Beth H. Shaz

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.

Guidelines on the use of therapeutic apheresis in clinical practice - Evidence-based approach from the writing committee of the american society for apheresis

The American Society for Apheresis (ASFA) JCA Special Issue Writing Committee is charged with reviewing, updating and categorizating indications for therapeutic apheresis. Beginning with the 2007 ASFA Special Issue (Fourth Edition), the committee has incorporated systematic review and evidence‐based approach in the grading and categorization of indications. This Sixth Edition of the ASFA Special Issue has further improved the process of using evidence‐based medicine in the recommendations by consistently applying the category and GRADE system definitions, but eliminating the “level of evidence” criteria (from the University HealthCare Consortium) utilized in prior editions given redundancy between GRADE and University HealthCare Consortium systems. The general layout and concept of a fact sheet that was utilized in the Fourth and Fifth Editions, has been largely maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. This article consists of 78 fact sheets (increased from 2010) for therapeutic indications in ASFA categories I through IV, with many diseases categorized having multiple clinical presentations/situations which are individually graded and categorized. J. Clin. Apheresis 28:145–284, 2013.

Improvements in early mortality and coagulopathy are sustained better in patients with blunt trauma after institution of a massive transfusion protocol in a civilian level I trauma center.

INTRODUCTION Transfusion practices across the country are changing with aggressive use of plasma (fresh-frozen plasma [FFP]) and platelets during massive transfusion with current military recommendations to use component therapy at a 1:1:1 ratio of packed red blood cells to FFP to platelets. METHODS A massive transfusion protocol (MTP) was designed to achieve a packed red blood cell:FFP:platelet ratio of 1:1:1 We prospectively gathered demographic, transfusion, and patient outcome data during the first year of the MTP and compared this with a similar cohort of injured patients (pre-MTP) receiving > or = 10 red blood cell (RBC) in the first 24 hours of hospitalization before instituting the MTP. RESULTS One hundred sixteen MTP activations occurred. Twelve non-trauma patients and 31 who did not receive 10 RBC (15 deaths, 16 early bleeding controls) were excluded. Seventy-three MTP patients were compared with 84 patients with pre-MTP who had similar demographics and injury severity score (29 vs. 29, p = 0.99). MTP patients received an average of 23.7 RBC and 15.6 FFP transfusions compared with 22.8 RBC (p = 0.67) and 7.6 FFP (p < 0.001) transfusions in pre-MTP patients. Early crystalloid usage dropped from 9.4 L (pre-MTP) to 6.9 L (MTP) (p = 0.006). Overall patient mortality was markedly improved at 24 hours, from 36% in the pre-MTP group to 17% in the MTP group (p = 0.008) and at 30 days (34% mortality MTP group vs. 55% mortality in pre-MTP group, p = 0.04). Blunt trauma survival improvements were more marked and more sustained than victims of penetrating trauma. Early deaths from coagulopathic bleeding occurred in 4 of 13 patients in the MTP group vs. 21 of 31 patients in the pre-MTP group (p = 0.023). CONCLUSIONS In the civilian setting, aggressive use of FFP and platelets drastically reduces 24-hour mortality and early coagulopathy in patients with trauma. Reduction in 30 day mortality was only seen after blunt trauma in this small subset.

Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia.

Summary.  The natural history of heparin‐induced thrombocytopenia (HIT) in the absence of thrombosis was previously established using functional assays for confirmation of diagnosis (e.g. 14C serotonin release assay). An enzyme‐linked immunosorbent assay (ELISA) that detects the presence of antibodies directed against the heparin–platelet factor‐4 (PF4) complex has largely replaced functional assays in many medical centers. Although the ELISA is highly sensitive for detecting HIT antibodies, its usefulness for predicting thrombotic outcomes has not been clearly established. We performed a retrospective chart review of all hospitalized patients at a university hospital who tested seropositive for HIT by a commercial ELISA during 2001 and 2002. A total of 63 inpatients were identified as HIT positive by ELISA. Forty‐eight patients had no apparent HIT‐associated thrombosis at the time of HIT seropositivity (i.e. isolated HIT) and only one was treated prophylactically with a direct thrombin inhibitor. The 30‐day thrombosis rate for patients with isolated HIT was 17% (eight of 48). Higher ELISA optical density (OD) measurements correlated significantly with thrombosis (1.41 ± 0.87 vs. 0.79 ± 0.46, P < 0.001). Patients with isolated HIT and an OD measurement of ≥ 1.0 demonstrated nearly a 6‐fold increased risk of thrombosis compared with those with OD values between 0.4 and 0.99 (odds ratio 5.74, 95% confidence interval 1.73, 19.0; absolute rate of thrombosis, 36% vs. 9%, respectively, P = 0.07). We conclude that in hospitalized patients with isolated HIT, the presence of heparin–PF4 antibodies detected by ELISA was associated with a significant risk of subsequent thrombosis and higher ELISA values were observed among patients suffering thrombotic events.

Increased number of coagulation products in relationship to red blood cell products transfused improves mortality in trauma patients

BACKGROUND: Recent data from military and civilian centers suggest that mortality is decreased in massive transfusion patients by increasing the transfusion ratio of plasma and platelet (PLT) products, and fibrinogen in relationship to red blood cell (RBC) products during damage control resuscitation and surgery. This study investigates the relationship of plasma:RBC, PLT:RBC, and cryoprecipitate:RBC transfusion ratios to mortality in massively transfused patients at a civilian Level 1 trauma center.

