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  1. Article ; Online: Cold-stored platelet function is not significantly altered by agitation or manual mixing.

    Shea, Susan M / Spinella, Philip C / Thomas, Kimberly A

    Transfusion

    2022  Volume 62, Issue 9, Page(s) 1850–1859

    Abstract: Background: Cold storage of platelets (CS-PLT), results in better maintained hemostatic function compared to room-temperature stored platelets (RT-PLT), leading to increased interest and use of CS-PLT for actively bleeding patients. However, questions ... ...

    Abstract Background: Cold storage of platelets (CS-PLT), results in better maintained hemostatic function compared to room-temperature stored platelets (RT-PLT), leading to increased interest and use of CS-PLT for actively bleeding patients. However, questions remain on best storage practices for CS-PLT, as agitation of CS-PLT is optional per the United States Food and Drug Administration. CS-PLT storage and handling protocols needed to be determined prior to upcoming clinical trials, and blood banking standard operating procedures need to be updated accordingly for the release of units due to potentially modified aggregate morphology without agitation.
    Study design and methods: We visually assessed aggregate formation, then measured surface receptor expression (GPVI, CD42b (GPIbα), CD49 (GPIa/ITGA2), CD41/61 (ITGA2B/ITGB3; GPIIB/GPIIIA; PACI), CD62P, CD63, HLAI), thrombin generation, aggregation (collagen, adenosine diphosphate [ADP], and epinephrine activation), and viscoelastic function (ExTEM, FibTEM) in CS-PLT (Trima collection, 100% plasma) stored for 21 days either with or without agitation (Phase 1, n = 10 donor-paired units) and then without agitation with or without daily manual mixing to minimize aggregate formation and reduce potential effects of sedimentation (Phase 2, n = 10 donor-paired units).
    Results: Agitation resulted in macroaggregate formation, whereas no agitation caused film-like sediment. We found no substantial differences in CS-PLT function between storage conditions, as surface receptor expression, thrombin generation, aggregation, and clot formation were relatively similar between intra-Phase storage conditions.
    Discussion: Storage duration and not condition impacted phenotype and function. CS-PLT can be stored with or without agitation, and with or without daily mixing and standard metrics of hemostatic function will not be significantly altered.
    MeSH term(s) Blood Platelets/metabolism ; Blood Preservation/methods ; Hemostasis ; Hemostatics/metabolism ; Platelet Aggregation ; Thrombin/metabolism
    Chemical Substances Hemostatics ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2022-07-27
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.17005
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  2. Article ; Online: Lysis of arterial thrombi by perfusion of N,N'-Diacetyl-L-cystine (DiNAC).

    Kim, Dongjune / Shea, Susan M / Ku, David N

    PloS one

    2021  Volume 16, Issue 2, Page(s) e0247496

    Abstract: The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or ... ...

    Abstract The search persists for a safe and effective agent to lyse arterial thrombi in the event of acute heart attacks or strokes due to thrombotic occlusion. The culpable thrombi are composed either primarily of platelets and von Willebrand Factor (VWF), or polymerized fibrin, depending on the mechanism of formation. Current thrombolytics were designed to target red fibrin-rich clots, but may be not be efficacious on white VWF-platelet-rich arterial thrombi. We have developed an in vitro system to study the efficacy of known and proposed thrombolytic agents on white clots formed from whole blood in a stenosis with arterial conditions. The agents and adjuncts tested were tPA, ADAMTS-13, abciximab, N-acetyl cysteine, and N,N'-Diacetyl-L-cystine (DiNAC). Most of the agents, including tPA, had little thrombolytic effect on the white clots. In contrast, perfusion of DiNAC lysed thrombi as quickly as 1.5 min, which ranged up to 30 min at lower concentrations, and resulted in an average reduction in surface area of 71 ± 20%. The clot burden was significantly reduced compared to both tPA and a saline control (p<0.0001). We also tested the efficacy of all agents on red fibrinous clots formed in stagnant conditions. DiNAC did not lyse red clots, whereas tPA significantly lysed red clot over 48 h (p<0.01). These results lead to a novel use for DiNAC as a possible thrombolytic agent against acute arterial occlusions that could mitigate the risk of hyper-fibrinolytic bleeding.
    MeSH term(s) Animals ; Cystine/analogs & derivatives ; Cystine/pharmacology ; Fibrinolytic Agents/pharmacology ; Swine ; Thrombolytic Therapy/methods ; Thrombosis/drug therapy ; Thrombotic Stroke/drug therapy
    Chemical Substances Fibrinolytic Agents ; Cystine (48TCX9A1VT) ; N,N-diacetylcystine (5545-17-5)
    Language English
    Publishing date 2021-02-25
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ISSN 1932-6203
    ISSN (online) 1932-6203
    DOI 10.1371/journal.pone.0247496
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  3. Article ; Online: Normative data on the foveal avascular zone in a young healthy Irish population using optical coherence tomography angiography.

