Barbara Bryant | University of Texas, Medical Branch at Galveston (original) (raw)

Papers by Barbara Bryant

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 15, 2004

... karyotype as follows: 52,XX,+add(1)(p10),+add(1)(p10), +i(2)(q10),t(3,6)(p21;q21),+6,+7,+9[5]... more ... karyotype as follows: 52,XX,+add(1)(p10),+add(1)(p10), +i(2)(q10),t(3,6)(p21;q21),+6,+7,+9[5]/ 46,XX[15]. ... Vinay Raja, Barbara Bryant, David J. Bessman, and Jack B. Alperin University of Texas Medical Branch, Galveston, TX © 2004 by American Society of Clinical Oncology ...

Transfusion, 2007

BACKGROUND: Bacterial contamination of platelet (PLT) concentrates occurs in 1 in 1000 to 1 in 30... more BACKGROUND: Bacterial contamination of platelet (PLT) concentrates occurs in 1 in 1000 to 1 in 3000 components and has been a leading cause of transfusion-associated morbidity and mortality. Two cases of Pasteurella multocida bacteremia in asymptomatic plateletpheresis donors are reported. Clinical outcomes were profoundly different, emphasizing the importance of robust methods to detect bacterial contamination. CASE REPORTS: The first case occurred before the implementation of bacterial testing of PLTs. A plateletpheresis component was collected from a 70-year-old man and transfused to an 88-year-old man, who developed rigors, tachycardia, and hypotension within 15 minutes of the start of the transfusion. Cardiopulmonary arrest ensued and he expired 6 hours after transfusion. Blood cultures collected after transfusion and cultures of the PLT component were positive for the presence of P. multocida. Investigation revealed that a feral cat had bitten the donor 100 minutes before his donation. He had not reported the event to the donor room staff. The second case involved a 74-year-old woman who developed a flulike syndrome 2 days after plateletpheresis donation. P. multocida was isolated in routine bacterial culture of her PLT component. The donor had several feral cats, and although there was no history of bite or scratch, one cat liked to lick her hands, which were chapped from gardening. CONCLUSION: Occult bacteremia with P. multocida transmitted by feral cats was the source of PLT contamination in two cases over 3 years. Bacterial testing of PLTs is critical in the prevention of transfusionacquired sepsis and allows the identification and treatment of asymptomatic bacteremic donors.

Transfusion, 2011

Therapeutic phlebotomy (TP) programs offer an important community service and often provide finan... more Therapeutic phlebotomy (TP) programs offer an important community service and often provide financial and donor unit resources for the hospital. This study assessed the financial impact and red blood cell (RBC) inventory contribution of a small, rural hospital-based TP program. TP procedures over 13 months were evaluated at a 142-bed rural hospital. The hospital had a Food and Drug Administration variance for a hereditary hemochromatosis (HH) donor program. The revenue for the non-HH therapeutic phlebotomies and the savings attained for units added to RBC inventory from allogeneic eligible HH donors were compiled. During the study, 84 patients were involved in the TP program. Of the 62 HH patients, 43 met eligibility requirements for allogeneic donations resulting in 207 donor units collected for the blood bank inventory and a savings of 21,000inbloodcosts.Additionally,22non−HHpatientsunderwent183TPproceduresearningthehospitalover21,000 in blood costs. Additionally, 22 non-HH patients underwent 183 TP procedures earning the hospital over 21,000inbloodcosts.Additionally,22non−HHpatientsunderwent183TPproceduresearningthehospitalover15,000 in net revenue. The TP program at this small, rural 142-bed hospital provided a financial gain of $36,000 during the 13-month study period. The HH donor program contributed approximately 4% to the RBC inventory. The TP program at this small, rural 142-bed hospital proved to be financially lucrative and provided a community service to patients.

Transfusion, 2011

A multisite blood center experienced unacceptable post-leukoreduction filtration white blood cell... more A multisite blood center experienced unacceptable post-leukoreduction filtration white blood cell (WBC) counts at a few centers. Since prefiltration storage time and temperature were suspect, whole blood (WB) units were stored in transport shippers for at least 2 hours, cooling toward 1-6 ° C, before filtration. This study compared the effect of storage times in transport shippers on the residual WBC counts of leukoreduced units. Collection and filtration of WB units were accomplished with the use of the Fenwal Express System with Integral Sepacell RZ-2000 WB Leukocyte Reduction Filter. Units were collected and placed in transport shippers containing ice. Leukoreduction filtration was performed at designated intervals post-collection. Acceptable leukoreduction was defined as < 5 × 10(6) residual WBC. Fifty donor units were selected randomly over 3 months. Units were held in transport shippers, and WBC reduction was performed at designated post-collection intervals. Storage times ranged from 28 to 458 minutes. All residual WBC counts were acceptable. Storage time of WB units in transport shippers did not play a role in the efficacy of the leukoreduction. This study demonstrated the 2-hour storage time before leukoreduction filtration could be eliminated resulting in time savings and increased efficacy in the component production laboratory.

