Older platelet (PLT) concentrates are believed to be at substantially increased risk of transfusion-associated infections.1 The fear that bacterial overgrowth increases with time of storage is often the basis for limiting the shelf life of PLT concentrates. The rationale for this belief is based on 1) the fact that slower growing organisms (e.g., Staphylococcus sp.) reach clinically significant concentrations over time and 2) the age of PLTs at the time of observed sepsis or death.1-3 Before the introduction of bacterial screening of PLTs, it was known that approximately two-thirds of clinical sepsis episodes or death were caused by Gram-negative organisms and only one-third by Gram-positive organisms.4, 5 However, in the case of contamination of PLTs assessed by culture, the reverse is true, with two-thirds of the organisms isolated being Gram positive.4, 5 With the introduction of early bacterial detection, virtually all cases of Gram-negative contamination can be interdicted.6 In those rare cases of Gram-negative sepsis that occur despite an early bacterial detection step, human error is frequently identified as the cause.7, 8 In addition to the fact that many Gram-positive organisms grow at a slower rate than Gram-negative organisms, a second and frequently overlooked possible contributing factor is the apparent differential extended lag times observed when such organisms are exposed to certain donor plasma. In one study of 48 PLT concentrates inoculated with the same isolate of Staphylococcus epidermidis, bacterial growth was seen with 91.7% of PLT concentrates 3 days after inoculation and with 98.0% of PLTs by Day 4.2 However, 1 PLT unit (2.1%) had demonstrable growth only on Day 7.2 Similarly, Murphy and colleagues found that when one isolate of Staphylococcus capitis was inoculated into PLT concentrates,3 quantitative cultures performed using 1-mL samples taken on Days 2, 3, 4, 5, 6, and 7 showed no growth in any unit until Day 4 in 3 units, Day 5 in a fourth unit, and Day 7 in the remaining 2 units. The second rationale for the heightened fear associated with older PLTs is the observed number of cases of sepsis and or death observed with older PLTs. For example, the American Red Cross reported the increasing number of PLT-associated sepsis (fatal and nonfatal) by days after collection of Day 1, none; Day 2, one; Day 3, two, Day 4, four, and Day 5, 13 (with two of these cases being fatal).1 At first glance such a presentation of their data appears to suggest an ascending stair-step increased risk of septic reactions with older PLTs, particularly Days 4 and 5. However, no data were provided as to the number of PLTs transfused by day after collection (the denominator in a rate calculation—the ratio between two related quantities). Without these data, one has no way to “normalize” the data and thus to compare apples to apples. The important question to ask is what is the number of septic transfusion reactions per number of PLTs transfused on a given day. Unfortunately, accurate data as to the age of PLT products on the day of transfusion is frequently not available. In the most recent National Blood Collection and Utilization Survey Report from the United States, of 708 hospitals (51.9% of hospitals overall) that responded to queries regarding the age of apheresis PLTs (the predominant PLT product transfused in the United States) at the time of transfusion, only 10.9% (74 hospitals) had the tools to calculate PLT component age.9 Without true rates of sepsis per number of units transfused on a given storage day, the observed higher rate of sepsis and death of older stored PLTs might simply be a function of a disproportionate number of PLTs being transfused near the end of their outdates. Fortunately, in this issue of TRANSFUSION a nationwide cohort study among buffy coat–derived PLT concentrates in PAS-C transfusion recipients in Denmark linked a nationwide database of positive blood cultures to Danish recipients of PLTs obtained from the Scandinavian Donations and Transfusions (SCANDAT2) database. Patients receiving PLTs stored 6 to 7 days (old) were compared to those receiving fresh PLTs (1 to 5 days).10 In total 9776 patients received 66,101 PLT transfusions. This group found that the incidence rate ratio of a positive blood culture the day after transfusion of at least one old PLT concentrate was 0.77 (confidence interval [CI], 0.54-1.09) compared to transfusion of fresh PLT concentrates. Comparing just one fresh to one old pool, they found that the incidence rate of a positive blood culture was actually lower the day after transfusion (incidence rate ratio, 0.57; CI, 0.37-0.87). This group concluded that, contrary to current thinking, transfusion of a single old PLT concentrate may actually decrease the risk of posttransfusion sepsis. This article makes us question the current dogma that older PLTs are inherently at higher risk of causing a septic transfusion reaction. How might one rationalize such an unexpected result? It is possible that a disproportionate number of PLTs are transfused during the late days of storage, thereby leading to a higher number of septic events observed on a late day of storage; this explanation simply reflects that more PLTs might be transfused on a given day closer to outdate. In fact, when one closely examines this study, they actually did report that 52.5% of PLTs were stored 1 to 5 days and 33.6% 6 to 7 days. If one assumes that no PLTs were transfused on Day 1 of storage, this observation would mean that on average 13.1% of PLTs were transfused on Days 2, 3, 4, and 5 of storage compared to 16.8% being transfused on Days 6 and 7. A more granular view of the number or percentage of PLTs transfused on each day of storage was not provided. Nevertheless, the data provided suggest that this may be one factor contributing to a higher number of septic events being reported in the literature with older PLTs but which are not borne out in this study. The possibility that older PLTs may actually be safer than younger PLTs is intriguing but a little more difficult to explain. It is possible that in some cases contaminated PLTs self-sterilize as a result of “natural bactericidal activity” during the first few days of storage.11, 12 Alternatively, patients receiving older PLTs may be hospitalized at a larger center with high PLT usage where older PLTs approaching outdate are shipped to minimize outdating the products. Such patients would be expected to be sicker, receiving more intensive therapy and might possibly be more likely to be receiving concomitant antibiotic therapy, thereby reducing the possibility of detectable posttransfusion sepsis. Like many good studies, the article by Kreuger and coworkers makes us question the current dogma, in this case, regarding the increased septic risk of older PLTs. Additional studies must be performed to confirm or refute their observations and if confirmed to elucidate the reason why older PLTs may actually be as safe or safer than younger PLTs. This verification is particularly important at this time, as many centers are facing the conundrum of choosing between bacterial detection versus pathogen reduction and the related question of the possible extension of PLT shelf life. The author has disclosed no conflicts of interest. Mark E. Brecher, MD e-mail: Mark.Brecher@LabCorp.com Laboratory Corporation of America Diagnostics Burlington, NC Department of Pathology and Laboratory Medicine University of North Carolina Chapel Hill, NC

