In my search for Spock, I found this little darling in a pound in Crawford County Ohio and named her Aeryn:
Aeryn was found to have Immune Mediated Hemolytic Anemia within a couple months of adopting her. This was a very difficult diagnosis to make. I give credit to Dr. Muller's group at the Animal Care Clinic in Huntsville Alabama specifically Dr. Marjorie Johnson for making a very difficult diagnosis. This is a condition that is rare in dogs and even rarer in cats. Basically IMHA is a condition where the immune system is attacking the red blood cells. The red blood cells are responsible for carrying oxygen from the lungs to the tissues and carbon dioxide in reverse order. The immediate symptom is of course anemia induced, sluggishness, tired, pale gums and mucous membranes and lethargic behavior. In essence IMHA is the body killing itself. Hemotocrit (HCT) is the measure of red blood cells (RBCs). Aeryn's HCT would drop from normal range (25-45) to the lethal range 10-15 very quickly perhaps within a few days. Not much is known as to what causes this. She always tested negative for Bartonella or Feline Leukemia which can result in very similar symptoms. When those are ruled out the diagnosis is left with IMHA. We ruled out chemicals or metals as the cause based pretty much not on basic chemistry tests as that seems to be a lost art, but rather on X-rays to make sure she hadn't ingested a coin from the coin jar and the absence of any other chemicals or items as she was strictly an indoor cat. We also ruled out aspirin or other drugs as we doubted her ability to remove a child proof cap pick out one or two pills swallow them and put the child proof cap back on all without any claw or tooth marks oh and of course putting it back in the medicine cabinet. Sounds crazy but you go through all these thoughts in trying to identify a cause to no avail. I personally believe she received this condition from a tainted FLV shot she received right after I picked her up and took her to a vet in Galion which was just 2 months prior to her first episode. Since I rescued her from the pound when she was maybe 6 months old and already was spade and front declawed, and we ruled out chemicals and whatnot that pretty much leaves the FLV shot theory. Some sources claim genetic but there is no way to test for it or prove or disprove it and I just don't believe that she would have gone that long before showing the condition. Especially having been spade and declawed and going for 8 months before the first episode. But nothing is conclusive.
After the first episode Prednisone 5mg every other day kept her in check. Keep in mind that when these episodes hit she was kept alive by transfusions every other day. After 6 years the Prednisone stopped working. I give credit to Dr. Anderson, Dr. Vaught and Dr. Horn at the Animal Care Clinic for the dedication and honesty and compassion with Aeryn and I as we went through these multiple episodes over the next 7 months. The first episode we were not able to get her immune system in check and her veins were basically messed up from all the poking and prodding from the transfusions and tests so they gave me a referral to Auburn. So in the middle of the night I went on a four hour trip to place I had never been to with terrible directions. But thanks to great teamwork of the family I arrived ok and although Aeryn's HCT was down to 6.5 she survived the trip.
Just like my local vets Dr. McIntire at Auburn is as fantastic as they come. She found a complication of Bartonella this time that was not found in a normal blood test. The western BLOT-N test which took weeks to get the results of showed a strong positive 4. The theory being that the Bartonella was in the bone marrow. We started her on Azithromycin 5 month protocol. So after many transfusions we tried Leukeran to suppress her immune system and increased the prednisone to 20mg per day which worked for a couple of months. Also in this time she had a blood clot from one of the many transfusions in her leg causing her middle two toes on one foot to become necrotic and had to be amputated with a skin graft from her side. That procedure was done here locally by Dr. Vaught at the Animal Care Clinic. Aeryn made it through that just fine and everything healed up. Thanks to the continued expertise of the folks at the Animal Care Clinic, Dr. Vaught, Dr. Horne and Dr. Anderson.
