I give blood regularly. As a midwife, I’ve seen how quickly and devastatingly a woman can lose half her circulating volume. Plus I have great veins which you can see from space, and iron levels so good it’s amazing I can ever get through airport security without beeping. And I love the orange club chocolate biscuit. I’ve given blood 68 times, kudos to me. I try to encourage fathers-to-be to go give blood as a sort of thank you to the NHS. One of the rewards of doing that is you get to find out your blood group. It’s kinda fun (geeky perhaps) to know although I thoroughly reject the possibility of using that information to decide what you should eat to lose weight. We check a woman’s blood group as soon as she comes to see us because we need to start planning for the blood transfusion that we hope she will never need. If we know what blood types might be required in the coming months, the blood bank can make sure they have the right mix. If she is found to have unusual antibodies, she’ll need special matching blood to be available just in case. But the most important thing we want to know is if she’s rhesus positive or negative.

Why do we care, I hear you ask… call me a nerd but I think that’s an excellent question.

Ok, I’m fascinated by our immune system. I take vitamin D, I eat my tangerines (I prefer oranges but I hate peeling them). I even take echinacea. Look, I believe in the placebo effect! Like most normal people, I hate being ill, and I’m all in favour of any hacks that can optimise my natural defenses.  Like most people, I’m not a scientist so the complexities of our immune system is out of my league. The knowledge I have gleaned is, I’m afraid, rather banal: we “simply” need to eat our veggies, sleep enough, and do some exercise. And get all the vaccines we are offered. I guess I’ve made an effort to understand it better because pregnancy really messes with  a woman’s immune system, and we’re always trying to improve a newborn baby’s immunity to diseases. We know they are born without a fully functioning immune system. Ok, sure. I hear you: you’re asking why I’m banging on about our immune system, when I said this was about Anti D… Stick with me. Because Anti D is linked to immune responses.

To cut a long story short, our immune system makes antibodies which are molecules that can kill pathogens such as bacteria or viruses. If the pathogen is new and fast-replicating and maybe vomits out poisonous toxins, our immune system might not be able to complete the clever but long-winded process of manufacturing antibodies quickly enough, and we die. If we we recover, it’s because our white blood cells managed to manufacture enough of the correct antibodies to kill the bug before it killed us. Added bonus: we won’t forget that pathogen and, should we encounter it again, we will barely even get sick because we’ll have created white blood cells which act as sentinels with really long memories, who remember how to make a sh!t-ton of the correct antibodies at short notice.  Better still, if we are lucky enough to have been vaccinated, our immune system will have been hoodwinked into making the correct sentinels which then lurk in our nooks and crannies ready to go full ninja should the real thing ever be detected so we never even get sick. Seriously good science.Sometimes our little ninjas get things wrong and go ballistic at things like peanuts. For reasons we don’t fully understand (at least I don’t) our immune system thinks the peanuts need to be annihilated in a nuclear-spectacular mutually assured destruction kinda way. The trouble is, once our ninjas think something is bad, it’s unbelievably difficult to convince them otherwise.  There are trials underway to retrain these grudge-holding warriors but it’s early days.

Anti D is like peanuts.

Sort of.

Let’s pretend Rhesus D is marmite:  you know what they say, you either love it or hate it! Let’s imagine that our mother has never encountered marmite. Now this mother is expecting a baby with a philistine dad who loves marmite (but she’s taken one whiff of the sticky pungent brown stuff and vowed she would remain marmite-free or die trying) . If mother and baby’s bloods never mingle, that’s fine. Often they don’t, so the mother continues in blissful marmite-ignorance. Sometimes, during labour or following a bunp to the mothers’s abdomen, the baby’s blood gets into the maternal circulation albeit in tiny quantities, and her immune system is duly alarmed. Turns out her immune system thinks marmite is absolutely sodding lethal and needs to be wiped out. So it does what a threatened immune system is meant to do and produces marmite destroying antibodies. Not only that, but when it has finished destroying that little bit of stray marmite, it keeps marmite’s fingerprints on record so next time marmite is detected, a whole army of marmite destruction units can be deployed. So far so reasonable.  I mean, it’s a bit OTT as reactions go, after all marmite isn’t THAT bad! [Full disclosure: I’m French,  I’m supposed to gag at the thought of marmite, but it is in fact yummy]. But there’s a problem: these marmite destruction units can easily cross the placenta and get into the baby’s blood stream. That’s because these units are tiny compared to the baby’s red blood cells that somehow accidentally got through.  The first baby tends to survive unscathed because the mother’s immune system doesn’t get the chance to go full-on paranoid. Maybe because the mixing happened at birth, so the mother only discovers the marmite as the fortunate baby exits. By the time a subsequent marmite baby is conceived, the mother’s overreacting bodyguards are primed to make a foolishly large quantity of these anti-marmite seek-and-destroy antibodies. If these make contact with the unsuspecting baby’s marmite-infested red blood cells, a full on immune response will be triggered and a gazillion antibodies are pumped out into the mothers blood stream, and these cross freely into the baby’s. They proceed to wipe out those vital, oxygen carrying red blood cells, leaving the baby severely anaemic or worse.Of course this doesn’t always happen. A marmite positive dad will have 2 copies of this gene to pass on to the baby, one of which might not be marmite-tainted. It’s 50/50. If the untainted one is passed on, the baby remains invisible to its mother, and no maternal immune reaction is engaged. Sometimes both the dad’s genes are marmite positive in which case his babies will always be positive.

