In patients with immune-mediated thrombotic thrombocytopenic purpura (iTTP), a recent study showed that some who received caplacizumab showed a delayed normalization of ADAMTS13 activity. Findings from this study were reported in the journal Blood.

A cohort of patients in this single-center study was treated for acute iTTP using caplacizumab in combination with plasma exchange (PEX) and immunosuppressive therapy during January 2016 through October 2021 (caplacizumab cohort). This cohort was treated with caplacizumab for 30 days following PEX but could receive an additional 28 days of it in the presence of severe ADAMTS13 deficiency (ie, “30+28” days).

Plasma samples were obtained for analyses of ADAMTS13 at the time of presentation, upon stopping caplacizumab, and at approximately 30+28 days. These analyses involved measurements of ADAMTS13 activity, ADAMTS13 antigen levels, and anti-ADAMTS13 immunoglobulin (Ig) G antibody.

Continue Reading

In addition to the caplacizumab cohort, a cohort of patients treated without caplacizumab (noncaplacizumab cohort) during an earlier period was evaluated. Additional outcomes, such as the time to achieve a normal platelet count and the duration of PEX treatment, were also evaluated for both cohorts.

There were 64 patients analyzed in the caplacizumab cohort and 50 in the noncaplacizumab cohort. No deaths occurred in the caplacizumab cohort, whereas 3 (6%) patients died in the noncaplacizumab cohort. Patients of the caplacizumab cohort received caplacizumab for a median duration of 35 days (range, 15-130). The caplacizumab cohort reached a sustained normal platelet count at a shorter time after initiating acute treatment than the noncaplacizumab cohort did (P <.0001), and the median duration of PEX required was shorter for the caplacizumab cohort (P <.0001).

Reaching a level of ADAMTS13 activity >30% occurred at a median of 31 days following PEX for the caplacizumab cohort, while it occurred at a median of 11.5 days for the noncaplacizumab cohort (P =.0004).

At the time of caplacizumab cessation, 28% of patients in the caplacizumab cohort demonstrated ADAMTS13 activity <10%, and these patients reached activity >30% at a median of 139 days after completion of PEX.

Additionally, 28% of patients who received caplacizumab for the extended period did not reach ADAMTS13 activity >30% by the time of caplacizumab cessation (approximately 30+28 days), compared with a rate of 8.5% of patients in the noncaplacizumab cohort at this time (P <.0001).

Patients with ADAMTS13 activity <10% upon caplacizumab cessation had significantly higher median levels of anti-ADAMTS13 IgG antibodies than responders did (P <.0001). Also, in patients with ADAMTS13 activity <10% upon caplacizumab cessation, TTP recurrence was more common in those who had an antigen level <30%. 

The investigators indicated the study suggests that ADAMTS13 antigen levels could serve as a laboratory marker for guiding safe discontinuation of caplacizumab therapy. “The precise mechanism causing delayed normalization of ADAMTS13 activity in a proportion of patients treated in the caplacizumab era remains to be characterized and requires further investigation,” the investigators wrote in their report. They also noted that caplacizumab has positively impacted patient care in acute TTP.

Disclosures: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of disclosures.


Prasannan N, Thomas M, Stubbs M, et al. Delayed normalization of ADAMTS13 activity in acute thrombotic thrombocytopenic purpura in the caplacizumab era. Blood. 2023;141(18):2206-2213. doi:10.1182/blood.2022018847