ALBERT

Description: Background The ability of a person with hemophilia to adhere to treatment recommendations aimed at preventing and controlling bleeding likely impacts clinical outcomes and resource utilization. Annual cost of replacement factor for persons with severe hemophilia on prophylaxis is estimated to be as high as $300,000 per year (Johnson KA and Zhou ZY. ASH Annual Meeting Educational Program. 2011; 413-418). Hemophilia care is optimized when delivered by a highly specialized hemophilia treatment center (HTC) (Soucie et al. Blood. 2000; 96: 437-442). Consolidation of care for persons with hemophilia from a large geographic region within an HTC results in demographic heterogeneity that may impact an individual's ability to adhere to treatment recommendations. Little is known regarding the impact of socio-demographic factors on treatment outcomes for persons with hemophilia. The purpose of this study was to identify disease-related, treatment-related and demographic variables that have a significant impact on morbidity and resource utilization. Methods We identified 69 persons with severe hemophilia treated at our HTC between June 2009 and June 2012. We collected data for the variables listed below in table 1. To assess morbidity and resource utilization, we collected data for total factor use, total outpatient cost, total inpatient cost, frequency of inpatient and outpatient encounters and length of stay when hospitalized. Risk factors were identified using linear regression. A subset analysis was performed to evaluate the impact of prophylaxis on patients without inhibitors. All statistical analyses were performed using STATA (version 12.0 College Station, TX). Statistical significance was defined as P 〈 0.05. Results Age and inhibitor status were the only variables to significantly impact cost in both inpatient and outpatient settings (Table 1). The statistically significant beneficial impact of prophylaxis was confirmed by subgroup analysis of patients without inhibitors with respect to number of hospitalizations and length of stay, but not total cost. Conclusions Identifying and addressing potential barriers to care will likely reduce morbidity and cost for persons with hemophilia. Caregiver status and age are demographic variables that may contribute to poor medical adherence resulting in increased morbidity and cost of care for persons with severe hemophilia. Disclosures: No relevant conflicts of interest to declare.

Description: 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. Disclosures: No relevant conflicts of interest to declare.