Current prophylactic plasma infusion protocols do not adequately prevent long‐term cumulative organ damage in the Japanese congenital thrombotic thrombocytopenic purpura cohort

Abstract

Congenital thrombotic thrombocytopenic purpura (cTTP), known as Upshaw-Schulman syndrome, is an ultrarare thrombotic disorder caused by ADAMTS13 gene mutations; however, its long-term outcomes have not been widely studied. A questionnaire survey was administered to physicians of patients in the Japanese cTTP registry to characterise these outcomes. We analysed 55 patients in remission, with 41 cases receiving prophylactic fresh frozen plasma (FFP; median dosage: 13Á2 ml/kg per month) and 14 receiving on-demand FFP. Patients receiving prophylactic FFP were considered as having a more severe form of the disease and had lower platelet counts and higher serum creatinine levels than those receiving on-demand FFP (median 138 9 10 9 /l vs. 243 9 10 9 /l, P = 0Á003 and 0Á71 mg/dl vs 0Á58 mg/dl, P = 0Á009, respectively). Patients who received prophylactic FFP more commonly developed organ damage, including renal impairment, cerebral infarctions, and cardiac hypofunction, than those who did not. Adverse FFPrelated events were seen in 78% of the prophylactic FFP group, with allergic reactions being most common. Since current protocols for FFP administration to the prophylactic FFP group in Japan may be insufficient for preventing cumulative organ damage, a higher dosage of ADAMTS13 supply using recombinant ADAMTS13 agent is needed in these patients.

TTP: From empiricism for an enigmatic disease to targeted molecular therapies

“…These aspects raise the question of the target ADAMTS13 activity to be maintained after an acute TTP event, and may propel in the future a revision of the current pre‐emptive strategies as well as clinical follow‐up and therapeutic evaluation according to underlying cardiovascular risk factors. Similar data were recently reported for cTTP patients 115,118–121 …”

“…Further, 11% of patients in the international cTTP registry had a reported transfusion‐transmitted viral disease, 115 and allergic reactions are also frequent, although manageable 111 . The recently published experience of the UK, 118 Swiss 119 and Japanese 120 TTP registries are all convergent: management standards in cTTP must be improved. RhADAMTS13 will allow refinements in the prophylactic regimens used in cTTP: a tighter prophylactic regimen with correct dosing of a pure form of ADAMTS13 will become available, may allow treatment to be continued at home, and may bring the possibility to prevent short‐term and long‐term comorbidities, as well as the possibility of applying a series of more standardized, yet personalized protocols, for example, depending on the mutations present, age of onset, or frequency of acute events 121,122 …”

No aggravation of congenital thrombotic thrombocytopenic purpura by mRNA-based vaccines against COVID-19: a Japanese registry survey

“…Between 2001 and 2020, only 226 patients with cTTP were reported worldwide [2]. As of 2021, we identified 67 patients with cTTP in Japan alone [3,4]. Theoretically, patients with cTTP are at a high risk for thrombosis due to COVID-19 infection.…”

Delayed diagnosis of congenital thrombotic thrombocytopenic purpura in a patient with recurrent strokes

“…Plasma is commonly used as source of ADAMTS13, and alternatives used mostly in Europe include intermediate-purity factor VIII concentrate [ 3 ]. However, plasma may be insufficient as illustrated by our patient’s recurrent stroke and ADAMTS13 level of 0% during the acute event, and as documented in a Japanese cohort [ 9 ]. Taylor et al [ 10 ] investigated the pharmacokinetic of ADAMTS13 in patients in cTTP, deriving two important observations.…”