While lipoprotein apheresis (LA) is established for lipid management in primary biliary cholangitis, the role of apheresis techniques in drug-induced cholestatic liver disease remains unexplored. We report the novel application of double filtration plasmapheresis (DFPP) for rapid reversal of severe hypercholesterolemia in iatrogenic cholestasis, where conventional therapies failed or were contraindicated. A 56-year-old male developed severe cholestatic hepatitis following the use of herbal agents. Laboratory investigation revealed extreme hypercholesterolemia, with a total cholesterol (TC) of 41.39 mmol/L and a low-density lipoprotein cholesterol (LDL-c) of 38 mmol/L. Standard medical therapy proved ineffective. Two sessions of DFPP resulted in > 90% reduction in cholesterol levels and simultaneous improvement in bilirubin and liver enzymes, with sustained normal levels at 1-year follow-up. DFPP may serve as a novel rescue therapy for drug-induced cholestatic hypercholesterolemia, providing simultaneous removal of cholesterol and bilirubin where other treatments are ineffective or at high risk.

Pre-set fixed-dose albumin replacement fluid for double filtration plasmapheresis (DFPP) can result in progressive albumin deficit, along with other untargeted protein, leading to loss of osmotic pressure, and subsequently hypotension. This can occur in up to 6% of DFPP procedures. In this study, we aim to determine the serum albumin deficit with fixed-dose replacement regime and estimate the required practical supplementary regime for the discrepancy. We compared the change in serum albumin level among patients treated with DFPP given fixed-dose 10% plasma replacement volume with albumin 5% concentration versus patients given additional replacement with albumin 20% concentration. Seventy-seven DPFF procedures were performed in 16 patients with various neurological disorders. In average, each patient received 4.8 DFPP procedures (Range 3-7) per treatment. Eight patients were given fixed-dose albumin replacement and remaining 8 had additional albumin 20% replacement. Twenty-one (27.3%) procedures had additional replacement. The average change in serum albumin post-DFPP procedures was a reduction of 2.4 g/L (SD 3.0) with fixed-dose replacement and an increment of 0.1 g/L (SD 2.8) for procedures with additional human albumin 20% replacement (p = 0.003). In average, additional 78.6 mL (50-500 mL in up to 5 divided replacements) of albumin 20% replacement given to patients with post-DFPP serum albumin lower than 34 g/L, or in those with post-DFPP negative serum albumin balance depending on severity effectively reduces post-DFPP albumin deficit. In conclusion, fixed-dose albumin replacement for DFPP results in progressive albumin deficits with successive procedures. Addition albumin supplementation may be required.

Lipoprotein apheresis (LA) is an established therapy for severe, drug-refractory dyslipidemias. Nevertheless, clinicians often monitor hepatic and muscle enzymes during treatment because transient biochemical shifts can be misinterpreted as injury. In this study, we synthesize the evidence on how repeated apheresis sessions affect circulating enzymes. We systematically searched PubMed, Scopus and Web of Science from inception to August 2025 for observational human studies reporting pre- and post-apheresis values (mean and SD) for aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), lactate dehydrogenase (LDH), and creatine phosphokinase (CPK). Effects were expressed as weighted mean differences (WMD, IU/L). Of 267 records screened, 9 articles (published 1998-2006) met eligibility for quantitative synthesis, yielding 9 ALT, 8 AST, 7 ALP, 6 GGT, 9 LDH and 6 CPK study estimates. Pooled analyses showed significant decreases in AST (WMD = -0.87; 95% CI: -1.51 to -0.23; p = 0.007), ALP (WMD = -6.28; CI: -11.75to -0.80; p = 0.02), LDH (WMD = -11.12; CI: -17.01 to -5.24; p = 0.001) and CPK (WMD = -6.91; CI: -13.06 to -0.75; p = 0.02). However, levels of ALT (WMD = -0.78; CI: -2.10 to 0.53; p = 0.29) and GGT (WMD = -2.64; CI: -8.71 to 3.44; p = 0.39) were unchanged. Across repeated-session studies, LA does not elevate hepatic or muscle injury markers and is associated with modest reductions in AST, ALP, LDH, and CPK. These findings support the biochemical safety profile of apheresis and suggest that routine enzyme monitoring should be interpreted in context.

