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  • 1
    In: Thrombosis and Haemostasis, Georg Thieme Verlag KG, Vol. 121, No. 02 ( 2021-02), p. 224-233
    Abstract: Background Direct oral anticoagulants (DOACs) are prescribed for atrial fibrillation (AF) and venous thromboembolism (VTE) and both occur more frequently in obese patients. Outcomes from DOAC trials included few individuals ≥ 120 kg leading to uncertainty whether high body weight (BW) reduces DOAC concentrations. Objectives This article investigates the relationship between factor Xa (FXa) inhibitor concentrations, BW, and renal function, and compares them in high BW patients with unselected populations. Methods Consecutive patients in two United Kingdom centers, weighing ≥ 120 kg receiving 5 mg twice daily apixaban or 20 mg once daily rivaroxaban for AF or VTE were prospectively included. Peak or trough concentrations were measured using specific chromogenic assays, expressed in mean or median (5th–95th percentiles). On-therapy range was the interval from the 5th percentile trough concentration to the 95th percentile peak concentration. Results One hundred patients were included; age range: 23 to 78 years, 31% were women, 58% had AF, creatinine clearance range: 67 to 474 mL/min. Median BW was 139 kg, and 84% had body mass index (BMI) ≥ 40 kg/m2. DOAC peak and trough concentrations varied from 44 to 727 and 14 to 299 ng/mL, respectively. There was no linear relationship between FXa inhibitor concentrations at peak or trough and BW or BMI, and creatinine clearance. Apixaban troughs in AF and rivaroxaban peaks in VTE were lower than in unselected populations. However, only two trough concentrations were below the expected range, and 109/116 were within the on-therapy range. Conclusion These data indicated that obese or high BW patients generally achieve therapeutic FXa inhibitor concentrations. However, further investigations assessing clinical outcomes are required.
    Type of Medium: Online Resource
    ISSN: 0340-6245 , 2567-689X
    Language: English
    Publisher: Georg Thieme Verlag KG
    Publication Date: 2021
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  • 2
    Online Resource
    Online Resource
    Springer Science and Business Media LLC ; 2018
    In:  Pathology & Oncology Research Vol. 24, No. 4 ( 2018-10), p. 915-919
    In: Pathology & Oncology Research, Springer Science and Business Media LLC, Vol. 24, No. 4 ( 2018-10), p. 915-919
    Type of Medium: Online Resource
    ISSN: 1219-4956 , 1532-2807
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2018
    detail.hit.zdb_id: 2002501-4
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  • 3
    Online Resource
    Online Resource
    Massachusetts Medical Society ; 2018
    In:  New England Journal of Medicine Vol. 378, No. 1 ( 2018-01-04), p. 92-93
    In: New England Journal of Medicine, Massachusetts Medical Society, Vol. 378, No. 1 ( 2018-01-04), p. 92-93
    Type of Medium: Online Resource
    ISSN: 0028-4793 , 1533-4406
    RVK:
    Language: English
    Publisher: Massachusetts Medical Society
    Publication Date: 2018
    detail.hit.zdb_id: 1468837-2
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  • 4
    Online Resource
    Online Resource
    Wiley ; 2019
    In:  Pediatric Anesthesia Vol. 29, No. 5 ( 2019-05), p. 405-413
    In: Pediatric Anesthesia, Wiley, Vol. 29, No. 5 ( 2019-05), p. 405-413
    Type of Medium: Online Resource
    ISSN: 1155-5645 , 1460-9592
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 2008564-3
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  • 5
    Online Resource
    Online Resource
    Informa UK Limited ; 2023
    In:  Critical Reviews in Clinical Laboratory Sciences
    In: Critical Reviews in Clinical Laboratory Sciences, Informa UK Limited
    Type of Medium: Online Resource
    ISSN: 1040-8363 , 1549-781X
    Language: English
    Publisher: Informa UK Limited
    Publication Date: 2023
    detail.hit.zdb_id: 2030111-X
    SSG: 12
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  • 6
    In: Thrombosis Update, Elsevier BV, Vol. 1 ( 2020-12), p. 100018-
    Type of Medium: Online Resource
    ISSN: 2666-5727
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2020
    detail.hit.zdb_id: 3024245-9
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  • 7
    In: Blood, American Society of Hematology, Vol. 133, No. 15 ( 2019-04-11), p. 1644-1651
