| 11. |
- Eichler, Petra, et al.
(författare)
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The new ID-heparin/PF4 antibody test for rapid detection of heparin-induced antibodies in comparison with functional and antigenic assays.
- 2002
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Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 116:4, s. 887-91
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Tidskriftsartikel (refereegranskat)abstract
- Heparin-induced thrombocytopenia (HIT) is an immune-mediated complication of heparin treatment. Several in vitro assays are available to detect the causative HIT antibodies: functional assays, usually requiring freshly prepared platelets and immunological tests based on the enzyme-linked immunosorbent assay (ELISA) principle. We compared a new, simple and rapid test based on the ID-microtyping particle agglutination system with 14C-serotonin release assay, heparin-induced platelet activation (HIPA) test and two ELISAs. Sera from 100 confirmed HIT patients, 20 serologically negative suspected HIT patients and 20 healthy blood donors were used. The specificity and sensitivity of the new test was similar to the functional assays. Compared with the ELISAs, specificity was better at the cost of reduced sensitivity. As in all other immunological tests, HIT antibodies against less typical antigens, such as interleukin (IL)-8 or neutrophil-activating peptide (NAP) 2 could not be detected. Thus, although the ID-Heparin/PF4 antibody test seems to be a quick, reliable and robust test to determine the presence of HIT antibodies, it should still be combined with a functional assay if possible. Evaluation of the test in a prospective setting as well as interlaboratory variation should be assessed as a next step.
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| 12. |
- Frelinger, Andrew L., 3rd, et al.
(författare)
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Consensus recommendations on flow cytometry for the assessment of inherited and acquired disorders of platelet number and function : Communication from the ISTH SSC Subcommittee on Platelet Physiology
- 2021
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Ingår i: Journal of Thrombosis and Haemostasis. - : John Wiley & Sons. - 1538-7933 .- 1538-7836. ; 19:12, s. 3193-3202
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Tidskriftsartikel (refereegranskat)abstract
- Flow cytometry is increasingly used in the study of platelets in inherited and acquired disorders of platelet number and function. However, wide variation exists in specific reagents, methods, and equipment used, making interpretation and comparison of results difficult. The goal of the present study was to provide expert consensus guidance on the use of flow cytometry for the evaluation of platelet disorders. A modified RAND/UCLA survey method was used to obtain a consensus among 11 experts from 10 countries across four continents, on the appropriateness of statements relating to clinical utility, pre-analytical variables, instrument and reagent standardization, methods, reporting, and quality control for platelet flow cytometry. Feedback from the initial survey revealed that uncertainty was sometimes due to lack of expertise with a particular test condition rather than unavailable or ambiguous data. To address this, the RAND method was modified to allow experts to self-identify statements for which they could not provide expert input. There was uniform agreement among experts in the areas of instrument and reagent standardization, methods, reporting, and quality control and this agreement is used to suggest best practices in these areas. However, 25.9% and 50% of statements related to pre-analytical variables and clinical utility, respectively, were rated as uncertain. Thus, while citrate is the preferred anticoagulant for many flow cytometric platelet tests, expert opinions differed on the acceptability of other anticoagulants, particularly heparin. Lack of expert consensus on the clinical utility of many flow cytometric platelet tests indicates the need for rigorous multicenter clinical outcome studies.
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| 13. |
- Greiser, Anne, et al.
