Successful Treatment With Bortezomib for Refractory and Complicated Acquired Thrombotic Thrombocytopenic Purpura in an Adolescent Girl

Abstract

Thrombotic thrombocytopenic purpura (TTP) is a rare, dangerous, life-threatening disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, along with organ dysfunction due to microangiopathy-related ischemia. Plasma exchange and steroids are used for initial treatment, and rituximab is often used in refractive patients. Caplacizumab, cyclophosphamide, and splenectomy are among other treatment options. It has been reported that bortezomib, a proteasome inhibitor, can be used in the management of refractory acquired TTP. Herein, we present a 16-year-old female patient who was monitored for acquired TTP and treated with high-dose steroids, plasma exchange, rituximab, cyclophosphamide, and N-acetylcysteine but developed renal, cardiac, gastrointestinal, and neurologic complications. The girl was then successfully treated with bortezomib, and she has been monitored in remission for 6 months. We consider that bortezomib is a beneficial treatment, especially in patients with refractory TTP.

Bortezomib, a promising alternative for patients with refractory or relapsed thrombotic thrombocytopenic purpura after rituximab treatment

“…4 We summarized nine refractory or relapsed TTP cases in Table 2 after Eskazan's report, who were unresponsive to rituximab and then transferred to bortezomib treatments. [3][4][5][6][7][8][9] Putting these cases together with ours, 25 patients with relapsed or refractory TTP were treated with bortezomib. The age distribution of these patients ranged from 5 to 76 years, suggesting that bortezomib could be used not only in adult, but also in the elderly 10 and children.…”

The Specificities of Thrombotic Thrombocytopenic Purpura at Extreme Ages: A Narrative Review

“…The autopsy revealed the presence of disseminated hyaline thrombi in the microcirculation of her heart, kidney, spleen, and liver [12]. Based on the scope of the scientific literature and the national registries for TTP since 2001, ~150 different cases of child-onset iTTP with a documented severe functional deficiency of ADAMTS13 (activity < 10 IU/dL per definition) and the presence of anti-ADAMTS13 autoantibodies have been reported [13][14][15][16][17][18][19][20][21][22][23][24][25]. The prevalence of child-onset iTTP is ~1 case per million children and its diagnosis remains challenging [13,25].…”

“…In child-onset iTTP, fever and neurological symptoms (such as headache, confusion, coma, seizures, strokes, or transient focal defects) are frequent (~40% and 40-55%, respectively), while renal or cardiac injury are less common (~40% and ~6-7%, respectively) [13][14][15][16][17][18][19][20][21][22][23][24][25].…”

“…The first episode of iTTP may be sudden and severe. By definition [7], all iTTP patients have an ADAMTS13 activity of less than 10 IU/dL and positive anti-ADAMTS13 autoantibodies at diagnosis [13][14][15][16][17][18][19][20][21][22][23][24][25].…”

Management of acquired, immune thrombocytopenic purpura (iTTP): beyond the acute phase

“…Of the two anti-CD38 agents reported, the proteasome inhibitor bortezomib has been used in the majority of cases. The use has been reported in case reports and case series, with remission in 16/18 cases of acute TTP, 25 , 48 – 53 although these data may be limited by the fact that bortezomib was used in conjunction with a number of other immunosuppressive agents. Intravenous or subcutaneous treatment can be used at doses of 1–1.3 mg/m 2 for between 2–4 doses, although up to 13 have been given in published data.…”