    Abstract: Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare thrombomicroangiopathy caused by an inherited deficiency of a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13 (ADAMTS13). There are limited data on genotype-phenotype correlation; there is no consensus on treatment. We reviewed the largest cohort of cTTP cases, diagnosed in the United Kingdom, over the past 15 years. Seventy-three cases of cTTP were diagnosed, confirmed by genetic analysis. Ninety-three percent were alive at the time of review. Thirty-six percent had homozygous mutations; 64% had compound heterozygous mutations. Two presentation peaks were seen: childhood (median diagnosis age, 3.5 years) and adulthood, typically related to pregnancy (median diagnosis age, 31 years). Genetic mutations differed by age of onset with prespacer mutations more likely to be associated with childhood onset (P = .0011). Sixty-nine percent of adult presentations were associated with pregnancy. Fresh-frozen plasma (FFP) and intermediate purity factor VIII concentrate were used as treatment. Eighty-eight percent of patients with normal blood counts, but with headaches, lethargy, or abdominal pain, reported symptom resolution with prophylactic therapy. The most common currently used regimen of 3-weekly FFP proved insufficient for 70% of patients and weekly or fortnightly infusions were required. Stroke incidence was significantly reduced in patients receiving prophylactic therapy (2% vs 17%; P = .04). Long-term, there is a risk of end-organ damage, seen in 75% of patients with late diagnosis of cTTP. In conclusion, prespacer mutations are associated with earlier development of cTTP symptoms. Prophylactic ADAMTS13 replacement decreases the risk of end-organ damage such as ischemic stroke and resolved previously unrecognized symptoms in patients with nonovert disease.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2019
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 8
    Online Resource
    Online Resource
    American Society of Hematology ; 2013
    In:  Blood Vol. 122, No. 21 ( 2013-11-15), p. 5591-5591
    In: Blood, American Society of Hematology, Vol. 122, No. 21 ( 2013-11-15), p. 5591-5591
    Abstract: High-grade non-Hodgkin lymphoma is an aggressive condition that requires equally aggressive management. Due to the possibility of curative treatment if the disease is effectively managed, rapid diagnosis, precise staging, and swift commencement of treatment are crucial. In Ireland there is little reliable data on how closely guidelines in non-Hodgkin lymphoma treatment are followed. In order to obtain better data, we replicated a recent study carried out in the Netherlands by Wennekes and colleagues (J Clin Oncol 2011 April 10;29(11): 1436-1444). Methods This study was carried out in two hospitals in Cork, Ireland. Ethical approval was obtained from the Cork Research Ethics Committee. We used the National Cancer Registry of Ireland and records of the Citywide Lymphoma Conference to identify high-grade non-Hodgkin lymphoma patients treated at the participating centers. 125 patient records were identified. This was similar to the sample size used by Wennekes. The quality markers used in the Dutch study were chosen as data points. This set was then slightly modified to account for local guideline differences. Data was obtained through a systematic, retrospective chart review. Results When analyzing the data, 90% adherence was set as a target. This was in keeping with previous research. Of our 22 quality markers, 11 reached the target level. Diagnosis and staging markers were generally well adhered to. 93% of non-CNS lymphoma patients received an RCHOP or DA-EPOCH-R regimen, 92.8% of patients were diagnosed with an appropriate biopsy, and 92% received a histological diagnosis before treatment was commenced. Scores regarding treatment were close to the target level. 83.5% of patients began chemotherapy within four weeks of diagnosis, and 74.1% of patients received a histological diagnosis within three weeks of presentation. Lower adherence was noted in areas relating to the communication of results. Use of the Cheson criteria to report radiological response was very limited. 12.8% of PET reports and 5% of CT reports used the Cheson criteria. In addition, the patient’s Ann Arbor staging was rarely included on CT and PET reports – 0% and 2.4% respectively. Conclusion This is the first replication of the Dutch study on non-Hodgkin lymphoma management. Irish hospitals are meeting non-Hodgkin lymphoma management guidelines in 11 of 22 areas. Adherence for the remaining areas ranges from 83.5% to 0%. Further studies in different Irish centers will provide important data to increase the external validity of this study. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2013
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 9
    Online Resource
    Online Resource
    American Society of Hematology ; 2012
    In:  Blood Vol. 120, No. 21 ( 2012-11-16), p. 4229-4229
    In: Blood, American Society of Hematology, Vol. 120, No. 21 ( 2012-11-16), p. 4229-4229
