Faculty Bibliography

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.

Factor XIII (FXIII) deficiency is a rare bleeding disorder characterized by unstable hemostatic clots due to defective fibrin cross‑linking. Congenital FXIII deficiency arises from variants in the F13A1 (FXIII-A subunit) or F13B (FXIII-B subunit) genes, and classically presents with delayed umbilical stump hemorrhage, soft‑tissue and intracranial bleeding, impaired wound healing, and recurrent pregnancy loss. Acquired deficiency stems from inhibitory autoantibodies or from reduced synthesis or consumption in critical illness and surgery. Routine coagulation screening tests are normal and diagnosis relies on quantitative FXIII activity assays with or without antigenic phenotyping and, when indicated, inhibitor testing and molecular confirmation. Plasma‑derived FXIII concentrate reduces spontaneous and intracranial bleeding; recombinant FXIII‑A2 is appropriate for F13A1 defects but not patients with F13B variants. Perioperative and obstetric care target activity thresholds suited to procedural risk and individual pharmacokinetics. This review synthesizes the molecular biology, epidemiology, clinical features, diagnostic methods, and evidence‑based management of FXIII deficiency, with practical guidance for assay selection, validation, and result interpretation.

Postpartum hemorrhage (PPH) remains the leading cause of preventable maternal mortality despite standard interventions. Recent fibrinogen trials failed to improve outcomes, prompting interest in coagulation factor XIII (FXIII). FXIII functions as "molecular cement," cross-linking fibrin and stabilizing clots. During pregnancy, FXIII activity decreases 20%-30%, with further depletion during PPH. Observational studies show low antepartum FXIII predicts bleeding risk, while ex vivo supplementation restores clot firmness. The SWIFT trial (NCT06481995) represents the first randomized controlled trial evaluating early FXIII supplementation in PPH. Although implementation challenges are significant (diagnostic accessibility, thrombotic monitoring, supply constraints), even modest hemostatic improvements could substantially reduce maternal mortality.

The American Society for Apheresis (ASFA) Attending Physician Subcommittee of the Physicians' Committee performed an annual review of articles published in 2024 related to apheresis medicine. The 10 seminal apheresis articles selected by the subcommittee members are summarized in this review. PubMed was used to identify manuscripts published in 2024 in four areas of interest: donor apheresis, therapeutic apheresis, apheresis education, and apheresis for cellular therapy. Only full length, peer-reviewed manuscripts in English with data from human subjects were included. Case reports, review articles, and meta-analyses were excluded. Articles were considered seminal if they met at least one of the following previously established criteria: novel finding(s), practice-altering outcomes, international in scope, randomized-controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA 9th special issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach.

Medical scams or grifting has long been a societal issue, though in recent years, the problem has become increasingly mainstream, especially as it relates to transfusion medicine, apheresis and biotherapies. Unfortunately, unsubstantiated medical claims, or unfounded interventions such as therapeutic plasma exchange for longevity or dangerous stem cell injections, are leading to significant medical waste and patient harm. Herein, we review contemporary medical grifts, cognitive biases and present a framework for managing these issues to ensure legitimate care and safety for patients.

Xenotransplantation of genetically-modified pig kidneys offers a solution to the scarcity of organs for end-stage renal disease patients.¹ We performed a 61-day alpha-Gal knock-out pig kidney and thymic autograft transplant into a nephrectomized brain-dead human using clinically approved immunosuppression, without CD40 blockade or additional genetic modification. Hemodynamic and electrolyte stability and dialysis independence were achieved. Post-operative day (POD) 10 biopsies revealed glomerular IgM and IgA deposition, activation of early complement components and mesangiolysis with stable renal function without proteinuria, a phenotype not seen in allotransplantation. On POD 33, an abrupt increase in serum creatinine was associated with antibody-mediated rejection and increased donor-specific IgG. Plasma exchange, C3/C3b inhibition and rabbit anti-thymocyte globulin (rATG), completely reversed xenograft rejection. Pre-existing donor-reactive T cell clones expanded progressively in the circulation post-transplant, acquired an effector transcriptional profile and were detected in the POD 33 rejecting xenograft prior to rATG treatment. This study provides the first long-term physiologic, immunologic, and infectious disease monitoring of a pig-to-human kidney xenotransplant and indicates that pre-existing xenoreactive T cells and induced antibodies to unknown epitope(s) present a major challenge, despite significant immunosuppression. It also demonstrates that a minimally gene-edited pig kidney can support long-term life-sustaining physiologic functions in a human.

Platelet transfusions are a cornerstone of hemorrhage management in patients with thrombocytopenia or platelet dysfunction, yet their indications and dosing are largely based on expert opinion and low-quality evidence. This review offers a timely and comprehensive analysis of platelet transfusion practices in the United States (U.S.), uniquely integrating clinical evidence, such as the pivotal PLADO trial, with emerging technological advancements. Using a holistic approach, this manuscript addresses not only conventional practices (such as dosing standards and storage methods), but also cutting-edge alternatives like cold-stored and freeze-dried platelets, pathogen reduction technologies, and synthetic platelet substitutes. By juxtaposing U.S. practices with international standards, it highlights inefficiencies in dosing and supply management, proposing actionable solutions like lower-dose transfusions and diversified platelet inventories. Furthermore, the manuscript's exploration of whole blood-derived platelets and the ethical debate surrounding paid donors adds a forward-looking perspective. By examining these innovations alongside strategies to optimize supply, this work aims to provide a comprehensive overview of how transfusion medicine is adapting to meet clinical and logistical demands.

In this first annual review article, the American Society for Apheresis (ASFA) Attending Physician Subcommittee (APSc) of the Physicians' Committee (PC) curated key apheresis literature in 2023 and presented their choices for the 10 most seminal apheresis articles. PubMed and OVID search engines were used to identify manuscripts from four topic areas: donor apheresis, therapeutic apheresis, education, and cellular therapy. To further identify seminal criteria, they had to present at least one of the following: novel findings, practice-altering outcomes, international scope, randomized controlled trial, relevant to current clinical practice, and/or provide evidence for category III or IV indications based on the ASFA ninth special issue of the Guidelines on the Use of Therapeutic Apheresis in Clinical Practice-Evidence-Based Approach. Inclusion criteria included: full-length, peer-reviewed, English language, and human subjects. Case reports, review articles, and meta-analyses were excluded.