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Importance Neuromyelitis optica/neuromyelitis optica spectrum disorder patients' response to therapeutic plasma exchange (TPE) is currently incompletely characterized. Objective Our study aims to understand the clinical status improvement of neuromyelitis optica/neuromyelitis optica spectrum disorder patients treated with TPE. Design, setting, and participants This is a multicenter retrospective study conducted between 1 January 2003 and 31 July 2017 at 13 US hospitals performing apheresis procedures. Subjects studied were diagnosed with neuromyelitis optica/neuromyelitis optica spectrum disorder who received TPE during presentation with acute disease. Main outcomes and measures The primary outcome was clinical status improvement in patients treated with TPE. Secondary measures were procedural and patient characteristics associated with response to treatment. Results We evaluated 114 patients from 13 institutions. There was a female predilection. The largest ethnic group affected was non-Hispanic Caucasian. The average age of diagnosis was 43.1 years. The average time to diagnosis was 3.1 years. On average, five procedures were performed during each treatment series. The most commonly performed plasma volume exchange was 1.0 to 1.25 using 5% albumin as replacement fluid. Most patients (52%) did not require an additional course of TPE and noted "mild" to "moderate" clinical status improvement. Maximal symptom improvement appeared by the fourth or fifth TPE treatment. Conclusion and relevance TPE improved the clinical status of patients. Adults responded more favorably than children. Procedural characteristics, including number of TPEs, plasma volume exchanged, and replacement fluid used, were similar between institutions. TPE was well-tolerated and had a low severe adverse event profile.

Arterial and venous thromboembolic disease, while less common in children than in adults, nevertheless can cause significant morbidity and mortality. In this chapter we will provide an overview of thrombotic disorders in children, with emphasis on common and unique manifestations in pediatrics, summarize diagnosis and treatment, and discuss laboratory diagnosis of thrombophilia.

Tremendous physiological changes occur with the birthing process. These include transformative changes in cardiovascular circulation, pulmonary function, and feeding, as the neonate must now perform gas exchange and obtain nutrients without the benefit of a placenta. Associated with these changes are remarkable increases in growth, skeletal development, and continued maturity of cardiovascular, hepatic, gastrointestinal, renal, hematopoietic, and nervous systems. When either prematurity or disease entities are present, normal development can be altered. Because neonatology is an enormous field, this chapter only discusses major biochemical and physiologic challenges that neonates face. There remain a great number of controversial issues within the field of neonatology, and the reader is encouraged to consult an excellent review in this area [M.R. Uhing, R.M. Kliegman (Eds.), Current Controversies in Perinatal Medicine, V. Clinics in Perinatology, WB Saunders, Philadelphia, PA, 2009, pp. 214].

Therapeutic plasma exchange is used to treat neurological diseases in the pediatric population. Since its first use in pediatric patients with hepatic coma in the form of manual whole blood exchange, therapeutic plasma exchange has been increasingly used to treat these disorders of the nervous system. This expansion is a result of improved techniques and apheresis instruments suitable for small children, as well as the recognition of its applicability to many diseases in the pediatric population. This review provides a historical overview of the use of therapeutic apheresis in children and highlights the most common applications for therapeutic plasma exchange to treat neurological disorders in children.

Background Immunomodulatory strategies in heparin-induced thrombocytopenia (HIT) include the use of intravenous immune globulin (IVIG) and therapeutic plasma exchange (TPE). The optimal application of these therapies is unknown and outcomes data are limited. We investigated treatment categories and laboratory and clinical outcomes of IVIG and/or TPE in HIT with a systematic literature review. Study design and methods We searched MEDLINE, Embase, and Web of Science through December 2019 for studies combining controlled vocabulary and keywords related to thrombocytopenia, heparin, TPE, and IVIG. The primary outcome was treatment indication. Secondary outcomes were platelet recovery, HIT laboratory parameters, heparin re-exposure, and post-treatment course. Case-level data were analyzed by qualitative synthesis. Results After 4241 references were screened, we identified 60 studies with four main categories of IVIG and/or TPE use as follows: (a) treatment of refractory HIT (n = 35; 31%); (b) initial therapy (n = 45; 40%); (c) cardiopulmonary bypass surgery (CPB; n = 30; 27%); and (d) other (n = 2; 2%). IVIG was most commonly used for the treatment of refractory HIT while TPE was primarily used to facilitate heparin exposure during CPB. Both IVIG and TPE were equally used as initial therapy. Heparin re-exposure occurred without thrombotic event in 29 TPE-treated patients and three IVIG-treated patients. Conclusion In patients with HIT, both TPE and IVIG are used for initial therapy or treatment of refractory HIT. However, TPE is more commonly used in patients undergoing CPB. Prospective studies may help clarify which treatment is indicated in HIT population subsets.

Introduction Red cell exchange (RCE) therapy is increasingly used to treat patients with acute or chronic manifestations of sickle cell disease (SCD). However, little is known regarding the most safe and effective practice parameters associated with this particular therapy. Methods A SCD subcommittee of members of the American Society for Apheresis (ASFA) developed a 122-question survey and administered it via email to other ASFA members. The survey inquired about clinical indications for treatment, practice patterns, and transfusion policies for RCE when used for patients with SCD. Results Ninety-nine distinct institutions completed the survey. Twenty-one (21%) were from outside of the US. Twenty-two (22%) provided chronic transfusion therapy to >10 patients, and both adult (25%) and pediatric-focused services (20%) were represented. Common acute indications for RCE included acute chest syndrome, acute ischemic stroke, and pre-surgical prophylaxis. Common chronic indications included primary stroke prophylaxis, secondary stroke prophylaxis, and recurrent acute chest syndrome. Respondents most commonly set a post-RCE treatment target of 30% for the hematocrit and hemoglobin S levels, regardless of the therapeutic indication. Units for RCE were phenotypically matched in 95% of cases. About 40% of respondents reported using isovolemic hemodilution. Conclusions This survey solicited the current practice variations in RCE from a diverse range of practice sites. Many sites reported similar practice patterns and challenges but some variations emerged. To our knowledge, this survey represents the largest and most in-depth investigation of the use of RCE for patients with SCD, and could inform future studies in the field.