Acquired thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia, thrombocytopenia, and commonly ADAMTS13 deficiency. Patients with TTP and severe ADAMTS13 deficiency have high risk of disease recurrence, yet the ability to predict which patients will have recurrence remains limited. We assessed whether the presence of persistent schistocytes in TTP patients with severe ADAMTS13 deficiency at the time of daily therapeutic plasma exchange (TPE) discontinuation was predictive of disease recurrence. We retrospectively reviewed the electronic medical records of all patients with a diagnosis of TTP treated with TPE at our university medical center between August 1991 and April 2013. Exacerbation was defined as disease recurrence within 30 days of cessation of daily TPE, and relapse was defined as disease recurrence >30 days after cessation of daily TPE. Comparisons were performed with a two-sided Fisher's exact test or chi 2 test. Of the 46 total TTP patients eligible for analysis, nine had residual schistocytosis (20%), four of the nine (44%) had exacerbations, and two of the nine (22%) relapsed. Of the 37 patients without residual schistocytosis, 16 (43%) had exacerbations and 11 (30%) relapsed. There were no statistically significant differences in the exacerbation or relapse rates with or without residual schistocytosis (P = 1.00 and 1.00, respectively). Residual schistocytes after discontinuation of daily TPE were not uncommon. The persistence of schistocytes had poor sensitivity, specificity, and both positive and negative predictive values. After the initial diagnosis of TTP is made, there is no reason to continue documenting the presence or absence of schistocytes.