But then she had another episode. After another trip to Auburn and many transfusions we swapped the Leukeran for Cyclosporine. The Leukeran or Chlorambucil has a nasty side effect of bone marrow suppression. So this was our working theory. It is also a chemotherapy drug and rubber gloves must be used when handling it along with proper biohazard disposal and has to be refrigerated. The Cylcosporine worked for a couple of months and Aeryn regenerated at the fastest rate I have seen yet, nearly 2 HCT points per day. During this time her sniffles that she had since I rescued her from the pound came back with a vengeance resulting in a boil on top of her nose and a blister on front of her nose. The feline upper respiratory virus is akin to herpes as it reoccurs from time to time and they never can get get rid of it. There was some talk of it being outright feline herpes and no, neither of these are transmittable to or from humans so nothing to worry about. To ease this condition we decided to give her Lysine Viralis and it actually works. I also have the feeling that the cyclo did such a good job of suppressing her T-cells that it accounts for the harshness of this reoccurrence of the feline upper respiratory virus. But alas, she started dropping slowly this time but dropping.
So 6 months since the prednisone stopped working back in January 2007, she is once again for the third time on her death bead alive only by blood transfusions every couple days. We are trying a new drug called MMF in place of the Cyclosporine. But at this point she is non-regenerative and has been so for a week and a half. Now the Leukeran has a side effect of suppressing bone marrow so the second trip to Auburn was understandable. But this third trip is not as Cyclosporine is not known to cause bone marrow suppression. And this is the first time that Aeryn has been totally non-regenerative, I mean 0.01% reticulocytes. Of note it takes Aeryn a long time to get her HCT back over 30. On the Leukeran she gained 1 point a day went to 33 then started dropping again. On the Cyclosporine she gained 2 points a day got to 33 and once again started dropping again. I had started her on IVAX Cyclosporine that they gave me at Auburn when I brought her home the second time. When that ran out I got the prescription refilled locally and was refilled with PRIMA brand Cyclosporine. I noticed her HCT was dropping at that time and finally found some of the original brand IVAX so she was only on the PRIMA brand for 1 week. Now normally I don't consider brand sensitivity to drugs. But there was a major difference between the two. The IVAX smelled like essence of skunk and the PRIMA had no smell at all. Also Aeryn's breath smelled like the IVAX all the time she was on it. And also it seemed awful coincidental that her HCT started dropping just at the time I had a brand change. So I had hoped that putting her back on the IVAX would solve the problem but it did not. Keep in mind she was on Prima for 1 week then back on IVAX for one and a half weeks, the last half of that at Auburn. So we had 2 working theories, either there was a brand sensitivity or her prescribed dosage of cyclosporine was just too much. After 2 and a half weeks of not having the Prima and one and a half weeks of being off the Cycosporine at all and on MMF, she is still not regenerative. Trough tests showed her Cyclosporine levels to be high but still therapeutic. At this point we have no theories. Tomorrow I will visit and we will talk with Dr. McIntire and go from there. I may loose my baby this time but as long as she has a fighting chance I will continue to give it to her. But if we believe she does not then we will be left with the final decision. Now I have cried myself to sleep many nights, the last several being no exception. My little girl and my little boy before her are like my daughter and son. I would gladly give my life if it would save theirs. But alas in life we are given only certain choices to make and we must play the hand we are dealt not the one we wish we had. But I still hope that once again we will cheat death and turn it into a fighting chance for life. We will see. Either way I am prepared. Here is a video of my baby girl at Auburn June 30 2007 - July 1 2007.
3 July 2007 today was the first good news in a couple of weeks, guarded optimism but good none the less. Her Complete Blood Count (CBC) test showed the beginnings of regeneration. The numbers are so small but we hope they are not an anomaly. The white blood cell count and platelet count has increased, in fact doubled but double of very small is still very small, but the reticulocytes have increased to .1%. The nurses and folks in the critical care ward at Auburn love Aeryn too, today they made her a bandana and signed it. One of the nurses Ashley and her current assigned student Sarah stopped in and said hello offering help and directions to hotels and opening their hearts and home. Aeryn was at HCT 14 and is getting another transfusion today so tomorrow we will see. Hopefully the trend will continue.