Transfusion, 2007

Polymerization of hemoglobin (Hb) S is exacerbated by acidic and hyperosmotic citrate anticoagula... more Polymerization of hemoglobin (Hb) S is exacerbated by acidic and hyperosmotic citrate anticoagulant solutions and often results in occlusion of leukoreduction filters by red blood cells (RBCs) from sickle cell trait (Hb AS) donors. This study evaluates a blood collection instrument that adds citrate anticoagulant in a metered fashion, thus mitigating adverse citrate effects. Collection of whole blood by a metered anticoagulant system was compared to traditional phlebotomy in 12 Hb AS and 12 non-sickle trait (Hb AA) donors. Each donated twice; on one occasion, units were filtered after 4-hour storage at 20 to 24 degrees C, and on the other, units were stored at 1 to 6 degrees C for 24 hours before filtration. Filtration times, RBC recoveries, and residual white blood cell (WBC) counts met defined criteria more often in Hb AS units collected by a metered anticoagulant system (9 of 12, 8 of 12, and 4 of 12, respectively) compared to traditional phlebotomy (1 of 12, 2 of 12, and 0 of 12, respectively). Overall, Hb AS units filtered better after storage at 1 to 6 degrees C for 24 hours, with units collected by a metered anticoagulant system undergoing filtration most effectively (5 of 6 had >85% RBC recovery, 3 of 6 had <5 x 10(6) residual WBC). Units exhibited similar changes in RBC storage parameters. Use of a metered anticoagulation instrument demonstrates potential for successful leukoreduction and acceptable storage of Hb AS units; however, the system needs further modifications and improvements before it can be utilized to collect and leukoreduce Hb AS blood.

Pathogen inactivation provides a proactive approach to cleansing the blood supply. In the plasma ... more Pathogen inactivation provides a proactive approach to cleansing the blood supply. In the plasma fractionation and manufacturing industry, pathogen inactivation technologies have been successfully implemented resulting in no transmission of human immunodeficiency, hepatitis C, or hepatitis B viruses by US-licensed plasma derivatives since 1985. However, these technologies cannot be used to pathogen inactivate cellular blood components. Although current blood donor screening and disease testing has drastically reduced the incidence of transfusion-transmitted diseases, there still looms the threat to the blood supply of a new or reemerging pathogen. Of particular concern is the silent emergence of a new agent with a prolonged latent period in which asymptomatic infected carriers would donate and spread infection. To review and summarize the principles, challenges, achievements, prospective technologies, and future goals of pathogen inactivation of the blood supply. The current published English-language literature from 1968 through 2006 and a historical landmark article from 1943 are integrated into a review of this subject. The ultimate goal of pathogen inactivation is to maximally reduce the transmission of potential pathogens without significantly compromising the therapeutic efficacy of the cellular and protein constituents of blood. This must be accomplished without introducing toxicities into the blood supply and without causing neoantigen formation and subsequent antibody production. Several promising pathogen inactivation technologies are being developed and clinically tested, and others are currently in use. Pathogen inactivation offers additional layers of protection from infectious agents that threaten the blood supply and has the potential to impact the safety of blood transfusions worldwide.

Laboratory Medicine, 2007

Human immunodeficiency virus (HIV) resistance testing utilizes pharmacogenomics to develop effect... more Human immunodeficiency virus (HIV) resistance testing utilizes pharmacogenomics to develop effective individualized therapeutic regimens for the treatment of HIV positive patients. HIV resistance testing employs 3 different approaches: phenotyping, genotyping, or a hybrid method known as "virtual phenotyping." 1 A phenotyping assay is based on the rate that a drug inhibits viral replication and is performed by purifying the virus' nucleic acids, converting them into cDNA, and cloning a portion of the cDNA into a reporter vector that permits the determination of the concentration at which 50% of the virus is inhibited by each drug (IC50). Genotyping uses the sequence data from the isolated virus and translates this information into amino acid sequences that can be analyzed to identify viral mutations. Viral mutation data are analyzed using rules-based software, which classifies the mutation as primary (causing resistance) or secondary (facilitating the fitness of the virus) and uses this information to statistically predict the likelihood of resistance to a known drug. This risk for drug resistance determined by the viral mutation is designated as "high," "possible," or "none." The VirtualPhenotype (Virco, Raritan, NJ) is a hybrid technique of phenotyping and genotyping. A relational database is used to link the viral genotype from the clinical isolate to the paired genotype-phenotype isolates in the database. The final virtual phenotype compares the fold change (FC) values to drug-specific biological or clinical cut-off values to quantitate drug resistance. The FC is calculated by dividing the patient's IC50 by the IC50 of the reference susceptible strain. A FC value that is equal to or less than 1 indicates that the virus is at least as sensitive to the drug as the reference strain.