    O'Shea, Susan M / O'Dwyer, Veronica M / Scanlon, Grainne

    European journal of ophthalmology

    2022  Volume 32, Issue 5, Page(s) 2824–2832

    Abstract: Purpose: To establish normative data on the size, shape and vascular profile of the foveal avascular zone (FAZ) in a young, healthy, Irish population, using the Cirrus 5000 HD-OCT. Certain diseases may alter FAZ appearance. Normative databases provide ... ...

    Abstract Purpose: To establish normative data on the size, shape and vascular profile of the foveal avascular zone (FAZ) in a young, healthy, Irish population, using the Cirrus 5000 HD-OCT. Certain diseases may alter FAZ appearance. Normative databases provide normal baseline values for comparison, thus improving diagnostic ability.
    Methods: One hundred and fifty-four subjects aged 18-35 years old were recruited. Superficial FAZ area, diameter, circularity, ganglion cell layer, central macular thickness (CMT), vascular perfusion and density were measured using the Cirrus 5000. Axial length was measured with the IOL Master and blood pressure was measured using the Omron sphygmomanometer.
    Results: Mean FAZ area was 0.22 ± 0.07 mm
    Conclusions: This study provides normative data for FAZ appearance and vascularity for the first time in a young, healthy, Irish population, using the Cirrus 5000 HD-OCT. Establishing machine and population specific normative data, particularly in relation to vessel density and perfusion is paramount to the early identification of ocular disease using Optical Coherence Tomography Angiography.
    MeSH term(s) Adolescent ; Adult ; Female ; Fluorescein Angiography/methods ; Fovea Centralis/blood supply ; Humans ; Macula Lutea/blood supply ; Male ; Retinal Vessels/diagnostic imaging ; Tomography, Optical Coherence/methods ; Young Adult
    Language English
    Publishing date 2022-01-10
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1089461-5
    ISSN 1724-6016 ; 1120-6721
    ISSN (online) 1724-6016
    ISSN 1120-6721
    DOI 10.1177/11206721211073446
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    Zs.A 3342: Show issues Location:
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  4. Article ; Online: Effects of pathogen reduction technology and storage duration on the ability of cryoprecipitate to rescue induced coagulopathies in vitro.

    Thomas, Kimberly A / Shea, Susan M / Spinella, Philip C

    Transfusion

    2021  Volume 61, Issue 6, Page(s) 1943–1954

    Abstract: Background: Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for ... ...

