Possible IMHA dog—now what?

Johnson,Carla;

Even after many years in practice, the dog with immune-mediated hemolytic anemia (IMHA) can still leave us baffled. Should we refer to a specialist, transfer to emergency, or send the dog home on medication? When should we recheck—tomorrow, in a week, in a month? What drugs do we pick? Or should we just run screaming from the building?

IMHA cases usually start out in the emergency room, but sometimes they are caught early during routine bloodwork or the patient presents in general practice with mild early disease. A better understanding of how to manage these cases will help with early diagnosis, catching relapses and even managing them on our own. You don’t need to become an expert to get the ball rolling on a good diagnostic and treatment plan. At a recent Fetch dvm360 conference, Elisa Mazzaferro, MS, DVM, PhD, DACVECC, shared her approach to IMHA cases.

This is the first of two articles on this topic. Here, we discuss the causes and diagnosis of IMHA. The second article will shed light on best practices for short- and long-term therapy as well as monitoring IMHA patients.

Disease background

IMHA is a disease in which the body attacks its own red blood cells (RBCs). It is among the most common immune-mediated diseases that we see in dogs.¹ IMHA has a 30% to 70% mortality rate despite aggressive therapy, Dr. Mazzaferro noted, and relapse rates range from 11% to 15%.^2,3 Upon initial diagnosis, Dr. Mazzaferro said she tells her clients that their hemolyzing pet has roughly a 40% to 50% chance for long-term survival, then she customizes this prognosis based on follow-up diagnostics and response to treatment. Many patients do not make it through the initial hemolytic crisis, but those that do can die later as a result of a thromboembolic disease, renal failure, liver failure, relapse or complications of medical therapy. Dogs with concurrent immune-mediated thrombocytopenia, hypoalbuminemia or very rapid hemolysis can have a significantly worse prognosis.

The median age at presentation is 6 years. Although most cases of IMHA occur in female dogs, males statistically have a worse prognosis. Cocker spaniels, sheepdogs and poodles, among others, are particularly susceptible. IMHA in susceptible breeds is usually far more severe and requires more rapid, aggressive treatment than that in non-predisposed breeds. Pit bull terriers are predisposed to Babesia and have secondary IMHA from this.

Intravascular hemolysis is less common than extravascular hemolysis. The difference between the two—besides the site of RBC destruction—is that with intravascular hemolysis you must be sure to rule out zinc toxicity (and some of the infectious diseases), and you should expect the clinical progression to be more severe, with a higher risk for disseminated intravascular coagulation (DIC). You still treat these patients the same way, but be prepared to be more aggressive, and don’t forget to address the thromboembolic and coagulopathy risks using medication and coagulation testing.

Seventy percent to 80% of canine IMHA cases are idiopathic,⁴ known as primary IMHA. Secondary IMHA is caused by an immunoglobulin (Ig) M or IgG antibody attack against RBCs in response to infection, neoplasia, an inflammatory condition, drug or toxin, and maybe vaccination. Some toxicities cause direct RBC damage, which can be mistaken for IMHA but is not immune mediated.

Diagnosing IMHA

Clinical presentation and history

Clinically, patients with IMHA present with lethargy, weakness, vomiting, diarrhea, pale or yellow gums, collapse, discolored urine and petechiae if they have immune destruction of both RBCs and platelets. Alternatively, patients can appear clinically normal with just spherocytes and a mild anemia on routine bloodwork.

They can have a regenerative or non-regenerative anemia. We are encouraged to see regeneration, but it takes the body four to five days to mount a significant regenerative response, so about 30% of cases are nonregenerative on presentation. Spherocytes are present in only 67% to 94% of dogs with IMHA.⁶ They are not pathognomonic to IMHA, but spherocytes are great markers for diagnosing and monitoring this disease. Very few other things cause this.

Slide agglutination testing

This type of test can be tricky. Here’s how to do it right.

Place one drop of blood from a purple-top tube on a slide, visualize it for clumping (agglutination), then add four tiny incremental drops of 0.9% saline with a needle-on syringe to the edges of the blood drop to see if the blood cells disperse or stay clumped. If they stay clumped, the result is positive.

Always look for macroagglutination first (you can see it with your own eyes). If macroagglutination is negative (RBCs either do not clump or disperse quickly with saline), then examine for microagglutination. Microagglutination is the same test but under a microscope, wet and unstained. Use a coverslip, and look for RBCs clinging or clumping together.

For both tests, if the blood cells disperse evenly with the saline, the result is negative. For the microagglutination test it is even more important to use the saline to differentiate agglutination versus rouleaux. Assess the slides immediately; letting the blood sit on the slide for even a few minutes can give the appearance of false-positives as the edges dry out.

If test results are unclear, the ACVIM consensus guidelines recommend washing the blood sample and retesting. Agglutination is caused by cross-linking of IgM immune complexes across RBCs, so it should still be happening after washing.

Testing

Getting a platelet estimate

To do a platelet estimate, count the number of platelets in each of 10 random views on high-power field (100x oil immersion) near the feathered edge. Add them up, divide by 10 (basically the average number of platelets per high-power field), and then multiply by 10 to 15. That is your platelet estimate range in thousands.

Now look at the feathered edge. If there are huge clumps of platelets, factor these in as best you can as they will falsely lower your total estimate.

The baseline diagnostic workup is more extensive than for most diseases and includes the following:

Dr. Johnson practices emergency medicine at Berkeley Dog and Cat Hospital in Berkeley, California, and general practice at Cameron Veterinary Hospital in Sunnyvale, California. Her nonveterinary loves are writing, dressage with her Iberian warmblood mare Synergy; watercolor painting on yupo; vinyasa yoga; and running with her dog Tyson. Try as she might, her curly-coated Scottish Fold, Hootie, refuses to go jogging with her.