Transfusion, 2005

BACKGROUND: Few cases of antibodies to the Cromer (a) antigen have been described during pregnanc... more BACKGROUND: Few cases of antibodies to the Cromer (a) antigen have been described during pregnancy. Interestingly, the anti-Cr a titers decreased during pregnancy, and although the newborns were Cr a + , the direct antiglobulin tests (DATs) were negative and hemolytic disease of the newborn (HDN) was not observed. Cromer antigens reside on the decayaccelerating factor (DAF), which is expressed on the fetal derived syncytiotrophoblast layer of the placenta. It has been postulated that Cromer antibodies are not transported to the fetus, but are bound to placental DAF, thereby protecting the fetus from HDN and causing the disappearance of Cromer antibody in maternal plasma. This report is the first to demonstrate Cromer antibody sequestration by the placenta. CASE REPORT: A G4P1 woman with an anti-Cr a presented for prenatal care during her fourth pregnancy. The anti-Cr a titer decreased from 64 at 7 weeks gestation to undetectable after 25 weeks. At delivery, the infant had no evidence of HDN. The infant's DAT was negative, and the maternal plasma, cord plasma, and the cord blood eluate were negative with screening cells, the infant's cord cells, and the mother's cells. Placental eluates revealed anti-Cr a . CONCLUSIONS: This is the fourth case report of a Cromer (a-) woman producing anti-Cr a during pregnancy, and the first demonstrating anti-Cr a sequestration in the placenta. The presence of anti-Cr a in the placental eluate, but not in the cord plasma, maternal plasma, or cord blood eluate, strongly supports the hypothesis that DAF at the fetomaternal interface absorbs anti-Cr a from the maternal circulation blocking its passage to the fetus.

Transfusion, 2009

Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell me... more Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell mean corpuscular volume (MCV) values (<80 fL) in the presence of an acceptable hemoglobin (Hb; >or=12.5 g/dL) could be due to iron deficiency or hemoglobinopathy. The etiology of a low MCV in a healthy apheresis donor population was assessed. Predonation samples for CBC were obtained from 1162 consecutive apheresis donors. Donors with a MCV of less than 80 fL were evaluated by CBC, iron studies (ferritin, serum iron, transferrin, percentage of transferrin saturation), and hemoglobin (Hb) electrophoresis. Iron deficiency was defined as a ferritin value below the reference range. Beta chain Hb variants were determined by Hb electrophoresis. Alpha thalassemia trait was presumed if the red blood cell (RBC) count was elevated, no variant Hbs were detected, and the iron studies were within normal ranges. In a 19-month period, 33 of 1162 apheresis donors had low MCV values. Iron deficiency was present in 64%; 49% had isolated iron deficiency and 15% had iron deficiency plus hemoglobinopathy. Hemoglobinopathy without concomitant iron deficiency was found in the remaining 36%. Iron deficiency is present in the majority of apheresis donors with repeatedly low MCV values and Hb levels of 12.5 g/dL or more. Hemoglobinopathy is also commonly present but may not be easily recognized in the setting of iron deficiency. The MCV is a useful screening tool to detect iron deficiency and hemoglobinopathy. Low MCV values should be investigated to determine if iron replacement therapy is indicated.

Vox Sanguinis, 2013

To determine the accuracy of fingerstick haemoglobin assessment in blood donors, the performance ... more To determine the accuracy of fingerstick haemoglobin assessment in blood donors, the performance of a portable haemoglobinometer (HemoCue Hb 201+) was prospectively compared with that of an automated haematology analyzer (Cell-Dyn 4000). Haemoglobin values obtained by the latter were used as the 'true' result. Capillary fingerstick samples were assayed by HemoCue in 150 donors. Fingerstick samples from two sites, one on each hand, were obtained from a subset of 50 subjects. Concurrent venous samples were tested using both HemoCue and Cell-Dyn devices. Capillary haemoglobin values (HemoCue) were significantly greater than venous haemoglobin values (HemoCue), which in turn were significantly greater than venous haemoglobin values by Cell-Dyn (mean ± SD: 14.05 ± 1.51, 13.89 ± 1.31, 13.62 ± 1.23, respectively; P < 0.01 for all comparisons among groups). Nine donors (6%) passed haemoglobin screening criteria (≥ 12.5 g/dl) by capillary HemoCue, but were deferred by Cell-Dyn values (false-pass). Five donors (3%) were deferred by capillary sampling, but passed by Cell-Dyn (false-fail). Substantial variability in repeated fingerstick HemoCue results was seen (mean haemoglobin 13.72 vs. 13.70 g/dl, absolute mean difference between paired samples 0.76 g/dl). Hand dominance was not a factor. Capillary samples assessed via a portable device yielded higher haemoglobin values than venous samples assessed on an automated analyzer. False-pass and false-fail rates were low and acceptable in the donor screening setting, with 'true' values not differing by a clinically significant degree from threshold values used to assess acceptability for blood donation.

