Immune-mediated haemolytic anaemia (IMHA) in dogs

Overview

Haemolysis means premature red cell destruction. In IMHA, the dog's own antibodies may attach to red cell surfaces. Targeted cells can be removed from circulation in the spleen, for example. They are also removed in the liver and marrow, where phagocytic cells break them down. Haemolysis can increase blood bilirubin, causing yellow skin and mucous membranes. Some cells can also break down inside blood vessels.

IMHA is usually regenerative, with the marrow increasing new red cell production. Following acute haemolysis, this response may take three to five days to appear in blood.

Causes

The immune reaction

The immune system reacts against structures on red cell surfaces. Attached antibodies can make cells stick together, or agglutinate. Complement forms part of immune defence; activation on a red cell's surface can destroy it directly within the bloodstream. Disease is called idiopathic when investigations identify no trigger. Treating a triggering disease can reduce immune-mediated red cell destruction.

Possible underlying factors

Babesia infection can trigger immune-mediated red cell destruction. Babesia is a protozoan living in red cells and can be transmitted by ticks. Investigations may also look for tumours or other inflammatory diseases. In a UK and Irish study of 222 dogs, 73, or 33%, had a possible IMHA-associated factor. Infection was identified as a possible factor in 17 of 222 dogs, or 8%. A tumour was a possible factor in 16, or 7%. Non-infectious inflammatory disease was a possible factor in 13, or 6%. A further 102 dogs, or 46%, had a finding considered probably incidental.

Risk factors

Increased risk has been described in Cocker Spaniels and Finnish Spitz. Miniature Schnauzers also have a reported predisposition. Dogs in the Irish hospital study represented 38 breeds. In that study of 104 patients, median age was six years, ranging from 0.7 to 14 years. Females accounted for 71%.

Tick-borne Babesia is more readily suspected after time spent in an affected area. In the UK and Irish hospital study, possible associated factors were found more often in older than younger IMHA patients.

Typical symptoms

In the Irish study of 104 dogs, median symptom duration before presentation was four days.

• Pale gums.
• Tiredness or marked weakness.
• Yellow whites of the eyes or gums.
• Faster breathing even at rest.
• Reduced walking stamina.
• Reduced appetite.
• Dark-red urine.

Pallor was found in 99% of dogs in the Irish study. Jaundice occurred in 60%. Fever occurred in 23%. Weakness was recorded in 75 dogs, or 72%, at the same hospital. Diarrhoea occurred in 22, or 21%.

Examination may reveal an increased heart rate even at rest. The spleen may feel enlarged during abdominal palpation.

Complications and consequences

Severe anaemia can reduce tissue oxygenation enough to require transfusion. IMHA increases blood clot risk. A clot can obstruct a pulmonary blood vessel. Death risk is greatest during the first two treatment weeks. Concurrent immune-mediated platelet destruction is called Evans syndrome. It can cause pinpoint haemorrhages or bruising on skin or mucous membranes. In the Irish study, a clot was the confirmed or suspected cause in nine of 15 IMHA-related deaths.

Anaemia recurred in six of 90 discharged dogs, or around 7%, in the Irish study. Median time to recurrence was 157 days, ranging from 30 to 692. Infections such as urinary tract infection can develop during immunosuppressive treatment.

Diagnosis at the vet

Anaemia and haemolysis

A blood count establishes whether platelets are reduced alongside red cells. Reticulocyte numbers show whether the marrow has had time to increase production. Around 30% of dogs have no regenerative response at diagnosis. Red cell clumping can distort analyser-calculated haematocrit. Packed cell volume can then be assessed by centrifuging the sample and measuring the red cell proportion.

Raised bilirubin can suggest haemolysis if liver or bile duct disease, for example, does not explain it. Haemoglobin released from red cells can be detected in urine. A smear made immediately after sampling may show ghost cells, membranes remaining from destroyed red cells, indicating intravascular haemolysis.

Demonstrating immune involvement

A smear is checked for spherocytes, smaller and rounder than normal red cells. They can arise for other reasons too, such as zinc-induced red cell injury. Saline agglutination testing examines red cell clumping. A direct Coombs test detects bound antibodies or complement components. Canine studies found sensitivity of 61–82%, so affected dogs can test negative. Specificity in canine comparison groups was 94–100%, meaning most controls tested negative. The blood sample is ideally collected before any transfusion.

