New aspects in the pathogenesis and treatment of thrombotic thrombocytopenic purpura and hemolytic uremic syndrome. Raife T, Montgomery R. Reviews in Clinical and Experimental Hematology 2001;5(3):236-261; discussion 311-2.

The thrombotic microangiopathy (TM) syndromes, thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS), are a rare and heterogeneous group of disorders characterized by widespread microvascular thrombosis and end organ injury. Decades of descriptive studies have defined clinical subsets of TM syndromes by clinical and laboratory features. Despite many advances, however, progress towards understanding of the etiology and pathogenesis of TM disorders remains limited. The rarity of occurrence and lack of natural animal models of TM syndromes have hampered progress in experimental and clinical studies. Treatment remains essentially empirical and options are limited. This paper provides an excellent resource on pathogenesis and treatment and cites nearly two hundred papers. Most relevant here are the implications for clinical management of TM patients. Patient management essentially relies on common blood and biochemical tests, although the development of the assay for von Willebrand factor (VWF)-cleaving protease activity may become an important addition to the laboratory tests currently utilized in TM. The value of VWF-cleaving protease activity is currently limited, as deficient protease activity is not diagnostically specific for active TM. Plasma-based therapy remains the standard of treatment for many TM syndromes. Plasma exchange (PE) therapy offers several possible benefits and is the most widely used and successful therapeutic treatment. The supernatant of cryoprecipitated plasma and solvent-detergent plasma (SDP) have been successfully used in the treatment of TM patients by PE. These solutions have exhibited VWF protease activity. It is unclear, though, what effect these products might have in TM patients with normal activity of VWF-cleaving protease, or in patients that may have abnormalities of hemostatic factors or regulatory proteins that are deficient in these products. SDP has been shown to be deficient in certain proteins, and there are reports of central venous catheter thromboses in TM patients. Immunosuppressants or agents that modulate the immune system have been reported to be of benefit in certain cases of TM. The ability to detect autoimmune etiologies of TM and to select appropriate patients for this type of therapy could potentially improve the success of this treatment modality. Intravenous immunoglobulin is a treatment that has been used with modest success as well. Its sporadic success may reflect efficacy against certain pathogenic mechanisms and suggest that it could be useful in appropriately selected patients. A number of other potential agents that may be candidates for future exploration are also described. Recent advances in the genetic and molecular understanding of subsets of TM disorders and the development of relevant animal models offer new resources to explore the pathogenic mechanisms and, with these new advances, more effective and individualized treatments for TM syndromes can be developed.