SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Lubenow Norbert) "

Sökning: WFRF:(Lubenow Norbert)

  • Resultat 1-50 av 64
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Zippelius, Alfred, et al. (författare)
  • Effector function of human tumor-specific CD8 T cells in melanoma lesions : a state of local functional tolerance.
  • 2004
  • Ingår i: Cancer Research. - 0008-5472 .- 1538-7445. ; 64:8, s. 2865-73
  • Tidskriftsartikel (refereegranskat)abstract
    • Although tumor-specific CD8 T-cell responses often develop in cancer patients, they rarely result in tumor eradication. We aimed at studying directly the functional efficacy of tumor-specific CD8 T cells at the site of immune attack. Tumor lesions in lymphoid and nonlymphoid tissues (metastatic lymph nodes and soft tissue/visceral metastases, respectively) were collected from stage III/IV melanoma patients and investigated for the presence and function of CD8 T cells specific for the tumor differentiation antigen Melan-A/MART-1. Comparative analysis was conducted with peripheral blood T cells. We provide evidence that in vivo-priming selects, within the available naive Melan-A/MART-1-specific CD8 T-cell repertoire, cells with high T-cell receptor avidity that can efficiently kill melanoma cells in vitro. In vivo, primed Melan-A/MART-1-specific CD8 T cells accumulate at high frequency in both lymphoid and nonlymphoid tumor lesions. Unexpectedly, however, whereas primed Melan-A/MART-1-specific CD8 T cells that circulate in the blood display robust inflammatory and cytotoxic functions, those that reside in tumor lesions (particularly in metastatic lymph nodes) are functionally tolerant. We show that both the lymph node and the tumor environments blunt T-cell effector functions and offer a rationale for the failure of tumor-specific responses to effectively counter tumor progression.
  •  
2.
  •  
3.
  • Auvinen, Marja-Kaisa, et al. (författare)
  • Patterns of blood use in Sweden from 2008 to 2017: A nationwide cohort study
  • 2020
  • Ingår i: Transfusion. - : WILEY. - 0041-1132 .- 1537-2995. ; 60:11, s. 2529-2536
  • Tidskriftsartikel (refereegranskat)abstract
    • Background Transfusion patterns in Sweden have not been characterized on a nationwide level. Study Design and Methods We conducted a nationwide descriptive cohort study in Sweden from 2008 to 2017. Data on blood donors, donations, component manufacture, transfusions, and transfused patients were extracted from Swedish portion of the Scandinavian Donations and Transfusions (SCANDAT3-S) database. Results A total of 708 436 patients received 5 587 684 red cell, plasma, or platelet transfusions during the study period. The age-standardized transfusion rate decreased markedly during the study period for red cell units (from 53 to 39 units/1000 persons) and plasma units (from 11 to 4.9 units/1000 persons), but remained relatively constant for platelet concentrates. The transfusion rate was 30%-40% higher in males than in females in the first year of life, and higher in males over 45 years than in females. Between age 20 and 45, the majority of red cells were transfused to female patients with obstetric indications, whereas trauma was the predominant indication for male contemporaries. In females over 80 years, the largest proportion of red cells were administered due to trauma. Overall, hematological patients received 36% of all platelet units. There were large regional differences in transfusion rates for red cell units, ranging from less than 30 to greater than 60/1000 persons. Conclusion Transfusion rates in Sweden remain high but have decreased strikingly during the study period - with the exception of platelet transfusions. Based on the available data, it is difficult to draw firm conclusions about whether transfusion rates can be further reduced.
  •  
4.
  • Berglund, David, et al. (författare)
  • Green plasma
  • 2015
  • Ingår i: Transfusion. - : Wiley. - 0041-1132 .- 1537-2995. ; 55:2, s. 245-245
  • Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
  •  
5.
  • Carlsson, Lena E, et al. (författare)
  • Platelet receptor and clotting factor polymorphisms as genetic risk factors for thromboembolic complications in heparin-induced thrombocytopenia.