(författare)
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The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population
- 2017
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Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 50:18, s. 1198-1202
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: Determination of cardiac troponin (cTn) is central in the emergency department (ED) for the diagnosis of myocardial infarction. In view of adverse effects of long waiting time on patient outcome, implementation of point-of-care-testing (POCT) is suggested if the turn-around-time is longer than 60min. The present study aimed to determine the 99th percentile and imprecision of two POCT in a healthy population measuring cTnI and cTnT and compare these analytical characteristics against three central laboratory test (CLT) for cTnI.DESIGN & METHODS: CTnI and cTnT were determined in parallel by means of the AQT90 FLEX analyzer in about 2250 plasma samples from individuals with known health status. Results were compared to previously determined performance data of three CLT.RESULTS: The 99th percentile of cTnI in the POCT was determined at 19ng/L, the lowest concentration with an imprecision of 10% was reached at 22ng/L while an imprecision of 20% was reached at 13ng/L. Age, sex, or physical activity did not affect the 99th percentile of cTnI. Compared to CLT the AQT90 cTnI POCT the analytical performance was equivalent. The cTnT POCT could not be assessed due a considerable number of high values and an inadequate imprecision profile.CONCLUSION: While the cTnI POCT showed analytical performance comparable to CLT, the results of the cTnT assay on the same device did not suffice to determine a reliable 99th percentile. The present evaluation supports the usage of the cTnI POCT, but application of the cTnT POCT needs further evaluation.
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| 14. |
- Hernandez, Victor Agmo, et al.
(författare)
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The adhesion and spreading of thrombocyte vesicles on electrode surfaces
- 2008
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Ingår i: Bioelectrochemistry. - : Elsevier BV. - 1567-5394 .- 1878-562X. ; 74, s. 210-216
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Tidskriftsartikel (refereegranskat)abstract
- The interaction of thrombocyte vesicles with the surface of metal electrodes, i.e., mercury, gold and gold electrodes modified with self assembled monolayers (SAM), was studied with the help of chronoamperometry, atomic force microscopy, and quartz crystal microbalance measurements. The experimental results show that the interaction of the thrombocyte vesicles with the surface of the electrodes depends on the hydrophobicity of the latter: whereas on very hydrophobic surfaces (mercury and gold functionalized with SAM) the thrombocyte vesicles disintegrate and form a monolayer of lipids. on the less hydrophobic gold surface a bilayer is formed. The chronoamperometric measurements indicate the possibility of future applications to probe membrane properties of thrombocytes. (C) 2008 Elsevier B.V. All rights reserved.
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| 15. |
- Hron, Gregor, et al.
(författare)
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Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test
- 2013
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Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:4, s. 279-284
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Tidskriftsartikel (refereegranskat)abstract
- Thrombocytopenia can cause diagnostic challenges in patients who have received heparin. Heparin-induced thrombocytopenia (HIT) is often considered in the differential diagnosis, and a positive screening can be mistaken as confirmation of the disorder. We present two patients who both received low-molecular-weight heparin for several days. In the first patient, clinical judgment rejected the suspicion of HIT despite a positive screening assay, and treatment for the alternative diagnosis of post-transfusion purpura was correctly initiated. In the second patient, the inaccurate diagnosis HIT was pursued due to a positive screening assay, while the alternative diagnosis of drug-dependent thrombocytopenia caused by piperacillin/tazobactam was rejected. This resulted in re-exposure to piperacillin/tazobactam which caused a second episode of severe thrombocytopenia. A positive screening assay for platelet factor 4/heparin-antibody should be verified by a functional assay, especially in patients with low pretest probability for HIT.
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| 16. |
- Juhl, David, et al.
(författare)
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Incidence and clinical significance of anti-PF4/heparin antibodies of the IgG, IgM, and IgA class in 755 consecutive patient samples referred for diagnostic testing for heparin-induced thrombocytopenia.
