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Original Contribution HIV-associated Thrombotic Thrombocytopenic Purpura – What We Know So Far Muriel Meiring, 1 Mike Webb, 2 Dominique Goedhals 3 and Vernon Louw 4 1. Associate Professor and Specialist Scientist, Department of Haematology and Cell Biology; 2. Senior Specialist, Division of Clinical Haematology, Department of Internal Medicine; 3. Pathologist and Senior Lecturer, Department of Medical Microbiology and Virology; 4. Associate Professor and Principal Specialist, Division of Clinical Haematology, Department of Internal Medicine, University of the Free State, Bloemfontein, South Africa Abstract Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disease characterised by microvascular platelet deposition and thrombus formation in selected organs, resulting in microangiopathic haemolytic anaemia, thrombocytopenia, neurological symptoms and renal failure. Typically a very rare disorder, TTP is being seen with increased frequency in patients infected with the human immunodeficiency virus (HIV). Deficiency of the von Willebrand factor cleavage protease, ADAMTS13, has been implicated as the cause of TTP. However, the pathophysiology of HIV-associated TTP and the thrombotic potential in these patients are not known. This article provides not only an overview of the literature regarding HIV-associated TTP, but also presents new data on this disease. We propose a mechanism for the initial onset of HIV-associated TTP that includes the release of extreme amounts of von Willebrand factor and the downregulation of ADAMTS13 and/or the production of autoantibodies to ADAMTS13. Keywords Thrombotic thrombocytopenic purpura, HIV, ADAMTS13, anti-ADAMTS13 antibodies, von Willebrand factor Disclosure: The authors have no conflicts of interest to declare. Received: 5 March 2012 Accepted: 9 April 2012 Citation: European Oncology & Haematology, 2012;8(2):89–91 Correspondence: Muriel Meiring, Associate Professor and Specialist Scientist, Department of Haematology and Cell Biology, University of the Free State, P.O. Box 339, Bloemfontein 9300, South Africa. E: GNHMSMM@ufs.ac.za Thrombotic thrombocytopenic purpura (TTP) is an acute prothrombotic disorder resulting from a deficiency of the von Willebrand factor cleavage protease ADAMTS13. 1 The enzyme ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats) cleaves the peptide bond between Tyr-842 and Met-843 of the mature subunit of von Willebrand factor (VWF) and prevents the interactions of the largest VWF multimers with platelets. In the plasma of patients with TTP, ultra large VWF multimers (ULVWF) have been observed that provoke widespread microvascular thrombosis. 2 TTP is characterised by microvascular platelet aggregation and thrombus formation resulting in thrombocytopenia, microangiopathic haemolytic anaemia, variable renal and neurologic dysfunction and fever. 3 Infection with the human immunodeficiency virus (HIV) is postulated as a direct precipitant of TTP, presumably through infection of vascular endothelial cells resulting in dysfunction, localised thrombin generation and consumption of ADAMTS13. 4 HIV-associated TTP was first described in 1987 by Jokela et al. 5 Since then, several case studies have been reported. The occurrence of TTP in association with HIV infection is now well recognised. 6,7 Prevalence of HIV-associated Thrombotic Thrombocytopenic Purpura Although congenital TTP is a very rare disease, the incidence of HIV-associated TTP is much higher. A group in South Africa estimated the incidence of TTP in HIV-infected individuals to be 15–40 times that in non-infected individuals. 8 Also, more than 80 % of TTP cases in South Africa are found to be HIV-related and it is expected that the incidence © TOUCH BRIEFINGS 2012 of HIV-associated TTP will continue to rise. 9 HIV-associated TTP cases were also described in other countries, such as the UK and Italy. 10–12 Features and Treatment of HIV-associated Thrombotic Thrombocytopenic Purpura HIV-associated TTP is a haematologic disorder observed in patients infected with HIV. As with congenital non-HIV-associated TTP, this syndrome is characterised by microangiopathic haemolytic anaemia, thrombocytopenia, renal dysfunction, fluctuating neurological abnormalities and fever. Treatment regimens include highly active antiretroviral therapy (HAART), infusion of fresh frozen plasma, plasma exchange, steroids and immunomodulatory agents. One case study stressed the importance of CD4 count and viral loads in HIV-associated TTP. 11 The patient presented with a normal CD4 count, a high viral load and a suboptimal response to plasma exchange while remission was obtained with combined antiretroviral therapy (cART). Other case studies confirmed that there may be a causative link between TTP and advanced HIV infection, since all patients presented with extremely low CD4 and CD8 counts. 12 This is not always the case in our experience (unpublished data). The treatment strategy in the case described by Miller et al. 11 included fresh plasma and a corticosteroid, but only after plasma exchange did the platelet count start to rise and the steroid was tapered; cART treatment was started afterwards. Another case study described a patient with myocardial injury in HIV-associated TTP who responded poorly to plasma infusion and steroid therapy, but recovered fully following plasma exchange. 9 89