INTRODUCTION Performing therapeutic plasma exchange (TPE) with albumin replacement decreases coagulation factor and platelet levels. No defined guidelines exist regarding laboratory testing to assess hemostasis in patients undergoing TPE. MATERIALS AND METHODS A survey to evaluate hemostasis testing with TPE was distributed using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 120 respondents per question. Descriptive analysis was performed with results reported as the number and/or frequency (%) of respondents to each question. RESULTS The practices represented vary by institution type, number of apheresis procedures per year, and performance of TPE on children. Prior to TPE planned with albumin replacement, many respondents obtain laboratory studies for almost all patients (54.9% outpatients and 68.7% inpatients); however, some do not routinely obtain laboratory studies (9.7% outpatients and 4.4% inpatients). Hemoglobin/hematocrit, platelet count, fibrinogen, partial thromboplastin time (aPTT), and international normalized ratio (INR) are obtained prior to all TPE by 62.5%, 53.4%, 31.0%, 18.1%, and 17.7% of respondents, respectively; however, 1.0%, 8.7%, 29.0%, 38.3%, and 35.4%, respectively, do not routinely obtain these studies. Variation was observed in laboratory threshold values for action; the most common reported were hemoglobin/hematocrit reference range and >1.5 times reference range (tied, 28.1%), and INR >1.5 (20.7%). CONCLUSIONS Practice variation exists in hemostasis laboratory testing and threshold values for action with TPE. Further studies are needed to determine optimal hemostasis testing strategies with TPE.

BACKGROUND Hemolysis is a reported side effect of intravenous immunoglobulin (IVIG) therapy in adults, but pediatric data are scarce. We determined the frequency of IVIG-associated hemolysis in patients with Kawasaki disease (KD) and characterized risk factors for hemolysis. We hypothesized that hemolysis is more common in children with KD than adults with other disorders, and hemolysis risk is related to IVIG dose and degree of inflammation. STUDY DESIGN AND METHODS This was an 8-year, single-center, retrospective cohort study. A total of 419 KD patients were identified; 123 had pre- and post-treatment complete blood counts allowing for assessment of anemia. Hemolytic anemia was defined as decrease in hemoglobin after IVIG greater than 1 g/dL with immunohematologic or biochemical studies supporting hemolysis. RESULTS 123 patients were stratified as having hemolysis (n = 18, 15%) or nonhemolysis (n = 105, 85%). Patients with hemolysis were more likely to have complete versus incomplete KD (65% vs. 39%, p = 0.04) and refractory versus nonrefractory course (78% vs. 16%, p < 0.001). Patients receiving 4 g/kg versus 2 g/kg IVIG were more likely to hemolyze (89% vs. 34%, p < 0.001). Patients with hemolysis had mostly non-O blood group (94%), positive direct antiglobulin tests (89%), and positive eluates (72%). Two-thirds of patients with hemolysis required RBC transfusion. CONCLUSIONS Hemolysis occurred in 15% of KD patients evaluated for anemia and is strongly associated with high-dose (4 g/kg) IVIG. KD patients receiving high-dose IVIG should have close hematologic monitoring to identify hemolysis.

Current chemistry analyzers measure ion concentration using ion- selective electrodes; however, may differ in the specific technology at the bedside versus the central laboratory. Instruments utilized for point-of-care testing (POCT) at the bedside use direct ion-selective electrodes, whereas central-laboratory analyzers use indirect ion-selective electrodes. Under most circumstances, these instruments will deliver the same result; however, various substances can cause interferences in one or the other. An 18-year-old Hispanic woman with a history of immune thrombocytopenic purpura (ITP) presented at Children's National Medical Center (CNMC) with a severe headache and required intravenous immunoglobulin (IVIG) therapy. Because a discrepancy developed between her point-of-care and central-laboratory sodium values, another instrument was used to retest the central-laboratory plasma specimens. The results were more in agreement with those from the point-of-care instrument and revealed a unique interference in sodium measurement related to IVIG use.

