Cat suffers from anemia and splenomegaly and no one knows why

My cat is 4 years old, spayed domestic, female. She was always healthy, but in March of 2022 was diagnosed with wet FIP. We treated her with GS for 4 months. When we started she was severely anemic to the point we were considering a transfusion. While on the treatment for FIP she was diagnosed with IMHA. Her anemia was improving on its own without any medication for it, it was regenerative. Her spleen also got enlarged into the first month of GS treatment and never got back to normal, even if HCT was in the normal ranges. On the ultrasound two vets don't see any issues with it other than enlargment. The vet had no idea why she has IMHA or why its improving on its own. She is negative for mycoplasma, toxoplasmosis, FIV and Felv (we did fiv and felv tests several times over the months just in case, all came back negative). After finishing the FIP treatment, her bloodwork continued to get better so I just took her for monthly check-ups without any real treatment. After the check-up in November I stopped taking her to not stress her out anymore, and I saw improvement in her behaviour, she was jumping, playing, eating and being very happy, until a few days ago when she suddenly became slower than usual. I took her to the vet and the bloodwork is worse than before, her RBCs, HCT and HGB are all low all of a sudden. Her biochemistry panel came back perfect. The vet is stumped and I'm still waiting on him to think what it could be and what we should do. Also the vet did the autoagglutination test and says it's negative now. Please help if you have any idea what it could be or if there are any other tests we can do, I'm really desparate to help her.  

It sounds as though you known that Immune-Mediated Haemolytic Anaemia (where the immune system breaks down the body's own red blood cells) can be caused by some broad groups of diseases.  It can be primary (i.e. caused by the immune system being out of control without provocation) but this is rare in cats.  Your vet will be able to research or speak to a specialist if they cannot already tell you how rare / unlikely this is.  Usually, AIHA is caused by something, i.e. an underlying disease or a toxin, which changes the surface of the red-blood cells in order that they become recognized as 'foreign' by the body's immune system and attacked.  Things that trigger such a change in the surface of red blood cells, can include cancer, infections (FeLV, FIP, FIV), Mycoplasma haemofelis which is a parasite, reactions to certain drugs or chemicals, reactions to toxins and so forth. Sometimes a stressful event can trigger one of these causes, which might have been latent in the body for a long time, to bring on the disease.  More to follow.

Your vet will have a few questions in their head right now.  I don't know much about the tests that have been done, but broadly they will be wondering which of the potential causes and triggers have not been fully ruled out.  Now, tests sadly do not always give 'yes' or 'no' answers, so sometimes a test that doesn't give a positive finding might not rule a disease out completely.  Good questions for your vets include, 'Which of these causes can we completely rule out?'  'Which ones are still possibilities?'  'Can we do any more to rule out more causes?'  'Is that a useful step?'  (Sometimes, identifying the cause is simply not the most important thing).  Another good question, if you haven't asked it already, might be, 'What does a negative autoagglutination test meant for my cat?'  'Would a specialist be able to tell us any more?' and 'would this affect my cat in a positive way?'  I'm sorry to raise more questions than answers, but hope that something there helps.  

I think that you are probably familiar with the information in our 'cat anaemia' blog-post, but never-the-less, here it is:  https://vethelpdirect.com/vetblog/2022/06/21/how-is-anaemia-in-cats-treated/

Splenomegaly (big spleen) could be much easier to explain than IMHA as it may be secondary to it:  if red blood-cells are being broken down, then the spleen will often increase in size in order to produce as many red blood cells as it can, to keep Oxygen Saturation high.  Of course, spleens can also be large due to inflammation or cancer, which could occur in any organ, but the red-blood-cell reason might be consistent with the anaemia.

Indeed, I might expect it.

Thank you so much for the detailed answer! I read that the spleen should go back to normal if HCT is in the normal ranges. Her HCT was normal for some time but the spleen was still large. Could it possibly be an issue with the spleen itself? In the ultrasound the vet doesn't see any changes to it, it looks normal except for the enlargement. Would you maybe do some tests for the spleen, like the biopsy or fine needle aspirate in this situation?

Hello- I think that this is really a question for your vet.  The spleen has been working very hard to produce extra red blood cells and could easily have produced excessive, lumpy inflammatory tissue that has not regressed.  Racing greyhounds retain big spllens into old age, for example.  This inflammatory tissue might look exactly like cancer on a scan, so the vet has a decision to make:  is the spleen as I'd expect it to look given the history that I know about this patient?  They may be able to obtain more specific data or guidelines from a pathologist;  as a vet, I used to get to know my local pathology labs very well, because for every unusual case I had seen, the pathologists would have seen a few like it.