BACKGROUND:The purpose of this survey was to describe current practices in the U.S. for treatment of acquired Thrombotic Thrombocytopenic Purpura (TTP), compare these with prior U.S. and current Canadian practices, and identify areas of clinical equipoise. STUDY DESIGN AND METHODS:A research team member administered the survey by telephone. Questions included an estimate of the annual patient volume treated, apheresis and medical therapy practices for acquired TTP. RESULTS:32 centers from 22 states were surveyed. ADAMTS13 activity is used for confirmation of the diagnosis of acquired TTP (97%). Most commonly, daily plasma exchange (therapeutic plasma exchange [TPE]) is initiated with plasma as replacement fluid (91%) at 1.0 Plasma Volume (72%) and stopped with a platelet count of 150 × 109 /L (66%), and then TPE is tapered off (69%). Compared with a U.S. survey from 1998, a greater proportion of centers use plasma exclusively as the replacement fluid exclusively (29/32 vs 2/14 in 1998; P < .0001) and taper TPE (22/32 vs 8/20 in 1998, P = .0499). Compared with Canadian survey in 2016, a greater proportion of U.S. centers use plasma over cryosupernatant (29/32 vs 2/13 CAG centers, P < .0001) and initiate TPE with 1.0 PV compared with 1.5 PV (23/32 vs 0/14 CAG centers, P < .0001). Corticosteroid use is common but not universal (U.S. and CAG) and use of rituximab heterogeneous. CONCLUSION:Treatment of acquired TTP in the U.S. remains heterogeneous. Points of clinical equipoise identified were PV exchanged (1.0 vs >1.0), tapering of TPE versus none, and rituximab use.

BACKGROUND:Bacterially contaminated platelets (PLTs) remain a serious risk. The Food and Drug Administration has issued draft guidance recommending hospitals implement secondary testing or transfuse PLTs that have been treated with pathogen reduction technology (PRT). The cost implications of these approaches are not well understood.STUDY DESIGN AND METHODS:We modeled incurred costs when hospitals acquire, process, and transfuse PLTs that are PRT treated with INTERCEPT (Cerus Corp.) or secondary tested with the PLT PGD Test (Verax Biomedical).RESULTS:Hospitals will spend $221.27 (30.0%) more per PRT-treated apheresis PLT unit administered compared to a Zika-tested apheresis PLT unit that is irradiated and PGD tested in hospital. This difference is reflected in PRT PLT units having: 1) a higher hospital purchase price ($100.00 additional charge compared to an untreated PLT); 2) lower therapeutic effectiveness than untreated PLTs among hematologic-oncologic patients, which contributes to additional transfusions ($96.05); or 3) fewer PLT storage days, which contributes to higher outdating cost from expired PLTs ($67.87). Only a small portion of the incremental costs for PRT-treated PLTs are offset by costs that may be avoided, including primary bacterial culture, secondary bacterial testing ($26.65), hospital irradiation ($8.50), Zika testing ($4.47), and other costs ($3.03).CONCLUSION:The significantly higher cost of PRT-treated PLTs over PGD-tested PLTs should interest stakeholders. For hospitals that outdate PLTs, savings associated with expiration extension to 7 days by adding PGD testing will likely be substantially greater than the cost of implementing PGD-testing. Our findings might usefully inform a hospital's decision to select a particular blood safety approach.

Journal of Clinical ApheresisVolume 32, Issue 4 p. 273-273 Apheresis Illustrated Management of Gardner–Diamond syndrome with therapeutic plasma exchange Peter A. Millward, Peter A. Millward Department of Pathology, Beaumont Hospital, Royal Oak, MichiganSearch for more papers by this authorAlice Ma, Alice Ma Division of Hematology/Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North CarolinaSearch for more papers by this authorShauna N. Hay, Shauna N. Hay Department of Allied Health, Clinical Laboratory Science, University of North Carolina, Chapel Hill, North CarolinaSearch for more papers by this authorMark E. Brecher, Corresponding Author Mark E. Brecher brechem@labcorp.com Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina Laboratory Corporation of America, Burlington, North CarolinaCorrespondence Mark E. Brecher, MD, Chief Medical Officer, Laboratory Corporation of America, 531, South Spring St., Burlington, NC 27215. E-mail: brechem@labcorp.comSearch for more papers by this authorNicholas Bandarenko, Nicholas Bandarenko Department of Pathology, Duke University, Durham, North CarolinaSearch for more papers by this author Peter A. Millward, Peter A. Millward Department of Pathology, Beaumont Hospital, Royal Oak, MichiganSearch for more papers by this authorAlice Ma, Alice Ma Division of Hematology/Oncology, Department of Internal Medicine, University of North Carolina, Chapel Hill, North CarolinaSearch for more papers by this authorShauna N. Hay, Shauna N. Hay Department of Allied Health, Clinical Laboratory Science, University of North Carolina, Chapel Hill, North CarolinaSearch for more papers by this authorMark E. Brecher, Corresponding Author Mark E. Brecher brechem@labcorp.com Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, North Carolina Laboratory Corporation of America, Burlington, North CarolinaCorrespondence Mark E. Brecher, MD, Chief Medical Officer, Laboratory Corporation of America, 531, South Spring St., Burlington, NC 27215. E-mail: brechem@labcorp.comSearch for more papers by this authorNicholas Bandarenko, Nicholas Bandarenko Department of Pathology, Duke University, Durham, North CarolinaSearch for more papers by this author First published: 17 August 2016 https://doi.org/10.1002/jca.21484Citations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume32, Issue4August 2017Pages 273-273 RelatedInformation

