Romiplostim for the Management of Perioperative Thrombocytopenia

Introduction

Romiplostim is a fusion protein agonist of the thrombopoietin receptor approved by the US FDA for the treatment of immune thrombocytopenia (ITP) after failure of glucocorticoid therapy. This agent has been examined in other settings, including its use in the management of chemotherapy-associated thrombocytopenia and its use for the treatment of refractory aplastic anemia (Gill et al., Br J Haematol 2016). Moderate-to-severe thrombocytopenia is associated with an increased risk of bleeding and increased postoperative mortality and therefore may prevent safe performance of necessary surgical procedures (Glance et al, Anesthesiology 2014). This study is a retrospective, single-center review of thrombocytopenic patients who received romiplostim to increase platelet count to allow for safe performance of elective or urgent surgical procedures.

Methods

We performed a retrospective review of patients with chronic thrombocytopenia of any cause who initiated single-agent romiplostim to increase platelet count in preparation for surgery. We collected patient demographics, dates and doses of romiplostim administration with corresponding platelet counts, and outcomes of therapy, including ability of patient to receive the surgery on the pre-planned operative date, receipt of packed red blood cell or platelet transfusions in the perioperative period, incidence of clinically significant bleeding, and incidence of venous thromboembolism.

Results

Review of pharmaceutical dispensation records from at our institution from January 1, 2010 through April 1, 2017 revealed 47 patients treated with single-agent romiplostim specifically to increase platelet count in preparation for surgery. These 47 patients had 51 discrete procedural cases for which single-agent romiplostim was initiated to manage perioperative thrombocytopenia. Procedures performed and patient demographics, including etiologies of thrombocytopenia (of which some patients had more than one), are listed in Table 1. Median pre-procedure platelet count at initiation of romiplostim was 47 x 10⁹/L, with pre-procedure platelet count at initiation of romiplostim ≤50 x 10⁹/L in 57% and ≤100 x 10⁹/L in 94% of cases. Patients were treated with weekly injections of romiplostim, with platelet count measured at the time of drug administration; the most common starting dose was 3 mcg/kg. The median duration of romiplostim therapy required to achieve a platelet count ≥100 x 10⁹/L (considered "therapeutic" in a vast majority of cases) was 13 days, and the median time to achieve peak preoperative platelet count (median 177 x 10⁹/L) was 19 days. A platelet count of ≥100 x 10⁹/L was achieved in 75% of cases after 2 doses of romiplostim and in 35% of cases after a single dose. Median platelet count at the time of surgery was 164 x 10⁹/L, a median difference of 105 x 10⁹/L from platelet count at initiation (Figure 1). Operations were performed on pre-planned operative date without delay in 96% of cases. During a 14-day perioperative window (defined as 7 days preoperatively and 7 days postoperatively), perioperative red blood cell transfusion was given in 6 cases, and perioperative platelet transfusion was given in 3 cases. While receiving romiplostim, 1 patient had a venous thromboembolic event (bilateral peroneal deep venous thrombosis on postoperative day 8 with a platelet count of 197 x 10⁹/L), and 4 patients had bleeding events (3 within 2 days of surgery and 1 at postoperative day 19; all were WHO grade 3, and occurred at platelet counts ranging from 82 x 10⁹/L to 185 x 10⁹/L).

Conclusion

In patients with chronic thrombocytopenia who need elective or urgent surgical procedures, this study provides evidence that romiplostim is safe and increases the platelet count sufficiently in a majority of patients to allow surgery to proceed safely and on schedule. The majority of patients achieved a "therapeutic" platelet count of ≥100 x 10⁹/L after two weekly doses of romiplostim.

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