Selective plasma exchange can reduce auto‐antibodies in patients with bullous pemphigoid without affecting factor XIII and fibrinogen

Abstract

Bullous pemphigoid (BP) is an autoimmune blistering skin disorder characterized by circulating serum IgG antibodies against two hemidesmosomal proteins: BP180 and BP230. Fundamentally, immunosuppressive therapies are administered to treat this disease, but plasmapheresis can be added for refractory patients. We experienced the case of a 63-year-old patient with refractory BP for which we administered double filtration plasmapheresis (DFPP). His skin lesions improved along with decreased IgG BP180 antibodies, but factor XIII (FXIII) and fibrinogen were also reduced by DFPP repetition. Reportedly, deficiency of those factors can cause lethal bleeding. Especially, decreased FXIII cannot be detected by prolongation of bleeding or coagulation time. To prevent further reduction of those factors and bleeding complications, DFPP was switched to selective plasma exchange (SePE), a new modality of plasmapheresis that uses a membrane plasma separator with smaller than ordinary pores. SePE further reduced pathogenic IgG BP180 antibodies, but FXIII and fibrinogen recovered. For this case, we measured the mean of reduction ratios in serum IgG and FXIII both before and after plasmapheresis sessions and detected the decreased levels of FXIII and fibrinogen during DFPP. We were able to switch to SePE from DFPP appropriately before any bleeding event occurred. The utility of SePE was demonstrated, especially for the reduction of pathogenic antibodies with retention of FXIII and fibrinogen, which have the longest half-lives among coagulation factors and which take a long time to recover.

Selective Plasma Exchange for the Removal of Pemphigus Autoantibodies, Fibrinogen, and Factor XIII in Pemphigus Vulgaris

“…lower rebound recovery in concentration) compared with other coagulation factors . Less than 10% decrease in FXIII, which cannot be detected by coagulation time or bleeding time, can cause spontaneous bleeding, major postoperative bleeding, or delayed wound healing . Only direct measurement of FXIII itself is needed for the diagnosis of FXIII deficiency .…”

“…EC‐4A has a relatively small pore size of 0.03 μm, which is around one‐tenth that of conventional plasma separators . Recently, the usefulness of SePE had been reported , but there was only one report on its treatment applications for dermatologic disorders and none for pemphigus vulgaris.…”

A Solution Kinetics Simulation Method for Conventional and Selective Plasma Exchange Using a Complete Mixed Reactor Model

“…Selective plasma exchange (SePE) uses a dedicated plasma separator to sieve the pathogenic substances and coagulation factors. Even if Alb solution is used as the substitute solution, loss of coagulation factors can be suppressed and the process is useful for the treatment of autoimmune diseases, removing substances below the IgG region . However, the user must understand the fractionation characteristics of the plasma separator and the removal rate of the pathogenic substances in the target diseases.…”

Reducing Fibrinogen and Factor XIII Using Double-Filtration Plasmapheresis for Antibody-Mediated Rejection: Predictive Models

“…For example, Nasu et al [2] reported on a patient treated with 4 sessions of DFPP by 53%, and IgG and fibrinogen by 56%. DFPP was subsequently converted to PP, resulting in FXIII being decreased to only 16% and there was no change to fibrinogen levels.…”

“…It allows larger volumes of plasma to be treated compared to standard plasmapheresis (PP). DFPP is not only used to treat patients with autoimmune disorders, such as myasthenia gravis [1] and bullous pemphigoid [2], but also to remove culprit antibodies in the setting of ABO-incompatible kidney transplantation [3][4][5].…”