Hemolysis mystery

[Yanxia]

Thank you ,Colin and Malcolm!

but are these presumed hyperactive macrophages located in the Spleen? It would make sence if they were given that the Spleen maintains a large population of Macrophages and the transfused RBC's go through a sequestering period in the Spleen before entering the circulation for the remainder of their circulating life.

And to rravkin@aol.com, I can't understand what is your meaning, do you mean the spleen sequestering is a cause of the unchanged hemoglobin level or is a cause of hemolysis? If you have time ,please help!

[LaraT23]

My two cents: We had a patient very similiar to this, and he eventually developed a positive DAT. We use Ortho reagents, and the poly AHG will detect all IgG subclass coating. I sent my specimen to my reference lab, who uses Immucor reagents, and they got a negative DAT. He was off and on incompatible with random units. I ended up sending most of what I had left to John Moulds at Lifeshare. He has some for research use only reagents of his own and after an investigation found the cells to be heavily coated with not onlyI gG4 but also IgA ( also not detected in Immucor reagents). So, perhaps that sheds a little light on things? My particular patient was A pos and R2R2, if he had not passed away I would have then tried to pick up some anti-f perhaps just with adsorption on rr cells.

[rravkin@aol.com]

Yanxia,

Somewhere along these posts I remember reading something about Macrophage involvement in this hyperhemolytic phenomenon. It would make sense that the macrophage population responsible for this occurence would reside in the Spleen given that the spleen has a large macrophage population normally and they are there to remove degenerating RBC's from the circulation. If this macrophage population were hyperactive in reponse to an RBC transfusion, or hyperactive without stimulation, and given that there is a time when the transfused RBC's are sequestered in the Spleen, then it seems likely that this is where the hemolysis would take place. This theory would also lend some explaination to the findings in the opening post of this thread; however it does not explain the one incompatible unit. I hope this explaination helps.

And, thank you Malcolm. I look forward to your post.

Edited January 4, 2011 by rravkin@aol.com

[Malcolm Needs ☆]

This could have been coincidental, and the antibody causing the incompatibility may, or may not have been clinically significant; don't know, just a thought????????

:ignore::ignore::ignore::ignore::ignore:

[Malcolm Needs ☆]

And, thank you Malcolm. I look forward to your post.

OK, I spoke to Nay today and he said the following.

In many of the cases he has seen, the hyperactivated macrophages are not necessarily in the spleen. Indeed, in many sickle cases, there has been a splenectomy, either through surgical intervention or through auto-splenectomy (where the spleen necroses). He also said that the hyperactivated macrophages are often in the bone marrow, but he has seen them phagocytosing the red cells in the peripheral circulation.

He said that he had not seen anything in the literature about giving small aliquots of blood, rather than a full unit, but he said that, in certain circumstances, the haemolysis would take place over a few days, rather than as an acute thing, and in other cases, once the acute phase has happened, although transfusion should be avoided if possible, once the acute phase is over, the hyperhaemolytic syndrome settles down, and never occurs again. He wondered if this had happened in the case of your co-worker.

Hope that helps (and I hope I have written what he said accurately)!!!!!!!!!!!!!!

:fear::fear:

[rravkin@aol.com]

OK, I spoke to Nay today and he said the following.

In many of the cases he has seen, the hyperactivated macrophages are not necessarily in the spleen. Indeed, in many sickle cases, there has been a splenectomy, either through surgical intervention or through auto-splenectomy (where the spleen necroses). He also said that the hyperactivated macrophages are often in the bone marrow, but he has seen them phagocytosing the red cells in the peripheral circulation.

He said that he had not seen anything in the literature about giving small aliquots of blood, rather than a full unit, but he said that, in certain circumstances, the haemolysis would take place over a few days, rather than as an acute thing, and in other cases, once the acute phase has happened, although transfusion should be avoided if possible, once the acute phase is over, the hyperhaemolytic syndrome settles down, and never occurs again. He wondered if this had happened in the case of your co-worker.

Hope that helps (and I hope I have written what he said accurately)!!!!!!!!!!!!!!

