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  • 1
    In: Pharmacogenomics, Future Medicine Ltd, Vol. 17, No. 11 ( 2016-07), p. 1235-1243
    Abstract: Antibody-mediated pure red cell aplasia is a rare but serious complication in chronic kidney disease patients receiving recombinant human erythropoietin (r-HuEpo). Between April 2012 and May 2013, eight such cases were reported in our institution. Their clinical features were reviewed and their HLA alleles were compared with those of healthy controls. All patients were exposed to epoetin alfa (Eprex ® ) with polysorbate-80 as stabilizer via subcutaneous route with a mean age of 61.9 years and mean exposure of 11.2 months of r-HuEpo before loss of efficacy. 87.5% of the cases were male and Chinese and received immunosuppression as treatment for pure red cell aplasia. All three of the successfully treated patients are alive compared with only 40% of the transfusion-dependent patients. DRB1*12:02 was more frequently expressed among the cases than healthy controls suggesting a plausible molecular link.
    Type of Medium: Online Resource
    ISSN: 1462-2416 , 1744-8042
    Language: English
    Publisher: Future Medicine Ltd
    Publication Date: 2016
    SSG: 15,3
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  • 2
    In: Vox Sanguinis, Wiley, Vol. 114, No. 3 ( 2019-04), p. 198-206
    Abstract: We compared the ex vivo haemostatic capacity of RTFP 24 with FFP upon thawing and 〉 24 h post‐thaw. We included thrombin generation ( TG ) as few studies had compared global haemostatic function, and most did not directly compare RTFP 24 with FFP 〉 24 h post‐thaw. Materials/methods Twenty units each of RTFP 24 and FFP were measured for coagulation factors and thrombin generation upon thawing (D0) and 4 days post‐thaw (D4). Labile factors were also measured from D1 to D3. 10 single cryoprecipitate units were each prepared from FFP and RTFP 24, and measured for FXIII , FVIII and fibrinogen at D0. Results At D0, RTFP 24 was comparable to FFP except for lower FV , protein S, endogenous thrombin potential ( ETP ) and higher FXIII . These differences were likely clinically insignificant since 95% and 80% of RTFP 24 met our laboratory's reference ranges for FV /protein S and ETP , respectively. There were no differences between RTFP 24‐ and FFP ‐derived cryoprecipitate. At D4, RTFP 24 was comparable to FFP except for lower FV , ETP , and higher FXI and FXIII . More RTFP 24 than FFP had ETP lower than our laboratory's reference range (45% vs 15%). Multiple coagulation factors and all TG parameters declined from their respective baselines. The percentage declines were comparable or less in RTFP 24, except for protein C, fibrinogen and time to peak. Conclusion RTFP 24 and FFP , and their derived cryoprecipitate have comparable haemostatic capacity upon thawing. RTFP 24 has poorer TG potential than FFP 〉 24 h post‐thaw, not supporting universal extension of RTFP 24's shelf life except to facilitate urgent transfusions for massive haemorrhage.
    Type of Medium: Online Resource
    ISSN: 0042-9007 , 1423-0410
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1483587-3
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  • 3
    In: Seminars in Thrombosis and Hemostasis, Georg Thieme Verlag KG, Vol. 49, No. 05 ( 2023-07), p. 561-564
    Type of Medium: Online Resource
    ISSN: 0094-6176 , 1098-9064
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2023
    detail.hit.zdb_id: 2072469-X
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  • 4
    In: International Journal of Laboratory Hematology, Wiley, Vol. 44, No. 1 ( 2022-02)
    Type of Medium: Online Resource
    ISSN: 1751-5521 , 1751-553X
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2268600-9
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  • 5
    Online Resource
    Online Resource
    SAGE Publications ; 2018
    In:  Clinical and Applied Thrombosis/Hemostasis Vol. 24, No. 7 ( 2018-10), p. 1144-1147
    In: Clinical and Applied Thrombosis/Hemostasis, SAGE Publications, Vol. 24, No. 7 ( 2018-10), p. 1144-1147
    Abstract: Race is touted as an independent risk factor for venous thromboembolism (VTE), although the basis for this is varied and contentious. Comparison of plasma thrombin generation (TG) using calibrated automated thrombogram (CAT) across races offers a modality that objectively measures global hemostatic function to evaluate this influence. Direct comparative data across races are currently not available. Aim is to establish the influence of race on plasma TG. Sixty normal participants, matched for age and gender, equally representing 4 races—Caucasian, Chinese, Indian, and Malay—were recruited. Thrombin generation parameters (lag time, time to peak, peak, and endogenous thrombin potential [ETP]) in platelet-poor plasma were measured using CAT. The mean ETP (standard deviation) for the different races were Caucasians: 1338.18 (194.19) nM·min; Chinese, 1318.91 (108.90) nM·min; Indians, 1389.81 (182.61) nM·min; and Malays, 1436.21 (184.24) nM·min. Caucasians had the longest mean lag time of 2.59 ± 0.37 seconds; Indians had the highest mean peak of 284.22 ± 30.74 nM, and Malays had the longest mean time to peak of 5.47 ± 0.59 seconds. Analysis based on race did not demonstrate any significant difference for all TG parameters. The greatest mean difference of ETP between any 2 races (Malays and Chinese) was 117.30 nM·min (95% confidence interval: −45.86 to 280.46 nM·min) which was within the predefined limit of equivalence. In a cohort of healthy participants, TG mediated by plasma factors is not influenced by race and does not explain the reported racial differences in VTE incidence. For the 4 racial groups studied, the use of separate normal ranges for plasma TG might not be essential.