She has been holding at HCT of 14 +/- on her own without transfusion since 3 July 2007. On 3 July we had decided not to transfuse her anymore as she was still non-regenerative, had become transfusion dependent, was not responding to medication and had 4 transfusions already since her admittance to Auburn for the 3rd time on 23 June. The theory at this point is that the cyclosporine levels were just too high, >1500ng/ml on June 23. After discontinued use of the cyclosporine her levels had dropped to 382ng/ml by 3 July. In talking with the clinical pharmacologist Dr. McIntire found that Azithromycin which Aeryn has been on for 3 months so far of a 5 month protocol for the Bartonella complication slows down the body's natural release of cyclosporine. Once the Cyclosporine was down to a negligible level by 10 July and she was still at .14% reticulocytes we decided to try the cyclosporine again and change her prednisone to prednisolone as a last ditch effort but using trough and level tests to determine the correct dosage by alternating days of azithro and cyclo and measuring before and 2 hours after (max concentration) administration of cyclo. Of note an IGG was discussed but is highly experimental as there is no record of doing it on cats, in the end we did not have to pursue this. There is another protocol for administering Azithromycin every other day for 3 months and that is what we are now doing. We found the right dosage to be 1 25mg geltab per day vice the 2 per day she used to be on. In 2 weeks we will take before and 2 hours after blood samples for another trough and level test of cyclosporine. I do not know if the brand change had anything to do with it but to eliminate that as a possibility we are staying with the IVAX brand. By 9 July her reticulocytes had increased from .14 to .3 on 9 July and by 13 July they had increased to .6%. On 13 July it was decided that she was holding her own and was starting to regenerate and that I should bring her home. On the evening of 13 July she was given a final transfusion and this time it held and raised her HCT from 14 all the way up to 20. Prior transfusions would only raise her from 12 to 14 or 14 to 16. It is believed that the cyclo is working and suppressing her immune system and that part of that 6 point increase was also due to Aeryns regeneration.
On 14 July I brought her home and she is doing well.
A few interesting notes. For the last week or so she has been eating like a horse. I'm not sure if it is the prednisolone or that we have the cyclo in the therapeutic range or something else they were giving her at Auburn not intended as an appetite stimulant just normal procedure such as flushing her jugular catheter etc but she has a fantastic appetite. Speaking of Catheter, her veins get all torn up quickly with all the transfusions and CBC and PCV tests which is what probably resulted in her loosing her 2 inner toes on her right foot before but its a good idea on patients that you know you are going to be constantly sticking to go ahead and do the catheter upfront. We seem to have to learn that every time. It can be a tricky procedure but with a top notch surgeon its the thing to do. The Viralis L-Lysine really works and her nose is all healed up and her sniffles gone. I attribute some of that to the fact that at least for a week we weren't suppressing her immune system that much. I am skeptical about the effects of the MMF. It appears to me that it's ability to suppress Aeryn's immune system is quite low. But we are afraid to change anything so we will continue it until her HCT reaches 35. MMF is untried in cats and data is almost unavailable but in dogs and humans it has the ability to suppress T and B cells and can be used in combination with cyclosporine and prednisone. Also in humans it has a possible side effect of bone marrow suppression which is why I plainly don't like it. The last thing an IMHA patient needs is bone marrow suppression and we have been there before with the Leukeran. This is one of 2 things I am afraid of. The other medication we are giving her is aspirin. A very small dose but it's aspirin. And aspirin in cats makes them anemic. Another thing that is not good for an IMHA patient. But since her platelets are regenerating faster than her rbc's, there is a possibility of thrombosis or blood clot. I will discontinue this as soon as I can. Lastly, we have a theory but no real direct proof. The theory is that her second episode this year was caused by the Leukeran suppressing her bone marrow, a known side effect and the third episode caused by excessive cyclosporine levels although it is not known to suppress bone marrow. This makes me uneasy. There are other theories postulated that might account for these episodes and probably some not yet postulated. But this is the theory we are going with and the blood test data supports them although not directly conclusive. To be conclusive one would have to perform a lot more tests to be sure. Bone marrow aspirates on Aeryn have been dicey at best, 2 out of 3 failed to yield a proper sample. The one that did from back in February showed that there was nothing wrong with her bone marrow. SO with that I'll finish with a couple postulated theories. One theory suggests that her immune system is adapting and evolving around whatever medication we try. Another theory is that her bone marrow is giving up. Another is a genetic defect. None of these theories can be proven or disproved at this time and I don't like them, obviously because there they have but one solution.