    Abstract: Abstract 4229 Introduction: Laboratory medicine services are critical to delivering high quality patient care. They operate to internationally recognized standards to ensure the quality and accuracy of their test results. Their responsibilities are wide ranging including enabling the clinician to confirm or exclude the presence of significant diseases, monitoring the progress of chronic conditions, providing expert advice in the management of patients with complex conditions, supporting research and development into new laboratory tests, systems and processes and supporting undergraduate teaching, postgraduate teaching and professional development. In the current economic climate, resources are diminishing in accordance with government austerity measures. At the same time, patients have increasing knowledge and therefore often have increasingly complex demands. To optimize primary care services, it is crucial that primary care physicians have appropriate access to tests. But a balance needs to be struck between a primary care physician's access and a laboratory's ability to limit access so that limited resources can be used to the maximum benefit of patients. Evidence based guidelines are critical. Laboratory tests can broadly be split into two categories: frequently ordered, inexpensive tests such as blood counts and infrequently ordered, expensive tests such as hereditary thrombophillia screens. In our institution, we chose to review vitamin B12 and folate testing as they are frequently requested, relatively inexpensive but time consuming assays. The aims of our study were to review the number of vitamin B12 and folate tests ordered by primary care physicians, to find out why the tests were being ordered and to see if they were being ordered appropriately. Methods: We reviewed our laboratory records to ascertain the number of vitamin B12 and folate assays carried out between 2004 and 2011. To find out why the tests was being ordered, the primary care physicians that use the laboratory in University Hospital Galway were sent out a questionnaire. To review whether or not clinical data was provided, 200 random request forms form March 2012 were reviewed. The literature was then reviewed to look at international guidelines. Results: The number of B12 and folate requests have risen year on year between 2004 and 2011, numbering 33,872 in 2004 and 96,544 in 2011. 69 of 172 primary health care centers responded to the survey. The main reasons given for ordering the test were unexplained neurological symptoms, macrocytosis, anemia and fatigue. 200 random request forms that the laboratory had received from primary care physicians were reviewed. 50% had clinical details. The reasons given for ordering the test were very varied, the most common being rountine screening and fatigue. 50 % had no clinical details provided. If the patient had had a recent full blood count in our laboratory, this was reviewed to see if any indication for the test could be ascertained. The majority (81%) had normal full blood counts. Discussion: According to the central statistics office, the population of our catchment area increased by 17% between 2002 and 2011. This did not account for the 185% increase in testing between 2004 and 2011. As vitamin B12 and folate were invariably requested in association with a ferritin level, this equates to €376,522 per year in assay cost alone. These tests are time consuming (around 40 minutes per batch) and labor intensive, which is increasingly a major factor as the main method for reducing laboratory costs to date has been to reduce the workforce. While the majority of primary care physicians knew the appropriate indications for B12 and folate testing when asked, this was not reflected in their practice. It was also worrying that many seemed unaware of important indications for testing such as unexplained cytopenias. On reviewing the literature, it is clear that there is no current guideline for vitamin B12 and folate testing. The most recent British committee for standards in hematology (BCSH) guideline was published in 1994 and is archived. Conclusion: In the current economic crisis, it is imperative that services are optimized so that patients do not suffer in the setting of decreased resources. This is best achieved when secondary and tertiary care institutions collaborate with primary care to deliver evidenced based health care. Disclosures: No relevant conflicts of interest to declare.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
    RVK:
    RVK:
    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2012
    detail.hit.zdb_id: 1468538-3
    detail.hit.zdb_id: 80069-7
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  • 10
    In: Clinical and Applied Thrombosis/Hemostasis, SAGE Publications, Vol. 22, No. 6 ( 2016-09), p. 554-562
    Abstract: The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P 〈 .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P 〈 .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies.
    Type of Medium: Online Resource
    ISSN: 1076-0296 , 1938-2723
    Language: English
    Publisher: SAGE Publications
    Publication Date: 2016
    detail.hit.zdb_id: 2230591-9
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