- 2006
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Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 76:5, s. 420-6
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Heparin-induced thrombocytopenia (HIT) is usually caused by anti-platelet factor 4 (PF4)/heparin antibodies, leading to intravascular platelet activation. These antibodies can be detected by PF4/polyanion antigen assays or platelet activation assays. While antigen assays are very sensitive and recognize immunoglobulin (Ig)G, IgA, and IgM antibodies, the role of IgM and IgA HIT-antibodies is debated. Platelet activation assays recognize IgG and are more specific for clinical HIT. METHODS: We analyzed sera from 755 consecutive patients referred for diagnostic testing for HIT using a PF4/heparin enzyme-linked immunosorbent assay (ELISA) for IgG, IgA, and IgM and by the heparin-induced platelet activation (HIPA) test. Clinical information was provided by the treating physicians. RESULTS: A total of 108 of 755 (14.3%) patients tested positive, 105 (13.9%) in the PF4/heparin IgG/A/M ELISA [28 (26.7%) only for IgM/A]; 53 (7.0%) sera were positive in the HIPA, of those 50 tested also positive in the ELISA. In 77 patients sufficient clinical information was provided. Available clinical information for 17 of the 28 patients who had only IgM and/or IgA detected showed plausible alternative (non-HIT) explanations in four of seven who had thromboembolic complications and in nine of 10 who had isolated HIT. CONCLUSION: Detection of IgG, IgM and IgA class antibodies by PF4/heparin ELISA yields a positive test result about twice as often as does a platelet activation assay, with only a minority of the additional patients detected likely having HIT. Thus, there is a potential for considerable over-diagnosis of HIT by laboratories that utilize only an ELISA for diagnostic testing.
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| 17. |
- Kjær, Mette, et al.
(författare)
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Maternal HPA-1a antibody level and its role in predicting the severity of Fetal/Neonatal Alloimmune Thrombocytopenia : a systematic review
- 2019
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Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007. ; 114:1, s. 79-94
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objectives: In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most commonly due to maternal HPA-1a antibodies. HPA-1a typing followed by screening for anti-HPA-1a antibodies in HPA-1bb women may identify first pregnancies at risk. Our goal was to review results from previous published studies to examine whether the maternal antibody level to HPA-1a could be used to identify high-risk pregnancies. Materials and Methods: The studies included were categorized by recruitment strategies: screening of unselected pregnancies or samples analyzed from known or suspected FNAIT patients. Results: Three prospective studies reported results from screening programmes, and 10 retrospective studies focused on suspected cases of FNAIT. In 8 studies samples for antibody measurement, performed by the monoclonal antibody immobilization of platelet antigen (MAIPA) assay, and samples for determining fetal/neonatal platelet count were collected simultaneously. In these 8 studies, the maternal antibody level correlated with the risk of severe thrombocytopenia. The prospective studies reported high negative predictive values (88–95%), which would allow for the use of maternal anti-HPA-1a antibody level as a predictive tool in a screening setting, in order to identify cases at low risk for FNAIT. However, due to low positive predictive values reported in prospective as well as retrospective studies (54–97%), the maternal antibody level is less suited for the final diagnosis and for guiding antenatal treatment. Conclusion: HPA-1a antibody level has the potential to predict the severity of FNAIT.
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| 18. |
- Kjeldsen-Kragh, Jens, et al.
(författare)
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Fetal/neonatal alloimmune thrombocytopenia : A systematic review of impact of HLA-DRB3∗01:01 on fetal/neonatal outcome
- 2020
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Ingår i: Blood Advances. - : American Society of Hematology. - 2473-9529 .- 2473-9537. ; 4:14, s. 3368-3377
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Forskningsöversikt (refereegranskat)abstract
- The most common, severe cases of fetal and neonatal alloimmune thrombocytopenia among whites are caused by antibodies against human platelet antigen 1a (HPA-1a). The aims of this systematic review and meta-analysis are to determine the association between maternal HLA-DRB3∗01:01 and: (1) HPA-1a-alloimmunization and (2) neonatal outcome in children born of HPA-1a-immunized women. A systematic literature search identified 4 prospective and 8 retrospective studies. Data were combined across studies to estimate pooled odds ratios (ORs) and the associated 95% confidence intervals (CIs). The population represented by the prospective studies was more than 150 000. In the prospective studies, there were 64 severely thrombocytopenic newborns (platelet count < 50 × 109/L) of whom 3 had intracranial hemorrhage. The mothers of all 64 children were HLA-DRB3∗01:01+. The number of severely thrombocytopenic children born of HPA-1a-alloimmunized women in the retrospective studies was 214; 205 of whom were born of HLA-DRB3∗01:01+ women. For HLA-DRB3∗01:01- women, the OR (95% CI) for alloimmunization was 0.05 (0.00-0.60), and for severe neonatal thrombocytopenia 0.08 (0.02-0.37). This meta-analysis demonstrates that the risk of alloimmunization and of having a child with severe thrombocytopenia are both very low for HPA-1a- women who are HLA-DRB3∗01:01-.
