Platelet Sequestration Patterns and Clearance Rates in Patients with ITP Compared to Healthy Individuals

Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder, characterized by low platelet counts and highly heterogeneous in its underlying pathophysiology. Immune-mediated platelet destruction may occur via the spleen and/or the liver and impaired platelet production also plays a role. Due to the considerable variability in presentation and treatment response, an improved understanding of the mechanisms leading to platelet clearance in ITP is highly needed. Platelet scintigraphy evaluates the site of platelet sequestration and the rate of platelet clearance. This technique, using indium-111 as an in vivo platelet label, has been predominantly used to identify which patients with ITP are favorable candidates for a splenectomy. A limitation for the use of this technique is that indium-111 studies comparing platelet clearance between healthy and thrombocytopenic subjects have not been extensively conducted.

We conducted a prospective cohort study to evaluate platelet sequestration patterns and clearance curves, with indium-111 platelet scintigraphy, in healthy adult individuals at two moments in time. We compared the results with the findings in a retrospective cohort of adult patients with ITP (n=84) (Amini et al., Blood Adv 2022). Ten healthy adults were included. Platelet sequestration and clearance were followed for 48 hours (hrs) at the first scan (S1). Additionally, a second indium-111 scan (S2) was performed in 8/10 participants with a median of 26.2 months between the two scans. For S2, the total scan duration was extended to 96 hrs. The spleen: liver (S:L) ratio at the final time point of the scan was used to categorize platelet sequestration patterns, with S:L ratios >= 1.4 being categorized as splenic, >= 0.8 and <1.4 as mixed and < 0.8 as liver clearance.

An increase in circulatory platelet-associated radioactivity (cPAR) was observed during the first 3 hrs in almost all healthy individuals (S1: 9/10 and S2: 8/8). Hence, the cPAR at subsequent time points was expressed as a percentage of the cPAR at 3hrs. Whole body images did not show other major sites of platelet accumulation besides the spleen and liver during these 3 hours. The amount of cPAR at 48hrs was in the same range, and differed only slightly between scans (cPAR comparison (n=6), median S1: 67.3% and S2: 74.1%, p = 0.03). A median of 50.5% of cPAR was still detected at 96hrs (only S2, n=8). Half of the healthy individuals (5/10) at S1 and 37.5% (3/8) at S2 had a splenic sequestration pattern. The S:L ratios of the first and the second scan were comparable at 48hrs (median S1: 1.39 and S2: 1.20, p = 0.294). These sequestration patterns were largely reproducible over time; only 1 out of 8 individuals shifted from a splenic to a mixed pattern at 48hrs (median variation in S:L ratio at 48hrs between two scans: 0.25 (range: 0- 0.75)).

The majority of patients with ITP (86.9%) elicited a higher clearance rate (median amount of cPAR at 48hrs: 40.3%) than the maximum observed clearance rate in healthy adults (64.8% during S1), underscoring the potential diagnostic application. Within the ITP cohort, 45% (38/84) had a splenic, 29% (24/84) a mixed and 26% (22/84) a hepatic sequestration pattern. No significant difference in S:L ratio was observed between the healthy study participants and the ITP cohort (median S:L ratio ITP cohort: 1.30, Wilcoxon rank test: p = 0.54 for comparison with S1 at 48hrs and p = 0.80 for S2 at 96hrs).

Overall, this study showed that the platelet sequestration sites as determined by the indium-111 scan remain largely constant in time in healthy adults. Interestingly, this study indicated that the S:L ratios or sequestration pattern distribution is highly variable in healthy adults and thus did not differ from adults with ITP. However, the higher clearance rate found in patients with ITP distinguished them from healthy controls. The findings of this study suggests that for detecting ITP-specific or ITP-therapy-related changes in platelet sequestration patterns, longitudinal data (multiple scans e.g. before and after treatment) rather than single measurements might be more informative. This study deepens our understanding of platelet sequestration and sets the stage for new diagnostic applications of the indium-111 scan beyond predicting splenectomy responses in ITP.

Nelson:Sobi: Research Funding. De Haas:Johnson and Johnson: Consultancy, Research Funding. Schipperus:Amgen: Research Funding. Netelenbos:Sobi: Research Funding.