Thrombotic Microangiopathy in the Setting of HIV Infection: A Case Report and Review of the Differential Diagnosis and Therapy

Abstract

Before the modern era of HIV/AIDS therapeutics, which enabled a cascade of early recognition of infection, prompt initiation of effective antiretroviral therapies, and close follow-up, severe forms of microvascular clotting disorders known as thrombotic microangiopathies (TMAs) were frequent in the setting of advanced HIV disease. Their incidence was as high as 7% in the period 1984-1999, but fell dramatically, to <0.5%, by 2002. This profound change was predicated on one critical development: availability of new classes of anti-HIV drugs, enabling reduction and maintenance of HIV viral loads to undetectable levels. Another development in the period 1999-2002 related to TMA therapy: with recognition of autoantibodies against the von Willebrand factor cleaving protease ADAMTS13 as the etiology of most cases of one major form of TMA, thrombotic thrombocytopenic purpura, it permitted appropriate use of life-saving interventions based on plasma exchange and immune suppression. A more recent factor in TMA therapeutics was the 2011 approval by the US FDA and European EMA of eculizumab, a humanized monoclonal antibody against complement component C5, for the treatment of atypical hemolytic uremic syndrome, another major form of TMA. Despite these milestones, life- and organ-threatening TMAs still occur in untreated HIV disease and, to a much lesser extent, in those patients with suppressed viral loads. Confusion in terms of the differential diagnosis of these TMAs also impedes use of directed treatments. This report utilizes a case study of a young woman with advanced AIDS who presented with a severe TMA, characterized by coma and renal failure, to highlight the diagnostic and therapeutic challenges raised by complex hematologic conditions occurring in the setting of HIV.

Kidney Disease in HIV Infection

“…Treatment of TTP driven by HIV is based on the institution of ART, plasma exchange, and immune suppression (second-line therapy) [46]. Anti-C5 monoclonal antibody (eculizumab) is instead effective for the treatment of aHUS [47].…”

Thrombotic thrombocytopenic purpura (TTP)-like syndrome in the HIV era

“…HIV confers an increased risk for acquired TTP with a 15–40 fold higher incidence in this patient population compared with the HIV-uninfected population [14] but the pathogenesis is poorly understood [15]. TTP is reported to be more common in HIV-infected patients with advanced disease, low CD4 + T cell counts and with comorbidities (including Kaposi sarcoma and cryptococcal meningitis) [15–17]. Published case reports have documented that almost 100% of patients with acquired TTP have severe (< 10%) underlying ADAMTS-13 deficiency but levels of this protease in HIV-infected patients with TTP are variable and may be relatively preserved [18].…”

Immunological Reconstitution Inflammatory Syndrome and Thrombotic Microangiopathy: Severe Complications in a Child With Acquired Immunodeficiency Syndrome

“…Still, HIV-associated TMA/TTP has sparse response to any treatment approach and very poor prognosis. 6-8…”

“…4 HIV-associated TMA has specific clinical aspects as well as a worse prognosis than idiopathic or congenital TMA. [4][5][6][7][8][9] The authors present the case of a 10-month-old boy with advanced HIV infection who developed IRIS complicated with HLH and TMA during the course of his treatment.…”