Evaluation of the efficacy and safety of amustaline/glutathione pathogen-reduced RBCs in complex cardiac surgery: the Red Cell Pathogen Inactivation (ReCePI) study-protocol for a phase 3, randomized, controlled trial.

BACKGROUND: Red blood cell (RBC) transfusion is a critical supportive therapy in cardiovascular surgery (CVS). Donor selection and testing have reduced the risk of transfusion-transmitted infections; however, risks remain from bacteria, emerging viruses, pathogens for which testing is not performed and from residual donor leukocytes. Amustaline (S-303)/glutathione (GSH) treatment pathogen reduction technology is designed to inactivate a broad spectrum of infectious agents and leukocytes in RBC concentrates. The ReCePI study is a Phase 3 clinical trial designed to evaluate the efficacy and safety of pathogen-reduced RBCs transfused for acute anemia in CVS compared to conventional RBCs, and to assess the clinical significance of treatment-emergent RBC antibodies. METHODS: ReCePI is a prospective, multicenter, randomized, double-blinded, active-controlled, parallel-design, non-inferiority study. Eligible subjects will be randomized up to 7 days before surgery to receive either leukoreduced Test (pathogen reduced) or Control (conventional) RBCs from surgery up to day 7 post-surgery. The primary efficacy endpoint is the proportion of patients transfused with at least one study transfusion with an acute kidney injury (AKI) diagnosis defined as any increased serum creatinine (sCr) level ≥ 0.3 mg/dL (or 26.5 µmol/L) from pre-surgery baseline within 48 ± 4 h of the end of surgery. The primary safety endpoints are the proportion of patients with any treatment-emergent adverse events (TEAEs) related to study RBC transfusion through 28 days, and the proportion of patients with treatment-emergent antibodies with confirmed specificity to pathogen-reduced RBCs through 75 days after the last study transfusion. With ≥ 292 evaluable, transfused patients (> 146 per arm), the study has 80% power to demonstrate non-inferiority, defined as a Test group AKI incidence increase of no more than 50% of the Control group rate, assuming a Control incidence of 30%. DISCUSSION: RBCs are transfused to prevent tissue hypoxia caused by surgery-induced bleeding and anemia. AKI is a sensitive indicator of renal hypoxia and a novel endpoint for assessing RBC efficacy. The ReCePI study is intended to demonstrate the non-inferiority of pathogen-reduced RBCs to conventional RBCs in the support of renal tissue oxygenation due to acute anemia and to characterize the incidence of treatment-related antibodies to RBCs.

Freeze-dried platelets are a promising alternative in bleeding thrombocytopenic patients with hematological malignancies.

Thrombosomes are trehalose-stabilized, freeze-dried group O platelets with a 3-year shelf life. They can be stockpiled, rapidly reconstituted, and infused regardless of the recipient's blood type. Thrombosomes thus represent a potential alternative platelet transfusion strategy. The present study assessed the safety and potential early signals of efficacy of Thrombosomes in bleeding thrombocytopenic patients. We performed an open-label, phase 1 study of single doses of allogeneic Thrombosomes at three dose levels in three cohorts, each consisting of eight patients who had hematologic malignancies, thrombocytopenia, and bleeding. Adverse events, dose-limiting toxicities (DLTs), World Health Organization (WHO) bleeding scores, and hematology values were assessed. No DLTs were reported. The median age was 59 years (24-71). Most patients had AML (58%) or ALL (29%), followed by MDS (8%) and myeloproliferative neoplasm (4%). The WHO scores of 22 patients who were actively bleeding at a total of 27 sites at baseline either improved (n = 17 [63%]) or stabilized (n = 10 [37%]) through day 6. Twenty-four hours after infusion, 12 patients (50%) had a clinically significant platelet count increase. Of eight patients who received no platelet transfusions for 6 days after Thrombosomes infusion, 5 had a clinically significant increase in platelet count of ≥5000 platelets/µL and 2 had platelet count normalization. Thrombosomes doses up to 3.78 × 108 particles/kg demonstrated safety in 24 bleeding, thrombocytopenic patients with hematological malignancies. Thrombosomes may represent an alternative to conventional platelets to treat bleeding. A phase 2 clinical trial in a similar patient population is underway.

