Summary by David Brouch.
On Friday, September 21 2012 Dr. Jose A. Bufill visited Professor Haldar’s Topics in Rare and Neglected Diseases class. Dr. Bufill is currently practicing at Michiana Hematology-Oncology, P.C., and has had a distinguished career in the medical field. He spoke about N-acetyl-cysteine (NAC) and its possible role as a treatment for Thrombotic Thrombocytopenic Purpura (TTP).
Dr. Bufill began his talk by explaining the clinical features of TTP and reviewing its pathogenesis. TTP had been considered a rapidly fatal clinical syndrome until the development of plasma exchange treatments in the 1990’s. This rare disease results from the altered metabolism of Von Willebrand Factor (VWF), a large molecule with an important role in normal blood clotting. Very large multimers of VWF produced by endothelial cells are normally broken down by a specialized enzyme into smaller multimers in small arteries and capillaries throughout the body. In the disease state known as TTP, this breakdown is impaired and “ultra-large” VWF strings accumulate in these small vessels. The accumulation of ultra-large multimers form a mechanical and chemical “sieve” which damages red blood cells and activate platelets as they pass through these high shear blood vessels. The enzyme which cleaves VWF and is impaired in TTP – recently named “A Disintegrin And Metalloproteinase with Thrombo Spondin Motifs type 1 – 13” (ADAMTS-13) –was discovered a few years ago, and is the subject of intense research interest today. This disease can affect a variety of patient types, but seems to most commonly affect overweight, middle-aged females. The most important clinical problems caused by TTP include neurological symptoms (confusion, seizures and coma) and renal failure. If left untreated, TTP results in the death of almost all affected patients.
The current standard treatment for patients with TTP – plasma exchange – is cumbersome and expensive. Taking into account new information about the biochemical basis of VWF physiology and the pathophysiology of TTP, investigators in Seattle and Houston recently suggested that N-acetyl-cysteine (NAC) may benefit patients with TTP. This compound is inexpensive and has been approved for human use for many years. It was proposed as a possible therapy for TTP because it weakens the disulfide bonds that link VWF multimers by means of a free thiol group. Experimental data published last year in the Journal of Clinical Investigation suggests that NAC may be of great benefit to TTP patients. Dr. Bufill concluded his talk by presenting his experience giving NAC infusions to a South Bend patient with severe, refractory TTP.