Clinical Study on the Treatment of Immune Thrombotic Thrombocytopenic Purpura Using Protein a Immunoadsorption Therapy

Objective: Thrombotic thrombocytopenic purpura (TTP) is a rare and severe thrombotic microangiopathy, with the main clinical features including microangiopathy, hemolytic anemia, thrombocytopenia, neuropsychiatric symptoms, fever and renal injury. iTTP accounts for about 95% of the total number of TTP cases. If therapeutic plasma exchange (TPE) is not performed in time, the mortality rate is as high as 90%. At present, TPE, glucocorticoids and rituximab are still used as first-line treatments in China where caplacizumab is unavailable. However, due to the limited source of plasma, infection, allergy and other risks, it is urgent to explore other (partial) alternatives to TPE in the clinic to reduce the use of plasma, avoid the risk of blood transfusion, and improve the treatment rate of iTTP patients. Immunoadsorption therapy refers to the removal of pathological IgG and other plasma components from the patient's own plasma through an adsorption column and then transfusing it back to the patient, avoiding allergies and blood-borne viral infections caused by exogenous plasma, and has the same adsorption effect as plasma exchange in general. Therefore, this study will explore the effectiveness and safety of immunoadsorption technology in the treatment of iTTP.

Methods: iTTP patients who underwent inadequate TPE were selected for immunoadsorption combined with plasma transfusion and/or partial TPE treatment. The results of blood routine, biochemistry, reticulocytes, ADAMTS13 enzyme activity and inhibitors before and on the second day of immunoadsorption were compared to evaluate the effect of immunoadsorption. Combined with the clinical manifestations of the patients, the effectiveness and safety of immunoadsorption in the treatment of iTTP were comprehensively evaluated.

Results: Our center has successfully appllied protein A immunoadsorption combined with plasma transfusion and/or partial TPE to treat two patients with refractory recurrent iTTP. The first case, a 20-year-old female patient, started immunoadsorption treatment due to limited plasma sources during COVID-19 pandemic in China. After immunoadsorption on the first day, the inhibitor turned negative immediately. At the same time, corticosteroids and bortezomib immunosuppression were started. After 3 intermittent immunoadsorptions, 2 plasma exchanges, and 1 course of bortezomib (1.3mg/m2, d1,4,8,11) treatment, platelets increased to be normal on Day 19. The second case was a 34-year-old female patient, who refused TPE initially and switched to immunoadsorption therapy after negotiation. After two adsorptions combined with plasma transfusion and corticosteroids treatment on Day 1 and Day 3, the inhibitor turned negative. The platelet count turned normal from Day 3. On Day 4, otlertuzumab was given to clear the antibody (1000 mg, d1, 15), and then the third immunoadsorption treatment was performed on Day 8 for consolidation. No common adverse reactions such as allergies, heart failure, decreased immunity, and infection occurred in the two patients during the follow-up period (18 months and 5 months, respectively).

Conclusion: Immunoadsorption may have important therapeutic value for iTTP, especially in China where caplacizumab is still unavailable. It can reduce the amount of plasma used, avoid the risk of blood transfusion, and improve the rescue rate of iTTP patients. It is worthy of further exploration and research.

No relevant conflicts of interest to declare.