Increasing hemoglobin concentration with an artificial oxygen carrier improves severe anemia-induced degraded cognitive function.

ABSTRACT: Before death, patients commonly experience impaired consciousness for a significant period, frequently preventing family and others from final interactions with the patient. Some of these episodes of cognitive impairment may be treatable, with treatment not offered owing to the perception of ultimate futility or expense, or both. One of the causes of terminal loss of consciousness or decreased lucidity can be inadequate cerebral oxygen delivery. We report five cases from four institutions where an infusion of a hemoglobin-based oxygen carrier to patients who were unconscious or not lucid owing to acute severe anemia (hemoglobin range, 2.1-5.2 g/dL) resulted in awakening or lucidity. We review briefly human cognitive function and anemia and remark about the use of a hemoglobin-based oxygen carrier for acute severe anemia when red cell transfusion is not an option.

Malignant risk of indeterminate pediatric thyroid nodules-An institutional experience.

BACKGROUND: Few studies focus on pediatric thyroid nodules categorized under indeterminate diagnostic categories. The current study was conducted to assess the risk of malignancy of indeterminate pediatric thyroid nodules. METHODS: A search of the institutional electronic pathology database from 01/2011 to 09/2018 was performed to identify pediatric (<21 years old) thyroid nodules that were interpreted as follicular lesion of undetermined significance (FLUS), suspicious for follicular neoplasm (SFN), or suspicious for malignancy (SFM) and subsequently managed with surgery, repeat fine-needle aspiration (FNA), or ≥ 6 months of clinical/imaging monitoring. Results of follow-up (F/U) surgical resections and repeat FNA/Afirma tests, and clinical and radiologic data were collected. RESULTS: We identified 46 cases from 42 patients (11-20 years old, 33 females and 9 males), including 30 FLUS, 10 SFN, and 6 SFM. Twenty-five FLUS, ten SFN, and six SFM cases underwent surgery. The histology revealed carcinomas in 36% of FLUS, 20% of SFN, and 100% of SFM categories; follicular adenomas in 32% of FLUS and 80% of SFN categories; and benign nodules in 32% of FLUS category. All five nonsurgically treated FLUS cases were considered benign based on the findings of repeat FNA/Afirma tests (n = 3, 3-22 months F/U) or clinical/radiologic exams (n = 2, 8-12 months F/U). CONCLUSIONS: Based on a limited study cohort, malignancy was identified in 36%, 20%, and 100% of surgically managed pediatric thyroid nodules categorized as FLUS, SFN, and SFM, respectively; suggesting a markedly higher malignant rate than the implied malignant risk for FLUS and SFM categories in adults.

Performance and safety of femoral central venous catheters in pediatric autologous peripheral blood stem cell collection.

INTRODUCTION: Autologous peripheral blood hematopoietic progenitor cell collection (A-HPCC) in children typically requires placement of a central venous catheter (CVC) for venous access. There is scant published data regarding the performance and safety of femoral CVCs in pediatric A-HPCC. METHODS: Seven-year, retrospective study of A-HPCC in pediatric patients collected between 2009 and January 2017. Inclusion criteria were an age ≤ 21 years and A-HPCC using a femoral CVC for venous access. Femoral CVC performance was examined by CD34 collection rate, inlet rate, collection efficiency (MNC-FE, CD34-FE), bleeding, flow-related adverse events (AE), CVC removal, and product sterility testing. Statistical analysis and graphing were performed with commercial software. RESULTS: A total of 75/119 (63%) pediatric patients (median age 3 years) met study criteria. Only 16% of children required a CVC for ≥ 3 days. The CD34 collect rate and CD34-FE was stable over time whereas MNC-FE decreased after day 4 in 80% of patients. CD34-FE and MNC-FE showed inter- and intra-patient variability over time and appeared sensitive to plerixafor administration. Femoral CVC showed fewer flow-related AE compared to thoracic CVC, especially in pediatric patients (6.7% vs. 37%, P = 0.0005; OR = 0.12 (95%CI: 0.03-0.45). CVC removal was uneventful in 73/75 (97%) patients with hemostasis achieved after 20-30 min of pressure. In a 10-year period, there were no instances of product contamination associated with femoral CVC colonization. CONCLUSION: Femoral CVC are safe and effective for A-HPCC in young pediatric patients. Femoral CVC performance was maintained over several days with few flow-related alarms when compared to thoracic CVCs.