Introduction: Antibodies that cause heparin-induced thrombocytopenia (HIT) can be detected with either antigenic or functional assays. Previously, it has been shown that antigenic (ELISA based) assays that detect anti-platelet factor 4 (anti-PF4) IgG, IgM, or IgA (polyspecific) antibodies are more sensitive but less specific than functional assays such as the unfractionated serotonin release assay (UFH SRA), and that the use of anti-PF4 assays that detect IgG antibodies only, would increase the specificity but decrease the sensitivity of these assays for the detection of HIT antibodies that are prothrombotic (associated with positive functional assay). To date large epidemiologic studies have not confirm these findings. To evaluate the relative performance of anti-PF4 polyspecific and IgG-specific antibodies in their ability to detect prothrombotic HIT antibodies, we evaluated results of non-reflexive HIT panels that contained either anti-PF4 polyspecific or IgG-specific assays and unfractionated heparin serotonin release assays over an eight-year period at a U.S. reference laboratory. Methods: Test results for 2 HIT detection panels were compared: 1 panel had UFH SRA plus the polyspecific PF4 ENHANCED® assay (GTI Diagnostics, Waukesha, WI) and 1 panel had UFH SRA plus the IgG-specific Zymutest HIA IgG assay (Hyphen Biomed, France). Test results were from the last 4 years of use for each panel (2009 to 2012 for the polyspecific panel; 2017 to 2020 for the IgG-specific panel). UFH SRA was performed as described by Sheridan et al, (1986) with positivity defined as ≥20% serotonin release by low dose UFH and >50% suppression of release at high dose (100 U/mL) UFH. For each year and assay, test results were stratified by optical density (OD) results, and the percent of results positive by UFH SRA was determined for each OD range. Median yearly UFH SRA positivity rates for each OD interval were compared for anti-PF4 polyspecific vs IgG-specific antibody assays using non-parametric statistical testing, Mann-Whitney U test, two-tailed, with significance defined as Results: HIT panels with either ELISA based assays detecting either anti-PF4 polyspecific or IgG specific antibodies demonstrated increasing UFH SRA positivity rates as OD increased. Approximately 50% UFH SRA positivity occurred when OD was in the 2.000 to range. No significant differences in SRA positivity were seen at any positive OD interval when comparing anti-PF4 polyspecific vs IgG-specific assays. A small but significant difference was seen when OD results were considered This observation may have been due to a in the review process (2017-2020): when a UFH SRA result was positive with a negative OD result, repeat UFH SRA testing was performed. Conclusions: Our study demonstrates that the correlations of UFH SRA positivity and OD measurements are similar for anti-PF4 IgG-specific and polyspecific antibody assays. These results suggest the assay types may perform similarly for the detection of HIT and importantly provide important predictive information as to when an optical density value will lead to a positive UFH SRA result. Figure 1 Figure 1. Disclosures Wong: Quest Diagnostics: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company. Worfolk: Quest Diagnostics: Current Employment. Bi: Quest Diagnostics: Current Employment. Noh: Quest Diagnostics: Current Employment. Espinoza: Quest Diagnostics: Current Employment. Wu: Quest Diagnostics: Current Employment. Sahud: Quest Diagnostics: Current Employment. Racke: Quest Diagnostics: Current Employment. Dlott: Quest Diagnostics: Current Employment.

Background: Venous thromboembolism (VTE) is one of the most common cardiovascular disorders after myocardial infarction and stroke. Primary manifestations include deep vein thrombosis and pulmonary embolism, which are often preventable and often underdiagnosed. Patients with inherited thrombophilia or family history of VTE are at increased risk for VTE. Acquired VTE risk factors include the use of oral hormonal contraceptives, such as combined oral contraceptive pills (COCPs) containing estrogen and progestin. Women with a family history of VTE are advised not to take COCPs; possible alternatives include use of progestin-only contraceptive pills or non-oral contraceptive methods. Currently it is unknown if young women at college are given information regarding this potential risk when seeking oral contraceptives. Thus, higher education websites can provide a potential venue to promote awareness of this risk. In this study, we reviewed a sample of higher education websites in the US to assess availability of information on oral hormonal contraceptives and their risks for young women. Methods: US higher education institutions for this survey and categorized into 5 major types: community colleges, liberal arts institutions, private for-profit institutions, public non-profit institutions, and private non-profit institutions; 25 institutions from each category were included for analysis. The study was conducted using the Google search terms "birth control pills," "oral contraceptive pills," OR plus the university name. Mention of contraindications, risk factors, and blood clot warnings was noted for each website and categorized as to whether the information appeared on the institution's webpage or as a link to an external reference source. Information listed was further classified by risk factors and contraindications mentioned. Results: A total of 125 US higher education institution websites were assessed. Eighteen (14.4%) of the 125 offered information on COCP-related clotting risks. Community colleges and private, for-profit institutions had no information on birth control available either on their webpage or through an external link. Only 3 of 25 (12%) liberal arts institutions discussed clotting risk information. Five of the 25 (20%) public, nonprofit institutions surveyed provided information on their student webpages; three of these 5 offering information through their website as well as through a link to an external website. Of the private, non-profit institutions surveyed, 2 (8%) provided information through their institution's website and 4 (16%) provided information through external sources. Regarding contraindications, 2 (8%) liberal arts schools provided information on their website only, identical to the percentages seen with private and public non-profit institutions. Additionally, 4 (16%) private non-profit universities and 2 (8%) public, non-profit institutions provided information only through external sources. Two (8%) public non-profit institutions provided information both on their website and through external links. Overall, only 6 (4.8%) of the 125 institutions described family history or inherited prothrombotic blood disorder as a potential contraindication or risk factor for COCP-related clotting, all 6 of which were public or private non-profit institutions. Conclusion: The results of this study raise the question of whether higher education institutions are providing the appropriate risk and contraindication information for women considering oral contraceptives as a birth control method. This suggests that there is an opportunity for more birth control education to be provided by higher education institutions. Figure 1 Figure 1. Disclosures Sarmiento: Quest Diagnostics: Current Employment. Sahud: Quest Diagnostics: Current Employment. Wong: Quest Diagnostics: Current Employment, Current equity holder in publicly-traded company, Current holder of individual stocks in a privately-held company, Current holder of stock options in a privately-held company.

