A novel approach to improving efficiency and cost saving in preoperative blood preparation.

BACKGROUND: Preoperative ordering of blood products has been an area of optimization due to considerable variability among physicians; overpreparation can lead to extra costs and underpreparation of blood can potentially compromise patient safety. STUDY DESIGN AND METHODS: We examined the potential cost savings of extending the storage interval of a presurgical type-and-screen sample from 7 to 14 days, thereby reducing the need for a new specimen on the day of surgery. RESULTS: Sensitivity analysis showed annual cost savings for our institution to be an estimated $38,770 ($22,420-$73,120). CONCLUSION: These results are even more robust when incorporating the additional potential savings from improved operating room efficiency.

Using HLA typing to support patients with cancer.

BACKGROUND: The human leukocyte antigen (HLA) system plays a crucial role in immune function, and HLA testing is often needed in the support of patients with cancer. METHODS: We briefly review the published literature to clarify the nomenclature of the HLA system, currently available methods for HLA testing, and commonly used HLA assays. The uses of HLA testing in pharmacogenomics, disease association, platelet transfusion support, and in the management of both solid organ and hematopoietic stem cell transplantation are also reviewed. RESULTS: HLA testing is commonly performed for select patient populations, including patients with cancer and in those requiring solid organ and hematopoietic stem cell transplantation. CONCLUSION: Newer molecular typing methods have helped improve patient outcomes following hematopoietic stem cell transplantation.

A Case of Fatal Clostridium perfringens Sepsis with Massive Hemolysis in the Setting of a Coincidental Platelet Transfusion.

A 62-year-old woman with acute myeloid leukemia (AML) died of shock and massive hemolysis shortly after receiving two platelet transfusions at a routine clinic visit. Subsequent investigation into what was initially believed to be an acute hemolytic transfusion reaction secondary to platelet transfusions revealed that the patient died of Clostridium perfringens sepsis leading to massive hemolysis. Further investigation ruled out bacterially-contaminated platelets since a patient blood sample from 2 days prior had Clostridium species. The unusual findings and management considerations for this oncology patient are reviewed and compared with previously reported cases of C. perfringens transfusion-transmitted infections. Oncology patients may be especially susceptible to unusual presentations involving unusual pathogens.

A National Survey of Outpatient Platelet Transfusion Practice.

OBJECTIVES: Platelets are a limited resource frequently subject to inventory shortages. It benefits all to transfuse judiciously, according to evidence-based guidelines. Several organizations have published recommendations for platelet transfusions, but none specifically focused on outpatients. The Clinical Hemotherapy subsection of the Association for the Advancement of Blood & Biotherapies (AABB) Transfusion Medicine Subsection Coordinating Committee conducted a survey targeting outpatient transfusions to understand current practice in the United States. METHODS: To determine use of platelets in the outpatient setting, a survey was developed, piloted, validated, and distributed by email to 735 AABB members. Frequencies were calculated and free-text comments categorized. RESULTS: A total of 317 responses were received (43% response rate) from 44 states. Half the respondents' institutions have formal outpatient platelet guidelines. Slightly more than half the respondents (51%) with guidelines used a threshold of less than 10,000/µL when transfusing stable, afebrile outpatients, with 29% using less than 20,000/µL. Fewer than half (45%) monitored outpatient platelet use by prospective and retrospective audits, with the next-largest group (25%) using retrospective audits only. CONCLUSIONS: Approximately half the respondents had outpatient guidelines, and half used a threshold of less than 10,000/µL when transfusing platelets to stable outpatients. Greater adoption of this threshold and monitoring may improve the nation's platelet inventory.

Clinical characteristics and prognostic factors of 70 patients with Sézary syndrome: a single-institutional experience at Moffitt cancer center.

Sézary syndrome (SS) is a rare and aggressive leukemic variant of cutaneous T-cell lymphoma, with a median overall survival (OS) rate of 2-4 years. Few studies have described the clinical outcome of SS patients since 2012. We retrospectively analyzed 70 patients diagnosed with SS treated at a high-volume tertiary cancer center between 2000 and 2018. Overall survival at 1 and 5 years was 84.1% and 50.7%, respectively. Univariate analyses identified older age (>65 years) and male sex as poor prognostic factors. Five patients presented with circulating large granular lymphocytic proliferation and had a favorable prognosis. Targeted therapies were effective in treating refractory/relapsed SS patients with a durable response. Therapeutic advancements and the comprehensive treatments used in a multidisciplinary clinic improved OS rates.

Acute Hemolytic Transfusion Reaction Due to Pooled Platelets: A Rare but Serious Adverse Event.

