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ABSTRACT: Platelet (PLT) storage adversely affects PLT structure and function in vitro and is associated with decreased PLT recovery and function in vivo. In pediatric transfusion medicine, it is not uncommon for small residual volumes to remain in parent units after aliquot preparation of leukoreduced apheresis-derived PLTs (LR-ADP). However, limited data exist regarding the impact of storage on residual small-volume LR-ADP.
Standard metabolic testing was performed on residual volumes of LR-ADP after aliquot removal and PLT aggregometry using a dual agonist of ADP and collagen was performed on stored, small-volume aliquots (10-80mL) created from an in vitro model of PLT storage.
Seventy-seven LR-ADP underwent metabolic (n=67) or metabolic and aggregation (n=10) studies. All products maintained a pH value of more than 6.89 throughout storage. Lactate and pCO(2) increased proportionally with longer storage time. Regardless of acceptable metabolism during storage, aggregation in 10- to 20-mL aliquots was impaired by Day 4 and aliquots less than 40 mL demonstrated the most dramatic decrease in aggregation from baseline.
Despite maintenance of acceptable metabolic conditions, residual volumes of LR-ADP develop impaired aggregation in vitro that may adversely affect PLT survival and function in vivo. At volumes below 40mL, LR-ADP revealed reduced aggregation. As a result, it is recommended to monitor and record volumes of LR-ADP used for pediatric transfusion. Moreover, once LR-ADP attain a volume of 50mL or less on Day 4 or Day 5 of storage, consider discarding these products until their in vivo efficacy can be studied.
Transfusion 05/2010; 50(10):2193-8. · 3.22 Impact Factor
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ABSTRACT: Lack of a dengue hemorrhagic animal model recapitulating human dengue virus infection has been a significant impediment in advancing our understanding of the early events involved in the pathogenesis of dengue disease. In efforts to address this issue, a group of rhesus macaques were intravenously infected with dengue virus serotype 2 (strain 16 681) at 1 x 10(7) PFU/animal. A classic dengue hemorrhage developed 3 to 5 days after infection in 6 of 6 animals. Blood chemistry appeared to be normal with exception of creatine phosphokinase, which peaked at 7 days after infection. A modest thrombocytopenia and noticeable neutropenia concomitant with slight decrease of hemoglobin and hematocrit were registered. In addition, the concentration of D-dimer was elevated significantly. Viremia peaked at 3 to 5 days after infection followed by an inverse relationship between T and B lymphocytes and a bimodal pattern for platelet-monocytes and platelet-neutrophil aggregates. Dengue virus containing platelets engulfed by monocytes was noted at 8 or 9 days after infection. Thus, rhesus macaques inoculated intravenously with a high dose of dengue virus produced dengue hemorrhage, which may provide a unique platform to define the early events in dengue virus infection and help identify which blood components contribute to the pathogenesis of dengue disease.
Blood 03/2010; 115(9):1823-34. · 9.90 Impact Factor
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ABSTRACT: In Jehovah's Witness patients, the use of red blood cells, platelets, and fresh frozen plasma is not optional. Various blood conservation techniques are available, but complex cardiac surgery remains a major challenge. The feasibility of fractions of "primary components" has not been fully considered in published case reports. For Jehovah's Witness patients who preoperatively give consent, factor IX concentrates may be acceptable for hemostatic therapy. We hereby describe a combination of "secondary components" to prevent excessive bleeding in a Jehovah's Witness patient undergoing complex replacement of the aortic arch.