Transfusion, 2009

A 39-year-old woman with T/NK-cell lymphoma developed microangiopathic hemolytic anemia (MAHA) as... more A 39-year-old woman with T/NK-cell lymphoma developed microangiopathic hemolytic anemia (MAHA) associated with cyclosporine A (CSA) toxicity 15 days after allogeneic peripheral blood stem cell transplantation. Her serum creatinine level increased from 0.4 mg/dL before transplant to 1.0 and 2.9 mg/dL on Days 9 and 15 posttransplant, respectively, leading to cessation of CSA therapy. Peripheral blood smears revealed a dramatic increase in schistocytes (4 per high-power field) on Day 14. Lactate dehydrogenase levels increased from 708 to 4103 U/L on Posttransplant Days 1 and 15, respectively. Declining hemoglobin concentration and platelet count were attributed initially to the transplant rather than to evolving MAHA. Because of her critical condition, a 5-day course of daily therapeutic plasma exchange (TPE) was initiated as an extreme measure._ 02155 1291..1292 Plasma removed during the first TPE (see figure, left) illustrates the classic tea color associated with MAHA. During the first 3 days of TPE, CSA levels were 113, 95, and 106 mg/L. Rifampin, a potent inducer of cytochrome 450 3A4, was administered on Days 18 and 19 to promote clearance of CSA. Rifampin stains body fluids a characteristic orange-red

Transfusion, 2005

ABBREVIATIONS: aPTT = activated partial thromboplastin time; DDAVP = 1-deamino-8-D -arginine vaso... more ABBREVIATIONS: aPTT = activated partial thromboplastin time; DDAVP = 1-deamino-8-D -arginine vasopressin; PT = prothrombin time; UTMB = University of Texas Medical Branch.

Transfusion, 2010

Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible dono... more Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible donor red blood cells (RBCs) in the component. Efficient reduction of RBCs in granulocyte units would result in safe transfusion of RBC-incompatible units. Granulocyte concentrates were collected by continuous-flow apheresis from granulocyte-colony-stimulating factor (G-CSF) and dexamethasone-stimulated volunteer donors, with 6% hydroxyethyl starch (HES) added continuously during apheresis as a RBC sedimenting agent to enhance granulocyte collection efficiency. After collection, the component was placed in a plasma extractor for 4 hours. A sharp line of demarcation between the starch-sedimented RBCs and the granulocyte-rich supernatant developed, and the supernatant was transferred to a sterilely docked transfer pack. RBC reduction and white blood cell recovery were determined. Gravity sedimentation was performed on 165 granulocyte concentrates. Mean sedimentation time was 267 minutes (range, 150-440 min). RBC depletion was 92% (range, 71%-99%) with mean residual RBC content of 3.2 +/- 1.4 mL. Twelve percent of components contained less than 2 mL of RBCs. Mean granulocyte and platelet (PLT) recoveries were 80 and 81%, respectively. There were no transfusion reactions or signs of hemolysis after transfusion of 66 RBC-incompatible granulocyte concentrates (RBC volume, 1.6-8.2 mL). The remaining concentrates were used for topical or intrapleural applications. RBCs were significantly reduced and granulocytes and PLTs effectively retained in G-CSF/steroid-mobilized granulocyte components collected with HES and processed by gravity sedimentation. This procedure allows safe transfusion of RBC-incompatible sedimented granulocyte units and may be used to expand the pool of available granulocyte donors for specific recipients.

American Journal of PharmacoGenomics, 2004

Pharmacogenomics classically focuses on host nuclear genetic polymorphisms that can be used to pr... more Pharmacogenomics classically focuses on host nuclear genetic polymorphisms that can be used to predict adverse drug reactions (ADRs). Because ADRs are defined as any noxious, unintended, and undesired drug effects, loss of efficacy due to the development of antiretroviral drug resistance and both acute and cumulative adverse effects of antiretroviral therapy can be considered ADRs. In order to address these types of antiretroviral-associated ADRs, pharmacogenomic testing methods have expanded to include molecular assays that characterize extranuclear genetic material (e.g. HIV and mitochondrial genomes), as well as the host nuclear genetic material. Recent molecular advances permit high resolution resistance testing that detects loss of therapeutic efficacy through the use of phenotypic, genotypic and/or virtual phenotypic resistance testing. These assays use complex technical and interpretative methods to improve the therapeutic efficacy of antiretroviral therapy. The resistance assays demonstrate the utility of pharmacogenomic testing for patients undergoing lifelong and complex antiretroviral therapies. Future applications of antiretroviral-directed pharmacogenomic tests range from quantitative detection of mitochondrial depletion as an early surrogate marker for drug toxicity, to qualitative analysis of host immune haplotypes, and metabolic/transporter genetic polymorphisms for predicting disease progression. In summary, pharmacogenomic testing for HIV-positive patients provides proof of principle that these tests can be used clinically to improve outcomes for patients undergoing complex and sustained drug regimens.