    Type of Medium: Online Resource
    ISSN: 1076-0296 , 1938-2723
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2018
    detail.hit.zdb_id: 2230591-9
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  • 6
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2022
    In:  Journal of Thrombosis and Thrombolysis Vol. 54, No. 1 ( 2022-07), p. 29-32
    In: Journal of Thrombosis and Thrombolysis, Springer Science and Business Media LLC, Vol. 54, No. 1 ( 2022-07), p. 29-32
    Type of Medium: Online Resource
    ISSN: 0929-5305 , 1573-742X
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2017305-2
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  • 7
    In: Transfusion, Wiley, Vol. 61, No. 12 ( 2021-12), p. 3420-3431
    Abstract: The procoagulant profile of platelet concentrates (PCs) following transfusion has been difficult to evaluate due to lack of specific markers. This study aimed to characterize procoagulant platelets in PCs and the effect of transfusion. Study design and methods Buffy coat‐derived PCs from 12 donors were pooled, split, then stored conventionally, cold (2–6°C) or cryopreserved (−80°C). Procoagulant platelet profiles were assessed by flow cytometry (GSAO + /P‐selectin + ), lactadherin‐binding, and calibrated automated thrombogram, during storage, unstimulated, or after thrombin and collagen stimulation and compared with blood from healthy volunteers. Platelet activation (P‐selectin) and procoagulant platelet formation potential were measured (flow cytometry) in patients receiving clinically indicated conventional PC transfusion. Results Independent of significant increases with storage, procoagulant platelet proportions with and without agonist stimulation were significantly blunted in conventionally stored PCs (stimulated day 5 conventional PC 4.2 ± 1.3%, healthy volunteer blood 11.1 ± 2.9%; p   〈  .0001). Cryopreserved PCs contained the highest proportion of procoagulant platelets (unstimulated: cryopreserved 25.6 ± 1.8% vs. day 5 conventional 0.5 ± 0.1% vs. day 14 cold‐stored 5.8 ± 1.0%, p   〈  .0001), but demonstrated minimal increase with agonist. Transfusion of PCs was associated with an increase in procoagulant platelets (2.2 ± 1.4% vs. 0.6 ± 0.2%; p  = .004) and reversal of the blunted agonist response (15.8 ± 5.9% vs. 4.0 ± 1.6%; p   〈  .0001). Procoagulant responses post‐transfusion were significantly higher than healthy controls, suggesting a priming effect. The P‐selectin agonist response was not restored upon transfusion (79.4 ± 13.9% vs. 82.0 ± 2.5%). Conclusion Storage blunts the procoagulant platelet response to agonist stimulation in PCs. Despite this, conventionally stored PCs have high procoagulant potential following transfusion, with a discordant, persistent reduction in P‐selectin response.
    Type of Medium: Online Resource
    ISSN: 0041-1132 , 1537-2995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2018415-3
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  • 8
    In: Transfusion, Wiley, Vol. 63, No. 9 ( 2023-09), p. 1649-1660
    Abstract: The short shelf‐life of liquid‐stored platelets (LP) at 20–24°C poses shortage and wastage challenges. Cryopreserved platelets have significantly extended shelf‐life, and were safe and efficacious for therapeutic transfusions of bleeding patients in the Afghanistan conflict and phase 2 randomized studies. Although hematology patients account for half of platelets demand, there is no randomized study on prophylactic cryopreserved platelet transfusions in them. Methods We performed a phase 1b/2a randomized cross‐over study comparing the safety and efficacy of cryopreserved buffy coat‐derived pooled platelets (CP) to LP in the prophylactic transfusions of thrombocytopenic hematology patients. Results A total of 18 adults were randomly assigned 1:1 to CP and LP for their first thrombocytopenic period (TP) of up to 28‐days. A total of 14 crossed over to the other platelet‐arm for the second TP. Overall, 17 subjects received 51 CP and 15 received 52 LP. CP‐arm had more treatment emergent adverse event (29.4% vs. 13.3% of subjects, 9.8% vs. 3.8% of transfusions) than LP‐arm but all were mild. No thromboembolism was observed. Both arms had similar bleeding rates (23.5% vs. 26.7% of subjects) which were all mild. Subjects in CP‐arm had lower average corrected count increments than LP‐arm (mean [SD] 5.6 [4.20] vs. 22.6 [9.68] ×10 9 /L at 1–4 h, p   〈  .001; 5.3 [4.84] vs. 18.2 [9.52] ×10 9 /L at 18–30 h, p   〈  .001). All TEG parameters at 1–4 h and maximum amplitude (MA) at 18–30 h improved from baseline post‐CP transfusion ( p   〈  .05) though improvements in K‐time and MA were lower than LP ( p   〈  .05). Discussion During shortages, CP may supplement LP in prophylactic transfusions of thrombocytopenic patients.
