Acquired factor XIII deficiency in patients under therapeutic plasma exchange: A poorly explored etiology

Abstract

Introduction: Factor XIII (FXIII) deficiency may cause bleeding under certain clinical circumstances. Therapeutic plasma exchange (TPE) may lead to a transient deficiency. Objectives: To describe the clinical evolution of patients with acquired FXIII deficiency secondary to TPE. Methods: We respectively studied a cohort of consecutive patients from 2014 to 2019 who were treated with TPE with FXIII levels <50%. The FXIII was measured after the start of the TPE course, on days between the TPE sessions, due to suspected acquired deficiency. All TPE were performed using continuous flow cell separator. In all cases, the initial replacement fluid applied was albumin. Apheresis procedures were held at 24to 48 hours intervals. Results: Eighteen patients were included, 13 of them were recipients of kidney transplants. The main TPE prescription was humoral rejection. Median FXIII at diagnosis (measured on days between sessions of the TPE course) was 19%(IQR17-25). The median of apheresis procedures before measurement of FXIII was 3(IQR2-4). Among the total cohort, 10 patients suffered hemorrhages. None of the patients without history of kidney transplants had bleeding (n = 5), however, 10/13 with kidney transplants did. Five kidney transplant patients received therapy with FXIII concentrate because of lifethreatening bleeding. In all cases, the bleeding stopped within the first 24 hours. All patients had their FXIII levels measured again after finishing the TPE course, with normal results. Conclusions: TPE is an under-diagnosed cause of acquired FXIII deficiency since routine coagulation tests remain unaltered. It might cause major bleeding, particularly in patients with a recent history of surgery like kidney transplants.

In hospitalized patients undergoing therapeutic plasma exchange, major bleeding prevalence depends on the bleeding definition: An analysis of The Recipient Epidemiology and Donor Evaluation Study‐III

“…Our finding of a 17.3% prevalence of major bleeding events exclusively following TPE initiation was within the broad range of other studies published in the literature showing bleeding prevalence that ranges from 0.6% to 55.5% 6,7,11,34,35 . On the higher end of the spectrum of reported bleeding events is a 55.5% bleeding prevalence reported in a study of 18 (mostly kidney transplant) patients with TPE‐associated acquired factor XIII deficiency 6 . In this study, bleeding occurred in 10/18 patients (55.5%).…”

“…Additionally, REDS‐III also allows the longitudinal analysis of the database by using the variable, “DaysSinceStartEncounter,” which was used to determine the Hgb decline in consecutive measurements 18 . Although the TPE procedure itself can cause a decline in the hematocrit and or Hgb, these changes are usually small (0%–6%) and not likely to be responsible for declines ≥2 g/dL in consecutive measurements 1,6,28‐30 …”

“…Although therapeutic plasma exchange (TPE) is a safe and effective procedure, it can be associated with adverse events, including major bleeding 1‐3 . Major bleeding is an important TPE safety endpoint because it is associated with worse outcomes, such as transfusion‐related complications, surgical intervention, procedure discontinuation, and increased mortality 1,4‐6 . In patients undergoing TPE, effective bleeding mitigation or prophylactic strategies depend on a clear understanding of the epidemiology, risk factors, and extent to which major bleeding events occur.…”

“…[1][2][3] Major bleeding is an important TPE safety endpoint because it is associated with worse outcomes, such as transfusion-related complications, surgical intervention, procedure discontinuation, and increased mortality. 1,[4][5][6] In patients undergoing TPE, effective bleeding mitigation or prophylactic strategies depend on a clear understanding of the epidemiology, risk factors, and extent to which major bleeding events occur. Previous studies have reported a wide variability in bleeding prevalence.…”

Predictive value of coagulation factor XIII on bleeding risk in ischemic stroke patients treated with intravenous thrombolysis

“…Moreover, increased FXIII levels may result in elevated incorporation of α2plasmin inhibitor (α2-PI), showing an association with the outcome of IVT therapy (39). Therapeutic plasma exchange or albumin solutions enriched FXIII, and purified plasma-derived FXIII may restore coagulation potential, which may be a promising treatment strategy and merits further verification (40,41,42). However, some limitations to our study should be addressed.…”