BACKGROUND Directed donation is associated with a higher prevalence of donations that are positive for infectious disease markers; however, little is known about the positive rates among parental-directed, non-parental–directed, and allogeneic donations. STUDY DESIGN AND METHODS We reviewed blood-collection records from January 1997 through December 2008, including infectious disease results, among parental, non-parental, and community donations. Infectious disease rates were compared by Mann-Whitney U test. RESULTS In total, 1532 parental, 4910 non-parental, and 17,423 community donations were examined. Among parental donors, the median rate of positive infectious disease testing was 8.66% (interquartile range (IQR), 4.49%) for first-time donors and 1.26% (IQR, 5.86%) for repeat donors; among non-parental donors, the rate was 1.09% (IQR, 0.98%) for first-time donors and 0% (IQR, 0.83%) for repeat donors; and, among community donors, the rate was 2.95% (IQR, 1.50%) for first-time donors and 0.45% (IQR, 0.82%) for repeat donors. The mean rate of positive infectious disease testing for first-time parental donors was significantly higher (7.63%), whereas all repeat donors had similar rates. However, the rate of positive infectious disease testing among first-time non-parental donors was significantly lower than that in the other groups, especially for the period from 2001 through 2008. CONCLUSION First-time non-parental and community donors had significantly higher infectious disease risk than the respective repeat donors. First-time parental donors had the highest rates of positive infectious disease testing. We suggest that first-time parental blood donation should be discouraged. Repeat community donors or first-time non-parental donors provide a safer alternative. These findings can foster better patient education, donor selection, and possibly a reduced risk of infectious disease.

Apheresis Medicine is a medical discipline that involves a variety of procedures (based on the targeted component to be removed or collected), indications (therapeutic vs. donation), and personnel (operators, management, and medical oversight). Apheresis services are accredited and/or regulated by a number of agencies and organizations. Given the complexity and the heterogeneity of apheresis services, it has been particularly challenging to formulate educational goals and define curriculums that easily cover all aspects of Apheresis Medicine. This review summarizes the current state of the discipline in the United States of America, and some of the challenges, strategies, and resources that Apheresis Medicine educators have used to ensure that Apheresis Medicine educational programs meet the health care needs of the relevant population within regulatory and accrediting entity frameworks.

INTRODUCTION: Anti-heparin/platelet factor 4 antibody immune complexes resulting from heparin-induced thrombocytopenia (HIT) are removed by therapeutic plasma exchange (TPE). We sought to define TPE in HIT practice patterns using an international survey. METHODS: A 31-item online survey was disseminated through the American Society for Apheresis. After institutional duplicate responses were eliminated, a descriptive analysis was performed. RESULTS: The survey was completed by 94 respondents from 78 institutions in 18 countries. Twenty-nine institutions (37%) used TPE for HIT (YES Cohort) and 49 (63%) did not (NO Cohort). Most NO respondents (65%) cited “no requests received” as the most common reason for not using TPE. Of the 29 YES respondents, 10 (34%) gave incomplete information and were excluded from the final analysis, leaving 19 responses. Of these, 18 (95%) treated ≤ 10 HIT patients over a 2-year period. The most common indications were cardiovascular surgery (CS; 63%) and HIT-associated thrombosis (HT; 26%). The typical plasma volume processed was 1.0 (63% CS and 58% HT). For CS, the typical replacement fluid was plasma (42%) and for HT, it was determined on an individual basis (32%). For CS, patients were treated with a set number of TPE procedures (37%) or laboratory/clinical response (37%). For HT, the number of TPE procedures typically depended on laboratory/clinical response (42%). CONCLUSION: In a minority of responding institutions, TPE is most commonly used in HIT to prophylactically treat patients who will undergo heparin re-exposure during cardiovascular surgery. Prospective studies are needed to more clearly define the role of TPE in HIT.

Apheresis technology has progressed significantly over the last 50-60 years from a predominately blood donation-based procedure to one that now includes a variety of therapeutic modalities. The last 25 years also has seen an increase in the number of diseases treated by therapeutic apheresis (TA) modalities. Because of ethical considerations, therapeutic modalities are often vetted first in adult populations before establishing utility in pediatric patients. TA is no different. The majority of published studies involve adult patients. Pediatric apheresis studies are traditionally retrospective, single-center experiences, single case reports, or case series. To confirm this, we evaluated the peer-reviewed published literature to assess the level of evidence of clinical pediatric apheresis studies published in the last 21 years. Adverse events experienced by pediatric patients undergoing TA procedures and procedural modifications necessary to accommodate pediatric patients receiving TA were also explored. Consideration was given to differences in disease outcomes in pediatric vs adult patients and evolution of TA treatment indications. A systematic search of the literature yielded >1000 pediatric apheresis publications. Only 370 articles specifically assessed TA in the treatment of a pediatric disease. Of those, the majority (98%) were single-center experiences, single case reports, or case series. The remaining 2% were prospective cohort studies or randomized controlled trials. This first formal assessment of the pediatric apheresis literature confirms the findings of previous anecdotal reports and expert opinion.