Jama the Journal of the American Medical Association, 2007

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Jan 15, 2004

... karyotype as follows: 52,XX,+add(1)(p10),+add(1)(p10), +i(2)(q10),t(3,6)(p21;q21),+6,+7,+9[5]... more ... karyotype as follows: 52,XX,+add(1)(p10),+add(1)(p10), +i(2)(q10),t(3,6)(p21;q21),+6,+7,+9[5]/ 46,XX[15]. ... Vinay Raja, Barbara Bryant, David J. Bessman, and Jack B. Alperin University of Texas Medical Branch, Galveston, TX © 2004 by American Society of Clinical Oncology ...

Transfusion, 2007

BACKGROUND: Bacterial contamination of platelet (PLT) concentrates occurs in 1 in 1000 to 1 in 30... more BACKGROUND: Bacterial contamination of platelet (PLT) concentrates occurs in 1 in 1000 to 1 in 3000 components and has been a leading cause of transfusion-associated morbidity and mortality. Two cases of Pasteurella multocida bacteremia in asymptomatic plateletpheresis donors are reported. Clinical outcomes were profoundly different, emphasizing the importance of robust methods to detect bacterial contamination. CASE REPORTS: The first case occurred before the implementation of bacterial testing of PLTs. A plateletpheresis component was collected from a 70-year-old man and transfused to an 88-year-old man, who developed rigors, tachycardia, and hypotension within 15 minutes of the start of the transfusion. Cardiopulmonary arrest ensued and he expired 6 hours after transfusion. Blood cultures collected after transfusion and cultures of the PLT component were positive for the presence of P. multocida. Investigation revealed that a feral cat had bitten the donor 100 minutes before his donation. He had not reported the event to the donor room staff. The second case involved a 74-year-old woman who developed a flulike syndrome 2 days after plateletpheresis donation. P. multocida was isolated in routine bacterial culture of her PLT component. The donor had several feral cats, and although there was no history of bite or scratch, one cat liked to lick her hands, which were chapped from gardening. CONCLUSION: Occult bacteremia with P. multocida transmitted by feral cats was the source of PLT contamination in two cases over 3 years. Bacterial testing of PLTs is critical in the prevention of transfusionacquired sepsis and allows the identification and treatment of asymptomatic bacteremic donors.

Transfusion, 2011

Therapeutic phlebotomy (TP) programs offer an important community service and often provide finan... more Therapeutic phlebotomy (TP) programs offer an important community service and often provide financial and donor unit resources for the hospital. This study assessed the financial impact and red blood cell (RBC) inventory contribution of a small, rural hospital-based TP program. TP procedures over 13 months were evaluated at a 142-bed rural hospital. The hospital had a Food and Drug Administration variance for a hereditary hemochromatosis (HH) donor program. The revenue for the non-HH therapeutic phlebotomies and the savings attained for units added to RBC inventory from allogeneic eligible HH donors were compiled. During the study, 84 patients were involved in the TP program. Of the 62 HH patients, 43 met eligibility requirements for allogeneic donations resulting in 207 donor units collected for the blood bank inventory and a savings of 21,000inbloodcosts.Additionally,22non−HHpatientsunderwent183TPproceduresearningthehospitalover21,000 in blood costs. Additionally, 22 non-HH patients underwent 183 TP procedures earning the hospital over 21,000inbloodcosts.Additionally,22non−HHpatientsunderwent183TPproceduresearningthehospitalover15,000 in net revenue. The TP program at this small, rural 142-bed hospital provided a financial gain of $36,000 during the 13-month study period. The HH donor program contributed approximately 4% to the RBC inventory. The TP program at this small, rural 142-bed hospital proved to be financially lucrative and provided a community service to patients.

Transfusion, 2011

A multisite blood center experienced unacceptable post-leukoreduction filtration white blood cell... more A multisite blood center experienced unacceptable post-leukoreduction filtration white blood cell (WBC) counts at a few centers. Since prefiltration storage time and temperature were suspect, whole blood (WB) units were stored in transport shippers for at least 2 hours, cooling toward 1-6 ° C, before filtration. This study compared the effect of storage times in transport shippers on the residual WBC counts of leukoreduced units. Collection and filtration of WB units were accomplished with the use of the Fenwal Express System with Integral Sepacell RZ-2000 WB Leukocyte Reduction Filter. Units were collected and placed in transport shippers containing ice. Leukoreduction filtration was performed at designated intervals post-collection. Acceptable leukoreduction was defined as < 5 × 10(6) residual WBC. Fifty donor units were selected randomly over 3 months. Units were held in transport shippers, and WBC reduction was performed at designated post-collection intervals. Storage times ranged from 28 to 458 minutes. All residual WBC counts were acceptable. Storage time of WB units in transport shippers did not play a role in the efficacy of the leukoreduction. This study demonstrated the 2-hour storage time before leukoreduction filtration could be eliminated resulting in time savings and increased efficacy in the component production laboratory.