  • 2003
  • Ingår i: Pharmacogenetics. - 0960-314X .- 1473-561X. ; 13:5, s. 253-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparin-induced thrombocytopenia (HIT) is an immune mediated adverse reaction to heparin treatment often associated with limb- and/or life-threatening thromboembolic complications (TECs). Presently, no prognostic marker has been identified that allows differentiation between mildly (isolated thrombocytopenia) and severely (TECs) affected patients. This study assesses the impact of platelet glycoprotein- and clotting factor polymorphisms in HIT-patients with isolated thrombocytopenia compared to HIT-patients with TECs. Sixty-three HIT-patients with isolated thrombocytopenia and 79 HIT-patients with HIT-related TECs were genotyped for GPIIb-IIIa polymorphisms (HPA-1, HPA-3), GPIa-IIa polymorphisms (HPA-5, GPIaC807T), GPIb-IX-V polymorphisms (HPA-2, Kozak-5, VNTR), and clotting factor polymorphisms (FV-Leiden R506Q, prothrombin PT-G20210A and MTHFR C677T). Women more often presented with TECs than men (P = 0.04). No differences in genotype frequencies could be seen on comparing HIT-patients with and without TECs. Analysing men and women separately, the C allele of the Kozak polymorphism was overrepresented in men who developed TECs (P = 0.034). The enhanced risk of women to develop HIT-associated TECs remains unexplained but it is potentially important in view of recent data on sex-hormone related changes of haemostasis. There was no correlation between platelet glycoprotein- and clotting factor polymorphisms and the risk to develop HIT-associated TECs. An association between the development of TECs and the Kozak-5C allele could be seen among male patients. However, this would need to be assessed in further larger studies. Most likely, the high levels of thrombin generation during acute HIT are so procoagulant that less pronounced risk factors such as polymorphisms are overshadowed.
  •  
6.
  • Cherif, Honar, et al. (författare)
  • Patient was wrongly diagnosed and repeatedly treated for immune thrombocytopenia for 50 years
  • 2018
  • Ingår i: Läkartidningen. - 0023-7205 .- 1652-7518. ; 115
  • Tidskriftsartikel (refereegranskat)abstract
    • We report on a patient with inherited macrothrombocytopenia, MYH9 related disease (MYH9-RD). The patient was wrongly diagnosed and repeatedly treated for immune thrombocytopenia (ITP) for nearly 50 years. Cases of misdiagnosed MYH9-RD and other hereditary thrombocytopenias have been described previously. Typical clinical features such as renal failure and/or progressive loss of hearing should give grounds to suspect hereditary thrombocytopenia. Initial laboratory diagnosis can start with a simple blood smear followed by immunohistochemistry and genotyping. Therapy with thrombopoietin receptor agonists may be beneficial in selected cases of MYH9-RD. ITP treatments including splenectomy are not indicated and may cause harm.
  •  
7.
  • Eichler, Petra, et al. (författare)
  • Antibodies against lepirudin are polyspecific and recognize epitopes on bivalirudin.
  • 2004
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 103:2, s. 613-6
  • Tidskriftsartikel (refereegranskat)abstract
    • Bivalirudin is a synthetic antithrombin sharing a sequence of 11 amino acids with the recombinant hirudin lepirudin. We investigated whether antilepirudin antibodies recognize epitopes on bivalirudin. Antilepirudin antibody-positive sera of 43 patients, treated with lepirudin for heparin-induced thrombocytopenia, were analyzed. Lepirudin- and bivalirudin-coated microtiter plates were used for antibody testing in an enzyme-linked immunosorbent assay (ELISA) system. Of the 43 sera-containing antibodies binding to lepirudin, 22 (51.2%) contained antibodies that also recognized bivalirudin. Binding of these antibodies to bivalirudin was inhibited by more than 70% by preincubation with high doses of bivalirudin. However, if lepirudin-coated microtiter plates were used, high concentrations of bivalirudin inhibited only 2 of the 43 positive sera by more than 30%. Therefore antihirudin antibodies must be polyspecific. The clinical consequences of this cross-reactivity are unknown but bivalirudin, targeted by antibodies of patients treated with lepirudin previously, could potentially boost antibody titers in such patients or even trigger an immune response by itself. Clinically significant antibody formation in response to bivalirudin monotherapy has not been observed, however. Yet, as lepirudin and antilepirudin antibodies have recently been implicated in severe anaphylactic reactions, caution is warranted when using bivalirudin in patients previously treated with lepirudin.
