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Round peg in a square hole: How doctors pulled off cross-blood transplant in patient with rare Bombay blood group

Posted on February 9, 2025 By admin


It was in his blood that the 30-year-old male should create history. Literally.

In mid-2024, the patient underwent a kidney transplant. Though he was relatively young for a transplant, that’s not where he stands unique. He had the extremely rare Bombay blood group, which prevented him from receiving organs or even blood transfusions from anyone who didn’t have the same blood group running through their veins.

But then that’s exactly what he did: his mother donated her kidney, though she did not have the Bombay blood group. Doctors at MIOT International in Chennai, who had performed cross-blood transplants for close to two decades, were willing to cross the rubicon into a sector with no precedence whatsoever: no one had attempted a cross-blood match on a Bombay group patient ever before.

A sheer miracle

In a recent paper published in the peer-reviewed journal Kidney International Reports, the team that worked on the transplant — Rajan Ravichandran, Yashwanth Raj T., and Kanakaraj Arumugam — chronicled for posterity how a team of doctors in Chennai pulled off what not long ago might have been put down as a sheer miracle. “It was impossible for Bombay blood group patients to receive blood or organs from another blood group, until it was not,” senior nephrologist Dr. Ravichandran explained.

The story he believes begins nearly two decades ago, when he was trained in Japan to perform cross-blood transplants, referring to the transplantation performed when donors and recipients have different blood types. In 2010, he and his team at MIOT Hospitals used a kidney from a donor with B blood group on a recipient with O blood group, successfully. Using a special procedure called double filtration plasmapheresis (DFPP) developed by the Japanese, the team had the patient discharged in a week and back at his software job in three months’ time.

“The most essential requirement in transplantation is a blood group match — ideally, the patient’s own blood group, or in the event it is not available any group for which his blood does not carry antibodies,” Dr. Ravichandran explained.

Antibodies are used by the body to detect and neutralise foreign bodies while antigens are proteins or carbohydrates found on the surface of red blood cells, white blood cells, and platelets, and they determine blood type. 

The Bombay blood group

The Bombay, a.k.a. HH, blood group is a rare blood group first discovered in Mumbai in 1952 by Y.M. Bhende. The key differences between the Bombay blood group and the common ABO blood groups lie in the presence (or absence) of the H antigen, which is the fundamental building block for the ABO blood group system.

In normal individuals, the H antigen serves as the base structure for building A and B antigens. In Bombay blood group individuals, the gene responsible for producing the H antigen is mutated or absent, so neither A nor B antigens can be formed.

Therefore, these people cannot receive blood transfusions from any ABO group, including type O, which has the H antigen. They can only receive blood from another Bombay blood group donor. Its prevalence is about 0.0004% (one in 4 million) of the total human population. While it drops to one in a million in the European population and one in 10,000 in Mumbai, the act of finding a donor is still daunting.

Clinical challenges

It was daunting for this index patient as well. The issue was not to find a donor for a kidney: his mother was eager to donate hers; the nub was that his body would reject it outright because they had differing blood groups. “We decided that it was time to use the principles of cross-blood matching that we use for the ABO type here as well. We assumed it was a similar situation and decided to use the Japanese technique of DFPP,” Dr. Ravichandran said.

“Once you identify the Bombay blood group, you know he has anti-H antibodies. Firstly, we measure anti-A and anti-B antibodies in the blood as we do in the case of ABO cross-blood matches. Here, additionally, you have to measure the levels for anti-H antibodies too, and titrate the levels. The next step is to give a monoclonal antibody injection to the patient to deplete B cells that produce antibodies,” he said.

As the authors detailed in the paper, the clinical challenges in such a scenario, even among those with rich cross-blood transplant experience in ABO, include determining a safe anti-H antibody titre cut-off, sufficient enough to stop the body from rejecting the organ from the donor.

Notably, there is no precedence for this, so one had to, again, assume a safe level of antibody concentration. There is a high risk of hyper-acute rejection as anti-H antibodies are more potent than anti-A or anti-B antibodies.

“After determining the titre (levels) of antibodies, we started plasmapheresis, which again removes the antibodies in the blood, lowering the chances of rejection. This was combined with immunosuppressive IVIG [intravenous immunoglobulin] to further suppress antibodies, thereby preventing hyperacute rejection of the organ.”

Every alternate day, the team measured the level of antibodies in the patient. “Normally for anti-A and anti-B, we consider a 1-in-16 concentration of antibody to be an ideal safe point to start transplant. It starts at 1-in-256, we then bring it down, lower the antibodies present. In anti-H there just is no cut off, so we made a few assumptions,” he said.

A new hope

At what was assumed to be a safe, no-rejection antibody titre, the transplant surgery was performed. The team scoured the State for units of Bombay blood group units, just in case the patient might need it during transplant surgery, since cross-blood transfusion is not possible. However, he did not need it. The surgery passed off a breeze and there were no complications during or after surgery, the team said.

While there is no published literature regarding accommodation of anti-H antibodies by the graft, as it had not been tested before, in this patient the doctors seemed to have achieved a no-rejection antibody titre status, and there was no rejection. The first two weeks, which are also crucial to decide if the organ will be rejected, also passed without incident, the doctors said.

Six months later, the patient is well and able to resume his pre-transplant activities, grateful at how the impossible became possible for him — and hopefully, for others in the Bombay blood group as well, if they are ever to require a transplant.

Published – February 10, 2025 03:22 am IST



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