Transfusion Management of Trauma Patients

The management of massively transfused trauma patients has improved with a better understanding of trauma-induced coagulopathy, the limitations of crystalloid infusion, and the implementation of massive transfusion protocols (MTPs), which encompass transfusion management and other patient care needs to mitigate the “lethal triad” of acidosis, hypothermia, and coagulopathy. MTPs are currently changing in the United States and worldwide because of recent data showing that earlier and more aggressive transfusion intervention and resuscitation with blood components that approximate whole blood significantly decrease mortality. In this context, MTPs are a key element of “damage control resuscitation,” which is defined as the systematic approach to major trauma that addresses the lethal triad mentioned above. MTPs using adequate volumes of plasma, and thus coagulation factors, improve patient outcome. The ideal amounts of plasma, platelet, cryoprecipitate and other coagulation factors given in MTPs in relationship to the red blood cell transfusion volume are not known precisely, but until prospective, randomized, clinical trials are performed and more clinical data are obtained, current data support a target ratio of plasma:red blood cell:platelet transfusions of 1:1:1. Future prospective clinical trials will allow continued improvement in MTPs and thus in the overall management of patients with trauma.

Transfusion-related acute lung injury: from bedside to bench and back

Over the past 60 years, the transfusion medicine community has attained significant knowledge regarding transfusion-related acute lung injury (TRALI) through the bedside to bench and back to the bedside model. First, at the bedside, TRALI causes hypoxia and noncardiogenic pulmonary edema, typically within 6 hours of transfusion. Second, bedside studies showed a higher incidence in plasma and platelet products than in red blood cell products (the fatal TRALI incidence for plasma is 1:2-300 000 products; platelet, 1:3-400 000; red blood cells, 1:25 002 000), as well as an association with donor leukocyte antibodies (∼ 80% of cases). Third, at the bench, antibody-dependent and antibody-independent mechanisms have been described, requiring neutrophil and pulmonary endothelial cell activation. Antibodies, as well as alternate substances in blood products, result in neutrophil activation, which, in a susceptible patient, result in TRALI (2-hit hypothesis). Fourth, back to the bedside, policy changes based on results of these studies, such as minimizing use of plasma and platelet products from donors with leukocyte antibodies, have decreased the incidence of TRALI. Thus, steps to mitigate TRALI are in place, but a complete mechanistic understanding of the pathogenesis of TRALI and of which patients are at highest risk remains to be elucidated.

Prevalence and significance of inflammatory bowel disease-like morphologic features in collagenous and lymphocytic colitis.

Collagenous colitis (CC) and lymphocytic colitis (LC) are clinical syndromes characterized by the presence of chronic watery diarrhea, few or no endoscopic abnormalities and biopsies that typically show normal crypt architecture, increased mononuclear inflammation in the lamina propria, absence of neutrophils, and increased intraepithelial lymphocytes. Patients with CC also have a thickened subepithelial collagen layer. We have noted, anecdotally, that biopsy specimens from some patients with CC or LC contain certain histologic features, such as Paneth cell metaplasia (PM), that are normally seen in inflammatory bowel disease (IBD), or other types of healed colitis, and thus may cause diagnostic difficulty. Therefore, the purpose of this study was to evaluate the prevalence and significance of IBD-like morphologic features in colonic mucosal biopsies from patients with CC or LC. Five hundred thirty-one routinely processed hematoxylin and eosin-stained colonic mucosal biopsies from 150 patients with clinically, endoscopically, and histologically confirmed CC (79 patients, male/female ratio: 14/65, mean age: 60 yr) or LC (71 patients, male/female ratio: 13/58, mean age: 55 yr) were evaluated in a blinded fashion for a variety of histologic features, including active crypt inflammation (cryptitis ± crypt abscess), surface ulceration, Paneth cell metaplasia, crypt architectural irregularity, number of intraepithelial lymphocytes, and thickness of the subepithelial collagen layer (CC only). The results were compared between CC and LC and correlated with the clinical and endoscopic data. None of the patients had or developed IBD during the study period. Active crypt inflammation was a common finding in both groups, seen in 24 of 79 CC patients (30%) and 27 of 71 LC patients (38%). Surface ulceration was not seen in any of the LC biopsies but was present in 2 of 79 (2.5%) CC patients. Paneth cell metaplasia was frequent in both groups and significantly more common in CC compared with LC patients. Forty-four percent of CC patients, but only 9 of 63 (14%) of LC patients had Paneth cell metaplasia (p <0.001). Crypt architectural irregularity, although rare, was present in 6 of 79 patients with CC (7.6%) and 3 of 71 (4.2%) patients with LC. In patients with CC, the presence of Paneth cell metaplasia was associated with more severe disease characterized by the presence of abdominal pain (p <0.001) and a higher frequency of bowel movements (>3 bowel movements/day) (p = 0.06). Also, active crypt inflammation correlated with antibiotic use at the time of clinical presentation (p = 0.04) and was present in the only two patients who had positive stool cultures (one each for Campylobacter jejuni and Salmonella). However, none of the other histologic findings correlated with any of the other clinical or endoscopic features, such as type of symptoms, stool consistency, type of medical treatment, associated autoimmune diseases or outcome (complete, partial, or no resolution) in either group of patients. Pathologists should be aware that some histologic features normally associated with IBD such as crypt irregularity and neutrophilic cryptitis and crypt abscesses are not uncommon in patients with CC or LC and that the presence of one or more of these features should not necessarily be interpreted as evidence against either of these diagnoses.

A novel mouse model of red blood cell storage and posttransfusion in vivo survival

BACKGROUND: Storage of red blood cells (RBCs) is necessary for an adequate blood supply. However, reports have identified potential negative sequelae of transfusing stored RBCs. An animal model would be useful to investigate the pathophysiology of transfusing stored RBCs. However, it has been reported that storage of rat RBCs in CPDA‐1 resulted in an unexpected sudden decline in posttransfusion survival. A mouse model of RBC storage and transfusion was developed to assess survival kinetics of mouse RBCs.