Presentation, Treatment, and Outcome for Twenty Consecutive Patients with Human Immunodeficiency Virus (HIV) Associated Thrombotic Microangiopathies (TMA).

Abstract 1432

TMAs occur frequently in association with HIV, although the exact mechanism leading to hemolysis is unclear (Crum-Cianflone NF, Weekes J, and Bavaro M., AIDS Patient Care and STDs. 2008, 22:771-778.) Thrombotic microangiopathies comprise a spectrum of diseases including thrombotic thrombocytopenic purpura (TTP) and the hemolytic uremic syndrome (HUS). The role of HIV infection in the development of TTP has been a topic of some controversy. Overlap between TTP and HIV associated pathological entities, including malignancy and malignant hypertension, may complicate the clinical presentation (Benjamin et al., CID. 2009, 48: 1129–1136). However, patients meeting a clinical diagnosis of TTP are treated successfully with plasma infusion therapy (Novitzky et al., B J Haematol. 2005, 128:373-379) suggesting a molecular process resulting in the depletion of plasma components. Such processes would include TTP/HUS and defects in complement regulation, but not disseminated malignancy or malignant hypertension. To further characterize the biology and outcome of TMA in HIV-infected patients, we reviewed the experience with these patients at the University of Maryland Greenebaum Cancer Center. All patients were from greater Baltimore, a city with 37.7 new HIV cases per 100,000 population, the second highest among U.S. cities (Baltimore City HIV/AIDS Statistics Fact Sheet, April 18, 2008. Department of Health and Mental Hygiene, State of Maryland). After obtaining IRB approval, we identified cases by review of all TMA patients treated by our plasma exchange service between 2000 and 2008. Twenty-one episodes of TMA occurred in twenty patients with HIV. One patient had had a prior episode of TMA, one in 1995 preceding our review, and one with multiple episodes in 2002 and then again in 2008. The median age of our patients was 43 years, all were African American, seven were men and fourteen were women. Seven patients were also infected with hepatitis C, one with hepatitis B, and two with both hepatitis B and C. Median CD4 cell count for all patients was 70 × 10⁶ cell/L. Twelve patients were on or previously prescribed antiretroviral medications and eight patients were not. There was no significant difference in CD4 counts between these groups. Three patients were diagnosed with HIV at the time of TTP presentation. Median duration of HIV infection prior to presenting with TMA was 7 years. Median LDH was 3301 units/L with all but two patients having a value greater than 1000 units/L. One of these patients had an LDH of 507 units/L. The other patient (LDH 274 units/L) had a history of TTP 6 years prior that responded to plasma exchange. Neurologic abnormalities were found in nine patients (excluding dizziness) and diminished renal function (Cr > 1.5 mg/dL) was noted in fourteen patients. ADAMTS13 levels were not measured. The median number of plasma exchanges was 13, with seven patients requiring more than 20 treatments. Four patients were treated with rituximab following failure of plasma exchange. Five patients died. Among these patients HIV viral load was variable ranging from undetectable to >750,000 copies, however four patients had CD4 cell counts < 50 × 10⁶ cells/L. All but one patient with CD4 cell counts ≥ 50 × 10⁶ cells/L responded to plasma exchange. Two patients with CD4 counts below 10 × 10⁶ cells/L responded to plasma exchange. Of the patients treated with rituximab, two patients had a prompt, favorable response and two ultimately died (Evans et al., AIDS Patient Care and STDs, 2010, 24: 349-52). One of the patients who died had a CD4 count of 2 at the time of rituximab treatment. The other patient had a history of previous TMA in 2002 that eventually responded to 32 plasma exchange treatments. In 2008, she again presented with TMA with thrombocytopenia, and was treated with 19 plasma exchanges prior to receiving rituximab. Her CD4 count at that time was 138 × 10⁶ cells/L. She did respond promptly to rituximab, but developed further thrombocytopenia 2 months later. On this final presentation she was diagnosed with lymphoma, to which she ultimately succumbed. HIV-associated TMA meeting clinical criteria for TTP is generally responsive to standard treatment with plasma exchange, however alternative diagnoses must be excluded. Rituximab may be effective in carefully chosen patients failing plasma exchange.