ITP treatments may raise clotting risk after spleen removal: Study

People with immune thrombocytopenia (ITP) who have had their spleens surgically removed may face an increased risk of clotting problems from ITP treatments called thrombopoietin receptor agonists (TPO-RAs), a study found.

While the study did not find a statistically significant link between TPO-RA use and clotting problems after spleen removal in ITP patients, there was a trend in that direction. The scientists called for further studies and, in the meantime, urged caution when treating patients.

“These findings support the continued use of TPO-RAs in appropriate post-splenectomy patients but emphasize the need for thoughtful timing, individualized thromboprophylaxis [blood clot preventive treatment], and future prospective studies to guide clinical practice in this population,” they wrote.

The study, “Beyond Platelet Counts: Assessing Safety of Post-Splenectomy TPO-RA Use in ITP,” was published in Blood Advances.

ITP is an autoimmune disorder marked by the destruction of platelets, which are cell fragments that help blood form clots. ITP is commonly marked by symptoms of easy and excessive bleeding, but emerging data have also shown that people with the disease are paradoxically at high risk of experiencing thrombosis, which is when dangerous clots form in blood vessels and can disrupt blood flow.

Data lacking on medication-splenectomy combo

TPO-RAs are medications approved for ITP that work to increase the body’s production of platelets. Examples include Alvaiz (eltrombopag tablets), Doptelet (avatrombopag), Nplate (romiplostim), and Promacta (eltrombopag).

Splenectomy — the surgical removal of the spleen — may also be used to help manage ITP, as it can help reduce the destruction of platelets that occurs in people with the disease.

Both TPO-RAs and splenectomy are known to be associated with an increased risk of thrombosis. However, there’s not much data on whether combining the two treatment approaches further increases thrombosis risk in ITP patients.

To learn more, the researchers analyzed the outcomes of 88 adults with ITP who underwent splenectomy at the Mayo Clinic between 2011 and 2024. Among these patients, 37 received TPO-RAs after the surgery, and the remaining 51 did not. In patients given TPO-RAs, the medications were usually started within a month after the surgery.

“While previous reports have examined thrombosis risk with TPO-RA or splenectomy individually, this analysis provides novel insights into the cumulative thrombotic implications when TPO-RAs are used in patients who have already undergone splenectomy,” the scientists wrote.

Results showed that over the course of follow-up, a higher proportion of patients given TPO-RAs experienced thrombosis (46% vs. 27%). The 10-year cumulative incidence of thrombosis was also higher in those treated with TPO-RAs after surgery (57% vs. 36%).

However, these differences weren’t statistically significant, meaning it’s mathematically plausible that they could be due to random chance. The scientists noted that the small number of patients in the study made it difficult to get statistically meaningful results.

Although overall thrombosis rates weren’t significantly different between the groups, researchers noted that among patients on TPO-RAs, nearly half of thrombosis events occurred within the first three months of starting TPO-RA treatment.

“This clustering raises concerns for a vulnerable early phase in which the additive thrombotic effects of recent surgery and TPO-RA exposure may converge,” the scientists wrote.

They stressed that the data don’t prove that using TPO-RAs after splenectomy increases the risk of thrombosis in ITP patients. Nonetheless, they said, the findings point to a potential trend that should be explored in further studies, and they urged clinicians to consider this possibility when recommending treatment for ITP patients.

“While clinical significance has not been established, possibly due to the modest sample size, these numerical and temporal patterns, including divergence that persisted through long-term follow-up, underscore the need for careful patient selection, cautious timing of TPO-RA initiation, and clinical vigilance, especially during the early period following splenectomy or in patients with additional thrombotic risk factors,” the scientists wrote.