We all know that aHUS is the result of an overactive complement system naturally creating its weapon the membrane attack complex ( C5b-9 is its numerical descriptor) to attack the linings of the very small blood vessels in a form of friendly fire creating micro-clots.
The damage blood vessels then need to be repaired so the platelets arrive and form a clot around the injured area including the clumps of the offending complement weapon. There will be a first clot at ground zero.
Although these are microscopic in relation to the width of blood vessel which is relatively larger and the gap that it leaves is smaller than the size of a red blood that needs to pass through it. But the surfaces of the inflamed blood vessels swell too. Under pressure from behind the red blood cell has to try and squeeze through but the stress on it is so great that it bursts and only the fragments can get past the clot and then go into the filtration system of the kidneys; which is not a good thing and they get clogged and close themselves down to protect themselves.
Of course there is more than one micro-clot as they are called , No one knows how many there around the body at the time but enough to cause aHUS and make it life threatening.
Going back to that first clot landing, the ground zero-micro-clot , it does the job it is meant to do and all the debris will dissolve away eventually when its part of the blood vessel is repaired and lining swelling stops.
But complement has not finished its havoc so back as the new MAC along comes and the process starts all over again. Meanwhile later micro-clots have also done their job and dissolve only for complement to reattack what they have repaired.
And this goes on and on. This is full blown aHUS.
Then a complement inhibitor appears in the blood and it “searches” for all the C5 components of complement and sticks to it so it cannot produce friendly fire (C5b-9) any more. It can take half an hour to an hour for the “biochemistry” to fully work . By the end of an infusion there are many more monoclonal antibodies than C5 proteins. And more C5 proteins are being made all the time .
Bit by bit it does this to all of them during the infusion. It cannot do anything about the MAC weapons already made.
But now there is a transition. Some still injuring and others stopped from doing it.
Old clots will dissolve by natural processes , the first micro-clot may have already disappeared by the first infusion, but and there may be existing weapons which will hit the repaired bit but eventually the ammunition will run out and new C5 cannot replace it .
So more and more repaired bits appear as the micro-clots dissolve and vessel lining swelling falls. Eventually the blood vessels are repaired. No more fragmented red blood cells are going to the kidneys.
Of course doctors cannot see this happening. Patients cannot feel it.
What doctors may being looking for is something on their measures for platelets to happen. They are looking for them to rise from the nothing or the very little that they have been. If they rise it is because new platelets are no longer needed to help repair the damage from complement.
Also doctors look for the level of LDH which is a measure of destroyed cells which rocket in the midst of aHUS it will start to fall. At this point the patient may feel no different.
Almost the reverse of what happened when micro-plots began appearing and took maybe a week for noticeable symptoms to manifest. Now the symptoms are apparent even though the micro-clots are disappearing and it could take a week or two for the last clot formed to dissolve.
It will take time but the crisis is over. That first micro-clot at ground zero has long gone and so will all those others that came after it.
Slower to return are the red blood cells numbers and kidneys working again.
Red blood cells can be transfused and the function of the kidneys can be replaced by dialysis therapy.
How long that takes for the body to get back to normal levels maybe influenced by the kidney which when working again produces a hormone to stimulate bone marrow into producing red blood cells.
Whether kidneys work again and at what level depends on how delayed complement inhibitor treatment was.
For some they will be in Stage 5, the end stage of kidney disease . For others with the respite now given by the complement inhibitor it is just a matter of time.
Recently in a closed to the public patient platform some data was reported which captured the experience of patients who had been at Stage 5 kidney failure on dialysis but had risen to Stage 3 or higher when on a complement inhibitor. Data from 15 participants had a range of 4 to 10 months to regain function , a median of 6 and an average of 6.5 months.
A small data set but one which supports the idea that in time with a complement inhibitor giving respite aHUS patients can get off dialysis and achieve a sufficient level of kidney function to live with. But it takes time and patience.
Article No. 830