BACKGROUND Hydroxyethyl starch (HES) is reportedly associated with an increased risk of renal failure and death when used for fluid resuscitation in critically ill patients. HES can be used during therapeutic leukocytapheresis (TL) procedures to enhance cell separation. The purpose of this study was to evaluate the occurrence of adverse events associated with HES during TL procedures. STUDY DESIGN AND METHODS We performed a retrospective review of patients who underwent TL with and without HES in the period 2009 to 2013 at six academic medical institutions. RESULTS A difference-in-difference regression analysis was used to estimate the mean change before and after TL in selected outcomes in the HES group relative to the average change in the non-HES group. Selected outcomes included serum creatinine, estimated glomerular filtration rate (eGFR), and white blood cell (WBC) count. A total of 195 patients who underwent 278 TL procedures were studied. We found no significant differences in serum creatinine levels and eGFR on Days 1 and 7 after TL procedure between patients who received and those who did not receive HES. The rate of adverse events and overall and early mortality were similar in both groups. Patients with acute myeloid leukemia who received HES had greater WBC reduction when HES was used. Additionally, patients who received HES had improvement in pulmonary leukostasis symptoms. CONCLUSION HES, used at low doses during TL procedures, was not associated with adverse events previously ascribed to its use as a volume expander.

Background Although many apheresis centers offer extracorporeal photopheresis (ECP), little is known about current treatment practices. Methods An electronic survey was distributed to assess ECP practice internationally. Results Of 251 responses, 137 met criteria for analysis. Most respondents were from North America (80%). Nurses perform ECP at most centers (84%) and the majority of centers treat adults only (52%). Most centers treat fewer than 50 patients/year (83%) and perform fewer than 300 procedures/year (70%). Closed system devices (XTS and/or Cellex) are used to perform ECP at most centers (96%). The most common indications for ECP are acute/chronic skin graft versus host disease (89%) and cutaneous T-cell lymphoma (63%). The typical wait time for ECP treatment is less than 2 weeks (91%). Most centers do not routinely perform quality control assessment of the collected product (66%). There are device-specific differences in treatment parameters. For example, XTS users more frequently have a minimum weight limit (P = 0.003) and use laboratory parameters to determine eligibility for treatment (P = 0.03). Regardless of device used, the majority of centers assess the clinical status of the patient before each procedure. Greater than 50% of respondents would defer treatment for hemodynamic instability due to active sepsis or heart failure, positive blood culture in the past 24 h or current fever. Conclusion This survey based study describes current ECP practices. Further research to provide evidence for optimal standardization of patient qualifications, procedure parameters and product quality assessment is recommended.

Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components.

Background Anti-muscle specific kinase antibody positive (MuSK Ab) myasthenia gravis (MG) patients are known to have different clinical course compared to anti-acetylcholine receptor Ab positive MG patients. Therapeutic plasma exchange (TPE) has been reported to be effective; however, little is known of the response and of TPE procedural information. An ASFA Apheresis Registry was developed to analyze those data. Methods The study collected detailed de-identified patient data, TPE procedures, and treatment outcome/complications. Collected data was described in aggregate. Results A total of 15 MuSK Ab MG patients with exacerbation of MG symptoms, 13 females/2 males, median age 44, were investigated. Thirty TPE courses (median 5 procedures/course, total 145 procedures) were evaluated. All TPE procedures were performed with citrate anticoagulation, 1 - 1.25 plasma volume exchange in 100% fluid balance, and 90% of courses used only albumin as replacement. Calcium was added to albumin or given orally as needed. TPE was performed every other day in 55% of courses. Adverse events occurred in 3.4% of procedures. Ten patients (67%) experienced relapses within a median of 7 weeks. Objective symptoms were resolved in more than 75% of courses. Overall subjective improvement rates were 94.1%/93.3% after 3/4 TPE procedures, respectively. Thirty-one percent of patients responded poorly with minimal recovery. Conclusion Overall subjective improvement was seen up to 94% of patients after one course of TPE. Some patients were poor-responders. Five TPE may be adequate for initial course with additional TPE as needed. Based upon this preliminary data, we will modify our future data collection. J. Clin. Apheresis 32:5-11, 2017. © 2016 Wiley Periodicals, Inc.

The unique challenges of pediatric transfusion medicine include tailoring one’s approach to treatment by taking into account many factors, such as the influence of patients’ age, developmental maturity on physiology and biology, and pathologic conditions involving the immunologic and hematologic systems. The main technical challenges include: (1) working with very small aliquots of blood components because of the inherently greater risk of volume overload and (2) the fact that risk of infection, product preservatives, and product storage breakdown can have an even greater effect in the pediatric population due to their unique physiology and biology. Research and evidence-based medicine in the field of pediatric transfusion is challenging due to the small number of experts and the challenge of designing research for such a vulnerable population. This chapter addresses core concepts in pediatric transfusion medicine, including: guidelines for the administration of blood products and component therapy; the associated relevant principles of immunology and hematology, and special considerations for certain pediatric populations.

BACKGROUND Patients undergoing therapeutic plasma exchange (TPE) may present with risks for hemorrhage or thrombosis. Use of replacement fluids devoid of coagulation factors will decrease factor levels and platelet levels. There are no established guidelines for hemostasis management in these situations. MATERIALS AND METHODS A survey to evaluate current hemostasis management practice during TPE was conducted using online survey software. One response per institution was analyzed based on a hierarchical algorithm, excluding membrane filtration users, resulting in a maximum of 107 respondents. Descriptive analysis was performed with results reported as the number and frequency (%) of respondents to each question. RESULTS Apheresis Medicine physicians, alone (59.4%) or jointly with the requesting provider (29.2%), choose the replacement fluid. Based on a theoretical patient case receiving five TPEs approximately every other day, the percent of respondents who would use albumin with or without normal saline was 94.7% with no history of a bleeding or clotting disorder, 1.1% with active bleeding, and 8.8% with hypofibrinogenemia (