    Abstract Background: Fibrinogen concentrates and cryoprecipitate are currently used for fibrinogen supplementation in bleeding patients with dysfibrinogenemia. Both products provide an abundant source of fibrinogen but take greater than 10 min to prepare for administration. Fibrinogen concentrates lack coagulation factors (i.e., factor VIII [FVIII], factor XIII [FXIII], von Willebrand factor [VWF]) important for robust hemostatic function. Cryoprecipitate products contain these factors but have short shelf lives (<6 h). Pathogen reduction (PR) of cryoprecipitate would provide a shelf-stable immediately available adjunct containing factors important for rescuing hemostatic dysfunction.
    Study design and methods: Hemostatic adjunct study products were psoralen-treated PR-cryoprecipitated fibrinogen complex (PR-Cryo FC), cryoprecipitate (Cryo), and fibrinogen concentrates (FibCon). PR-Cryo FC and Cryo were stored for 10 days at 20-24°C. Adjuncts were added to coagulopathies (dilutional, 3:7 whole blood [WB]:normal saline; or lytic, WB + 75 ng/ml tissue plasminogen activator), and hemostatic function was assessed by rotational thromboelastometry and thrombin generation.
    Results: PR of cryoprecipitate did not reduce levels of FVIII, FXIII, or VWF. PR-Cryo FC rescued dilutional coagulopathy similarly to Cryo, while generating significantly more thrombin than FibCon, which also rescued dilutional coagulopathy. Storage out to 10 days at 20-24°C did not diminish the hemostatic function of PR-Cryo FC.
    Discussion: PR-Cryo FC provides similar and/or improved hemostatic rescue compared to FibCon in dilutional coagulopathies, and this rescue ability is stable over 10 days of storage. In hemorrhaging patients, where every minute delay is associated with a 5% increase in mortality, the immediate availability of PR-Cryo FC has the potential to improve outcomes.
    MeSH term(s) Blood Coagulation Disorders/blood ; Blood Coagulation Disorders/therapy ; Blood Coagulation Factors/analysis ; Blood Coagulation Factors/pharmacology ; Blood Safety/methods ; Factor VIII/analysis ; Factor VIII/pharmacology ; Fibrinogen/analysis ; Fibrinogen/pharmacology ; Hemostasis/drug effects ; Hemostatics/analysis ; Hemostatics/pharmacology ; Humans ; Sterilization/methods
    Chemical Substances Blood Coagulation Factors ; Hemostatics ; cryoprecipitate coagulum ; Factor VIII (9001-27-8) ; Fibrinogen (9001-32-5)
    Language English
    Publishing date 2021-03-23
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.16376
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  5. Article: Mathematical and Computational Modeling of Device-Induced Thrombosis.

    Manning, Keefe B / Nicoud, Franck / Shea, Susan M

    Current opinion in biomedical engineering

    2021  Volume 20

    Abstract: Given the extensive and routine use of cardiovascular devices, a major limiting factor to their success is the thrombotic rate that occurs. This both poses direct risk to the patient and requires counterbalancing with anticoagulation and other treatment ... ...

    Abstract Given the extensive and routine use of cardiovascular devices, a major limiting factor to their success is the thrombotic rate that occurs. This both poses direct risk to the patient and requires counterbalancing with anticoagulation and other treatment strategies, contributing additional risks. Developing a better understanding of the mechanisms of device-induced thrombosis to aid in device design and medical management of patients is critical to advance the ubiquitous use and durability. Thus, mathematical and computational modelling of device-induced thrombosis has received significant attention recently, but challenges remain. Additional areas that need to be explored include microscopic/macroscopic approaches, reconciling physical and numerical timescales, immune/inflammatory responses, experimental validation, and incorporating pathologies and blood conditions. Addressing these areas will provide engineers and clinicians the tools to provide safe and effective cardiovascular devices.
    Language English
    Publishing date 2021-09-28
    Publishing country England
    Document type Journal Article
    ISSN 2468-4511
    ISSN 2468-4511
    DOI 10.1016/j.cobme.2021.100349
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  6. Article ; Online: Novel tubing connectors reduce ECMO circuit thrombosis.

    Bresette, Christopher A / Shea, Susan M / Wagoner, Scott / Bakshi, Saagar / Deshpande, Shriprasad R / Maher, Kevin O / Ku, David N

    The International journal of artificial organs

    2024  , Page(s) 3913988241252255

    Abstract: Background: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit ... ...