Transfusion, 2007

Polymerization of hemoglobin (Hb) S is exacerbated by acidic and hyperosmotic citrate anticoagula... more Polymerization of hemoglobin (Hb) S is exacerbated by acidic and hyperosmotic citrate anticoagulant solutions and often results in occlusion of leukoreduction filters by red blood cells (RBCs) from sickle cell trait (Hb AS) donors. This study evaluates a blood collection instrument that adds citrate anticoagulant in a metered fashion, thus mitigating adverse citrate effects. Collection of whole blood by a metered anticoagulant system was compared to traditional phlebotomy in 12 Hb AS and 12 non-sickle trait (Hb AA) donors. Each donated twice; on one occasion, units were filtered after 4-hour storage at 20 to 24 degrees C, and on the other, units were stored at 1 to 6 degrees C for 24 hours before filtration. Filtration times, RBC recoveries, and residual white blood cell (WBC) counts met defined criteria more often in Hb AS units collected by a metered anticoagulant system (9 of 12, 8 of 12, and 4 of 12, respectively) compared to traditional phlebotomy (1 of 12, 2 of 12, and 0 of 12, respectively). Overall, Hb AS units filtered better after storage at 1 to 6 degrees C for 24 hours, with units collected by a metered anticoagulant system undergoing filtration most effectively (5 of 6 had >85% RBC recovery, 3 of 6 had <5 x 10(6) residual WBC). Units exhibited similar changes in RBC storage parameters. Use of a metered anticoagulation instrument demonstrates potential for successful leukoreduction and acceptable storage of Hb AS units; however, the system needs further modifications and improvements before it can be utilized to collect and leukoreduce Hb AS blood.

Pathogen inactivation provides a proactive approach to cleansing the blood supply. In the plasma ... more Pathogen inactivation provides a proactive approach to cleansing the blood supply. In the plasma fractionation and manufacturing industry, pathogen inactivation technologies have been successfully implemented resulting in no transmission of human immunodeficiency, hepatitis C, or hepatitis B viruses by US-licensed plasma derivatives since 1985. However, these technologies cannot be used to pathogen inactivate cellular blood components. Although current blood donor screening and disease testing has drastically reduced the incidence of transfusion-transmitted diseases, there still looms the threat to the blood supply of a new or reemerging pathogen. Of particular concern is the silent emergence of a new agent with a prolonged latent period in which asymptomatic infected carriers would donate and spread infection. To review and summarize the principles, challenges, achievements, prospective technologies, and future goals of pathogen inactivation of the blood supply. The current published English-language literature from 1968 through 2006 and a historical landmark article from 1943 are integrated into a review of this subject. The ultimate goal of pathogen inactivation is to maximally reduce the transmission of potential pathogens without significantly compromising the therapeutic efficacy of the cellular and protein constituents of blood. This must be accomplished without introducing toxicities into the blood supply and without causing neoantigen formation and subsequent antibody production. Several promising pathogen inactivation technologies are being developed and clinically tested, and others are currently in use. Pathogen inactivation offers additional layers of protection from infectious agents that threaten the blood supply and has the potential to impact the safety of blood transfusions worldwide.

Laboratory Medicine, 2007

Human immunodeficiency virus (HIV) resistance testing utilizes pharmacogenomics to develop effect... more Human immunodeficiency virus (HIV) resistance testing utilizes pharmacogenomics to develop effective individualized therapeutic regimens for the treatment of HIV positive patients. HIV resistance testing employs 3 different approaches: phenotyping, genotyping, or a hybrid method known as "virtual phenotyping." 1 A phenotyping assay is based on the rate that a drug inhibits viral replication and is performed by purifying the virus' nucleic acids, converting them into cDNA, and cloning a portion of the cDNA into a reporter vector that permits the determination of the concentration at which 50% of the virus is inhibited by each drug (IC50). Genotyping uses the sequence data from the isolated virus and translates this information into amino acid sequences that can be analyzed to identify viral mutations. Viral mutation data are analyzed using rules-based software, which classifies the mutation as primary (causing resistance) or secondary (facilitating the fitness of the virus) and uses this information to statistically predict the likelihood of resistance to a known drug. This risk for drug resistance determined by the viral mutation is designated as "high," "possible," or "none." The VirtualPhenotype (Virco, Raritan, NJ) is a hybrid technique of phenotyping and genotyping. A relational database is used to link the viral genotype from the clinical isolate to the paired genotype-phenotype isolates in the database. The final virtual phenotype compares the fold change (FC) values to drug-specific biological or clinical cut-off values to quantitate drug resistance. The FC is calculated by dividing the patient's IC50 by the IC50 of the reference susceptible strain. A FC value that is equal to or less than 1 indicates that the virus is at least as sensitive to the drug as the reference strain.

