess regeneration. IMHA classically is a strongly regenerative, severely haemolytic anaemia.

• Blood smear examination: In IMHA, spherocytes are commonly seen on blood film examination. These are red blood cells which have been partially phagocytosed, and appear as small, round cells with no central pallor. Evidence of regeneration (polychromasia) is also classically seen.

• In-saline agglutination test: This is a simple and quick test used to diagnose IMHA. The patient’s blood is mixed with saline on a microscope slide and observed for any RBC agglutination. If it is present, cells should be examined under the microscope, to check rouleaux formation (a normal artefact where the RBCs ‘stack up’ on the slide) is not being seen instead.

• Coombs test: Also known as the direct antiglobulin test. This combines washed red blood cells with an antiserum solution and determines whether agglutination occurs.

• Biochemistry: Performed to determine whether any other contributing diseases may be present, and to assess any potential systemic effects of IMHA. Hyperbilirubinaemia, elevated ALT and ALP, and hypoalbuminaemia may be seen.

• Infectious disease testing: Performed to rule out primary causes of IMHA or other causes of anaemia, such as tick-borne diseases in dogs, or Mycoplasma haemofelis, FeLV and FIV in cats.

• Thoracic or abdominal imaging: Ultrasound, radiography or CT may be performed to determine the presence of any neoplasia causing secondary IMHA, and guide FNAs of the liver and/or spleen where required.

Treatment

A number of treatment considerations exist in IMHA patients, including:

• Fluid therapy: correction of perfusion deficits is required as a priority in the IMHA patient. In addition, crystalloids can avoid blood ‘sludging’ and minimise the risk of thrombosis (clot formation), as well as help to eliminate free haemoglobin from the bloodstream and minimise the damage this may have on the kidneys.

• Immunosuppression: Immunosuppressive treatment is the mainstay of treatment in the IMHA patient. Usually, combination treatment is used, as this minimises the side effects of using one agent alone. A variety of immunosuppressive agents are available, including glucocorticoids (steroids), azathioprine, ciclosporin, chlorambucil and mycophenolate. Each agent has their own nursing and health and safety considerations; PU/PD, gastrointestinal signs, and bone marrow suppression are risks associated with immunosuppressive medications, and the veterinary nurse should monitor for these signs, and advise clients accordingly. Immunosuppressive medications should be handled wearing appropriate PPE since transdermal absorption is possible.

• Blood product transfusion: Depending on the degree of anaemia and the patient’s clinical signs, replacement of red blood cells may be required. This replenishes the patient’s oxygen-carrying capacity and provides cardiovascular support. Prior to transfusion, the patient should be blood typed and (if appropriate) cross-matched with a type-matched unit of packed red blood cells (or whole blood if this is all you have available). Ideally, packed cells would be used in the IMHA patient; as there is no plasma loss, we are therefore able to replace ‘like for like’ and minimise the risk of volume overload, associated with excessive plasma volumes.

• Antithrombotics: Patients with IMHA are at risk of thrombosis, and antithrombotic medications should be started at an early stage. Most commonly this is achieved through the administration of clopidogrel, though the use of heparin and low-dose aspirin is also reported.

Nursing care

IMHA patients generally have significant systemic illness at the time of presentation and often have intensive nursing requirements. These include:

• Monitoring: These patients present with varying degrees of cardiovascular instability and require intensive monitoring, especially where blood products are administered. Vital signs and perfusion parameters (pulse quality, demeanour, heart rate, blood pressure, peripheral temperature, core temperature, mucous membrane colour and CRT) should be assessed at appropriate intervals. Monitoring should also include observation for any changes in patient status or deterioration, including the development of thrombosis. Thrombi commonly affect the lungs in these patients (pulmonary thromboemboli or PTE), and their respiration should be observed closely for any changes. Thrombi can also affect the central nervous system and other areas such as limbs; the latter is associated with significant pain, oedema and loss of function, and nursing care is directed at provision of analgesia, warming/massaging the limb and supporting mobility.

• Recumbent patient care: Patients with acute IMHA often present collapsed and may be recumbent. Nursing care of these patients should include regular turning, management of eliminations (bearing in mind that if thrombocytopenia is present, urinary catheterisation may be contraindicated), physiotherapy, and the provision of padded, wicking bedding.

• Nutrition: These patients typically present with a history of progressive hyporexia or anorexia. They should have their resting energy requirement calculated for their current weight, and food volumes offered and consumed should be measured. Where hyporexia or anorexia persists for >2-3 days, appropriate enteral nutritional support should be provided. This is typically achieved through the use of a naso-oesophageal feeding tube (as these can be placed quickly and easily in the conscious patient), providing the patient has sufficient platelet levels to minimise the risk of significant epistaxis.

• Fluid Balance: The patient’s perfusion and hydration status should be regularly assessed, and appropriate fluid therapy provided. The rate of any fluids administered should be adjusted as required, based on patient assessment. Intravenous catheters should be flushed and checked regularly for signs of thrombophlebitis, including a 12-hourly bandage change and full site inspection.

• Barrier Nursing: Due to the high doses of immunosuppressive agents these patients require, they may be at an increased risk of significant infection control challenges within the hospital. They should, therefore, be barrier nursed, and strict aseptic technique should be followed when performing nursing procedures or interventions. This will help minimise the risk of a hospital-acquired infection developing.

• General Nursing Care: These patients often have a high number of checks and interventions performed; this can be quite stressful and significantly impact sleep and rest. Lights-out time should be scheduled to allow periods of recuperation, and treatments should be grouped together as much as possible to facilitate this. These patients also often tire easily due to their anaemia, and so may require careful management of exercise, with regular short walks, or being carried out to the toileting area. The importance of grooming and TLC also cannot be overlooked and should be incorporated into any nursing plans made for these patients.

So as you can see, lots to consider in the IMHA patient, which really makes them fantastic cases to nurse! What are your biggest take-aways from today’s post? Let me know in the comments below, and be sure to check out our other posts in the haematology series.

As ever, references used in today’s post are below, and I look forward to seeing you in the next one!

References

1. Day, MJ and Kohn, B. 2012. BSAVA Manual of Canine and Feline Haematology and Transfusion Medicine. 2nd ed. Gloucester: BSAVA.

2. Merrill, L. 2012. Small Animal Internal Medicine for Veterinary Technicians and Nurses. 1st ed. Iowa: Wiley-Blackwell.