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| 19. |
- Klenner, Anne F, et al.
(författare)
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Heparin-induced thrombocytopenia in children : 12 new cases and review of the literature.
- 2004
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Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 91:4, s. 719-24
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Tidskriftsartikel (refereegranskat)abstract
- Immune-mediated heparin-induced thrombocytopenia (HIT) is a rare but severe adverse effect of heparin therapy. Only few data are available on clinical presentation, diagnosis and management of HIT in children. Records of all patients sent to our laboratory between 1995 and November 2003 were reviewed. To identify literature reports a Medline search was performed, the reference lists of those publications were screened and the abstracts of meetings on thrombosis and hemostasis between 2000 and 2003 were assessed. We identified 12 new HIT patients between 13 months and 18 years of age from our laboratory and 71 reports on HIT in children in the literature. For the assessment of frequency of HIT all studies enrolling > 100 patients were analyzed. HIT is rare in children. In pediatric patients, there seem to be two risk groups: newborns and infants under 4 years of age undergoing cardiac surgery (incidence approximately 1-2%), and teenagers treated with heparin for thrombosis. For confirmation of HIT in children, antigen assays are most important. There are conflicting data on the optimal cut-off, with one randomized, double-blind trial indicating that the cut-off established in adults is appropriate. There are no systematic studies on alternative anticoagulants in children affected by HIT. Most data are available for lepirudin and danaparoid. Substitution of unfractionated heparin by low-molecular-weight heparins for regular anticoagulation may reduce the incidence of HIT.
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| 20. |
- Leinoe, Eva, et al.
(författare)
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Highly impaired platelet ultrastructure in two families with novel IKZF5 variants
- 2021
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Ingår i: Platelets. - : Informa UK Limited. - 0953-7104 .- 1369-1635. ; 32:4, s. 492-497
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Tidskriftsartikel (refereegranskat)abstract
- Heterozygous variants in the IKZF5 gene, encoding transcription factor Pegasus, were recently discovered to be causal of inherited thrombocytopenia (IT). We screened 90 patients suspected of inherited thrombocytopenia for variants in 101 genes associated with inherited bleeding disorders and report the clinical presentation of two Danish families with novel variants in IKZF5. Platelet ultrastructure and cytoskeleton were evaluated by immunofluorescent microscopy (IF) and found to be highly abnormal, demonstrating severe disturbances of distribution and expression of non-muscular myosin, filamin, β-tubulin and α tubulin. Number of alpha granules were reduced, and platelets elongated when evaluated by TEM. In both families a child carrying a rare IKZF5 variant was affected by developmental delay. The proband of family A presented with recurrent infections and was examined for an immunodeficiency. The concentration of naive B-cells was found moderately reduced by leucocyte subpopulation examination, indicating an impaired cellular immunity. T-cells were marginally low with reduced share and concentration of CD45RApos, CD31pos, CD4pos recent thymic immigrants as signs of reduced thymic output. The novel IKZF5 variants co-segregated with thrombocytopenia in both families and both probands had significant bleeding tendency. Through comprehensive characterizations of the platelet morphology and function linked to the specific phenotypes we add novel insight to IKZF5-associated thrombocytopenia, which may help to identify and classify more cases with IKZF5 associated IT.
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