    Type of Medium: Online Resource
    ISSN: 0041-1132 , 1537-2995
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2023
    detail.hit.zdb_id: 2018415-3
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  • 9
    In: Blood, American Society of Hematology, Vol. 136, No. Supplement 1 ( 2020-11-5), p. 25-26
    Abstract: Introduction An increasing number of evidence have reported the association of COVID-19 with increased incidence of thrombotic events. High incidences were initially reported in critically ill COVID-19 patients, but subsequently an increased incidence was also noticed in non-critically ill general ward patients. This has led to a universal recommendation of thromboprophylaxis for all COVID-19 patients by ASH and ISTH. As the data on COVID-19 and thrombosis continue to develop and evolve, we examined the data in two aspects. Firstly, other non-SARS-CoV-2 viral respiratory infections have also been reported to be associated with thrombotic events, be it arterial or venous. Thus, we aimed to compare the thrombotic rates between these two groups of patients directly to hopefully ascertain the actual thrombotic tendency in COVID-19 infections. Secondly, global hemostatic assays such as thromboelastogram and clot waveform analysis (CWA) have been used to demonstrate hypercoagulability in COVID-19 patients, albeit in a small group of patients and only in the critically ill. Incorporating these laboratory results into the management of thromboprophylaxis in COVID-19 is an attractive notion but more data and studies are definitely needed. Here, we evaluate the dynamic changes of hemostatic assays in patients with COVID-19 to better understand the overall coagulation profiles of COVID-19 infection. Methods We performed a single center, retrospective cohort study. All consecutive patients admitted to our hospital between 15 January and 10 April 2020 that were tested positive for COVID-19 or other non-SARS-CoV-2 respiratory viruses were included in our study. The main coagulation assays studied were prothrombin time and activated partial thromboplastin time and its associated CWA, min1, min2 and max2. Findings We included a total of 181 COVID-19 patients and 165 patients with non-SARS-CoV-2 respiratory viral infections. The respiratory viruses were rhinovirus (n=65), influenza A and B (n=46), adenovirus (n=13), human coronavirus 229E/NL63/OC43 (n=15), human enterovirus (n=3), metapneumovirus (n=6), parainfluenza virus 1 to 4 (n=11), respiratory syncytial virus (n=6) and human bocavirus 1 to 4 (n=0). The median age of COVID-19 patients was 37 (interquartile range [IQR], 30.5-51 years) versus 35 (IQR, 29-51.5) in the non-SAR-CoV-2 respiratory viruses group (P=0.12). Comorbidities, assessed by Charlson score, was also not statistically different between both groups (median score 0 (IQR, 0-1) in both groups, P=0.39). Majority of our patients had relatively mild infection as reflected by the low proportions of them requiring oxygen supplementation (11.0% in COVID-19 vs 4.8% in non-SARS-COV-2, P=0.035). COVID-19 patients had longer hospital stay (7 days (IQR, 5.5-13) vs 3 days (IQR, 2-3), P & lt;0.001) and more required ICU support (5.0% vs 1.2%, P=0.04). Mortality rate was low in both groups. We reported two (1.0 event/1000-hospital-days) and one (1.8 event/1000-hospital-day) thrombotic events amongst COVID-19 group and non-SARS-COV-2 group respectively (P=0.63). All were myocardial infarction and occurred in intensive care unit. No venous thrombotic event was noted. There was no significant difference in all the coagulation parameters throughout the course of mild COVID-19 infection (Table 1). However, CWA parameters were significantly higher in severe COVID-19 infection compared with mild disease (min1: 6.48%/s vs 5.05%/s, P & lt;0.001; min2: 0.92%/s2 vs 0.74%/s2, P=0.033), suggesting hypercoagulability in severe COVID-19 infection (Table 2 and Figure 1). We also observed that critically ill COVID-19 patients had higher absolute CWA parameters as compared to non-SARS-CoV-2 patients, albeit in small number of patients (Table 3). Conclusion The thrombotic rates were low in both groups and did not differ significantly between COVID-19 and Non-SARS-CoV-2 patients. Nonetheless, our analysis of hemostatic parameters demonstrated hypercoagulability in COVID-19 as a dynamic process with the risk highest when the patients are critically ill. These changes in hemostasis could be detected by CWA. With our findings, we suggest that a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is probably preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and warrants further research. Disclosures Lee: Sanofi: Honoraria, Other: travel grants; Pfizer: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees, Other: travel grants ; Medtronics: Membership on an entity's Board of Directors or advisory committees; Novartis: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2020
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: SSRN Electronic Journal, Elsevier BV
    Type of Medium: Online Resource
    ISSN: 1556-5068
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
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