Autologous ¹¹¹In-Labeled Platelet Sequestration Studies in Patients with Primary Immune Thrombocytopenia (ITP): A Report From the United Kingdom Registry.

Primary immune thrombocytopenia (ITP) is an autoimmune disease characterized by elevated reticuloendothelial destruction and suboptimal megakaryocytic production of platelets. Although a common second-line treatment eliciting a response among two-thirds of patients with primary ITP, splenectomy remains controversial owing to its long-term failure rate and risks of surgical sequelae and opportunistic infection. The pattern of platelet sequestration may be a possible predictor of response to splenectomy in patients with primary ITP.

To evaluate the utility of autologous ¹¹¹In-labeled sequestration studies in predicting the short- and long-term outcomes of splenectomy in patients with primary ITP who have failed at least two treatment modalities or who require permanent administration of high doses of corticosteroids.

The investigation comprised patients diagnosed with primary ITP undergoing an autologous ¹¹¹In-labeled platelet sequestration study prior to possible splenectomy at Barts & The London NHS Trust between March 1994 and May 2007. Patients were required to have platelet counts of 5-100×10⁹/L; no antibody therapies were permitted four weeks prior to the study.

¹¹¹In platelet-labeling was performed in accordance with recommendations of The International Committee for Standardization in Hematology (J Nucl Med 1988). At 0.5, 3, 24, and 48 hours post-injection, blood samples (5 mL) were taken and surface counting performed, with the gamma camera set to register ¹¹¹In-photon peaks at 171 and 245 KeV. Surface counting, corrected for background and decay, was performed over the heart, liver, and spleen using the geometric mean of anterior and posterior views. Regions of interest were drawn over these organs using the 0.5 hour acquisition and transferred to subsequent acquisitions to ensure analysis of identical anatomical areas.

A graph of platelet-associated radioactivity versus time was constructed to derive the platelet half-clearance time (t_50%), which was used in the algorithm, 1.44× t_50%, to compute mean platelet lifespan (MPLS). To assess the degree of splenic sequestration, the relative increase in the spleen:liver (S:L) ratio from 0.5 hours to 80% platelet destruction was calculated. An S:L ratio increase, X > 2.0 was classified as a purely splenic pattern, 1.4 < X ≤ 2.0 as predominantly splenic, 0.8 < X ≤ 1.4 as mixed, and X ≤ 0.8 as hepatic (Najean et al., Brit J Haem 1992).

At least one-year following the studies, hematologists were questioned as to whether patients underwent splenectomy and asked to provide 1-3 month and 6-12 month post-surgery platelet counts as well as platelet count and ITP-specific treatment status at most recent follow-up if they did.

Surgical failure was defined as a platelet count less than 100×10⁹/L or reliance on an ITP-specific treatment [most recent follow-up only]). The odds ratio of failure for patients with hepatic and mixed patterns versus purely splenic and predominantly splenic patterns were calculated at 1-3 and 6-12 months post-surgery and most recent follow-up using logistic regression. Covariates included age at surgery, gender, and post-surgical follow-up time (most recent follow-up only).

Between March 1994 and May 2007, 232 patients with primary ITP took part in autologous ¹¹¹In-labeled platelet sequestration studies, of which 82 (35.3%) patients, 74 adults (≥ 16 years at surgery) and 8 children, underwent splenectomy.

Among the splenectomized cohort, median age at surgery was 29.3 years (range: 7.8-67.5 years). Purely and predominantly splenic patterns of sequestration were noted in 64 (78.0%) patients while mixed and hepatic patterns were seen in 18 (22.0%) patients. As illustrated in Table 1, patients constituting the latter group exhibited statistically significant, increasing odds ratio of failure at each follow-up interval.

This investigation provides evidence of an increased risk of failure from splenectomy in primary ITP patients with mixed and hepatic patterns of platelet sequestration.

Sarpatwari:GSK: Consultancy, Research Funding; Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding. Provan:GSK: Equity Ownership, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Baxter: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. Erqou:GSK: Consultancy. Newland:Amgen Inc.: Consultancy, Honoraria, Research Funding, Speakers Bureau; GlaxoSmithKline: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pangenetics: Consultancy; Schering Plough: Consultancy; Baxter: Research Funding; Genentech: Research Funding; Gilead: Research Funding.