Transfusion, 2005

BACKGROUND: Few cases of antibodies to the Cromer (a) antigen have been described during pregnanc... more BACKGROUND: Few cases of antibodies to the Cromer (a) antigen have been described during pregnancy. Interestingly, the anti-Cr a titers decreased during pregnancy, and although the newborns were Cr a + , the direct antiglobulin tests (DATs) were negative and hemolytic disease of the newborn (HDN) was not observed. Cromer antigens reside on the decayaccelerating factor (DAF), which is expressed on the fetal derived syncytiotrophoblast layer of the placenta. It has been postulated that Cromer antibodies are not transported to the fetus, but are bound to placental DAF, thereby protecting the fetus from HDN and causing the disappearance of Cromer antibody in maternal plasma. This report is the first to demonstrate Cromer antibody sequestration by the placenta. CASE REPORT: A G4P1 woman with an anti-Cr a presented for prenatal care during her fourth pregnancy. The anti-Cr a titer decreased from 64 at 7 weeks gestation to undetectable after 25 weeks. At delivery, the infant had no evidence of HDN. The infant's DAT was negative, and the maternal plasma, cord plasma, and the cord blood eluate were negative with screening cells, the infant's cord cells, and the mother's cells. Placental eluates revealed anti-Cr a . CONCLUSIONS: This is the fourth case report of a Cromer (a-) woman producing anti-Cr a during pregnancy, and the first demonstrating anti-Cr a sequestration in the placenta. The presence of anti-Cr a in the placental eluate, but not in the cord plasma, maternal plasma, or cord blood eluate, strongly supports the hypothesis that DAF at the fetomaternal interface absorbs anti-Cr a from the maternal circulation blocking its passage to the fetus.

Transfusion, 2009

Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell me... more Apheresis donors are routinely evaluated with a complete blood count (CBC). Low red blood cell mean corpuscular volume (MCV) values (<80 fL) in the presence of an acceptable hemoglobin (Hb; >or=12.5 g/dL) could be due to iron deficiency or hemoglobinopathy. The etiology of a low MCV in a healthy apheresis donor population was assessed. Predonation samples for CBC were obtained from 1162 consecutive apheresis donors. Donors with a MCV of less than 80 fL were evaluated by CBC, iron studies (ferritin, serum iron, transferrin, percentage of transferrin saturation), and hemoglobin (Hb) electrophoresis. Iron deficiency was defined as a ferritin value below the reference range. Beta chain Hb variants were determined by Hb electrophoresis. Alpha thalassemia trait was presumed if the red blood cell (RBC) count was elevated, no variant Hbs were detected, and the iron studies were within normal ranges. In a 19-month period, 33 of 1162 apheresis donors had low MCV values. Iron deficiency was present in 64%; 49% had isolated iron deficiency and 15% had iron deficiency plus hemoglobinopathy. Hemoglobinopathy without concomitant iron deficiency was found in the remaining 36%. Iron deficiency is present in the majority of apheresis donors with repeatedly low MCV values and Hb levels of 12.5 g/dL or more. Hemoglobinopathy is also commonly present but may not be easily recognized in the setting of iron deficiency. The MCV is a useful screening tool to detect iron deficiency and hemoglobinopathy. Low MCV values should be investigated to determine if iron replacement therapy is indicated.

Vox Sanguinis, 2013

To determine the accuracy of fingerstick haemoglobin assessment in blood donors, the performance ... more To determine the accuracy of fingerstick haemoglobin assessment in blood donors, the performance of a portable haemoglobinometer (HemoCue Hb 201+) was prospectively compared with that of an automated haematology analyzer (Cell-Dyn 4000). Haemoglobin values obtained by the latter were used as the 'true' result. Capillary fingerstick samples were assayed by HemoCue in 150 donors. Fingerstick samples from two sites, one on each hand, were obtained from a subset of 50 subjects. Concurrent venous samples were tested using both HemoCue and Cell-Dyn devices. Capillary haemoglobin values (HemoCue) were significantly greater than venous haemoglobin values (HemoCue), which in turn were significantly greater than venous haemoglobin values by Cell-Dyn (mean ± SD: 14.05 ± 1.51, 13.89 ± 1.31, 13.62 ± 1.23, respectively; P < 0.01 for all comparisons among groups). Nine donors (6%) passed haemoglobin screening criteria (≥ 12.5 g/dl) by capillary HemoCue, but were deferred by Cell-Dyn values (false-pass). Five donors (3%) were deferred by capillary sampling, but passed by Cell-Dyn (false-fail). Substantial variability in repeated fingerstick HemoCue results was seen (mean haemoglobin 13.72 vs. 13.70 g/dl, absolute mean difference between paired samples 0.76 g/dl). Hand dominance was not a factor. Capillary samples assessed via a portable device yielded higher haemoglobin values than venous samples assessed on an automated analyzer. False-pass and false-fail rates were low and acceptable in the donor screening setting, with 'true' values not differing by a clinically significant degree from threshold values used to assess acceptability for blood donation.

