ADAMTS13 kinetics after therapeutic plasma exchange and plasma infusion in patients with Upshaw‐Schulman syndrome

Abstract

Background Hereditary thrombotic thrombocytopenic purpura, also called Upshaw‐Schulman syndrome (USS), is a rare disease caused by genetic mutations in the ADAMTS13 gene, which severely decrease the activity of ADAMTS13, a metalloprotease that cleaves von Willebrand factor multimers (VWF). Genotypically identical patients can show great phenotypic diversity. Objectives Comparison of selected laboratory parameters and ADAMTS13 pharmacokinetics among patients with USS was performed. Patients/methods Six patients with USS on prophylactic plasma therapy have been reviewed, retrospectively. Blood counts, lactate dehydrogenase (LDH), and ADAMTS13 activity at various time‐points before and after different treatment cycles were evaluated. Results ADAMTS13 recovery and pharmacokinetics were affected by treatment modality, and also reflected the patients' comorbidities and their current physiological and clinical condition. Conclusions Our present findings support a multifactorial contribution to treatment efficacy, and confirm the importance of adaptability and individualization of USS therapy. Therapeutic plasma exchange even in hereditary TTP is an option that can in some patients prolong intervals between plasma administration.

Insights from the Hereditary Thrombotic Thrombocytopenic Purpura Registry: Discussion of Key Findings Based on Individual Cases from Switzerland

“…A plasma infusion trial with a full ADAMTS13 recovery and plasma half-life of 2 to 4 days. 38,40,41 Patients fulfilling criteria 1, 2, and either 3a or 3b are enrolled as confirmed patients. Patients are enrolled as suspected patients when criteria 1 and 2 are met, but molecular analysis of the ADAMTS13 gene lacks, or when only one ADAMTS13 mutation is identified and a plasma infusion trial to assess ADAMTS13 recovery and half-life is lacking.…”

Diagnosis of Hereditary TTP Caused by Homozygosity for a Rare Complex ADAMTS13 Allele After Salmonella Infection in a 43-Year-Old Asylum Seeker

“…We suppose that part of the infused ADAMTS13 will be trapped by binding to endothelial cell-attached VWF multimers. There seems to be no significant difference between ADAMTS13 half-life of cTTP patients with prior plasma exchange vs. patients just receiving plasma infusions (21).…”

Infection as Trigger for Congenital Thrombotic Thrombocytopenic Purpura in an Adult Patient

“…TPE has been reported in the literature as an effective emergency treatment, but it is not a viable option in the prophylactic setting because of logistic reasons and the increased exposure to FFP donors. One retrospective study by Kovarova et al concluded that TPE is an option for prophylaxis that can prolong the need for FFP infusion (21 vs. 14 days of the need of new TPE or FFP infusion, respectively), although there were no differences in ADAMTS-13 activity immediately after these two procedures (P > 0.5) [ 11 ]. There are currently no clinical trials comparing both treatments.…”