41 | Help, my patient is yellow! How to stabilise and care for IMHA patients

HaematologyPodcastEmergency and Critical Care
Written By Laura Jones

When I say ‘IMHA’, what comes to mind?

 

For me, it’s the most challenging case I have ever cared for: a patient who had such severe anaemia that their jaundice made them neurological, earning them a few days on a propofol CRI due to seizures.

Whilst not every IMHA case is like this—thankfully—these patients do need intensive nursing care and monitoring, and with this, there are many skills we can use when caring for them.

But to do that, we first need to understand IMHA, how it affects our patients, and how we manage it—exactly what we’re covering in this episode.

So, what is IMHA?

Immune-mediated haemolytic anaemia is a disease where the body creates antibodies which destroy its own red blood cells.

It’s either a primary (non-associative) or secondary (associative) disease. Non-associative IMHA has no obvious underlying cause or trigger and is most commonly seen in dogs, especially cocker spaniels and poodles.

Secondary or associative IMHA is strongly associated with infectious diseases, such as Babesia infection in dogs or Mycoplasma haemofelis infection in cats. It’s also linked to feline leukaemia virus (FeLV) infection, neoplasia, vaccination, certain medications, bee stings and snake bites. This form of IMHA is seen more common in cats.

What happens when a patient gets IMHA?

IMHA is an antibody-mediated disease in which the immune system creates autoantibodies and activates the complement system to break down its own red blood cells (haemolysis). The complement system is a group of proteins that helps the immune system destroy pathogens.

The haemolysis we see with IMHA can be either extravascular—i.e., taking place outside of the blood vessels—or intravascular—taking place within the blood vessels.

Extravascular haemolysis occurs more frequently than intravascular haemolysis. With this form of the disease, macrophages inside organs like the spleen phagocytose and destroy RBCs. This causes haemoglobin to build up inside these macrophages, which is eventually turned into bilirubin, leading to jaundice.

Intravascular haemolysis is seen when antibodies and complement attach to the RBC surface and cause direct cell lysis within the circulation. This causes lots of haemoglobin to be released into the bloodstream, leading to haemoglobinaemia, haemoglobinuria and even acute kidney injury, as the haemoglobin can damage the nephrons as it filters through the kidney.

Most IMHAs are regenerative—i.e., the bone marrow responds to the anaemia by releasing new RBCs, which starts around 3-5 days after the patient becomes anaemic. However, some IMHAs are actually non-regenerative. This is either because our patients end up iron-deficient (and iron is needed to create RBCs) or because the immune system is attacking the immature RBCs in the bone marrow as well as the circulating RBCs.

What signs do we see in our IMHA patients?

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

  • Tachycardia and tachypnoea (compensatory, due to anaemia)

  • Cardiac murmur (due to decreased blood viscosity associated with anaemia, causing a so-called ‘flow murmur’)

  • 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 of this 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)

Some IMHA patients will have concurrent thrombocytopenia. The combination of IMHA and IMTP is referred to as Evan’s syndrome; where thrombocytopenia is also present, patients can have petechiation, bruising, melena and haematuria.

A known complication of IMHA is thrombi formation; these patients have a high risk of thromboembolism, and the location of one of these clots determines the clinical signs we see. If the patient develops pulmonary thromboembolism, they’ll have acute-onset dyspnoea and hypoxaemia, for example.

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

And how do we diagnose IMHA?

Alongside evaluating the patient themselves and their clinical history, several diagnostic tests are performed on patients suspected to have IMHA. These tests include:

Let’s start by looking at haematology

A complete blood count is the first step in diagnosing IMHA. Including a reticulocyte count is important here—we need to assess regeneration since around two-thirds of IMHA patients will be strongly regenerative. Most patients have moderate-to-marked anaemia with features of regeneration, such as an increased MCV and decreased MCHC. Around 55% of IMHA patients will have mild-to-moderate decreases in platelet levels, whilst around 25% of patients will have very low platelet levels.

Haemolysis and agglutination of RBCs can affect automated results, especially causing inaccuracies in haematocrit (HCT) and RBC levels. This means we must always double-check our haematology results against a blood smear examination.

Speaking of blood smears…

Spherocytes are commonly seen on the blood smears of IMHA patients. These are red blood cells that have been partially phagocytosed and appear as small, round cells with no central pallor. 

Alongside spherocytosis, evidence of regeneration (AKA polychromasia) is also classically seen. These cells appear as large, pale lilac RBCs with no distinct area of central pallor. Occasionally, the odd nucleated RBC can also be seen because the bone marrow is busy creating lots of new RBCs and occasionally throws one out too early!