Use of allogeneic apheresis stem cell products as an interlaboratory proficiency challenge.

BACKGROUND: AABB Standards requires that laboratories participate in a proficiency test (PT) program for critical analytes. Institutions can purchase commercial PT materials; however, PT can also be performed through interlaboratory exchange. We investigated the utility of allogeneic hematopoietic progenitor cell apheresis (HPC-A) products as an interlaboratory PT challenge for total nucleated cell count (TNC) and CD34 assessment. STUDY DESIGN AND METHODS: Three-year retrospective and comparative review of unrelated allogeneic HPC-A products received by the University of Michigan between January 2011 and December 2013. Internal TNC and CD34 count were compared to the external collecting facility by paired t test and linear regression. The absolute and percent difference between external and internal counts and 95% limits of agreeability (95% LA) were determined. Results were analyzed relative to donor center location (international, domestic), time zone (domestic), and calendar year. RESULTS: There was a strong correlation between internal and external TNC, regardless of donor center location or year. For CD34, there was a good correlation between centers (R = 0.88-0.91; slope = 0.95-0.98x) with a median difference of -1% (95% LA, -50%, +47%). This was considerably better than commercial PT challenges, which showed a persistent negative bias for absolute CD34 and CD3 counts. CONCLUSION: Allogeneic HPC-A products represent an interlaboratory PT exchange for all critical analytes, including TNC and CD34 count, cell viability, and sterility. Allogeneic HPC-A products, which are fresh and transported under validated conditions, are less subject to preanalytical variables that may impact commercial PT samples such as aliquoting and sample homogeneity, commercial additives, and sample stability during manufacturing and transport.

Procedure-related complications and adverse events associated with pediatric autologous peripheral blood stem cell collection.

INTRODUCTION: Autologous peripheral blood hematopoietic progenitor cell collection (A-HPCC) in pediatric patients is considered relatively safe although technically challenging. Very little is known regarding the incidence, risk factors and impact of procedure-related adverse events (AE) on pediatric A-HPCC outcomes. METHODS: Prospective 4.5-year review of AE associated with pediatric A-HPCC. AE were graded by severity and type. Potential demographic and procedural risk factors, and the impact on product quality, were compared by t-test, chi-square, and linear regression. RESULTS: Sixty-two children underwent 110 A-HPCC, including 36 (58%) under 20 kg. Fifty-five AE were documented in 25.4% A-HPCCs and 39% of children (citrate 25%, access 19%, technical 11%, cardiovascular 0%, allergic 1.8%). No AE were noted in children < 10 kg anticoagulated with heparin. Access and technical AE accounted for 73% of severe AE, with line-related problems underlying most technical AE (87.5%, P = 0.006). AE were more likely in older (P = 0.012), heavier patients (P = 0.02), who frequently required more than one A-HPCC (P = 0.012). In contrast, young children were more likely to experience citrate AE with gastrointestinal symptoms (median age, 6 years; P = 0.076). AE had no impact on CD34 collection rates; however, mean CD34 yields (4.2 vs. 20.4 million/kg; P = 0.0035) were decreased in patients with technical AE due to lower peripheral CD34 counts and a high number of aborted procedures (37%). CONCLUSION: Venous access and flow-related issues are a major factor associated with moderate and severe AE, effecting ∼10% of patients. AE are more frequent with increasing patient age, weight, and number of procedures. J. Clin. Apheresis 32:35-48, 2017. © 2016 Wiley Periodicals, Inc.

