Positive Coombs test - AIHA - and relation to blood transfusions
 

On 1 Nov I had a negative coombs test.

On 2 Nov I had my first RBC and platelet transfusion

On 18 Nov I had my second and last RBC transfusion

On Tuesday (18 Dec) with a retic count of 3.5 and my hemoglobin falling my doctors thought I must have developed PNH. So they ran tests for PNH. The PNH came back as negative (slight reading of below 1%). But another test (haptoglobin) came back with a low reading so they decided to check for coombs and the coombs test came back positive. So they ran additional tests which showed that I am positive for warm auto-immune hemolytic anemia (WAIHA) but at this stage the reading is only a slight positive. Who knows whether it has only just developed or whether I have had for a few weeks.

My hgb is sitting at around 8.1 to 8.5 and has been at this level for about the past week with a retic count increasing over the past 2 weeks from 2 to 3.5 (possibly higher today as still waiting on result). It is the increasing retic count and the hgb not responding that generated the concern from the doctors.

The doctors are thinking it could be a reaction to the rbc transfusions or a possibility that my body has developed a reaction to the cyclosporine. I would be interested to know whether anyone else has encountered this scenario.

The good news is that just over a month post ATG my platelets are at 82 and ANC at 1.45. I stopped prednisone about 12 days ago but have started again today due to the WAIHA.

Has anyone encountered this?

It feels like I take a couple of steps forward and then a few step back.

I more or less went through the same thing with the RBC. It first stableized but dropped 0.1-0.2 every couple weeks. I think it is all party of the process. Hopefully it is all part of the AA and not a separate condition.

Hi Scott, as always good to hear from you. I hope it is part of the process but the positive result concerns me that it is yet another disease for me to deal with. I am frustrated about being back on the steroids yet again. Just when I thought I was finally done with one drug.

Anyway here is hoping that I receive some more positive news on Monday.

Happy holidays to you and your family.

hemolysis
 

Hi TASHMAC,

I don't post often, but this topic interests me bacause I have had similar issues since April. I'll try not to be too lengthy, but it is complicated. A couple of weeks after my second ATG (4/12), I was hospitalized with tanking counts, especially PLTs. With every transfusion, I would get a good bump, but 24 hours later the count would be basically zero. This went on for two weeks, and it was not serum sickness. My reds were tanking too, but not as quickly. And then, after a few weeks of this, I began hemolyzing my RBCs. I had lots of tests, as you can imagine, (with, interestingly, both negative and positive Coombs tests). I underwent two rounds of IVIG in May, and finally got back to a transfusion schedule that would allow me to go home, although the IVIG had seemingly no effect. The hemolysis continued, and I had a course of Rituxan in August. The Rituxan didn't seem to help much either. I was also on prednisone all this time, as well as a high-ish (for my body weight) dose of CSA. Still nothing worked against the hemolysis. Then in October, I was scheduled for an MRI because of hip pain, and a BMB to see what was happening in my marrow. At about the same time, my MD and NP took another look at the latest blood smear, and determined that the CSA was part of the problem! They quickly reduced my dose to 100mg/day (from 450). The results of the MRI showed avascular necrosis in my hip, so they weaned me off the prednisone as fast as they safely could. Lo and behold, for the first time since I was diagnosed, my counts began going up on their own, and I haven't had any transfusions since Oct. My PLTs are now at 60, and my hgb is 9.5, and slowly rising, which for me is great. My whites have never been a particular issue, and they are in the low normal range. AND no more hemolysis! So...sorry to be long-winded, but going off, or reducing, my meds is essentially what worked in taming the hemolysis, even though it seems counter-intuitive. Two little things on the down side: I now have the hip issue from the prednisone, which will probably lead to hip replacement. I've been on crutches for 10 weeks, and the hip has gotten worse, not better. Also, my last BMB (10/12) showed still almost empty marrow, with multi-lineage dysplasia and ringed sideroblasts. My ferritin is still high, although we may try Exjade again. I previously had to discontinue it due to kidney problems.

Phew, I'm done. Sorry about that. But I'm wondering if you should talk to your MD about the possibility that the meds you're on are having unintended consequences.