:fear::fear:

Malcolm,

Thank you for this post. Unfortunately cases like this leave more speculation and questions than answers. I did consider the idea that the spleen may or may not be present and given what Nay has said, and the vast area of the circulation, this hyperactivity could take place anywhere. At the end of the day I guess we are all still left wondering what is the cause of the hemolysis. I hope that QCDan can provide some conclusion. Thank you again Malcolm.:)

[macarton]

Since you are a gel user, how you called Ortho about sending it to their reference lab?

[Ajac]

This may be a stretch, but your patient isn't developing PNH are they? MDS patients sometimes end up with PNH.

[Yanxia]

Yanxia,

Somewhere along these posts I remember reading something about Macrophage involvement in this hyperhemolytic phenomenon. It would make sense that the macrophage population responsible for this occurence would reside in the Spleen given that the spleen has a large macrophage population normally and they are there to remove degenerating RBC's from the circulation. If this macrophage population were hyperactive in reponse to an RBC transfusion, or hyperactive without stimulation, and given that there is a time when the transfused RBC's are sequestered in the Spleen, then it seems likely that this is where the hemolysis would take place. This theory would also lend some explaination to the findings in the opening post of this thread; however it does not explain the one incompatible unit. I hope this explaination helps.

And, thank you Malcolm. I look forward to your post.

Thank you rravkin.

But I think the macrophage will not cause the hemoglobin urine.

[Yanxia]

And I agree with Ajac, this patient maybe developing PNH.

[Malcolm Needs ☆]

Thank you rravkin.

But I think the macrophage will not cause the hemoglobin urine.

They most certainly will. What you have to remember is that the macrophage will phagocytose several red cells each. These will be destroyed by the enzymes in the macrophage. There will be millions and millions of macrophages all doing this and, eventually, free haemoglobin will be released into the circulation. This free haemoglobin will be excreted from the circulation (as it would in any acute haemolytic transfusion reaction) and you would, therefore, see free haemoglobin in the urine. Indeed, in the case of a sickle cell disease patient who is undergoing hyperhaemolysis, you can test the haemoglobin in the urine, and detect HbS, as well as HbA, thus proving that autologous red cells are involved, as well as the transfused red cells.

[Yanxia]

But Malcolm I think the macrophage will bind the free haemoglobin, we will not see the free haemoglobin, this is the mechanism of Vessel outside hemolysis( sorry , I must spell it wrong). I will recheck it.

[Yanxia]

Malcolm,you are right!

[Malcolm Needs ☆]

Sorry shily!

[mrmic]

You might consider reviewing the transfusion policy of your outpatient clinic. Check to see if they are only transfusing with saline, not adding any meds or giving chemo simoultaneously. Actually gone there physically and check, what's written is not always practice. It could be a med problem, which is a pretty complicated workup, not done by many labs. Check what meds the patient is taking as prescribed and if they are taking anything else at home (not prescribed) herbal or some old quinine for leg cramps etc. If the research on the med suggest that one might be involved, see if the physician will discontinue or switch for awhile. Although, there are a lot of antibodies out there demonstrable by one technique or another and could be missed, you want to rule out other non-red cell antibody causes as well.

good luck

[rravkin@aol.com]

Malcolm,

Can you give some expansion on the PNH possibility?

[Malcolm Needs ☆]

I don't think it is PNH.

The haemolysis appears to be associated with transfusion, whereas, with PNH, haemolysis is exacerbated by slight acidosis during sleep, followed by haemaglobinuria upon wakening.

[QCDan]

...well the good news is that our patient was transfused with two units of phenotypically similar blood and had a Hgb increase from 6.8 to 8.8 g/dl without a transfusion reaction:D. The bad news is that we still do not know what exactly caused the hemolysis in the first place. This patient is also receiving HLA matched platelet pheresis transfusions without complications. If we find anything else on this patient I will be sure to update this discussion thread. Thank you very much for all the input and suggestions on this subject. It is a very interesting case and we will be following this one for a while here at the hospital.

Now lets keep on shaking tubes:).

[Malcolm Needs ☆]

Thank you too for this exceedingly interesting case, and I do hope you get to the bottom of it, because I am intregued.

[Yanxia]

[

Malcolm,

Can you give some expansion on the PNH possibility?

I have ask a friend who is the doctor of a PNH patient, his patient hemolysis after transfusion but when washed the blood , no hemolysis occur again.

About this he think this is perhaps because the transfused complement or something can active the complement caused the hemolysis.

I will ask another seasoned doctor about this.

