Joseph Schwartz

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Apheresis Applications Committee of the American Society for Apheresis

The American Society for Apheresis (ASFA) Apheresis Applications Committee is charged with a review and categorization of indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (fourth edition), the subcommittee has incorporated systematic review and evidence‐based approach in the grading and categorization of indications. This Fifth ASFA Special Issue has further improved the process of using evidence‐based medicine in the recommendations by refining the category definitions and by adding a grade of recommendation based on widely accepted GRADE system. The concept of a fact sheet was introduced in the Fourth edition and is only slightly modified in this current edition. The fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis. The article consists of 59 fact sheets devoted to each disease entity currently categorized by the ASFA as category I through III. Category IV indications are also listed. J. Clin. Apheresis, 2010.

Guidelines on the Use of Therapeutic Apheresis in Clinical Practice—Evidence-Based Approach from the Writing Committee of the American Society for Apheresis: The Sixth Special Issue

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence‐based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence‐based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149–162, 2016.

Platelet transfusion refractoriness

The platelet, a fascinating anucleate cell, is critically important for haemostasis. Platelet transfusions have greatly reduced the incidence of major haemorrhagic complications associated with the management of haematological and oncological disorders. However, some patients fail to receive the full benefit of platelet transfusions because they do not achieve the appropriate platelet count increment following transfusion. This review will discuss the aetiology, diagnosis, and management of refractoriness to platelet transfusion, a complicated problem for both the treating physicians and the transfusion services supporting these patients. Although advances have been made in the diagnosis and treatment of immune‐mediated platelet refractoriness, which is usually caused by anti‐human leucocyte antigen antibodies, non‐immune causes, such as sepsis, remain problematic.

Immune regulation in chronically transfused allo-antibody responder and nonresponder patients with sickle cell disease and β-thalassemia major.

Red blood cell alloimmunization is a major complication of transfusion therapy. Host immune markers that can predict antibody responders remain poorly described. As regulatory T cells (Tregs) play a role in alloimmunization in mouse models, we analyzed the Treg compartment of a cohort of chronically transfused patients with sickle cell disease (SCD, n = 22) and β‐thalassemia major (n = 8) with and without alloantibodies. We found reduced Treg activity in alloantibody responders compared with nonresponders as seen in mice. Higher circulating anti‐inflammatory IL‐10 levels and lower IFN‐γ levels were detected in non‐alloimmunized SCD patients. Stimulated sorted CD4+ cells from half of the alloimmunized patients had increased frequency of IL‐4 expression compared with nonresponders, indicating a skewed T helper (Th) 2 humoral immune response in a subgroup of antibody responders. All patients had increased Th17 responses, suggesting an underlying inflammatory state. Although small, our study indicates an altered immunoregulatory state in alloantibody responders which may help future identification of potential molecular risk factors for alloimmunization. Am. J. Hematol. 2011.

Posttraumatic stress due to an acute coronary syndrome increases risk of 42-month major adverse cardiac events and all-cause mortality

Approximately 15% of patients with acute coronary syndromes (ACS) develop posttraumatic stress disorder (PTSD) due to their ACS event. We assessed whether ACS-induced PTSD symptoms increase risk for major adverse cardiac events (MACE) and all-cause mortality (ACM) in an observational cohort study of 247 patients (aged 25-93 years; 45% women) hospitalized for an ACS at one of 3 academic medical centers in New York and Connecticut between November 2003 and June 2005. Within 1 week of admission, patient demographics, Global Registry of Acute Coronary Events risk score, Charlson comorbidity index, left ventricular ejection fraction, and depression status were obtained. At 1-month follow-up, ACS-induced PTSD symptoms were assessed with the Impact of Events Scale-Revised. The primary endpoint was combined MACE (hospitalization for myocardial infarction, unstable angina or urgent/emergency coronary revascularization procedures) and ACM, which were actively surveyed for 42 months after index event. Thirty-six (15%) patients had elevated intrusion symptoms, 32 (13%) elevated avoidance symptoms, and 21 (9%) elevated hyperarousal symptoms. Study physicians adjudicated 21 MACEs and 15 deaths during the follow-up period. In unadjusted Cox proportional hazards regression analyses, and analyses adjusted for sex, age, clinical characteristics and depression, high intrusion symptoms were associated with the primary endpoint (adjusted hazard ratio, 3.38; 95% confidence interval, 1.27-9.02; pxa0=xa0.015). Avoidance and hyperarousal symptoms were not associated with the primary endpoint. The presence of intrusion symptoms is a strong and independent predictor of elevated risk for MACE and ACM, and should be considered in the risk stratification of ACS patients.

Therapeutic plasma exchange for the treatment of anti-NMDA receptor encephalitis

Anti‐N‐methyl‐D‐aspartate receptor (NMDA‐R) encephalitis is thought to be one of the common paraneoplastic‐associated encephalitides. Between February 2001 and February 2011, nine patients were diagnosed with this disorder at Columbia University Medical Center: eight females (mean age 23 years) and one male (3 years of age). Four female patients had ovarian teratomas, which were removed as part of their treatment. Therapeutic plasma exchange (TPE) was used as one of the treatment modalities in addition to immunosuppressive therapy, including corticosteroids, intravenous immunoglobulin (IVIG), and/or rituximab. A total of 56 TPE procedures were performed in these patients on alternate days (range, 5–14 procedures/patient). Approximately 1 plasma volume (PV) was processed for all patients; 5% albumin and 0.9% normal saline were used as replacement fluid. Complications occurred in 20% of TPE procedures; 9% were possibly due to underlying disease. The remaining 11% of complications were hypotensive episodes that rapidly responded to either a fluid bolus or a vasopressor treatment. One patient demonstrated immediate clinical improvement after three TPE treatments, and four patients had significant improvement at time of discharge from the hospital. Long‐term follow‐up showed that early initiation of TPE appears to be beneficial, and patients who received IVIG after TPE did better than those who received IVIG before TPE. However, the number of patients in this series is too small to provide statistically significant conclusions. Overall, TPE is a relatively safe treatment option in patients with anti‐NMDA‐R encephalitis. Further studies are needed to elucidate the benefit of TPE in this disease. J. Clin. Apheresis, 2011.