Critically ill children can develop bleeding complications when treated with heparin-like drugs. These events are usually attributed to the anticoagulant activity of these drugs. However, previous studies showed that fibroblast growth factor-2 (FGF-2), a heparin-binding growth factor released in the circulation of these patients, could precipitate intestinal hemorrhages in mice treated with the heparin-like drug pentosan polysulfate (PPS). Yet very little is known about how FGF-2 induces bleeding complications in combination with heparin-like drugs. Here, we examined the mechanisms by which circulating FGF-2 induces intestinal hemorrhages in mice treated with PPS. We used a well-characterized mouse model of intestinal hemorrhages induced by FGF-2 plus PPS. Adult FVB/N mice were infected with adenovirus carrying Lac-Z or a secreted form of recombinant human FGF-2, and injected with PPS, at doses that do not induce bleeding complications per se. Mice treated with FGF-2 in combination with PPS developed an intestinal inflammatory reaction that increased the permeability and disrupted the integrity of submucosal intestinal vessels. These changes, together with the anticoagulant activity of PPS, induced lethal hemorrhages. Moreover, a genetically modified form of the endothelial ligand angiopoietin-1 (Ang-1*), which has powerful antipermeability and anti-inflammatory activity, prevented the lethal bleeding complications without correcting the anticoagulant status of these mice. These findings define new mechanisms through which FGF-2 and Ang-1* modulate the outcome of intestinal bleeding complications induced by PPS in mice and may have wider clinical implications for critically ill children treated with heparin-like drugs.

Purpose Wilson's disease is a rare autosomal recessive genetic disorder that results in accumulation of copper in the liver, brain, cornea and kidney. Therapeutic plasma exchange (TPE) has been used to remove copper and provide a bridge to liver transplantation. We report here the collective experiences through the ASFA apheresis registry on Wilson's disease. Methods The ASFA apheresis registry is a multi-center registry study. Both prospective and retrospective data, with the latter involving data collection back to January 2000 are entered in the registry. The registry includes patient demographics, apheresis procedural information, treatment schedules, and treatment outcomes and complications. Results A total of 10 patients (3 males and 7 females) with Wilson's disease treated between 2005 and 2013 were included. Median age of first diagnosis and first TPE were 16 and 17 years, respectively. Via central venous access, these patients underwent a total of 43 TPEs; the median number of TPE procedures per patient was 3.5. All of the TPEs used ACD-A as anticoagulation, 42/43 TPEs targeted 1–1.25 plasma volumes, and 41/43 TPEs were performed with 100% fluid balance. Post TPE procedures, 9 patients underwent liver transplantation; all 10 patients had at least a 6-month survival. Conclusions All 10 patients with Wilson's disease who underwent TPE had a positive outcome in terms of 6-month survival. In this first report of the ASFA apheresis registry study, we have demonstrated the value of using this registry to collect apheresis-related patient outcomes from multiple centers. J. Clin. Apheresis, 2015. © 2015 Wiley Periodicals, Inc.

BACKGROUND Kawasaki disease (KD) is an idiopathic, multisystem disorder characterized by vasculitis of arteries, veins, and capillaries, affecting pediatric patients, and is the leading cause of acquired heart disease in childhood. The mainstays of therapy for KD are high-dose intravenous immunoglobulin (IVIG) and aspirin, which are thought to prevent or modify the most serious cardiac sequelae. A well-documented complication of high-dose IVIG infusion in adults is hemolytic anemia due to passive transfer of anti-A and anti-B. Risk factors for hemolysis in another case series included patient blood group (group A, B, or AB), a high cumulative dose of IVIG, and concomitant inflammation documented by one or more markers like ferritin, fibrinogen, erythrocyte sedimentation rate, or C-reactive protein. STUDY DESIGN AND METHODS A 3-year retrospective case review of patients previously recognized with apparent IVIG-related hemolytic anemia identified by standard blood bank testing was performed at a tertiary care pediatric hospital. RESULTS Five patients were identified with severe anemia each requiring RBC transfusion for anemia. All five patients demonstrated a positive direct antiglobulin testing. Four of five patients had anti-A, anti-B, and/or anti-A1 with elution assays. All patients had signs of extravascular hemolysis with reticulocytosis, spherocytosis, and other hemolysis markers. One child died. CONCLUSION Our cases represent dose-dependent hemolysis caused by IVIG in association with severe anemia requiring transfusion with an average yearly incidence rate of 0.36%. Hemolysis is an underrecognized complication of IVIG administration. KD patients are at greater risk for anemia because of their lower baseline hemoglobin concentration, underlying acute inflammation, and oxygen requirements during acute illness.

Extracorporeal photopheresis (ECP) is an effective therapy in children with refractory graft-versus-host disease (GVHD). The two most frequently used instruments are UVAR-XTS® and CELLEX®. We performed a retrospective chart review of ten patients who underwent ECP with both UVAR-XTS® and CELLEX® instruments for steroid-refractory acute or chronic GVHD to compare instrument run times, percentages of cells treated, and complication rates. We found that compared to the UVAR-XTS® instrument, use of the CELLEX® instrument resulted in shorter run times, increased percentage of mononuclear cells treated, reduced incidence of line occlusions requiring TPA treatment, and decreased incidence of patient-related complications.