Metastatic ductal carcinoma of the breast to the thyroid gland diagnosed with fine needle aspiration: A case report with emphasis on morphologic and immunophenotypic features.

Metastases to the thyroid are uncommon [<0.2% of thyroid fine needle aspirations (FNA)]. Of metastases to the thyroid, breast carcinoma is relatively common. The diagnosis of metastasis to the thyroid has important therapeutic and prognostic implications. To our knowledge, a morphologic and immunophenotypic comparison of metastatic ductal carcinoma of the breast and primary thyroid carcinomas has not been reported. Here, we report the case of a 37-year-old female with a history of metastatic ductal carcinoma of the breast (modified Bloom-Richardson grade 2; ER+, PgR+, HER2+) diagnosed 6 years prior. She developed hoarseness, prompting a CT scan. Multiple thyroid nodules were found, including a 1.5 cm hypoechoic, solid, irregularly-shaped nodule. On FNA, cells were arranged singly and in crowded groups, varied in size and degree of pleomorphism, and exhibited rare nuclear grooves, inconspicuous nucleoli, and rare intracytoplasmic lumina with no nuclear pseudoinclusions or colloid (Figs. 1A and B). These findings raised the differential of papillary thyroid carcinoma (Fig. 1C), follicular neoplasm (Fig. 1D), medullary carcinoma (Fig. 1E), parathyroid (Fig. 1F), and metastatic breast carcinoma. Immunostaining for GATA-3 (+), ER (+), PAX-8 (-), and TTF-1 (-) was consistent with metastatic breast carcinoma (Fig. 2). We conclude that metastatic breast carcinoma to the thyroid may morphologically mimic primary thyroid carcinoma on FNA; a panel of immunomarkers, such as GATA-3, hormonal marker(s), PAX-8, and TTF-1, may be useful in some cases. GATA-3 immunostaining for metastatic breast carcinoma was helpful in our case and has not been previously reported in a thyroid metastasis sampled by FNA. Diagn. Cytopathol. 2016;44:530-534. © 2016 Wiley Periodicals, Inc.

Comparison of two leukocytapheresis protocols in a case of idiopathic hypereosinophilic syndrome.

BACKGROUND: Hypereosinophilic syndrome (HEOS) is rare, and the efficacy of leukocytapheresis in this context is unclear. We here report the successful treatment of a patient with idiopathic HEOS with four leukocytapheresis procedures using two protocols. CASE: A 4-year-old female presented with cardiac and respiratory dysfunction, and WBC of 225 K/µL with 96% eosinophils. Leukocytapheresis was started after initiation of methylprednisolone and hydroxyurea. She received two leukocytapheresis with polymorphonuclear cell (PMN) protocol, followed by initiation of imatinib therapy, then two leukocytapheresis with mononuclear cell (MNC) protocol. After the fourth leukocytapheresis, her WBC decreased to 69 K/µL with 82% eosinophils. She was discharged on hospital day 21 under stable condition with WBC of 22 K/µL with 86% eosinophils. WBC count and eosinophil percentage continued to decrease, and were 6.4 K/µL and 52% by 2 weeks and 3.9 K/µL and 4.9% by 3 months after discharge, respectively. FINDINGS: WBC and absolute eosinophil (aEO) counts decreased by an average of 29.0 and 30.4% per leukocytapheresis, respectively. Normalized to estimated blood volume, procedures with PMN and MNC protocols changed, on average, WBC by -10.7 and -12.1%, aEO by -10.4 and -13.4%, platelet by -8.1 and -19.2%, and fluid balance by -129 and -47 mL, respectively. CONCLUSION: Leukocytapheresis was effective in decreasing WBC and aEO counts in HEOS, with PMN and MNC protocols achieving similar reductions. However, PMN protocol resulted in greater negative fluid balance and MNC protocol resulted in greater platelet loss. J. Clin. Apheresis 31:481-489, 2016. © 2015 Wiley Periodicals, Inc.

Maintenance plasma exchange treatment for muscle specific kinase antibody positive myasthenia gravis patients.