Definitive diagnosis requires anaemia, evidence of haemolysis and immune involvement in red cell destruction. Two complementary findings, such as positive agglutination and Coombs tests, are generally used to demonstrate immune involvement. Anaemia, haemolysis and persistent red cell agglutination after washing are together sufficient for diagnosis.

Investigating a trigger

Investigations consider medicines, travel and possible tick exposure. Suspected Babesia can be assessed with blood PCR and antibody testing together. X-rays or ultrasound can look for an underlying tumour. If the first Babesia test is negative despite high risk, PCR looking for parasite genetic material can be repeated.

Treatment

Supporting circulation and suppressing the immune reaction

A red cell product is given if the dog shows signs of inadequate tissue oxygenation. The transfusion decision takes account of symptom severity and how quickly anaemia developed. Donor blood typing is part of blood bank practice. The recipient's blood type is ideally established before transfusion to reduce reaction risk. If a previous transfusion was more than three days ago, the vet may crossmatch donor and recipient blood. Several transfusions may be needed before immunosuppressive medicines take effect. In the Irish hospital study of 104 dogs, 67, or 64%, received a transfusion. In that study, 23% needed more than one.

Glucocorticoids are the first-line immunosuppressive treatment. Diagnostic samples are ideally collected before immunosuppression if this does not delay urgent treatment. If the disease is immediately life-threatening, the vet may consider adding a second immunosuppressive medicine from the outset. Treatment usually also includes antithrombotic medication unless platelet numbers are very low. This can start at diagnosis. If Babesia infection underlies haemolysis, treatment also aims to eliminate the red cell-damaging parasite.

Recovery and monitoring

Immunosuppressive treatment is often prolonged. During follow-up, haematocrit is usually checked every one to three weeks. Red cell agglutination and bilirubin can be monitored for evidence of continuing haemolysis. A fully recovered dog's blood count may still be monitored for four weeks after medication ends.

In the Irish hospital study of 104 dogs, 87% survived to discharge. Among the 82 with no possible associated factor identified, one-month mortality was 16%. Three-month mortality in that group was 31%. Low platelet numbers were associated with poorer survival even after accounting for age. Raised bilirubin was also associated with poorer survival. For dogs surviving the first three months with no associated factor identified, median survival in this study was 2,664 days.

Prevention

Effective tick protection reduces Babesia infection risk where the parasite occurs. Daily skin checks help detect ticks. Remove attached ticks as soon as possible to reduce the risk of infections they transmit. Ticks are particularly likely to attach to the face, ears and between the toes. A purpose-made tick removal tool can be used. Small larvae and nymphs can be missed during checks. Donor dogs can be screened for blood-borne pathogens to help prevent transfusion-transmitted infections.

Important for dog owners

Tell the vet how quickly weakness, pallor or urine colour changes developed. Mention any previous transfusion, as it can affect blood smear findings. Attend scheduled blood tests so the vet can monitor treatment response. Watch for changes in drinking and urination during treatment, as these can be related to glucocorticoids. Glucocorticoids can also increase panting. Report urinary symptoms developing during treatment, as reduced immunity predisposes to urinary tract infections.

Frequently asked questions

Is IMHA contagious?

IMHA does not spread between dogs: red cell destruction results from the affected dog's own immune response. If Babesia infection is involved, the parasite itself can infect another dog, usually through a tick. Some Babesia species can also be transmitted through bite wounds.

Is a Coombs test enough to diagnose IMHA?

A Coombs test helps show whether antibodies are attached to red cells. The vet interprets it alongside other findings. Diagnosis also involves establishing anaemia and evidence of red cell destruction. Strong red cell agglutination can prevent the test being performed.

Why is clot prevention needed in IMHA?

The disease increases blood clot risk, particularly during the acute phase. A clot reaching the pulmonary blood vessels can be life-threatening. The vet considers platelet numbers when deciding whether antithrombotic medication can be used. Clot risk may fall as immunosuppressive treatment brings the disease under control.

How long does IMHA treatment take?

Prolonged immunosuppressive treatment is often needed. The vet monitors red cell values so medication can be adjusted according to response. Blood counts may be checked for four weeks after a recovered dog's medication ends.

Can a dog develop IMHA again?

IMHA can recur after hospital discharge. In the Irish hospital study, recurrence was recorded in around 7% of dogs discharged alive. Contact a vet immediately if the gums become pale again or your dog suddenly becomes weak.