In the good old bad old days, there wasn’t much you could do about this. If the baby survived til birth, you could give it a blood transfusion.  This would give it a much-needed red blood cell boost, allowing the baby to get oxygen around its body. But the discovery of Anti D was a complete game changer.

Here’s how it works:We give the marmite negative mother a bunch of anti-marmite seek-and-destroy antibodies. Ahem, I hear you say, didn’t you just say that these are the CAUSE of the problem? Nothing gets past you, loyal reader. But here’s the thing. If you give just enough of these pesky antibodies to wipe out any baby blood cells that might accidentally have got into its mother’s circulation, then her immune system won’t be triggered to make them. It’ll never see them because they will have been destroyed by the foreign anti-marmite (aka anti-D). And if she never makes them, she won’t have bodyguards armed with a ‘WANTED’ poster and a long memory, out to destroy marmite-tainted red blood cells forever, and the baby in effect goes under the radar. I suppose it’d be as if a foreign marmitey spy came to your country,  but got dealt with surreptitiously by counter spies from a third country. Your country never even knew there’d been a spy. Thus your country doesn’t decide to invade the marmite spy country on principle. Voilà! Countless lives are saved.

This is fascinating, I hear you say, and you are right! But wait, there’s more: I haven’t told you how they make Anti D…  And I know you are, quite rightly, curious about that. Because you might have heard its a blood product, which is kinda mysterious…  we tell all our rhesus negative women before they receive Anti D that it is a blood product, in case they are Jehova’s Witness, and because of the theoretical (but as yet unheard of) risk of blood-bourne infections, I guess. But until just now, I had no clue what that meant in practice. Then I came across an excellent essay by a fellow midwife (Kieran Froese, 2023) which blew my mind. I discovered that it was initially manufactured rather unethically by injecting positive blood into rhesus negative male (at least they wouldn’t be getting pregnant) prisoners from the legendary SingSing jail (I’m guessing they weren’t asked if they felt like participating). This caused the men to develop antibodies (in the same way as pregnant women do) but these antibodies aren’t harmful in smallish quantites, as far as I can tell. The harm to those men would more likely have come from dodgy rhesus positive blood donors as (back in the days)  it wouldn’t have been tested for any infections… anyhoooow, they then harvested the antibodies and gave them to a known rhesus negative pregnant women, who went on to have seven healthy kids despite the fact that the dad was confirmed positive. The process is basically unchanged today, except the donors who consent to receiving rhesus positive blood in order to make Anti D have explicitly consented to being total heroes.

As Kieran Froese (who is, as it turns out, one such heroine) puts it:

“Voluntary sensitising is achieved by receiving repeated transfusions of closely matched positive blood. Not everyone creates antibodies, even when intentionally trying, and there is no test to predict who will. Most donors are men and I felt I had to assert myself to be taken seriously. Importantly, I had to provide evidence of my infertility via medical records of my hysterectomy. Once I was accepted into the program My first transfusion was 40ml given by slow push and I felt… nothing. I had smaller top up transfusions every three months. It wasn’t until my third transfusion boost when I was told that I had, in fact become sensitised and was actively producing antibodies…. My current titre is 42 international units of anti-D per ml of donated plasma. At about 850mls per donation and about 20 donations a year, that equals 1142 doses of anti-D a year. Anti-D is made from pooled plasma which means that my plasma is pooled together with the plasma of other anti-D donors.”

So there you have it! Y’all know how I love a vaccine: well this is as close as I come to being antivax, because it’s a life-saving intervention that specifically prevents antibodies from being made. The not so good news is that this Anti D has to be given by injection, and unlike a vaccine jab (tiny dose, teeny weeny needle, no pain) this one is quite a substantial jab. Not gonna lie, I feel a bit bad when I give it. Luckily, we now have a blood test (tiny needle, no pain) which allows us to predict if a baby will be rhesus positive. We only give the Anti D to those babies’ mothers.

Obviously we cannot all volunteer to donate self-generated Anti D, but most of us can give blood. If you, loyal reader, haven’t yet got round to making a new year’s resolution, you could do worse than giving a pint of your finest red stuff. I thank you warmly.