The American Society for Apheresis (ASFA) guidelines serve as a global standard for therapeutic apheresis practice. However, our analysis of the 2023 guidelines reveals discordance between the strength of recommendation and the quality of evidence. Among 166 indications, one-third carry strong recommendations, yet only 8% are supported by high-quality evidence. Over half (55%) are informed by low- or very-low quality evidence. This mismatch is most pronounced for Category I indications, where apheresis is considered first-line therapy: nearly one-third are based on low-quality data, yet 89% receive strong recommendations. Weak evidence is nine times more likely to prompt a strong recommendation for Category I versus Category III indications. This misalignment risks overutilization of apheresis, introduces ethical hurdles for clinical trials by diminishing equipoise, and may mislead patient expectations during informed consent. We advocate for greater transparency by stating the rationale underlying strong recommendations despite low-quality evidence, acknowledgment of uncertainty where applicable, and suggested research to strengthen the evidence.

Calculating the collection efficiency (CE) of CD34+ cells in leukocytapheresis (LVL) is critical to understanding the performance of cell collection. Traditional CE values are typically based on both pre- and post-apheresis calculations of the pooled cells (CE1), or they may be based only on the pre-procedure pool calculation (CE2) and total blood volume (TBV) processed. However, determining the actual CD34+ concentration in peripheral blood (PB) during LVL is more problematic. New crude CE (CruCE) takes into account the recruitment and extraction of CD34+ cells during LVL. This study aims to retrospectively compare traditional (CE2, CE1) and CruCE and to assess the variables that influence new CruCE-including donor characteristics, procedure characteristics, and device setting parameters-in both large-volume LVL and non-LVL. Data from adult donors who underwent autologous and allogeneic collections of PB stem cells between January 2020 and April 2023 were retrospectively included. Our series comprises 123 autologous and 37 allogeneic LVL procedures. The median of CD34+ CE2, CE1, and CruCE was 51%, 65%, and 74% in autologous donors and 58%, 69%, and 76% in allogeneic donors. In multivariate analysis, TBV processed and prior CD34+ cell count in PB showed a positive and a negative correlation with CruCE in autologous and allogeneic settings, respectively. In conclusion, CruCE may be closer to actual CE in comparison to CE2 and CE1. LVL and low CD34+/μL prior to the procedure may enhance CD34+ cell CE.

ABSTRACTChronic graft‐versus‐host disease (cGVHD) remains a major cause of morbidity and mortality following allogeneic hematopoietic stem cell transplantation. Many cGVHD patients require prolonged systemic immunosuppression with corticosteroids, which carry significant adverse effects, and alternative therapies are often required. Extracorporeal photopheresis (ECP) has historically shown promise as a cGVHD treatment, but recent efficacy data have been limited and inconsistent. To evaluate the efficacy of ECP as a treatment for cGVHD patients according to the 2014 NIH Consensus Criteria. We retrospectively analyzed 53 patients treated with ECP for cGVHD at our center from 2010 to 2024. ORR was 51%, with 3 CRs (5.7%) and 24 PRs (45.3%). Highest organ‐specific responses were seen in the gastrointestinal tract (70%) and liver (69.2%), and lowest in joints/fascia (15.4%) and lung (21.4%). A total of 23 (43.4%) patients experienced at least one treatment‐related complication (TRC), with a median time to first TRC of 29.3 weeks (IQR = 7.4–55.2). The estimated 1‐ and 3‐year OS was 79.2% (95% CI = 65.7%–87.9%) and 70.1% (95% CI = 55.0%–80.9%), respectively. The estimated 1‐ and 3‐year FFS was 75.5% (95% CI = 61.5%–84.9%) and 43.1% (95% CI = 28.6%–56.9%), respectively. Of the 37 patients who were on corticosteroids at the start of ECP, 22 (59.5%) were able to decrease their daily dose by ≥ 50% by the time of ECP discontinuation. Multivariable analyses revealed that patients on tacrolimus and other non‐steroid immunosuppressive treatments (ISTs) had better outcomes in clinical benefit, steroid‐sparing, overall survival, and failure‐free survival. ECP was a safe and effective treatment for cGVHD in our population and showed promising efficacy when used in combination with tacrolimus or other ISTs.