Transfusion, 2009

A 39-year-old woman with T/NK-cell lymphoma developed microangiopathic hemolytic anemia (MAHA) as... more A 39-year-old woman with T/NK-cell lymphoma developed microangiopathic hemolytic anemia (MAHA) associated with cyclosporine A (CSA) toxicity 15 days after allogeneic peripheral blood stem cell transplantation. Her serum creatinine level increased from 0.4 mg/dL before transplant to 1.0 and 2.9 mg/dL on Days 9 and 15 posttransplant, respectively, leading to cessation of CSA therapy. Peripheral blood smears revealed a dramatic increase in schistocytes (4 per high-power field) on Day 14. Lactate dehydrogenase levels increased from 708 to 4103 U/L on Posttransplant Days 1 and 15, respectively. Declining hemoglobin concentration and platelet count were attributed initially to the transplant rather than to evolving MAHA. Because of her critical condition, a 5-day course of daily therapeutic plasma exchange (TPE) was initiated as an extreme measure._ 02155 1291..1292 Plasma removed during the first TPE (see figure, left) illustrates the classic tea color associated with MAHA. During the first 3 days of TPE, CSA levels were 113, 95, and 106 mg/L. Rifampin, a potent inducer of cytochrome 450 3A4, was administered on Days 18 and 19 to promote clearance of CSA. Rifampin stains body fluids a characteristic orange-red

Transfusion, 2005

ABBREVIATIONS: aPTT = activated partial thromboplastin time; DDAVP = 1-deamino-8-D -arginine vaso... more ABBREVIATIONS: aPTT = activated partial thromboplastin time; DDAVP = 1-deamino-8-D -arginine vasopressin; PT = prothrombin time; UTMB = University of Texas Medical Branch.

Transfusion, 2010

Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible dono... more Transfusion of granulocytapheresis concentrates can be limited by the volume of incompatible donor red blood cells (RBCs) in the component. Efficient reduction of RBCs in granulocyte units would result in safe transfusion of RBC-incompatible units. Granulocyte concentrates were collected by continuous-flow apheresis from granulocyte-colony-stimulating factor (G-CSF) and dexamethasone-stimulated volunteer donors, with 6% hydroxyethyl starch (HES) added continuously during apheresis as a RBC sedimenting agent to enhance granulocyte collection efficiency. After collection, the component was placed in a plasma extractor for 4 hours. A sharp line of demarcation between the starch-sedimented RBCs and the granulocyte-rich supernatant developed, and the supernatant was transferred to a sterilely docked transfer pack. RBC reduction and white blood cell recovery were determined. Gravity sedimentation was performed on 165 granulocyte concentrates. Mean sedimentation time was 267 minutes (range, 150-440 min). RBC depletion was 92% (range, 71%-99%) with mean residual RBC content of 3.2 +/- 1.4 mL. Twelve percent of components contained less than 2 mL of RBCs. Mean granulocyte and platelet (PLT) recoveries were 80 and 81%, respectively. There were no transfusion reactions or signs of hemolysis after transfusion of 66 RBC-incompatible granulocyte concentrates (RBC volume, 1.6-8.2 mL). The remaining concentrates were used for topical or intrapleural applications. RBCs were significantly reduced and granulocytes and PLTs effectively retained in G-CSF/steroid-mobilized granulocyte components collected with HES and processed by gravity sedimentation. This procedure allows safe transfusion of RBC-incompatible sedimented granulocyte units and may be used to expand the pool of available granulocyte donors for specific recipients.

American Journal of PharmacoGenomics, 2004

Pharmacogenomics classically focuses on host nuclear genetic polymorphisms that can be used to pr... more Pharmacogenomics classically focuses on host nuclear genetic polymorphisms that can be used to predict adverse drug reactions (ADRs). Because ADRs are defined as any noxious, unintended, and undesired drug effects, loss of efficacy due to the development of antiretroviral drug resistance and both acute and cumulative adverse effects of antiretroviral therapy can be considered ADRs. In order to address these types of antiretroviral-associated ADRs, pharmacogenomic testing methods have expanded to include molecular assays that characterize extranuclear genetic material (e.g. HIV and mitochondrial genomes), as well as the host nuclear genetic material. Recent molecular advances permit high resolution resistance testing that detects loss of therapeutic efficacy through the use of phenotypic, genotypic and/or virtual phenotypic resistance testing. These assays use complex technical and interpretative methods to improve the therapeutic efficacy of antiretroviral therapy. The resistance assays demonstrate the utility of pharmacogenomic testing for patients undergoing lifelong and complex antiretroviral therapies. Future applications of antiretroviral-directed pharmacogenomic tests range from quantitative detection of mitochondrial depletion as an early surrogate marker for drug toxicity, to qualitative analysis of host immune haplotypes, and metabolic/transporter genetic polymorphisms for predicting disease progression. In summary, pharmacogenomic testing for HIV-positive patients provides proof of principle that these tests can be used clinically to improve outcomes for patients undergoing complex and sustained drug regimens.

Jama the Journal of the American Medical Association, 2007