22 July 2007 She has been home a week now and judging by her gums and behavior she has steadily dropped HCT to around the 14-16 area. Her appetite has diminished to what I would call normal so it must have been something else they were giving her that caused her to be so ravenous. She is not in pain nor suffering but she is tired and she knows her HCT is low. At this point there is nothing I can do but hold to the med plan. Either she will pull out of this or she won't. It makes no sense for me to take her to the local vet for a CBC as the current med plan is the best we can do. All a CBC would tell me is what I already know, her HCT is low and whether she is regenerating or not it doesn't matter. I have suspended the aspirin and I have suspended the Lysine. Her sniffles are completely gone and her nose completely healed.
23 July 2007 Aeryn continues to drop HCT and her behavior degrades, I am thinking the only very very last thing to do is try double cyclosporine again. I will not try leukeran aka chlorambucil it's side effects are bone marrow suppression. I am not overjoyed with the MMF either as one of it's potential side effects is anemia. I will call tomorrow if she doesn't improve tomorrow morning.
24 July 2007 In consultation with Dr. McIntire and Dr. Anderson we have decided to stop the azithra and change the cyclo to two a day due to Aeryn's continued downward trend. At this point we are really taking a stab in the dark.
25 July 2007 She seems to have stabilized at a low HCT level and defecated.
26 July 2007 She seems worse, not eating not defecating. Tomorrow may be the day.
27 July 2007 she is hungry and eating and defecated again. Am almost out of the MMF and no one locally has it and they can't get it until Monday. Have added water to the bottle and scraped crust of the lid, may not be full doses until Monday but is best I can do. Not real worried though as I don't think the MMF is doing much. Her HCT just continues to steadily decline.
28 July 2007 She is eating little and has not defecated and seems a little worse than yesterday. To get her to eat I gave her some cyproheptadine. The Cyp takes about 30 minutes to kick in and she did eat a little bit and then defecated. Her stool was soft and even diarrheic at the end. After this she wanted to sleep. Curiously she took her spot next to the door where she waits on me to come home from work instead of in bed with me or in her spot next to the bed.
29 July 2007
She got worse over night. I found her at the front door in the morning. I gave her some food and she ate a fair amount then I gave her the morning dose of cyclosporine and prednisolone. Within minutes she became sick to her stomach and threw up. I do not believe it is the cyclosporine but I don’t know. The reason I say that is, back when she was on one dose a day of cyclosporine her nictitating membrane would come up indicating she didn’t feel well even on the 12 hour round she did not get cyclosporine. I thought it was the MMF. But now that she is not getting the MMF that makes me believe it might have been the prednisolone all along. But then again, her HCT may be so low that just eating makes her sick.
What is most concerning is her behavior. At present she can only lay down. If she tries to get up and walk a couple feet or just eat, she gets sick to her stomach, crouches back down and cries gutturally and sometimes heaves. By placing fresh food under her nose I can get her to eat. She is eating I think to help her stomach but it too makes her feel bad. Her nictitating membrane is way up indicating she is feeling very bad. Her gum color is the worst I have seen it, her tongue is nearly transparent. She is weak I can tell when I pick her up. I have not seen her drink today at all. I do not know what to do so I called the local vet. After discussing it I agree it is because her HCT is so low. After I got off the phone I went to back my baby girl up off the bed and put her on my chest to lay down with her and she urinated on me and cried that low guttural cry. She is definitely suffering now. No more tricks left in the hat. She cannot live on constant transfusions. Her veins are tore up and I doubt it's a good idea to try another jugular catheter having the last one in only 2 weeks. At this point she would transfusions every week or so. There is nothing left to do. We have taken this to the ultimate limits, it is time to end her suffering.