What about the in-saline agglutination test?

The in-saline agglutination test or slide agglutination test 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 that rouleaux formation (a standard artefact where the RBCs ‘stack up’ on the slide) is not being seen instead.

How does the ISA differ from a Coombs test?

A Coombs test is also known as the direct antiglobulin test. This combines washed red blood cells with an antiserum solution and determines whether agglutination occurs. It’s similar to in-saline agglutination in that the same antibodies cause the positive result in both tests—though it’s performed differently. You can either run an in-house Coombs using a test kit or send it to an external laboratory.

What about biochemistry?

Biochemistry is performed to determine whether any other contributing diseases may be present and to assess any potential systemic effects of IMHA. Hyperbilirubinaemia is seen in around two-thirds of patients with IMHA, and elevated ALT and ALP are seen in over half of them.

Not forgetting infectious disease testing

Infectious disease testing is important 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.

And last of all… Diagnostic 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 spleen where required.

In non-associative IMHA, imaging is usually unremarkable, with the exception of splenomegaly. The spleen is involved in extravascular haemolysis and can also respond to anaemia and make new RBCs (known as extramedullary haematopoiesis).

So that’s your patient diagnosed, but how do we treat them?

Since IMHA is an immune-mediated disease, our treatment aims to suppress the immune system to control the disease and then provide supportive care to keep the patient stable while the immunosuppressants kick in.

But first, there’s stabilisation

Before we do that, though, we need to stabilise them. These patients often present to us in hypovolaemic shock, with reduced oxygen-carrying capacity due to their anaemia, resulting in a lack of oxygen delivery to tissues. They’re usually bradycardic or tachycardic (depending on how well they’re compensating for their anaemia), have weak or bounding pulses, are pale, and need urgent circulatory support.

We tend to start by giving them crystalloid boluses until an appropriate blood product can be sourced - yes, this might mean we haemodilute them and drop their PCV more, but if their circulating volume is low, we need to do something to support that in the short term, and that’s usually fluids.

If your patient has a pulmonary thromboembolism, they’ll be hypoxaemic and need oxygen support. The lower their SpO2, the more inspired oxygen we’ll need to give them—i.e., the higher FiO2 we’ll need to reach. So consider the method of oxygen supplementation used with these patients—something like flow-by probably won’t be enough, and we’ll need to think about something like nasal cannulas in most cases.

Let’s talk 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. Various immunosuppressive agents are available, including steroids, azathioprine (in dogs only), ciclosporin, leflunomide and mycophenolate mofetil. 

Each agent has its own nursing, health, and safety considerations. PU/PD, gastrointestinal signs, and bone marrow suppression are risks associated with immunosuppressive medications, and we need to monitor for these signs and advise clients accordingly. Immunosuppressive medications should be handled wearing appropriate PPE since transdermal absorption is possible.

And then there’s blood transfusions

We may need to replace those lost RBCs depending on the degree of anaemia and the patient’s clinical signs. When we do this, we never base decisions to transfuse on numbers alone—we always want to look at the patient’s clinical signs and determine whether they’re transfusion-dependent.

A transfusion will replenish the patient’s oxygen-carrying capacity and provide cardiovascular support. Before 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 can replace ‘like for like’ and minimise the risk of volume overload associated with excessive plasma volumes.

What other treatments do we use?

Anticoagulants are an essential treatment in IMHA. We know that patients with IMHA are at risk of thromboembolism, and anticoagulant medications should be started at an early stage to prevent this. 

This is most commonly achieved through the administration of clopidogrel and/or rivaroxaban. The ACVIM consensus guidelines on treating IMHA provide further guidance on the use of these drugs.

For patients with non-associative IMHA who are poorly responsive to these therapies, human intravenous immunoglobulin (IVIG) has been used as a salvage treatment. Studies currently don’t show significant improvements in time to discharge or survival rates, though they have been small, and further investigation is needed.

So that’s an overview of IMHA - what it is, how it affects our patients, and how we stabilise and manage them! Our role in nursing these patients is vast, encompassing triage and stabilisation, transfusion administration, monitoring, and supportive care. And whilst these cases can be challenging, they’re also really rewarding to nurse, and allow us to use lots of our nursing skills.

Did you enjoy this episode? If so, I’d love to hear what you think. Take a screenshot and tag me on Instagram (@vetinternalmedicinenursing) so I can give you a shout-out and share it with a colleague who’d find it helpful!

Thanks for learning with me this week, and I’ll see you next time!

References and Further Reading

Laura Jones
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