    Abstract Background: Thrombosis within extracorporeal membrane oxygenation (ECMO) circuits is a common complication that dominates clinical management of patients receiving mechanical circulatory support. Prior studies have identified that over 80% of circuit thrombosis can be attributed to tubing-connector junctions.
    Methods: A novel connector was designed that reduces local regions of flow stagnation at the tubing-connector junction to eliminate a primary source of ECMO circuit thrombi. To compare clotting between the novel connectors and the traditional connectors, both in vitro loops and an in vivo caprine model of long-term (48 h) ECMO were used to generate tubing-connector junction clots.
    Results: In vitro, the traditional connectors uniformly (9/9) formed large thrombi, while novel connectors formed a small thrombus in only one of nine (
    Conclusion: Both in vitro and in vivo validation experiments successfully recreated circuit thrombosis and demonstrate that the adoption of novel connectors can reduce the burden of circuit thrombosis.
    Language English
    Publishing date 2024-05-14
    Publishing country United States
    Document type Journal Article
    ZDB-ID 80456-3
    ISSN 1724-6040 ; 0391-3988
    ISSN (online) 1724-6040
    ISSN 0391-3988
    DOI 10.1177/03913988241252255
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  7. Article: Correlation between Thrombin Generation, Standard Coagulation Assays, and Viscoelastic Assays for Hemostatic Assessment in Critically Ill Children.

    Thomas, Kimberly A / Shea, Susan M / Saini, Arun / Muszynski, Jennifer A / Spinella, Philip C

    The journal of applied laboratory medicine

    2022  Volume 7, Issue 5, Page(s) 1108–1119

    Abstract: Background: Accurate assessment of hemostatic function is essential to guide care in critically ill children with acute and acquired coagulopathies. Thrombin generation (TG) provides a global assessment of procoagulant and anticoagulant factors and is ... ...

    Abstract Background: Accurate assessment of hemostatic function is essential to guide care in critically ill children with acute and acquired coagulopathies. Thrombin generation (TG) provides a global assessment of procoagulant and anticoagulant factors and is commonly used in hemostasis research laboratories. Our objective was to determine the correlation of clinically available hemostasis assays with TG in critically ill children.
    Methods: Children (<18 years old, >3 kg in weight) in the intensive care unit were enrolled from March 2016 to December 2019 in a prospective 2-center study. Coagulation tests were prothrombin time, activated thromboplastin time, anti-Xa assay, viscoelastic assays (thromboelastography [TEG], rotational thromboelastometry [ROTEM]), and TG (induced by 20 pM tissue factor in platelet poor plasma and reported as endogenous thrombin potential [ETP; nM*min]). Data are reported as median (interquartile range) or Spearman coefficient (ρ).
    Results: Patients (n = 106, age 10.2 years [3.8-15.3]) were divided into 3 groups: (a) no anticoagulation (n = 46), (b) anticoagulation (unfractionated heparin) without extracorporeal life support (n = 34), or (c) with extracorporeal life support (n = 26). ETP was decreased in anticoagulated compared to non-anticoagulated patients (group 1: 902.4 [560.8-1234], group 2: 315.6 [0.0-962.2], group 3: 258.5 [0.0-716.6]; P < 0.0001). Across all patients, ETP correlated best with TEG kinetic time (TEG-K), in min (ρ = -0.639), followed by TEG reaction time, in min (ρ = -0.596). By group, ETP correlated best with international normalized ratio for group 1 (ρ = -0.469), TEG-K time for group 2 (ρ = -0.640), and anti-Xa for group 3 (ρ = -0.793).
    Conclusions: Standard and viscoelastic assays have varying correlation with TG in critically ill children. TEG-K time had the most consistent moderate correlation with ETP across all groups.
    MeSH term(s) Adolescent ; Blood Coagulation Tests ; Child ; Child, Preschool ; Critical Illness/therapy ; Hemostasis ; Hemostatics/pharmacology ; Heparin ; Humans ; Prospective Studies ; Thrombin/pharmacology
    Chemical Substances Hemostatics ; Heparin (9005-49-6) ; Thrombin (EC 3.4.21.5)
    Language English
    Publishing date 2022-08-26
    Publishing country England
    Document type Journal Article
    ISSN 2576-9456
    ISSN 2576-9456
    DOI 10.1093/jalm/jfac030
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  8. Article ; Online: Doing more with less: low-titer group O whole blood resulted in less total transfusions and an independent association with survival in adults with severe traumatic hemorrhage.