At 1430 hours 29 July 2007 Aeryn was eased into the next dimension, her suffering is over but ours continues. She made that low guttural cry only once on the way to the local vet, usually she complains the whole way. I'm glad it was easy on her, she only really suffered half a day.
My heart goes out to all the victims and families of IMHA or AIHA. IT is a frustrating disease. Most would have given up the first time 6 years ago even more 6 months ago. Aeryn has had a very good and loving life, even the last 6 months. I post this information here in hopes it will help others. We pressed on with Aeryn until the very end of the line when nothing left existed and the humane thing was to end her suffering. Perhaps someday a better understanding or better treatment will be found. Until then I encourage all affected with this affliction to fight until the bitter end. I have nothing but warm regards and the best possible admiration and gratitude for all the people at the Auburn Veterinary clinic and the people at the Animal Care Clinic.
I loved my babies with all my heart, still do and always will. I will have others I think this time I will get a pair that are used to being together so they will have someone to play with when I'm away.
IMHA Notes:
Aeryn would eat litter and lick walls when her HCT was low. We of course thought of lead or other toxic chemical poisoning but that was not the case. So in these situations there are two things you can try. One is use worlds best cat litter made from corn, it even works in my automatic boxes. Secondly provide a licking stone. Not a salt block but find a stone they can lick that is not toxic and lean it against the wall where they normally lick. Remember scolding and discipline don't work on cats you have to be inventive and then reward the right behavior.
We can't turn back time but if I were once again in this predicament and wanted to take this into even further unexplored territory, I have a thought. If the IMHA gets to the point where glucocorticosteroids don't work and I'm once again in the experimental stage, I would try a med plan that suppresses both B and T cells right off the bat, not just one or the other. See, the problem is finding a B cell suppressant that doesn't have nasty potential side effects like bone marrow suppression or anemia. If one could find the correct or small enough dose levels that work, then I believe the chance of side effects are minimized. Meaning if I was once again faced with this situation when all that is left is experimental medicine with little or no data, that is what I would try. It would require trough and level testing of both medications. Perhaps some day a better B cell suppressant for felines will be found. At the time of writing this, I think the combination I would try would be Mycophenolate Mofetil and Cyclosporine. If that didn't work then I would try substituting Chlorambucil for the MMF. My theory behind this is that when the prednisone stopped working it was because of a complicating malady. And that malady in combination with one or the other suppressants caused her immune system to adapt. What we needed was to suppress her just long enough to get rid of the other malady then we could have gone back to prednisone or prednisolone. So next time I would try both at the same time and see what happens. It may still be all for naught but it is what I would do. The other potential is to try an IGG but I believe in Aeryn's case her platelets were too high. If at the same time I was thrust into this predicament and her platelets were low, I would try the IGG. It's tough to make that call as the procedure is risky and there is not a lot of data on felines.
Aeryn was a world class heavy weight fighter through all this. That is due I believe to the exceptional life at home. Lots and lots of love, every meal a buffet and the buffet is all day and all night, and every toy Petsmart sells plus some they don't. I can tell you that all the trips to the vet, all the stays at the vet and all the surgeries and poking and prodding was offset by just one day of home. Many would have given up and a few vets at Auburn suggested so. All I can say is if you treat your babies like mine, just one good day of TLC wipes out the many bad. Don't give in until there is nothing left but suffering.
If you have questions drop me an email.
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Epilogue
I still mourn for all my departed babies but let not that deter you. The day after Aeryn passed away I went down to the pound and rescued 2 more and named them Trip and T'Pol. I still cry for and miss Aeryn, and Spocky, and all the dogs I had as a child, I always will. None replaces the other, they each add to the foundation of love.
