Clinical Features, Treatment, and Outcome of Severe HIV-Associated Immune Thrombocytopenic Purpura In the HAART Era

The association between HIV and immune thrombocytopenic purpura (ITP) is well documented. Although HIV-associated ITP responds both to highly active anti-retroviral therapy (HAART) and treatments used in classic ITP, the clinical features of HIV-associated ITP were documented prior to the widespread use of HAART, and there are currently no widely accepted guidelines for the management of HIV-associated ITP. Here we describe the clinical features, treatment, and outcomes of patients diagnosed with severe HIV-associated ITP in the HAART era.

We searched the BC Centre for Excellence in HIV/AIDS (CFE) database to identify patients with ≥ 1 platelet count <20 × 10⁹/L since January 1996, the year HAART was widely adopted in British Columbia. The cutoff value of <20 × 10⁹/L was chosen as a clinically relevant platelet count since these patients generally require treatment. Patient charts were reviewed, clinical data extracted, and only patients with a diagnosis of ITP made by a hematologist were included in the analysis. Descriptive statistics were used to summarize the data.

Of 8922 patients in the CFE database since 1996, 31 (0.3%) with a diagnosis of ITP and a platelet count <20 × 10⁹/L were identified. The median age at ITP diagnosis was 37 (range 27–66) years and 25 (81%) were male. The median platelet count was 6 (2-19) × 10⁹/L and median hemoglobin 129 (34-165) g/L. Eighteen patients (51%) presented with clinical bleeding and 4 (13%) required packed red blood cell transfusion. Sixteen (62%) of 26 patients with a documented HIV risk factor had a history of injection drug use (IDU). Four patients (13%) were coinfected with the hepatitis B virus and 12 (39%) with hepatitis C. At ITP diagnosis, 8 of 29 patients (28%) had a CD4 count <200 cells/mL and the median CD4 was 290 (20-600) cells/mL; 5 had a prior AIDS-defining opportunistic infection or neoplasm. Although 29 patients received antiretrovirals at some point, only 10 (32%) were receiving HAART at ITP diagnosis. A bone marrow aspirate and biopsy was performed in 6 patients (19%) and was consistent with ITP in all. Initial ITP treatment included: IVIG, n=12; steroids, n=10; anti-RhD, n=8; HAART, n=3. The median number of treatments received was 1 (0-3) and median time to a platelet count >20 × 10⁹/L was 13.5 (1-1379) days. Median platelet response within 30 days was 58 (5-322) × 10⁹/L (n=26) but only 3 patients (10%) achieved a platelet count in the normal range. At a median follow-up of 48 (0.2-138) months, 27 patients (87%) required secondary ITP treatment for a recurrent platelet count <20 × 10⁹/L; median 10 (5-20) × 10⁹/L, including 8 of 13 patients receiving HAART with initial ITP therapy. Secondary ITP treatment included: IVIG, n=9; anti-RhD, n=6; steroids, n=4; splenectomy, n=3; danazol, n=1; and HAART, n=1. Median platelet response to secondary treatment was 42 (21-198) × 10⁹/L. Response to ITP treatment was not significantly associated with treatment received but was lower in the following patients: 4/15 with comorbidities (5 related to the liver) vs 10/16 without; 1/21 IDU vs 4/10 with sexual HIV risk; and 4/13 with hepatitis B or C coinfection vs 13/16 without (p<0.05 for all). Complications of ITP treatment occurred in 2 patients: psychiatric effect of steroids, n=1; and post-splenectomy fever and hematoma, n=1. There were 4 deaths, causes were: GI bleed, n=2; Evan's syndrome and hepatic failure, n=1; advanced HIV, n=1. Of the 4 patients that died, 3 had a history of IDU. Comorbidities in patients who died included: hepatitis C, n=3; hepatic cirrhosis, n=2; portal hypertension, n=1; hepatocellular failure, n=1. One patient who died of GI bleeding had a history of IDU, hepatitis C coinfection, and died of variceal bleeding despite a normal platelet count following splenectomy.

Most patients with severe HIV-associated ITP diagnosed in the HAART era achieved a safe platelet count with primary ITP treatment and there were few treatment complications. However, nearly all required retreatment for severe ITP, including 8 of 13 patients receiving HAART with initial ITP therapy. Inferior platelet response was associated with a history of IDU, comorbidities, and hepatitis B or C coinfection, and 3 of 4 deaths occurred in patients with a history of IDU, therefore new approaches to the treatment of severe ITP in this patient population are needed. This is to our knowledge the largest series of HIV-associated ITP reported in the era of HAART.

No relevant conflicts of interest to declare.