A female patient aged 65 years with blood group A with relapsed lymphoma had thrombocytopenia; leukocyte-reduced group O prestorage pooled platelet concentrates (PPLTs) were transfused without adverse events. She was discharged home, but 1.5 hours later she returned with fever and dark urine. Hypotension and tachycardia developed; she was admitted to the intensive care unit. Post-transfusion blood and urine samples were obtained. Serial dilutions from 5 donor testing tubes and a simulated PLT pool were performed and read at immediate spin and IgG. Testing confirmed an acute hemolytic transfusion reaction (AHTR): elevated lactate dehydrogenase (996 U/L; normal range 135 U/L-225 U/L) and undetectable haptoglobin (<10 mg/dL; normal range 30 mg/dL-200 mg/dL) levels. Urinalysis showed dark amber urine but no significant quantity of red blood cells. At 37ºC the simulated pool and donor number 5 had high-titer anti-A. As a precaution, the donor was permanently deferred. Research has shown that PLT-associated AHTR has occurred with apheresis platelets but is very rare with whole blood-derived PLTs.

Proteomic contributions to personalized cancer care.

Cancer impacts each patient and family differently. Our current understanding of the disease is primarily limited to clinical hallmarks of cancer, but many specific molecular mechanisms remain elusive. Genetic markers can be used to determine predisposition to tumor development, but molecularly targeted treatment strategies that improve patient prognosis are not widely available for most cancers. Individualized care plans, also described as personalized medicine, still must be developed by understanding and implementing basic science research into clinical treatment. Proteomics holds great promise in contributing to the prevention and cure of cancer because it provides unique tools for discovery of biomarkers and therapeutic targets. As such, proteomics can help translate basic science discoveries into the clinical practice of personalized medicine. Here we describe how biological mass spectrometry and proteome analysis interact with other major patient care and research initiatives and present vignettes illustrating efforts in discovery of diagnostic biomarkers for ovarian cancer, development of treatment strategies in lung cancer, and monitoring prognosis and relapse in multiple myeloma patients.

Fatal group C streptococcal infection due to transfusion of a bacterially contaminated pooled platelet unit despite routine bacterial culture screening.

BACKGROUND: An elderly man with chronic myelomonocytic leukemia developed respiratory distress and died less than 48 hours after transfusion of a pool of eight whole blood-derived platelets (PLTs). Blood cultures from the recipient and cultures of remnants from the pooled PLT bag grew group C streptococci (GCS). An investigation was conducted to identify both the infection's source and the reasons for the false-negative screening result. STUDY DESIGN AND METHODS: Red blood cell (RBC) units (cocomponent from the eight donations) were traced, quarantined, and cultured. Specimens from the implicated donor were obtained. Isolates were identified and typed by 16S rRNA and pulsed-field gel electrophoresis (PFGE). The blood center screening method was reviewed. RESULTS: beta-Hemolytic GCS, cultured from 1 of 8 RBC units, linked the fatal case to a single donor. The donor's throat swab collected 20 days after donation was positive for the presence of GCS, identified as Streptococcus dysgalactiae subsp. equisimilis. Isolates from the recipient, RBC unit, residual PLTs, and donor's throat swab were indistinguishable by PFGE. The donor denied any symptoms of infection before or after donation. PLT bacterial screening at the blood center was performed using a commercially available bacterial detection system (BacT/ALERT, bioMérieux) with a threshold of 15 colony-forming units per bag. CONCLUSION: An asymptomatic donor was implicated as the source of GCS-contaminated PLTs. Current screening methods for PLTs are not sufficient to detect all bacterial contamination. Pooled PLTs are a particular challenge because the small volume of individual units places limits on culturing strategies. Improved detection of bacterial contamination of PLTs is needed.

Evaluation of toxicity following electrically mediated interleukin-12 gene delivery in a B16 mouse melanoma model.

PURPOSE: Interleukin-12 (IL-12) has potential as an immunotherapeutic agent for the treatment of cancer but is unfortunately associated with toxicity. Delivery of a plasmid encoding IL-12 with electroporation induces an antitumor effect in the B16 mouse melanoma model without serious side effects. To translate this observation to the clinic, an evaluation of toxicity was done in the mouse model. EXPERIMENTAL DESIGN: Weight change, tumor response, blood chemistry and hematology values, and serum IL-12 levels were evaluated. Multiple tissues were analyzed histopathologically. RESULTS: A pronounced reduction in tumor volume, including a large percentage of complete regressions, was observed after electrically mediated gene therapy. No significant increases in serum IL-12 levels were detected. Tumor-bearing mice showed an increased number of atypical hematology values when compared with normal naive controls. Statistically significant differences in chemistry and hematology values were observed sporadically in most of the standard chemistry and hematology categories in all groups. The only histopathologic abnormality specific to the animals receiving both plasmid and electroporation was inflammation associated with the kidney at the last time point. CONCLUSIONS: In general, mice that received both plasmid and electroporation showed the least abnormal histopathologic findings and were found to be in the best health, reflecting the reduced burden of disease. No significant toxic effects due to the IL-12 gene therapy were observed.