Therapeutic plasma exchange (TPE) is used to lower triglyceride levels in patients with severe hypertriglyceridemia-associated acute pancreatitis (HTG-AP). However, evidence supporting the effectiveness of TPE in preventing end-organ damage remains limited. This retrospective cohort study was conducted using the TriNetX database to evaluate adults with acute pancreatitis, triglyceride levels > 1000 mg/dL, and "worrisome criteria", defined as clinical indicators of disease severity such as fever, leukocytosis, elevated lactate, or signs of shock. Patients receiving TPE within 3 days of diagnosis were compared with patients with no TPE within 30 days. Outcomes included triglyceride reduction to < 500 mg/dL, ICU admission, end-organ damage, and mortality. Of 14 188 patients with HTG-AP, 3% (n = 419) received TPE; 97% (n = 13 237) were treated without TPE. After 1:1 propensity-score matching, 2 well-matched, 412-patient cohorts were created. More patients in the TPE cohort had a reduction in triglyceride levels to < 500 mg/dL at 1 week (81% vs. 40%, p < 0.001) and 1 month (86% vs. 48%, p < 0.001). However, the TPE cohort also had higher ICU admission rates (39% vs. 19%, p < 0.001). No significant differences in organ failure rates were observed at 1 week (4.4% vs. 3.3%, p = 0.47) or 1 month (5.8% vs. 5.0%, p = 0.71). Similarly, 30-day (4.4% vs. 6.3%, p = 0.21) and 3-month (5.3% vs. 7.8%, p = 0.16) all-cause mortality were comparable between the cohorts. In patients with HTG-AP, use of TPE within 3 days of diagnosis reduces triglyceride levels effectively but does not significantly reduce the risk of end-organ damage or mortality. TPE is associated with increased ICU care requirements, which may reflect protocolized ICU admission.

Data sharing not applicable to this article as no datasets were generated or analyzed during the current study.

Hemoglobin S (HbS) polymerization inhibitor drugs such as voxelotor can result in a split peak in HbS as well as additional peaks with hemoglobin A in quantitative methods of HbS measurement. It is unclear how these results should be used to make transfusion decisions. The goal of this study is to compare RBC exchange (RBCX) replacement volumes calculated with HbS-Vox + HbS versus HbS alone. Patients aged 15-58 years who had variant hemoglobin quantitation performed for clinical care purposes with evidence of voxelotor treatment (split peak in HbS and/or additional peaks with hemoglobin A) were identified by investigator review of variant hemoglobin quantitation test results from the clinical laboratory. The RBCX replacement volume calculated with HbS% total (RBCX volume HbS% total) was compared to the RBCX replacement volume calculated with HbS unmod% (RBCX volume HbS unmod%) in each case. The mean difference between RBCX volume total HbS% and RBCX volume HbS% unmod is 398 mL with 95% CI (198, 598) and RBCX volume total HbS is significantly different from RBCX volume HbS unmod (p value = 0.0006). If the HbS total is not used to calculate RBCX replacement volumes in patients taking voxelotor, there is a significantly lower amount of RBC that would be ordered, which would lead to higher HbS after RBCX. Additional studies regarding the role of transfusion in such patients are necessary.