The Annals of thoracic surgery 11/2009; 88(5):1666-8. · 3.74 Impact Factor
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ABSTRACT: Although used for many years, a detailed understanding of the mechanism of action and metabolism of anticoagulants has become available only recently. After the addition of pharmacogenetic data to the drug label by the U.S. Food and Drug Administration, interest in the pharmacogenetics of warfarin and its clinical application has grown exponentially. Dosing algorithms have been developed and continue to be refined that incorporate the polymorphisms of P450 2C9 and vitamin K epoxide reductase. Widespread adoption of these algorithms has been slow because of factors such as physician education, timely testing, complexity of dosing calculations, dietary variations, and other confounding variables. Although most useful before the first dose, these tests are also being used to explain labile responses to warfarin. Current protocols are capable of predicting a large portion of interindividual dosing variation and, as more data become available, truly personalized dosing of warfarin should be achievable, improving patient safety and clinical efficacy.
Clinics in laboratory medicine 01/2009; 28(4):513-24. · 1.17 Impact Factor
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Blood Coagulation and Fibrinolysis 08/2006; 17(5):425-6. · 1.24 Impact Factor
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Thomas Heffron,
David Welch,
Todd Pillen,
Massimo Asolati,
Gregory Smallwood,
Phil Hagedorn,
Chang Nam, Alexander Duncan,
Mark Guy,
Enrique Martinez,
James Spivey,
Patricia Douglas,
Carlos Fasola,
Jill De Paolo,
John Rodriguez,
Rene Romero
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ABSTRACT: Transplanting blood group A, B, or O (ABO)-incompatible (ABO-I) liver grafts has resulted in lower patient and graft survival with an increased incidence of vascular and biliary complications and rejection. We report that, without modification of our standard immunosuppression protocol, crossing blood groups is an acceptable option for children requiring liver transplantation. In our study, ABO-I liver grafts -- regardless of recipient age -- have comparable long-term survival (mean follow-up of 3.25 yr) with ABO-compatible grafts without any difference in rejection, vascular or biliary complications. From January 1, 1999 to October 1, 2005, we studied 138 liver transplants in 121 children: 16 (13.2%) received an ABO incompatible liver allograft. One-year actuarial patient survival for ABO-matched grafts vs. ABO-I grafts was 93.0% and 100%, respectively, whereas graft survival was 83.4% and 92.3%. Additionally, 6 of 16 (37.5%) ABO-I transplanted children had 8 rejection episodes, whereas 47 patients (44.8%) had 121 rejection episodes in the ABO-compatible group. There were no vascular complications and 2 biliary strictures in the ABO-I group. Plasmapheresis was not used for pretransplantation desensitization and was only required in 1 posttransplantation recipient. No child was splenectomized. Six of the 16 children were older than 13 yr of age, suggesting the possibility of successfully expanding this technique to an older population. In conclusion, our outcomes may support the concept of using ABO-I grafts in a more elective setting associated with split and living donor liver transplants.
Liver Transplantation 07/2006; 12(6):972-8. · 3.39 Impact Factor
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ABSTRACT: High-resolution melting curve analysis using a fluorescent DNA binding dye can detect sequence variations in a closed-tube system without labeled primers or probes. We developed and verified a melting analysis assay for common single nucleotide polymorphisms of cytochrome P-450 (CYP) 2C9 that affect warfarin metabolism. We used this method to genotype 84 patients receiving warfarin. For wild-type, *1/*1, 50% fluorescence corresponded to a mean+/-SD of 87.17+/-0.05 degrees C, whereas *2/*2 was 0.4 degrees C lower. The *1/*2 melting curve was easily distinguished from *1/*1 and *2/*2 based on transition temperature and shape. Exon 7 showed a more complex melting curve; however, genotypes *1/*1, *1/*3, and *3/*3 were easily distinguishable. Melting curves were highly reproducible (SD of temperature for multiple fluorescence values 0.04 degrees C-0.11 degrees C; mean, 0.06 degrees C). Heterozygotes (*1/*2 or *1/*3) required significantly lower mean maintenance warfarin doses compared with wild-type (30.67 and 29.56 vs 42.81 mg/wk; P<.05). High-resolution melting analysis provides a simple and accurate method for genotyping of CYP2C9.
American Journal of Clinical Pathology 05/2006; 125(4):584-91. · 2.60 Impact Factor