Dr Norman Bethune established one of the first mobile transfusion services during the Spanish CivilWar (see figure, Dr Bethune beside two of his mobile transfusion trucks; reproduced courtesy of the Library and Archives Canada). 1 Established in 1936, his unit the Servicio canadiense de transfusion de sangre took blood donated by civilians in bottles to wounded soldiers near the front lines. At its peak it has been estimated that this team was involved in up to 100 transfusions per day. Dr Bethune subsequently lost his life in 1939 while serving as a surgeon for the communist forces in the second Sino-Japanese war. Dr Bethune is best remembered in China where he is considered a model of international human compassion. The Norman BethuneMedal, established in 1991, considered to be the highest honor in terms of medicine in China, is awarded annually to physicians making outstanding contributions to Chinese health.

Guidelines exist for chronic kidney disease (CKD) but are not well implemented in clinical practice. We evaluated the impact of a guideline-based clinical decision support system (CDSS) on laboratory monitoring and achievement of laboratory targets in stage 3–4 CKD patients.

Acquired thrombotic thrombocytopenic purpura (TTP) is a disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, in addition to variable fever and neurologic and renal dysfunction, without an underlying cause. Recent advances in elucidating the pathophysiology of acquired TTP have led to new testing that we have incorporated into our current management of patients with suspected acquired TTP. Despite these developments, much of the treatment for acquired TTP beyond therapeutic plasma exchange (TPE) is based on low-quality evidence. Our group has a sustained interest in studying and optimizing the use of TPE, along with other concurrent therapies, in acquired TTP patients. Described herein is a summary of how our apheresis consult service approaches requests for TPE in patients with suspected acquired TTP.

The American Society for Apheresis (ASFA) conducted a 1 day consensus conference on Thrombotic Thrombocytopenic Purpura (TTP) during its annual meeting in Atlanta, GA, on April 10, 2012. The authors of this article, a subcommittee of ASFA's Clinical Applications Committee, developed several questions with regard to definitions, classification, pathophysiology, diagnosis, management, and future research in TTP. These questions were provided to the seven invited speakers who are the experts in the field of TTP. Two moderators conducted the proceedings of the conference which was attended by more than 100 participants. After each presentation, there was an open discussion that included moderator‐selected written questions submitted by the audience. A medical writer‐generated transcript of the proceedings as well as each presentation was made available to the authors. Each summary was reviewed and approved by the respective speaker before submission of this article. The subcommittee also developed seven key questions for blinded, electronic polling conducted by the moderators to generate a consensus amongst the speakers. This article includes these presentation summaries as well as results of the electronic poll. J. Clin. Apheresis 29:148–167, 2014. © 2013 The Authors. Journal of Clinical Apheresis Published by Wiley Periodicals, Inc.

BackgroundTesting of platelets (PLTs) for bacterial contamination is required by the AABB Standards but is not fully standardized. On January 31, 2011, a new AABB Standard, 5.1.5.1.1, specified that bacterial detection methods for PLT components shall use assays either approved by the Food and Drug Administration (FDA) or validated to provide sensitivity equivalent to these FDA‐approved methods.MethodsAn Internet‐based survey of AABB member institutions was conducted from May to June 2012, to document current practices used in 2011 for bacterial detection in different PLT products and to assess the impact of the new standard.ResultsOf 1053 AABB member institutions surveyed, 40 of 99 blood centers (40.4%) and 184 of 954 hospital blood banks or transfusion services (19.3%) responded. Sixty‐four respondents manufactured PLTs. Apheresis PLTs (APs) were predominantly screened with the BacT/ALERT system (89.5%); the majority (95.2%) were cultured with at least 8 mL of product. There was substantial variation in the minimum incubation time of cultures before release of PLTs (range, 0 to >24 hr). Recalls of released AP for possible bacterial contamination were largely successful (67.3%); successful interdiction before transfusion was associated with incubation for more than 12 hours before release (p < 0.01). After Standard 5.1.5.1.1 took effect, there was a decrease in production of whole blood–derived PLT concentrates (WBPCs). Point‐of‐issue (“rapid”) immunoassays were used to screen a substantial proportion of WBPC PLTs, but were rarely used as secondary tests for previously cultured APs.ConclusionThe survey identified variability in culture methods and release times with AP, while use of WBPC decreased after AABB Standard 5.1.5.1.1 became effective.