Home is where the heart is: do blood transfusions belong there too?

Blood transfusions performed outside of the hospital (OOH), particularly those in the patient's home, require special attention to reduce the added risk of being at an increased distance from emergency medical care. The situation must be carefully evaluated to be sure that the added risk is minimal and is balanced by substantial benefit to the patient. Consideration should be given in advance as to which patients will be eligible for OOH transfusions and what criteria must be met for the location of the transfusion. When blood transfusions are performed in the home, a second adult should be available to be able to assist the transfusionist and to monitor the patient after the transfusionist leaves. A facility engaged in OOH transfusions must adhere to all regulations and should establish quality assurance measures concerning this OOH transfusion practice. An OOH blood transfusion program must address these and other issues before the first patient is enrolled.

Quantification of peptides from immunoglobulin constant and variable regions by LC-MRM MS for assessment of multiple myeloma patients.

PURPOSE: Quantitative MS assays for Igs are compared with existing clinical methods in samples from patients with plasma cell dyscrasias, for example, multiple myeloma (MM). EXPERIMENTAL DESIGN: Using LC-MS/MS data, Ig constant region peptides, and transitions were selected for LC-MRM MS. Quantitative assays were used to assess Igs in serum from 83 patients. RNA sequencing and peptide-based LC-MRM are used to define peptides for quantification of the disease-specific Ig. RESULTS: LC-MRM assays quantify serum levels of Igs and their isoforms (IgG1-4, IgA1-2, IgM, IgD, and IgE, as well as kappa (κ) and lambda (λ) light chains). LC-MRM quantification has been applied to single samples from a patient cohort and a longitudinal study of an IgE patient undergoing treatment, to enable comparison with existing clinical methods. Proof-of-concept data for defining and monitoring variable region peptides are provided using the H929 MM cell line and two MM patients. CONCLUSIONS AND CLINICAL RELEVANCE: LC-MRM assays targeting constant region peptides determine the type and isoform of the involved Ig and quantify its expression; the LC-MRM approach has improved sensitivity compared with the current clinical method, but slightly higher inter-assay variability. Detection of variable region peptides is a promising way to improve Ig quantification, which could produce a dramatic increase in sensitivity over existing methods, and could further complement current clinical techniques.

Extremely high brain natriuretic peptide does not reflect the severity of heart failure.

Brain natriuretic peptide (BNP) is important in the diagnosis and management of heart failure (HF). Sometimes, very high BNP levels encountered in clinical settings seem to be out of proportion to the severity of HF. The authors retrospectively identified 113 patients with 129 admissions with a BNP value >3000 pg/mL regardless of diagnosis. The data set was analyzed using the Student t test and bivariate analysis. Fewer than half of patients were admitted for HF. In 14 patients (10.9%), no signs of HF were found. The BNP level of those with and without HF was similar. There was no difference in BNP level in patients with and without systolic dysfunction or renal dysfunction and between different age groups. Extreme values of BNP do not necessarily correlate with the presence of HF, cardiomyopathy, or kidney dysfunction. When the magnitude of BNP elevation is very high, its clinical significance is limited.

Urine collection and processing for protein biomarker discovery and quantification.

BACKGROUND: Urine is a useful source of protein for biomarker discovery and assessment because it is readily available, can be obtained by noninvasive collection methods, and enables monitoring of a wide range of physiologic processes and diseases. Urine aliquots provide enough protein for multiple analyses, combining current protocols with new techniques. CONCLUSIONS: Standardized collection and processing protocols are now being established and new methods for protein detection and quantification are emerging to complement traditional immunoassays. The current state of urine collection, specimen processing, and storage is reviewed with regard to discovery and quantification of protein biomarkers for cancer.

Leptomeningeal myeloma as the sole manifestation of relapse: an unusual presentation.