[Colin Barber]

...well the good news is that our patient was transfused with two units of phenotypically similar blood and had a Hgb increase from 6.8 to 8.8 g/dl without a transfusion reaction:D. The bad news is that we still do not know what exactly caused the hemolysis in the first place. This patient is also receiving HLA matched platelet pheresis transfusions without complications. If we find anything else on this patient I will be sure to update this discussion thread. Thank you very much for all the input and suggestions on this subject. It is a very interesting case and we will be following this one for a while here at the hospital.

Now lets keep on shaking tubes:).

I have a slightly off the wall thought - ? was the patient on antibiotics. I remember spending a lot of time investigative a supposed delayed haemolytic transfusion reaction in one of our sickle cell patients and it turned out to be a drug induced haemolytic episode, but because it followed a transfusion we naturally initially assumed it was the transfusion that caused the haemolysis.

[crummer]

Hyper Haemolytic syndrome?

[Brenda K Hutson]

Coming in on this late (as usual) and some of this will be repetitive, but here were my thoughts as I read this Thread:

1. 1st, we had a patient at one Medical Center I worked at that kept hemolyzing, but the Antibody Screen was always Negative and we could not elute anything. We had a phenotype and the patient was Jka-. We decided to just "take a shot at it" and give Jka- blood products. No more hemolysis. Those darn Kidd antibodies can disappear quickly.

2. Have seen hyperhemolysis in a SS patient. Hemoglobin went down to 2.6!

3. This really is not like your case in that the patient had not been transfused recently (according to the patient), but of interest; we had a patient come into the ER with hemoglobinuria and hemoglobinemia. The patient had been out on a boat the day before; no unusual circumstances. Just became ill and came into the Hospital. We never did figure out what that was all about but luckily the patient recovered.

Brenda Hutson, CLS(ASCP)SBB

Here is a good one we have been working on...

Patient with MDS (myelodysplastic syndrom) presented to the clinic needing a transfusion. Patient received two units of Leukorduced RBC's without complications(Hgb increased form 6.9 to 7.5). O pos, antibody screen negative (2 cell solid Phase screen galileo), electronic crossmatch performed. Patient called the clinic and came back in the following day with hemoglobinurea, blood in the urine, samples were drawn and found to be hemolysed, LDH extremly elevated, bilirubin elevated, slight lower back pain. Sounds like a classic transfusion reaction at this point. Pre- and Post transfusion samples were evaluated, testing performed included (ABORh, ABSC (gel), DC(poly)), all results remaind unchanged, O pos, negative screen, negative DC (poly). The segements of the two units that were transfused were retrived and crossmatched through gel and one of them had a 2+ incompatible result. We were at this point thinking a Low incident antigen might be causing the problem. Antibody ID was performed, samples were sent (pre and post transfusion) to the ARC reference lab. All cells had a negative reaction.

On her next go around, we did a serologic crossmatch for the two units of LRBC's she was about to get in the clinic. Antibody screen was negative in gel and solid phase. Two gel compatible O Pos LRBC's were transfused(Hgb increased from 6.7 to 7.3). Patient had no complications during the transfusion so we thought we were out of the woods. Fast Forward to the next day when she came back in with the exact same symptoms of a hemolytic transfusion reaction. The transfusion reaction work-up had the same results as it did before. Our next step is to give phenotypically similar blood for transfusion, and get HLA matched platelets in for this patient. Further down the road, since this patient will now be chronically transfused due to her MDS, we might even get one of her HLA platelet donors donate some blood for her if the phenotypically matched blood still causes her to hemolyse the transfused RBC's.

Has anyone out there ever run into something like this? It is really starting to frustrate us not being able to pin-point the cause of her hemolysis.

Thanks and I'll keep updating as we find new results.

[janet]

Reading this thread a little late too - but I am reminded of our MDS patient; group A who received group O platelets ..... he had severe hemolytic reaction - we started titering incompatible platelets, gave him a low titre group O again and he had another reaction (realize now how stupid that was!). The hematologist diagnosed him with PNH, stated PNH can develop in MDS patients (15%!??) and explained his severe reactions because his cells were already primed with complement. Not sure if any of our experience could translate here - antibody in the donor clearing some of his primed cells or as Shily stated something in the transfusion starting the complement process!?!