    Shea, Susan M / Mihalko, Emily P / Lu, Liling / Thomas, Kimberly A / Schuerer, Douglas / Brown, Joshua B / Bochicchio, Grant V / Spinella, Philip C

    Journal of thrombosis and haemostasis : JTH

    2023  Volume 22, Issue 1, Page(s) 140–151

    Abstract: Background: Low-titer group O whole blood (LTOWB) or component therapy (CT) may be used to resuscitate hemorrhaging trauma patients. LTOWB may have clinical and logistical benefits and may improve survival.: Objectives: We hypothesized LTOWB would ... ...

    Abstract Background: Low-titer group O whole blood (LTOWB) or component therapy (CT) may be used to resuscitate hemorrhaging trauma patients. LTOWB may have clinical and logistical benefits and may improve survival.
    Objectives: We hypothesized LTOWB would improve 24-hour survival in hemorrhaging patients and would be safe and equally efficacious in non-group O compared with group O patients.
    Methods: Adult trauma patients with massive transfusion protocol activations were enrolled in this observational study. The primary outcome was 24-hour mortality. Secondary outcomes included 72-hour total blood product use. A Cox regression determined the independent associations with 24-hour mortality.
    Results: In total, 348 patients were included (CT, n = 180; LTOWB, n = 168). Demographics were similar between cohorts. Unadjusted 24-hour mortality was reduced in LTOWB vs CT: 8% vs 19% (P = .003), but 6-hour and 28-day mortality were similar. In an adjusted analysis with multivariable Cox regression, LTOWB was independently associated with reduced 24-hour mortality (hazard ratio, 0.21; 95% CI, 0.07-0.67; P = .004). LTOWB patients received significantly less 72-hour total blood products (80.9 [41.6-139.3] mL/kg vs 48.9 [25.9-106.9] mL/kg; P < .001). In stratified 24-hour survival analyses, LTOWB was associated with improved survival for patients in shock or with coagulopathy. LTOWB use in non-group O patients was not associated with increased mortality, organ injury, or adverse events.
    Conclusion: In this hypothesis-generating study, LTOWB use was independently associated with improved 24-hour survival, predominantly in patients with shock or coagulopathy. LTOWB also resulted in a 40% reduction in blood product use which equates to a median 2.4 L reduction in transfused products.
    MeSH term(s) Adult ; Humans ; Resuscitation/adverse effects ; Resuscitation/methods ; Blood Transfusion/methods ; Hemorrhage/therapy ; Proportional Hazards Models ; ABO Blood-Group System ; Wounds and Injuries/complications ; Wounds and Injuries/diagnosis ; Wounds and Injuries/therapy
    Chemical Substances ABO Blood-Group System
    Language English
    Publishing date 2023-10-04
    Publishing country England
    Document type Observational Study ; Journal Article
    ZDB-ID 2112661-6
    ISSN 1538-7836 ; 1538-7933
    ISSN (online) 1538-7836
    ISSN 1538-7933
    DOI 10.1016/j.jtha.2023.09.025
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  9. Article ; Online: A rapid ABO and RhD test demonstrates high fidelity to blood bank testing for RhD typing.

    Younes, Reem / Spinella, Philip C / Shea, Susan M / Bailey-Kroll, Lilith / Neal, Matthew D / Leeper, Christine / Yazer, Mark H

    Transfusion

    2023  Volume 63 Suppl 3, Page(s) S208–S212

    Abstract: Background: The rapid provision of blood products is life-saving for patients with massive hemorrhage. Ideally, RhD-negative blood products would be supplied to a woman of childbearing potential whose Rh type is unknown due to the risk of D- ... ...