We report a case of a 57-year-old African American male patient with standard risk (IIIA) IgA kappa multiple myeloma. This patient presented with neurologic complaints (manifesting as generalized muscle weakness and swallowing dysfunction associated with a poor cough reflex) 10 months after achieving a very good partial remission and without evidence of systemic progression. Examination of the cerebrospinal fluid revealed leptomeningeal involvement. Very little is known about the mechanisms of myelomatous spread to the leptomeninges, a very rare event, and the presentation of this case could raise awareness of this rare complication in those involved in caring for patients with multiple myeloma.

Dispermic chimerism identified during HLA typing for stem cell transplantation.

BACKGROUND: Chimerism is defined as the presence of two genetically distinct cell populations in an organism. Few cases of phenotypically normal dispermic chimeras have been reported and most showed abnormalities on blood typing. CASE REPORT: A 32-year-old man was diagnosed with acute myelomonocytic leukemia. He clearly typed as group A, D-. No abnormalities of sexual development were identified on multiple physical exams, previous exploratory surgery, or CT scans. Molecular HLA typing (sequence-specific primers) in preparation for stem cell transplant showed the patient to have three HLA-B* and three HLA-Cw* alleles. Initial serologic HLA typing reported two haplotypes, but on subsequent review reactions for a third HLA-B antigen that were initially deemed to be false-positive reactions were identified. Two of 10 microsatellite short tandem repeat (STR) loci also showed three distinct alleles in blood and buccal samples. In all studies the third allele was attributable to a dual paternal contribution. CONCLUSION: This case represents dispermic chimerism, with one maternal and two paternal haplotypes variably distributed throughout body tissues in a phenotypically normal man without abnormalities in blood typing. The presence of additional alleles that may have been undetected or dismissed by serologic typing should be carefully investigated and verified by molecular techniques. Molecular HLA typing may increase the accurate identification of phenotypically normal chimeras and aid in selecting proper donors for transplantation to reduce graft-versus-host disease and transplant rejection in these patients.

Career activities of physicians taking the subspecialty board examination in blood banking/transfusion medicine.

BACKGROUND: Changes in blood banking and transfusion medicine (BB/TM) in the past 15 years may have made BB/TM a less attractive career choice than previously for physicians. STUDY DESIGN AND METHODS: To evaluate this, we developed a survey of professional activities and sent it to all physicians who took the BB/TM specialty examination offered by the American Board of Pathology (ABP) between 1995 and 2004. RESULTS: The examination was taken by 390 physicians (range, 25-68/year). Responses to the survey were received by 151 (39%). The number of candidates did not appear to be declining during the 10 years. All physicians who responded had practiced BB/TM and 94 percent were still doing so. Forty-three percent were engaged in BB/TM full-time and another 10 percent for at least 75 percent of the time. Most of the remaining time was devoted to pathology. Forty-three percent practiced in a university hospital, 22 percent in a community hospital, and 21 percent in a blood center. Examples of practice activities included transfusion service (85%), therapeutic apheresis (63%), stem cell collection (46%), stem cell laboratory (32%), and coagulation laboratory (29%). Sixty-six percent are involved in research. DISCUSSION: Interest in BB/TM careers is not decreasing as evidenced by the number of physicians taking the ABP specialty examination. Most currently practice BB/TM, many in an academic environment. Their activities are diverse. Many are involved in research and have presented abstracts at professional meetings. Approximately 60 percent combine the practice of BB/TM with pathology, but only a few (6%) practice hematology.

Acute and delayed hemolytic transfusion reactions secondary to HLA alloimmunization.

BACKGROUND: HLA antibodies may be directed against HLA antigens on RBCs, but these antibodies are generally not considered to be clinically significant in transfusion practice. A case of a multiparous woman who had hemolytic transfusion reactions due to HLA-related Bg antibodies is reported. CASE REPORT: A 37-year-old woman was admitted with anemia. No unexpected RBC antibodies were identified. Two group O, D+ RBC units were transfused. Ten days later she returned with hemolysis and anemia. Two more RBC units were ordered, no unexpected RBC antibodies were identified, and two crossmatch-compatible units were issued. During the transfusion, the patient developed symptoms of an acute reaction, and the posttransfusion sample showed evidence of intravascular hemolysis. RESULTS: Repeat RBC antibody screen showed anti-Bg. HLA antibody screen identified anti-HLA-A2, A28, B7, B7 cross-reactive group (CREG). The two RBC units from the first transfusion episode and one RBC unit from the second transfusion episode were HLA incompatible with the patient. No other cause for the hemolytic reactions was identified. The patient was later successfully transfused with one RBC unit from an HLA-compatible donor. CONCLUSION: HLA antibodies should be considered in patients with hemolytic transfusion reactions when RBC-specific antibodies are not found to be the etiology.