BACKGROUND: Anti-muscle specific kinase antibody positive myasthenia gravis (MuSK MG) is often characterized by a relatively severe and progressive course, refractoriness to standard myasthenia gravis (MG) medications, and an increased risk of myasthenic crisis. We report here successful management of three MuSK MG patients using maintenance therapeutic plasma exchange (TPE) treatment for up to 4.5 years. MATERIALS: The study was a 5-year retrospective review of all MG patients treated with TPE between 2008 and 2013 at University of Michigan. Inclusion criteria of MuSK MG were positive for anti-MuSK antibodies and a diagnosis of MuSK MG by staff neurologists. Patient data included age, gender, diagnostic testing results, medications, and the dates and response to TPE treatments. RESULTS: A total of 153 MG patients underwent at least one course of TPE between 2008 and 2013. A total of 12 patients (7.8%) were positive for anti-MuSK antibodies. Patients were predominantly female (83.3%) and a median age of onset was 46-years old. Three MuSK MG patients were successfully managed with maintenance TPE. CONCLUSION: Maintenance TPE may be an effective option for MuSK MG patients. The key of successful maintenance treatment at our institution has been to tailor the TPE frequency for each individual, and to modify the treatment interval in conjunction with medical management.

A case of extravascular hemolysis with Tk-activation.

KEY CLINICAL MESSAGE: A 50-year-old female with ovarian cancer for 4 years presented with abdominal pain. She started antibiotics for possible infection, and developed extravascular hemolysis. All antigen detection tests were negative, but lectin panel suggested Tk-activation. Additional laboratory testing in conjunction with blood bank is essential to investigate rare cause of hemolysis.

The impact of recent vincristine on human hematopoietic progenitor cell collection in pediatric patients with central nervous system tumors.

BACKGROUND: Central nervous system (CNS) malignancies represent 20% of all childhood cancers. To improve outcomes in infants and children with high-risk disease, treatment can include adjuvant chemotherapy and early autologous peripheral blood human progenitor cell collection (AHPCC), followed by high-dose chemotherapy and stem cell rescue. In many protocols, postoperative chemotherapy includes the administration of weekly vincristine (VCR) between induction chemotherapy cycles, regardless of scheduled AHPCC. We observed anecdotal AHPCC failures in children receiving midcycle VCR (MC-VCR). STUDY DESIGN AND METHODS: The study was an 8-year retrospective chart review of all children with a CNS malignancy and who underwent AHPCC. Information included patient demographic and clinical data, mobilization regimen, VCR administration, product yields, infusion toxicity, and patient charges. Data were analyzed relative to MC-VCR administration. Graphics and statistical analysis (t-test, chi-square, linear regression) were performed with commercial software. RESULTS: Twenty-four patients and 47 AHPCCs were available for analysis. Nine patients (37%) received MC-VCR within 7 days of scheduled AHPCC. MC-VCR was associated with delayed marrow recovery (17.9 days vs. 14.9 days, p=0.0012), decreased median peripheral CD34 counts (75 × 10(6) CD34/L vs. 352 × 10(6) CD34/L, p=0.03), decreased median CD34 yields (2.4 × 10(6) CD34/L vs. 17.8 × 10(6) CD34/kg, p=0.08), more AHPCCs per mobilization (2.9 vs. 1.1, p=0.01), and an increased rate of remobilization (33% vs. 6%). Mean patient charges were 2.5× higher in patients receiving MC-VCR than controls (p=0.01). CONCLUSION: MC-VCR should be withheld before scheduled AHPCC to optimize CD34 collection.

How do I allocate blood products at the end of life? An ethical analysis with suggested guidelines.

Blood products are scarce resources requiring prudent and reasoned allocation. The utilization of red blood cells and platelets in terminally ill patients can be complicated and requires guidelines tempered by individualized considerations. Representative cases are discussed in which blood products are requested or utilized by patients at the end of life. Relevant literature is reviewed and ethical issues pertaining to each case are discussed. A practical approach to blood product utilization at the end of life is suggested.

Group consensus review minimizes the diagnosis of "follicular lesion of undetermined significance" and improves cytohistologic concordance.

