Initial Experience with Thrombopoetin Receptor Agonists (TRA) in 5 Patients with Refractory HIV-Associated Immune Thrombocytopenic Purpura (ITP)

Abstract Introduction: In the pre-highly active anti-retroviral therapy (HAART) era, ITP was a relatively common hematologic abnormality, which was seen in as many as 30% of patients infected with HIV. With the advent of HAART, the incidence of HIV-associated ITP has been reduced substantially, with some epidemiological studies showing contemporary rates as low as 1 to 3% (Vannappagari, Platelets 2011). In cases where HAART does not lead to adequate improvement in platelet counts, next lines of therapy have traditionally consisted of corticosteroids, including dexamethasone and prednisone, intravenous immunoglobulin (IVIG), anti-Rho(D) immune globulin, rituximab and, in the current era, more sparingly, splenectomy. When platelet counts remain persistently Methods: Herein we perform a retrospective chart review of 5 patients with HIV-related ITP treated from 2009-2014. All 5 patients with HIV-associated ITP had failed at least two lines of ITP therapy before they received a TRA (table). Mean age was 34 years (18-47), 3 males and 2 females. 4 patients had CD4+ counts >200 cells/ µL, viral loads Results: Each patient responded to TRA use with a mean pre-treatment platelet count of 15 x 109/L, and this increased to a mean of 110 x 109/L 6 weeks following treatment initiation. 2 of the patients have maintained a sustained response with adequate platelet counts 3 years after discontinuing TRA therapy. 1 patient succumbed to a myocardial infarction while on eltrombopag and 1 patient, while on romiplostim, expired from complications of a presumed pulmonary embolus after undergoing lumbar spine surgery. Abstract 5014. Table: . Characteristics of HIV-related ITP patients given TRA Case Nadir CD4+ count (cells/µL) /HIV viral load (copies/mL) HAART Regimen CD4+ count (cells/µL) /HIV viral load (copies/mL) at time of use of TPA Platelet count pre-TRA treatment Lines of ITP treatment before TRA TRA (dose where response was observed and sustained) 6 month f/u platelet count Sustained Response after stopping TRA (duration) Case 1 261/ 5,000 Atripla® 340 / 20 x 109/L 1. Pred + IVIG 2.Rituximab + Dex Romiplostim (4µg/kg) 158 x 109 /L Yes (3 years) Case 2a 284/ 74,743 Atripla® 300/ 2 x 109/L 1. Pred 2. Pulse Dex 3.Rituximab + Dex 4. IVIG Romiplostim, then Eltrombopag (50mg) N/A N/A Case 3 261/ 5,000 Atripla® >300 / 13 x 109/L 1. Pred + IVIG 2.Rituximab + Dex Romiplostim (2µg/kg) 128 x 109 /L Yes (3 years) Case 4 100/ 100,000 Zidovudine + Epivir + Nevirapine 180 / 39 x 109/L 1. IVIG 2. Pred 3. Rituximab Romiplostim (3µg/kg) 52 x 109 /Lb N/A Case 5 100/ 2,400 Truvada + darunavir + detravirine + raltegravir + ritonavir >200 / 54,000 13 x 109/L 1. Anti-Rho(D) 2. IVIG 3. Rituximab 4. Pulse Dex 5. Pred 6.Rituximab + Dex Eltrombopag (50mg) 48 x 109 /Lc No aPatient expired prior to 6 month f/u due to myocardial infarction bPatient sustained response for 2 weeks after discontinuation of TRA cPatient to be reinitiated on maintenance therapy due to lack of compliance Abbreviations: efavirenz, tenofovir, and disoproxil fumarate (Atripla®); prednisone (Pred) dexamethasone (Dex); follow-up clinic visit (f/u) Discussion: Due to insufficient evidence, a definitive association between TRA use and the two patients who suffered thrombotic events remains speculative. Nonetheless, these events emphasize the importance of using these TRAs cautiously during periods of heightened risk of thrombosis such as post-surgery and during periods of immobility, or in patients with risk factors for thrombotic complications. While HIV-associated ITP remains an important clinical problem in the era of widespread HAART use, the availability of both romiplostim and eltrombopag give medical providers additional options in treating this disease. Further experience is needed, however, to better determine the effectiveness and, most importantly, the safety of these drugs in the context of HIV-associated ITP. Disclosures No relevant conflicts of interest to declare.