Introduction Paediatric apheresis (PA) has distinct characteristics compared to adult apheresis and requires specialized knowledge and experience to perform safely, particularly in low-weight patients. As evidence-based medicine advances the field of therapeutic apheresis, increased attention must be paid to paediatric patients with conditions for which apheresis is indicated. Methods An electronic survey of >5000 potential participants throughout the world was conducted to ascertain the scope and the current state of practice. Results The survey elicited 159 responses from 12 countries; 107 of the responses provided sufficient information for analysis. Participants performed an average of 176 PA procedures/year (range 1–2000). The types of PA procedures were therapeutic plasma exchange (TPE, 92% of centres), red cell exchange (RCE, 86%), leucocyte depletion (LD, 87%) and peripheral blood hematopoietic progenitor cell collection (HPC, 72%). More than 65% of the centres had treated children older than 5 years with PA. Many centres had also performed PA on younger children; 40% have treated patients

Development of hematology analyzers has been predicated on the use of adult blood specimens without consideration for the unique morphologic and cellular content seen in pediatric patient populations. Because both dramatic qualitative and quantitative cellular changes occur in red and white blood cells and platelets from birth to early adulthood, development of pediatric reference intervals is necessary. Because testing is often performed on a small volume of blood, laboratories are required to develop unique approaches in specimen handling and analysis. Many newer instruments offer alternative cellular analysis allowing for unique insights into the hematopoietic response in disease and nondisease states.

Congenital malaria is rare in the United States, but is an important diagnosis to consider when evaluating febrile infants. Herein, we describe a case of congenital Plasmodium falciparum malaria in a 2-week-old infant born in the United States to a mother who had emigrated from Nigeria 3 months before delivery.

Pediatric cardiac transplant patients with antibody-mediated rejection (AMR) often undergo therapeutic plasma exchange (TPE) to remove pathologic donor specific antibodies (DSA). In cases where DSA persist, it is unclear how long TPE should be continued. We report a case of a 17-year-old cardiac transplant patient with AMR where use of a C1q complement fixing antibody assay helped guide TPE cessation. This report adds to the existing literature that highlights the potential clinical significance of C1q antibodies in AMR management.

Encephalopathic neonates undergoing therapeutic hypothermia have increased risk for coagulopathy secondary to perinatal asphyxia and effects of cooling on the coagulation enzyme cascade. Thromboelastography (TEG) allows for a comprehensive assessment of coagulation that can be regulated for temperature. TEG has not been previously evaluated in newborns undergoing hypothermia treatment.Encephalopathic neonates treated with systemic hypothermia were enrolled in this prospective observational study. Daily blood specimens were collected for standard coagulation tests and platelet counts during hypothermia and after rewarming. Concurrent TEG assays were performed at 33.5 and 37.0 °C for comparison.A total of 48 paired TEGs from 24 subjects were performed. Forty percent of the subjects were males, the mean (± SD) birth weight was 3.2 ± 0.7 kg, and the mean gestational age was 38.4 ± 1.4 wk. TEG results differed significantly between assays performed at 37.0 vs. 33.5 °C, indicating more impaired coagulation at 33.5 °C. TEG parameters clot kinetics, angle, maximum amplitude (MA), and coagulation index were significantly associated with clinical bleeding (P0.05). These remained significant (except for MA) after controlling for transfusion therapy.TEG results are affected by temperature, consistent with the known association of hypothermia with coagulopathy. Several TEG parameters are predictive of clinical bleeding in newborns undergoing hypothermia. Selected cutpoints to predict bleeding risk are temperature dependent.

Blood banking/immunohematology is an area of laboratory medicine that involves the preparation of blood and blood components for transfusion as well as the selection and monitoring of those components following transfusion. The preparation, modification, and indications of both traditional and newer products are described in this review, along with special considerations for neonates, patients undergoing hematopoietic stem cell transplantation, those with sickle cell disease, and others. Immunohematological techniques are critical in the provision of blood and blood products and are briefly discussed.

Introduction: Pediatric apheresis (PA) has distinct characteristics compared to adult apheresis, and requires specialized knowledge and experience to perform safely, particularly in low-weight patients. As evidence-based medicine advances the field of therapeutic apheresis, increased attention must be paid to pediatric patients with conditions for which apheresis is indicated. Methods: An electronic survey of >5,000 potential participants throughout the world was conducted to ascertain the scope and the current state of practice. Results: The survey elicited 159 responses from 12 countries; 107 of the responses provided sufficient information for analysis. Participants performed an average of 176 PA procedures/year (range: 1–2,000). The types of PA procedures were therapeutic plasma exchange (92% of centers), red cell exchange (86%), leukocyte depletion (87%) and peripheral blood hematopoietic progenitor cell collection (72%). More than 65% of the centers had treated children older than 5 years with PA. Many centers had also performed PA on younger children; 40% have treated patients

Introduction Neonatal extracorporeal membrane oxygenation ECMO has been clinically used for the last 25 y. It has been an effective tool for both cardiac and non cardiac conditions. The impact of ethno-demographic changes on ECMO outcomes however remains unknown. We evaluated a single institution's experience with non cardiac neonatal ECMO over a 28-y period. Methods A retrospective review of all neonates undergoing noncardiac ECMO between the y 1984 and 2011 was conducted and stratified into year groups I, II, III (≤1990, 1991–2000, and ≥2001). Demographic, clinical, and outcome data were collected. The patient specifics, ECMO type, ECMO length, blood use, complications, and outcomes were analyzed. Univariate, bivariate, and multivariate analyses were then performed. Results Data was available for 827 patients. The number of African-American and Hispanic patients increased over the last 27 y (27.5% versus 45.0% and 3.3% versus 21.5%, year group I versus year group III, respectively). The proportion of congenital diaphragmatic hernia (CDH) patients by ethnicity also increased for African-Americans and Hispanics between the two year groups (22.0% to 33.0% and 4.9% to 33.0%, respectively). Similar pattern was noted for non-CDH diagnoses. Low birth weight, low APGAR scores, CDH, primary pulmonary hypertension, central nervous system hemorrhage, and ECMO were independent predictors of mortality. Ethnicity, in itself however, was not associated with mortality on adjusted analysis. Conclusion More African-Americans and Hispanics have required ECMO over the years with a concurrent decrease in the number of Caucasians. While ethnicity was not an independent predictor of mortality, it appears to be a surrogate for fatal but sometime preventable diagnoses among minorities. Further investigations are needed to better delineate the reason behind this disparity.