    Abstract Background: The rapid provision of blood products is life-saving for patients with massive hemorrhage. Ideally, RhD-negative blood products would be supplied to a woman of childbearing potential whose Rh type is unknown due to the risk of D-alloimmunization and the potential for hemolytic disease of the fetus and newborn to occur if RhD-positive blood products are transfused. Therefore, there is a need for a test that rapidly determines her RhD type. This study compared the RhD type determined using a rapid ABO and RhD test to the RhD type determined by an immunohematology reference laboratory.
    Methods: After receiving ethics review board approval, 200 random, unique, deidentified patient samples that had undergone routine pretransfusion testing in an immunohematology reference laboratory using column agglutination technology were collected and tested using a rapid ABO and RhD test (Eldoncard Home kit 2511). The RhD typing results from these two methods were compared to determine the accuracy of the rapid ABO and RhD test.
    Results: The rapid ABO and RhD test produced results that were concordant with the transfusion service's results in 199/200 (99.5%) of cases, with a negative predictive value of 98.2% and 99.3% sensitivity. The single outlier was likely an RhD variant due to its serological characteristics.
    Discussion: These data indicate that this rapid ABO and RhD test could be used for the rapid determination of a patient's RhD type, perhaps even in the emergency department, which could guide the selection of blood products provided during their resuscitation.
    MeSH term(s) Humans ; Female ; Infant, Newborn ; Blood Banks ; Rh-Hr Blood-Group System ; Blood Transfusion ; Hematologic Diseases ; Hematologic Tests
    Chemical Substances Rh-Hr Blood-Group System
    Language English
    Publishing date 2023-04-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 208417-x
    ISSN 1537-2995 ; 0041-1132
    ISSN (online) 1537-2995
    ISSN 0041-1132
    DOI 10.1111/trf.17326
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  10. Article ; Online: The effect of platelet storage temperature on haemostatic, immune, and endothelial function: potential for personalised medicine.

    Shea, Susan M / Thomas, Kimberly A / Spinella, Philip C

    Blood transfusion = Trasfusione del sangue

    2019  Volume 17, Issue 4, Page(s) 321–330

    Abstract: Reports from both adult and paediatric populations indicate that approximately two-thirds of platelet transfusions are used prophylactically to prevent bleeding, while the remaining one-third are used therapeutically to manage active bleeding. These two ... ...

    Abstract Reports from both adult and paediatric populations indicate that approximately two-thirds of platelet transfusions are used prophylactically to prevent bleeding, while the remaining one-third are used therapeutically to manage active bleeding. These two indications, prophylactic and therapeutic, serve two very distinct purposes and therefore will have two different functional requirements. In addition, disease aetiology in a given patient may require platelets with different functional characteristics. These characteristics can be derived from the various manufacturing methods used in platelet product production, including collection methods, processing methods, and storage options. The iterative combinations of manufacturing methods can result in a number of unique platelet products with different efficacy and safety profiles, which could potentially be used to benefit patient populations by meeting diverse clinical needs. In particular, cold storage of platelet products causes many biochemical and functional changes, of which the most notable characterised to date include increased haemostatic activity and altered expression of molecules inherent to platelet:leucocyte interactions. The in vivo consequences, both short- and long-term, of these molecular and cellular cold-storage-induced changes have yet to be clearly defined. Elucidation of these mechanisms would potentially reveal unique biologies that could be harnessed to provide more targeted therapies. To this end, in this new era of personalised medicine, perhaps there is an opportunity to provide individual patients with platelet products that are tailored to their clinical condition and the specific indication for transfusion.
    MeSH term(s) Animals ; Blood Platelets/cytology ; Blood Platelets/immunology ; Blood Platelets/metabolism ; Blood Preservation/methods ; Cell Communication ; Cold Temperature ; Endothelial Cells/cytology ; Endothelial Cells/immunology ; Endothelial Cells/metabolism ; Hemostasis ; Humans ; Leukocytes/cytology ; Leukocytes/immunology ; Leukocytes/metabolism ; Platelet Transfusion/methods ; Precision Medicine/methods
    Language English
    Publishing date 2019-08-05
    Publishing country Italy
    Document type Journal Article ; Review
    ZDB-ID 2135732-8
    ISSN 2385-2070 ; 0041-1787 ; 1723-2007
    ISSN (online) 2385-2070
    ISSN 0041-1787 ; 1723-2007
    DOI 10.2450/2019.0095-19
    Database MEDical Literature Analysis and Retrieval System OnLINE

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