Paroxysmal nocturnal hemoglobinuria is characterized by the presence of thromboses and these are extensive but almost uniquely limited to the intraabdominal venous network. Thrombocytopenia leading to hemorrhage, definitely there. Not dramatically common and then red cell hemolysis is constantly going on in these people with PNH. Here’s the clinical features; young adults. This is an illness of male and female, slight preponderance in females, not dramatic. Anemia for the reasons that I’ve already mentioned, and this frequently leads to rather impressive iron deficiency. Hemoglobinuria, hemosiderinuria, abdominal pain is very very common - and what the reason for that is, I wish I had a clue - and it is without question an acquired problem. This is the overall survival in a sizable number of people that we and others have looked at. It’s not good. It’s not great. Again, here is the survival with PNH.
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This is the hallmark feature. Somebody gets up in the morning and passes this very rosy plus-colored urine. Looking at the peripheral blood smear one sees the rather impressive degree of hypochromia, some degree of fragmentation, plenty of platelets here - this is not really the DIC process but this looks very much like a terrible iron deficiency. And it is. There are three populations of red cells in individuals with this disorder, and that is a group here that’s very very sensitive to the presence of complement, less sensitive here and then there is another population, a third population that has essentially a normal red cell survival time. These are brought about in three categories of type I red cells, where the survival is nearly normal; type II, and these are missing on the membrane, acetylcholinesterase decay-accelerating factor. There are components here of complement. Type III, more things are missing here on the red cell membrane, and this is what makes them very sensitive even to the normal activity of the complement system, bringing about red cell lysis. The red cell abnormalities, absence of acetylcholinesterase decay-accelerating factor, and these are things that avoid or prevent the complement system from doing in the red cell membrane. But unhappily they are missing and they are missing because of a link that doesn’t allow attachment of those proteins onto the membrane. Leukopenia, about 60% of the patients.
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Alkaline phosphatase classically reduced to near zero again because it is missing, because the link isn’t there to hold it on. No cytogenetic abnormalities have been identified. Thrombocytopenia is very common. The survival here is pretty good. The function is normal and the real problem here is that these cells are very very sensitive to antigen antibody-type reaction and some individuals use PNH cells to detect, with other techniques, undetectable antigen antibody-type of interaction. They are very very sensitive.
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And here’s the ball-game here. What’s missing is this phosphatidylinositol link in the PNH patient. Here’s the normal individual and it’s this phosphatidylinositol glycosyltransferase that’s missing here and fails to put this on and we see in the PNH there is some trans-membrane protein here but the majority of this is missing. This is what makes these cells very very sensitive. Here’s the glycolipid anchored abnormalities. These things are all missing because of the absence of that trans-membrane link, decay-accelerating factor, membrane inhibitor-releasing factor and so on down the line. This is the one to really look for today, employing flow cytometry which makes the diagnosis. Here in the past, the diagnostic test they used a sucrose hemolysis with peripheral blood. It’s still a very good and reliable, fairly simple type of test to do. But if flow cytometry is available to you, ask them to look for CD59 and in this illness it’s gone. It’s not there. That will promptly make the diagnosis. Otherwise sucrose hemolysis is very very good, and again absence of alkaline phosphatase. Why? Because the “linker” is gone and the alkaline phosphatase is not on the cell.
Feb 06
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