Click here to view next page of this article New Treatments for Thrombotic Thrombocytopenic PurpuraThrombotic thrombocytopenic purpura is characterized by the presence of thrombocytopenia, striking hemolytic anemia and neurologic abnormalities; anything from a headache to profound coma, and fever almost 100% of the time, and renal disease. Now the renal disease may be anything from microscopic hematuria all the way to azotemia, uremia and anuria. It’s recognized that there is a considerable familial occurrence; siblings, husband and wife have been reported, or people living in the same domicile, not necessarily related. There is also an association with pregnancy. By removing the pregnancy, making the delivery and so on. The frequency here is not particularly common. Certainly there is probably more than 3 or 4,000 patients reported in the world’s literature today. Distribution-wise, age; it’s more common in infancy through 80 years and the peak frequency is in the third decade. Without question there is about an 8 to 9 to 10:1 female preponderance. The reason for this I have no good explanation or clue. This is from some of our early studies here. You can see the high frequency is in the third decade. Some people, because of the relative infrequency of this problem, say, "Oh yes I remember the last time we saw a patient with this. This is probably seasonal." No, everyone we’ve looked at, and we’ve looked at this very very carefully as have others and it’s found uniformly around the calendar. The clinical complaints that these people have, the neurologic abnormalities; hemorrhage, bleeding, malaise, fatigue, nausea, vomiting, very nonspecific things here. Fever, pallor because of this striking anemia, jaundice and myalgias. Nothing really unique. The physical examination, once again, fever essentially 100%. Thrombocytopenia, by definition, is clearly there. He tells me he’s got a terrible patient with thrombocytopenia purpura but yet the platelet count is normal. If it’s normal, you don’t have that illness. You just do not. There is no normal platelet counts in thrombotic thrombocytopenia purpura. Anemia here is essentially the same at 100%. Renal disease, again this can be anything from hematuria all the way to azotemia and aneuria. Leukocytosis, this figure is high. In fact anytime that I see the white blood count elevated above normal I worry, very seriously worry, that we are not dealing with this entity of TTP. Because most of the time the white count, virtually almost all the time, the white count is normal. Every time I see an elevated white count there is an infection and that’s the treatment, not what I’m going to get into for treating this illness. Laboratory findings here; some rare problems, biologic faults, positivity, and I really can’t put frequency on here because these are fairly rare in a reasonably rare illness. HIV positivity much more often showing up now. If there is any problem of making this diagnosis, biopsy of gingiva is the number one site we go for, and this shows intra-lumenal vascular occlusion, hyalin thrombosis, fibrin, platelets and so on. Specific staining techniques with IgM, IgG, complement and so on has not uniformly shown this to be an immune-mediated process. This just shows here laboratory data and people when they are admitted with this problem, and you see here, with respect to the hematocrit value, this is impressively low. Again the white count here is essentially normal. With respect to the etiology; again, virtually every branch of medical science has been called to duty here. Is this a toxin, an infectious agent? So the etiology here remains to be identified. There are a number of features of this entity associated with various chemotherapeutic agents and some people think that this really isn’t TTP. Well, I don’t want to get into a real argument with such individuals but if there is a recognizable cause, no it’s not TTP. For TTP we do not know the Relapse is unhappily a very common type problem and it’s most common within the first month. After that we very seldom if ever see any relapses. What is it that initiates the relapses? Again, I see this working at the bedside, removing the plasma with plasmapheresis and exchange, saving the plasma, looking in the plasma to find out a clue. Again, too stupid to know what it is but this is a very common problem in TTP. Here are these laboratory data when these patients are discharged home and you can see here that the situation is essentially in normality. The survival, female, male and here’s the survival since we’ve been employing our protocol. This is taking into consideration everybody that we’ve looked at since the 1970’s and I have not had a demise since 1984. Here is the Kaplan-Meyer curve and when I took this over … had this done by someone who had the software in the Oncology Department, they said, "Wow, what illness is this? You’re not from Oncology." And I said, "No, I’m not." So with TTP again the optimal treatment here is initially corticosteroids. Some respond to that, and if not one moves on to plasma therapy of some sort and exchange, plasma exchange is clearly the optimal way to go. Antiplatelet agents, splenectomy and these other things that are done are simply not realistic. This is one very important thing here; do not infuse these people with platelets because they respond very adversely to this and oftentimes there is a very short time interval between a platelet transfusion and transport to the autopsy room. Again, it probably makes some sense because as I mentioned the number one target organ damaged there is the endothelial cell. It’s denuded, it’s damaged, it’s disturbed. You give platelets and you are going plug up everything. Now this survival here; what’s this due to? A dramatic turnaround in survival going from not a single survivor reported when we started, now to a 95, 96 and so on percent. Certainly it’s due to better general medical care. Earlier diagnosis and definitely the use of plasma in some form or other, and the optimal way is plasmapheresis and exchange, not simply infusion of |