Thanks so much for listening, and hope I've been of some help.

Marmab

Hi Marmab

Thanks so much for your post....this is exactly why I think this forum is so important for AA patients. For some reason I am of the view that with a rare disease like AA that we AA sufferers need to play a really active role in the disease as I feel that between us our efforts may actually help to find a cure other than BMT for this disease or even help with treatment options.

As for me, I am on 20 mgs of prednisone and after 3 days at this level of prednisone my hgb has increased to 8.8 and the coombs test came back negative this time. My coombs test before was only a slight positive. Mt retic count is above 6!!! After going back and reviewing my labs though it appears that some form of hemolysis has been going on since early November and from late November my LDH levels were slightly higher than normal. The issue is that with the high retic count my hgb levels should really be climbing more than they are so something is going on. They have decided to switch cyclosporine brands to see if that will help. At this stage I am taking 300 mg of cyclosporine a day. I am back in for more tests on Friday so will keep you posted as to whether there is anymore change. I will also mention to my doctors about whether we should look at reducing the cyclosporine.

Take care and wishing you a happy holiday season.

H Tashmac
 

Happy holidays to you too! It is my understanding that a high retic count, high LDH and low haptoglobin are signs of hemolytic anemia. So I'm not sure that a high retic count would mean that your hgb should be going up. Rather, I think that the opposite would be true (red blood cells are being hemolyzed resulting in a greater proportion of reticulocytes), although I'm not 100% sure on this. I would have to go back and read up on this topic -- it's been awhile and I just don't remember.

But, as many have pointed out, each case is different, and hopefully you and your medical team can figure this out for you. I don't know if rituximab (Rituxan) would be indicated or work for you. Evidently it is successful in many hemolytic anemia cases (just not mine). As I mentioned, I too was on prednisone, which is typical for hemolytic anemia, but prednisone is definitely a mixed bag. It can be an essential part of treatment and do wonderful things, but it also can have nasty side effects.

Keep us posted!

Marmab

Forgot something
 

I forgot to mention something. The brand of cyclosporine does matter. Different brands have different bioavailability, I believe. Good luck! And hope you continue to have rising hgb.

Marmab

My doctor says she and her peers like to use the brand name Neoral when they can. She says it is better than the generic, but there are always insurance issues.

I have been on the generic brand of cyclosporine and they have now switched me to Neoral so will be interesting to see if this has any impact.

Prednisone is a right nightmare of a drug....thankfully my side effects have not been too bad but I just do not want to be on it for too long. It seems to cause me chest pain on the right side which the doctors seem to think is heartburn of some sort.

Marmab I also hope that your hip does not get any worse. So sorry to hear about that. I am also going to look up about the high retic count and hemolysis as my doctors have not mentioned this they have more suggested that the high retic count is an indicator that my bone marrow is trying to make up for the rbc's being destroyed by the hemolysis and is a positive sign that my bone marrow is working .... ??? ....

Today my retic count was at 8.5 and doctors have confirmed that retic count is an indication that my bone marrow is working and producing red blood cells. It is inflated because of the low hgb and my bodies attempt to try and ramp up my hgb levels. But even though my retic count is on the up my hgb has still not jumped - 8.7 today. So they are now having me take a combo of prednisone and danazol to see if that helps. I really just want to be off the steroids and wonder if they are doing anything at all other than giving me the typical steroid side effects.

It is my understanding that steroids are the traditional treatment for hemolytic anemia. Don't know about the Danazol. You are right in that your marrow is trying to churn out red blood cells, but the hemolysis is destroying them, affecting your hgb number. The prednisone, etc., as you know, are prescribed in order to tame the hemolysis.

Thanks for your thoughts about my hip problem. Fortunately most people do not get this side effect (AVN) from steroids, although it is not as rare as many people are led to believe. So, as is usually the case with drugs, it is a matter of weighing the benefits against the risks, and steroids do offer benefits in many folks with hemolysis. If you do not see improvement, though, I think it is important to consider the consequences of staying on steroids long term.

That said, I hope the new combo of meds works for you -- might be just the thing!

Marmab