Use of Peptide Thrombopoietin Receptor Agonist Romiplostim (Nplate) in a Case of Primary HIV-Associated Thrombocytopenia

Abstract

Thrombocytopenia is frequently encountered in HIV-infected patients, and the predominant cause is primary HIV-associated thrombocytopenia (PHAT). Standard treatment regimens include optimization of antiretroviral therapy, intravenous immunoglobulin, anti-D, and corticosteroids. Retreatment due to the inability to sustain remission or inferior responses is common, and investigation into the safety and efficacy of alternative therapies is warranted. We describe novel and effective treatment of PHAT with the peptide thrombopoietin receptor agonist romiplostim in a patient with a minimal response to conventional therapy.

Introduction

HIV infection is associated with individual or concomitant cytopenias, with thrombocytopenia being a common finding in HIV-infected patients. Thrombocytopenia can occur at any stage of HIV infection, and the most common cause is primary HIV-associated thrombocytopenia (PHAT). ¹ HIV-associated thrombocytopenia has been identified both prior and after the highly active antiretroviral therapy (HAART) era. Standard regimens of treatment for PHAT are based on the mechanism of this disease being similar to idiopathic thrombocytopenic purpura (ITP). As such, intravenous immunoglobulin (IVIG), anti-D, and prednisone are among the therapies used to treat this malady. However, due to the common requirement for retreatment due to the inability to sustain remission or inferior responses to treatment in IV drug users, investigation into the safety and efficacy of alternative therapies is warranted. ²

Case Report

A 50-year-old African American man with HIV (CD4 count of 62 cells/mm³, viral load of 70 copies/mL on darunavir boosted by ritonavir [DRV/r], abacavir [ABC], lamivudine [3TC]), and biopsy proven HIV-associated nephropathy (HIVAN) presented with complaints of fatigue, associated shortness of breath, and generalized weakness. The patient denied any melena or hematochezia but did have 1 episode of hematemesis in our emergency department. He endorsed adherence with his antiretroviral regimen that had been started 6 months prior to presentation, when he was diagnosed with HIVAN. Examination was significant for temperature of 100.7°F, tachycardia, conjunctival pallor, and a petechial rash on the flexural surface of his arms.

The patient was found to have severe thrombocytopenia and anemia with a platelet count of 3 K/µL (140-377 K/µL) and hemoglobin of 3.6 g/dL (12.8-17.1 g/dL). The decrease in the patient’s platelet count was acute (within 1 month) based on prior laboratory test results. Peripheral blood smear noted severe thrombocytopenia, but there were no platelet clumping, schistocytes, and blasts. The patient was admitted to the intensive care unit, received 7 units of packed red blood cells, and appropriately responded. However, he failed to respond to platelet transfusion. Workup for infection including blood cultures, mycobacterial blood cultures, bartonella DNA polymerase chain reaction and serology, cytomegalovirus DNA, histoplasma serology and urinary antigen, coccidioides complement fixation and immunodiffusion, and quantiferon was unremarkable.

Bone marrow biopsy revealed a hypercellular marrow with trilineage hematopoiesis, with no evidence of viral cytopathic changes and histochemical stains for organisms as well as negative cultures. These data coupled with clinical presentation, and ruling out of secondary causes of thrombocytopenia, were consistent with PHAT. Treatment for PHAT was begun with daily IVIG (1 mg/kg) and dexamethasone (40 mg intravenously) for 5 days, without response. At this time, romiplostim was started at 1 µg/kg (80 µg) subcutaneously (SQ) weekly, and the patient received 1 dose as an inpatient. The regimen plan was to titrate to a maximum of 10 µg/kg weekly with the goal of achieving a platelet count of >50 K/µL. Within 48 hours of the first dose, the platelet count rose to 12 K/µL. The patient expressed the desire to leave against medical advice, and in the absence of evidence concerning for opportunistic infections, he was discharged with planned clinic follow-up. Upon outpatient follow-up 2 weeks postdischarge, the patient’s platelet count had rebounded to 328 K/µL, and further doses of romiplostim were held, given the significant and rapid response. At 3, 4, and 12 weeks after discharge, the platelet count was 382, 308, and 292 K/µL, respectively, achieving what appeared to be a sustained response.

Discussion

In our case, the use of romiplostim was attempted given the patients’ minimal response to conventional therapies for PHAT. There is one other case report in the literature in which romiplostim was utilized to treat thrombocytopenia in HIV, but this was in the setting of recent auto–stem cell transplant for acute myeloid leukemia and failed platelet engraftment. ³

Romiplostim is a “peptibody,” a peptide with the ability to stimulate the thrombopoetin receptor, coupled to the Fc region of human immunoglobulin G1 κ heavy chain. ⁴ This structure allows the peptide to avoid the problem of rapid degradation of peptides in the body plus the increased affinity by Fc dimerization. ⁴ Indications are for chronic ITP refractory to standard treatments, and dosing is weight and response based. Per label, dosing is begun at 1 µg/kg once weekly and increased by 1 µg/kg/week to achieve a platelet count ≥50 K/µL. Common reported side effects include headache, dizziness, insomnia, abdominal pain, and musculoskeletal pain. ⁵ The response in our case was fairly brisk, although response to thrombopoietin (TPO) receptor agonists is not necessarily predictable or dose dependent and differs from patient to patient. ^5,6 In conclusion, TPO receptor agonist therapy may be considered in therapy for PHAT.