The Leukotrap PLT pooling system. A Leukotrap PLT pooling bag with a clamp placed across the protruding pocket is in the middle of the figure. With a capacity of 450 mL, this bag could accommodate a pool of up to 6 units of whole blood–derived PLT or an apheresis PLT concentrate. After transfer, the bag would be placed in a Leukotrap centrifuge cup (on the left of the figure). A Leukotrap clamping device was used to apply the clamp after centrifugation (on the right of the figure). The Leukotrap PLT pooling bag, shown inserted in the Leukotrap centrifuge cup before centrifugation. Leukoreduction of platelets (PLTs) is a well-accepted approach to decrease the risk of HLA alloimmunization (and the resulting refractoriness to PLT transfusion), febrile nonhemolytic transfusion reactions, and cytomegalovirus transmission. Leukoreduction is typically achieved by either filtration or differential centrifugation. A novel approach to leukoreduction based on the latter principle introduced in the 1980s by Cutter Laboratories (Berkeley, CA), involved the use of a PLT pooling bag (for either whole blood–derived or apheresis PLT concentrates) with a protruding pocket at the bottom of the bag in which heavier cellular elements were collected (see figure, left). Centrifugation involved the use of a custom centrifuge cup with a hole in the bottom in which the pocket was inserted (see figure, right). After centrifugation a clamp was applied across the pocket. Leukoreduction of 77% to 99% (approx. 1-2 log) was achieved and the resulting product was found to be effective in reducing febrile nonhemolytic transfusion reactions. Increasing demands for greater leukoreduction of blood products resulted in the abandonment of this method. Currently, leukoreduction using apheresis equipment during donation or a leukoreduction filter removes 99.9% of the white blood cells. We thank Vincent J. Moylan, Jr, MS, PA (ASCP), for assistance with the photographs. We have no conflict of interest to report.

Exchange transfusion is frequently used as an adjunctive treatment of severe malaria, although the efficacy of exchange transfusion as therapy for severe malaria remains controversial. The major perceived benefit of exchange transfusion is the rapid reduction of parasite load. However, no previous report has shown the dynamic change in parasitemia shortly following an acute load reduction. We report a 20‐year‐female who developed cerebral malaria and 30% parasitemia after traveling to Africa. In addition to antimalarial treatment, red cell exchange (RCX) was begun emergently with an automated blood‐cell separator. Parasitemia dropped from 30 to 15% immediately after the procedure but rapidly increased to 25% after 50 min. The second procedure was performed 12 h after the first procedure. Her neurologic status returned to baseline on Day 2, and she was discharged on Day 6. Rapid increases in parasitemia can be observed after mechanical load reduction following RCX. J. Clin. Apheresis, 2011. © 2011 Wiley Periodicals, Inc.

Most cases of thrombotic thrombocytopenic purpura (TTP) are considered idiopathic without an identifiable etiologic agent. It has been previously reported that a number of patients with TTP had a urinary tract infection (UTI). Apheresis records were searched for patients with TTP from 1999 through 2007. Records were examined for evidence of UTI, and the patients were divided into 4 groups: 1, laboratory evidence of UTI on admission; 2, UTI just before admission; 3, UTI that developed during hospitalization; and 4, weak laboratory evidence of a UTI. The study included 90 TTP "visits." (A visit was defined as all admissions for TTP for a specific patient within a 1-month period.) Of the TTP visits, 21 (23%) were associated with UTIs. Group 1 included 7 patients; group 2, 10 patients; group 3, 3 patients; and group 4, 1 patient. This suggests that UTIs might serve as a TTP stimulus. Owing to the relatively strong association of UTIs with TTP, all patients with TTP should be screened for UTI and treated accordingly.