We conducted a group consensus review of thyroid aspirates that were previously interpreted as "atypia of undetermined significance/follicular lesion of undetermined significance" (AUS/FLUS) and followed by surgical interventions. The study aimed to investigate if consensus review would minimize the diagnosis of AUS/FLUS with an optimal interobserver agreement and also promote a better cytohistologic concordance. A group of reviewers who were blinded to the corresponding histologic findings simultaneously evaluated a total of 50 aspirates at a multiheaded light microscope. Using the Bethesda System for Reporting Thyroid Cytopathology as a guideline, a consensus interpretation was reached upon review of each aspirate. Interobserver agreement was calculated and recorded. The cytohistologic correlation was then performed between the consensus interpretation and the corresponding histologic diagnosis. The consensus review reclassified 26 (52%) aspirates as non-neoplasia/benign, 10 (20%) as follicular neoplasm/suspicious for a follicular neoplasm, 1 (2%) as papillary thyroid carcinoma, and 2 (4%) as nondiagnostic. Eleven (22%) aspirates remained AUS/FLUS. The interobserver agreement across the five diagnostic categories ranged from 71.6% to 100% with an average level of 88.8%. Cytohistologic concordance was achieved in 24 of 26 (92.3%) and 9 of 11 (81.8%) aspirates that were reclassified as non-neoplasia/benign and neoplasia/malignancy, respectively. A diagnostic accuracy of 89.2% (33/37) was obtained in reclassified cases. In conclusion, the group consensus review minimized AUS/FLUS, offered an optimal level of interobserver agreement, and most importantly, promoted excellent cytohistologic concordance in reclassified cases and, therefore, could play a substantial role in the future in reducing reaspiration and/or unnecessary surgeries.

Evidence-based practice guidelines for plasma transfusion.

BACKGROUND: There is little systematically derived evidence-based guidance to inform plasma transfusion decisions. To address this issue, the AABB commissioned the development of clinical practice guidelines to help direct appropriate transfusion of plasma. STUDY DESIGN AND METHODS: A systematic review (SR) and meta-analysis of randomized and observational studies was performed to quantify known benefits and harms of plasma transfusion in common clinical scenarios (see accompanying article). A multidisciplinary guidelines panel then used the SR and the GRADE methodology to develop evidence-based plasma transfusion guidelines as well as identify areas for future investigation. RESULTS: Based on evidence ranging primarily from moderate to very low in quality, the panel developed the following guidelines: 1) The panel suggested that plasma be transfused to patients requiring massive transfusion. However, 2) the panel could not recommend for or against transfusion of plasma at a plasma : red blood cell ratio of 1:3 or more during massive transfusion, 3) nor could the panel recommend for or against transfusion of plasma to patients undergoing surgery in the absence of massive transfusion. 4) The panel suggested that plasma be transfused in patients with warfarin therapy-related intracranial hemorrhage, 5) but could not recommend for or against transfusion of plasma to reverse warfarin anticoagulation in patients without intracranial hemorrhage. 6) The panel suggested against plasma transfusion for other selected groups of patients. CONCLUSION: We have systematically developed evidence-based guidance to inform plasma transfusion decisions in common clinical scenarios. Data from additional randomized studies will be required to establish more comprehensive and definitive guidelines for plasma transfusion.

A prospective randomized trial of two popular mononuclear cell collection sets for autologous peripheral blood stem cell collection in multiple myeloma.