Socioeconomic and Psychosocial Factors Mediate Race Differences in Nocturnal Blood Pressure Dipping

BACKGROUNDnReduced nocturnal blood pressure (BP) dipping is more prevalent among blacks living in the United States than whites and is associated with increased target organ damage and cardiovascular risk. The primary aim of this study was to determine whether socioeconomic and psychosocial factors help to explain racial differences in dipping. In order to address the limited reproducibility of dipping measures, we investigated this question in a sample of participants who underwent multiple ambulatory BP monitoring (ABPM) sessions.nnnMETHODSnThe study sample included 171 black and white normotensive and mildly hypertensive participants who underwent three ABPM sessions, each 1 month apart, and completed a battery of questionnaires to assess socioeconomic and psychosocial factors.nnnRESULTSnAs expected, blacks showed less dipping than whites, after adjusting for age, sex, body mass index (BMI), and mean 24-h BP level (mean difference = 3.3%, P = 0.002). Dipping was related to several of the socioeconomic and psychosocial factors examined, with higher education and income, being married, and higher perceived social support, each associated with a larger dipping percentage. Of these, marital status and education were independently associated with dipping and together accounted for 36% of the effect of race on dipping.nnnCONCLUSIONSnWe identified a number of socioeconomic and psychosocial correlates of BP dipping and found that reduced dipping among blacks vs. whites is partially explained by marital status (being unmarried) and lower education among blacks. We also present results suggesting that repeated ABPM may facilitate the detection of associations between dipping and other variables.

A comparison of adverse reaction rates for PAS C versus plasma platelet units.

Plasma constituents have been implicated in some types of platelet (PLT) transfusion reactions. Leukoreduced apheresis PLTs stored in InterSol have 65% less plasma than apheresis PLTs stored in 100% plasma (PPs). This study compared transfusion reaction rates in InterSol PLTs (PLT additive solution [PAS] C) versus PPs.

How do I approach ABO‐incompatible hematopoietic progenitor cell transplantation? (CME)

H uman leukocyte antigen (HLA) matching is critically important for successful hematopoietic progenitor cell (HPC) transplantation because the rates of engraftment and transplant outcomes are strongly influenced by the degree of match. This is largely because HLA antigens are expressed on immature pluripotent stem cells. In contrast, ABO incompatibility is not a barrier to successful HPC transplantation because ABO blood group antigens are not expressed on pluripotent or early committed HPCs. HLA and ABO antigens are encoded by different genes; thus it is common that potential donors who are fully HLA matched have an ABO incompatibility. Approximately 40 to 50% of HPC transplants are ABO incompatible and are now performed using bone marrow (HPC-M), apheresis-derived peripheral blood progenitor cells (HPCA), and umbilical cord blood (HPC-C) as HPC sources. Three types of ABO incompatibility exist: major, minor, and bidirectional. A total of 20 to 25% of HPC transplants have a major ABO incompatibility, 20 to 25% a minor ABO incompatibility, and up to 5% a bidirectional incompatibility. Each presents a unique set of potential adverse consequences, including early acute hemolysis that can be ameliorated through HPC product processing to remove incompatible red blood cells (RBCs) or plasma (Table 1). In these cases, the recipient must be closely monitored both at the time of the infusion and in the posttransplant period because serious events can occur many days later. Accreditation agencies such as AABB and the Foundation for the Accreditation of Cellular Therapy (FACT) require that all donors be tested for ABO group and D type before the collection of HPC-A or HPC-M and that HPC-C be typed after product processing before cryopreservation. The testing and its required documentation in the medical record need to be done in accordance with institutional standard operating procedures. Current FACT standards also require that “for allogeneic cellular therapy products containing RBCs at the time of administration, a test for ABO group and Rh type shall be performed on the first product collected, or on blood obtained from the donor at the time of the first collection.” At our institution, the donor ABO group and D type is tested as part the donor evaluation process. Additional donor ABO group and D testing is performed on each collection day from blood samples obtained at time of collection. If donor blood sample is not available for a particular collection, confirmatory typing is performed on a product sample on the day of product processing. For all fresh HPC products received from outside facilities, confirmatory ABO group and D testing is performed before further product processing. HPC-C units are received in the frozen state and are not subject to repeat testing.

Update on extracorporeal photopheresis in heart and lung transplantation

Transplant rejection of solid organs remains a threat to thousands of patients despite modern immunosuppressive regimens. The currently available drugs are associated with severe complications such as hypertension, diabetes mellitus, renal failure, risk of infections, and malignancies among many others and, often enough, still allow episodes of rejection. New and less‐toxic immunologic measures are desperately needed to accomplish the desired tolerance to the transplant without the undesirable side effects. Extracorporeal photopheresis (ECP) has been shown to benefit especially patients with cardiac transplants, but also those who received lung allografts. ECP likely modulates the recipients antigen‐specific immune responses and inflammation in transplantation by in vivo generation of apoptotic leukocytes. This review will highlight the need for ECP, how it is thought to act, and the published evidence for its role in cardiac and pulmonary transplantation. J. Clin. Apheresis, 2011.