Since 2012, a number of case reports have described the occurrence of thrombotic microangiopathy (TMA) following IV abuse of extended-release oxymorphone hydrochloride (Opana ER), an oral opioid for long-term treatment of chronic pain. Here, we present unique clinical features of 3 patients and investigate IV exposure to the tablet’s inert ingredients as a possible causal mechanism. Guinea pigs were used as an animal model to understand the hematopathologic and nephrotoxic potential of the inert ingredient mixture (termed here as PEO+) which primarily contains high-molecular-weight polyethylene oxide (HMW PEO). Microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury were found in a group of 3 patients following recent injection of adulterated extended-release oxymorphone tablets. Varying degrees of cardiac involvement and retinal ischemia occurred, with TMA evident on kidney biopsy. A TMA-like state also developed in guinea pigs IV administered PEO+. Acute tubular and glomerular renal injury was accompanied by nonheme iron deposition and hypoxia-inducible factor-1α upregulation in the renal cortex. Similar outcomes were observed following dosing with HMW PEO alone. IV exposure to the inert ingredients in reformulated extended-release oxymorphone can elicit TMA. Although prescription opioid abuse shows geographic variation, all physicians should be highly inquisitive of IV drug abuse when presented with cases of TMA.

Ceftriaxone-induced immune hemolytic anemia (CIHA) is the second most common cause of drug-induced hemolytic anemia. Prompt recognition of this drug reaction is essential because brisk hemolysis can be deadly. The extent to which ceftriaxone antibodies persist after CIHA is unknown; rechallenging patients who have experienced CIHA is not recommended. We report a case of CIHA in a neurooncology patient, which is the first to show anticeftriaxone antibodies with Rh specificity and persisted for 8 months after the drug reaction. These findings have implications for understanding the mechanism of CIHA.

To develop normative ranges for citrate-modified and heparinase-modified thromboelastography (TEG) in term neonates.Prospective observational study.An outborn neonatal and cardiac intensive care unit in a free-standing academic children's hospital.Thirty term neonates were enrolled as control subjects. Seventeen infants with clinically documented bleeding requiring blood transfusion were enrolled in the comparison group.Citrate-modified and heparinase-modified TEG parameters were calculated from blood specimens drawn via peripheral arterial stick or arterial line.TEG in neonates differs from older children and adults; clotting time (R) and clot kinetics (K) values are generally lower while fibrinolysis or rate of clot breakdown (LY30) and coagulation index (CI) are often higher in neonates. TEG values in term neonates calculated as median (Q1-Q3) are as follows: R 4.150 (3.200-6.200), K 1.550 (1.200-1.800), α angle (α) 70.100 (66.000-72.900), maximum amplitude (MA) 61.850 (59.400-66.000), LY30 1.050 (0.100-1.600) and CI 1.950 (0.100 to 2.900). Cut points selected for optimal predictive value for bleeding using receiver operating curve analyses were R6.3 (sensitivity 82.4%, specificity 80%); K2.5 (sensitivity 82.4%, specificity 96.7%); α59 (sensitivity 82.4%, specificity 96.7%); MA57 (sensitivity 82.4%, specificity 86.7%); CI-0.15 (sensitivity 88.2%, specificity 83.3%).The reference ranges and cut points for citrate-modified and heparinase-modified TEG can be used to diagnose and evaluate coagulopathy in term neonates.

The discipline of Transfusion Medicine (also known as “Blood Banking”) includes: (i) the collection, testing, processing, and preparation of blood and blood components; (ii) the selection of the most appropriate products and transfusion practice based on laboratory findings and patient need; and (iii) the monitoring of the effectiveness of transfusion as modified by disease, physiological status, or the procedure(s) performed. Certain patient groups (e.g., neonates, oncology patients, hematopoietic progenitor cell transplant recipients, those with sickle cell disease, and others); often require complex pretransfusion processing and specialized product selection and modification.

Milestones represent the essential knowledge, skills, and attitudes required for the practice of a medical discipline. Defining these milestones for each medical specialty has become a focus for the American Council of Graduate Medical Education (ACGME). Practitioners of Apheresis Medicine come from a variety of medical specialties making it challenging to establish the essential educational milestones for all. The American Society for Apheresis (ASFA) has an interest in promoting standards of excellence for Apheresis Medicine. ASFA's Physician's Curriculum Content Committee is a group of physician educators in the field of Apheresis Medicine, both donor and therapeutic, from across the United States, who have met regularly for several years to discuss the appropriate educational milestones in Apheresis training. The committee members teach residents and fellows from Pathology, Transfusion Medicine, Hematology/Oncology, Nephrology and other specialties. In this document, we have outlined the basic set of Apheresis milestones required in the ACGME defined competency areas of Patient Care and Medical Knowledge. We have also recommended methods of evaluation and estimated the time necessary for the acquisition of these cognitive and behavioral elements.