BACKGROUND: The COBE Spectra AutoPBSC collection set (AUTO-kit; CaridianBCT) is a popular dual-stage collection set for peripheral blood progenitor (PBPC) collection. Although the AUTO-kit is purportedly equivalent to the white blood cell (WBC) collection set (WBC-kit) for PBPC collection, improved CD34 yields after switching from the AUTO-kit to the WBC-kit were anecdotally observed, particularly in patients with higher WBC counts. A prospective, randomized trial of the AUTO- and WBC-kits for PBPC collection in multiple myeloma (MM) patients was therefore designed. STUDY DESIGN AND METHODS: Sixty-eight MM patients were prospectively randomly assigned to either the WBC-kit or the AUTO-kit for PBPC collection. Primary study variables included the number of leukapheresis procedures per transplant, CD34/kg yield per procedure, and cumulative CD34/kg yield per mobilization cycle. Results were compared relative to collection kit and mobilization regimen. Statistics and graphics were performed with commercial software. RESULTS: CD34/kg yields were higher with the WBC-kit, with 94% of chemotherapy-mobilized MM patients collecting 6 million CD34/kg in a single mobilization (p = 0.06). The WBC-kit also had a faster CD34 collection rate relative to peripheral CD34 counts. The AUTO-kit was significantly sensitive to high WBC counts, with a 50% decrease in CD34 collection efficiency and CD34 collection rate. This effect was specific to MM and not observed in lymphoma patients. Granulocyte-colony-stimulating factor mobilization and the AUTO-kit were associated with an increased incidence and severity of infusion reactions. CONCLUSIONS: The WBC-kit performed consistently better than the AUTO-kit for PBPC collection in chemotherapy-mobilized MM patients, with fewer procedures per mobilization, superior collection rates, and a decreased incidence of infusion reactions.

Use of B-natriuretic peptide as a diagnostic marker in the differential diagnosis of transfusion-associated circulatory overload.

BACKGROUND: Transfusion-associated circulatory overload (TACO) occurs when the transfusion rate or volume exceeds the capacity of a compromised cardiovascular system. Characteristic symptoms and signs associated with TACO are neither sensitive nor specific. B-natriuretic peptide (BNP) is a 32-amino-acid polypeptide secreted from the cardiac ventricles in response to ventricular volume expansion and pressure overload. This study was performed to explore the usage of BNP in the differential diagnosis of TACO. STUDY DESIGN AND METHODS: Pre- and posttransfusion BNP levels were determined in 21 patients with suspected TACO and 19 control patients. The BNP was considered significant if the posttransfusion-to-pretransfusion ratio was at least 1.5 and the posttransfusion BNP level was at least 100 pg per mL. RESULTS: The BNP test has a sensitivity and specificity of 81 and 89 percent, respectively, in diagnosis of TACO. It has a positive predictive value of 89 percent, a negative predictive value of 81 percent, and an accuracy of 87 percent. In logistic regression analysis, BNP was found to have significant predictive power independent of other clinical variables in models predicting which patients had TACO. CONCLUSIONS: Our study suggests that in patients who present symptoms suggestive of TACO, BNP can be a useful adjunct marker in confirming volume overload as the cause of acute dyspnea and symptoms related to cardiovascular compromise.

Delayed platelet engraftment in group O patients after autologous progenitor cell transplantation.

BACKGROUND: Fucosylated glycans, including H-antigen, play critical roles in hematopoietic progenitor cell homing, adhesion, growth, and differentiation. H-active antigens are strongly expressed on CD34+ progenitor cells and committed megakaryocytic progenitors and may mediate adhesion to marrow stromal fibroblasts. We examined the possible influence of donor ABO type on platelet (PLT) engraftment after autologous peripheral blood progenitor cell transplant (PBPCT). STUDY DESIGN AND METHODS: A retrospective analysis of all patients who underwent a single autologous PBPCT between 1996 and 2000 were reviewed. Neutrophil and PLT engraftment were compared by patient ABO type and CD34+ cell dose by t test, chi-square test, analysis of variance, Kaplan-Meier probability, and log-rank test. RESULTS: Engraftment data was available in 195 patients. PLT engraftment was delayed in all patients, regardless of ABO type, at CD34+ PBPC doses of 2x10(6) to 3x10(6) per kg (p<0.001). When examined by ABO type, late PLT engraftment (PLT count>50x10(9)/L) was significantly delayed in group O patients relative to all non-group O patients (32.4 days vs. 19.6 days, p<0.001). Approximately 50 percent of group O patients required more than 40 days to achieve late PLT recovery (p<0.005). CONCLUSIONS: A group O phenotype may be associated with delayed PLT engraftment at lower CD34 doses.