  •  
8.
  • Eichler, P, et al. (författare)
  • Antihirudin antibodies in patients with heparin-induced thrombocytopenia treated with lepirudin : incidence, effects on aPTT, and clinical relevance.
  • 2000
  • Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 96:7, s. 2373-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Hirudin, a potent and specific thrombin inhibitor, is a protein of nonhuman origin and therefore potentially immunogenic. The primary objectives of this investigation were to determine the incidence of antihirudin antibodies (ahir-ab) in patients with heparin-induced thrombocytopenia (HIT) who received lepirudin as parenteral anticoagulation and to determine the incidence of death, limb amputation, new thromboembolic complications (TECs), and major hemorrhage in patients who had ahir-ab, compared with patients who were ahir-ab negative. The investigation used data from 2 prospective multicenter studies with the same study protocol, in which HIT patients received 1 of 4 intravenous lepirudin dosage regimens. The treatment duration was 2 to 10 days. Ahir-ab were determined by a newly developed enzyme-linked immunosorbent assay (ELISA). Eighty-seven of 196 evaluable patients (44.4%) had ahir-ab of the IgG class. Development of ahir-ab was dependent on the duration of treatment (ahir-ab-positive patients 18.6 days vs ahir-ab-negative patients 11.8 days; P =.0001). Fewer ahir-ab-positive than ahir-ab-negative patients died (P =.001). Ahir-ab did not cause an increase in limb amputation (P =.765), new TECs (P >.99), or major bleedings (P =.549). In 23 of 51 (45.1%) evaluable patients in whom ahir-ab developed during treatment with lepirudin ( = 12% of all lepirudin treated patients), the ahir-ab enhanced the anticoagulatory effect of lepirudin. Ahir-ab are frequent in patients treated with lepirudin for more than 5 days. Ahir-ab are the first example for a drug-induced immune response causing enhanced activity of a drug. Therefore, during prolonged treatment with lepirudin, anticoagulatory activity should be monitored daily to avoid bleeding complications.
  •  
9.
  • Eichler, Petra, et al. (författare)
  • The new ID-heparin/PF4 antibody test for rapid detection of heparin-induced antibodies in comparison with functional and antigenic assays.
  • 2002
  • Ingår i: British Journal of Haematology. - 0007-1048 .- 1365-2141. ; 116:4, s. 887-91
  • 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.
  •  
10.
  • Greinacher, A, et al. (författare)
  • Anaphylactic and anaphylactoid reactions associated with lepirudin in patients with heparin-induced thrombocytopenia.
  • 2003
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 108:17, s. 2062-5
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Lepirudin (Refludan) is a hirudin derivative. It is a direct thrombin inhibitor obtained by recombinant technology from the medicinal leech and is approved for treatment of heparin-induced thrombocytopenia complicated by thrombosis. Because 3 cases of fatal anaphylaxis possibly associated with use of lepirudin have been reported, we initiated an investigation of putative lepirudin-associated anaphylaxis. METHODS AND RESULTS: Aided by the manufacturer (Schering AG, Berlin, Germany), we used the lepirudin study databases to identify all patients in whom possible anaphylaxis/severe allergy was recorded from 1994 to September 2002. The 26 possible cases identified were reviewed independently by 2 investigators. After excluding patients with mild skin reactions, reactions likely caused by concomitant medications, poorly documented cases, and reactions that did not correspond temporally with lepirudin use, there remained 9 patients judged to have had severe anaphylaxis in close temporal association with lepirudin. All reactions occurred within minutes of intravenous lepirudin administration, with 4 fatal outcomes (3 acute cardiorespiratory arrests, 1 hypotension-induced myocardial infarction). In these 4 cases, a previous uneventful treatment course with lepirudin was identified (1 to 12 weeks earlier). We recorded high-titer IgG-anti-lepirudin antibodies in an additional patient with anaphylaxis. Because lepirudin has been used in approximately 35 000 patients, the risk of anaphylaxis is approximately 0.015% (5 of 32 500) on first exposure and 0.16% (4 of 2500) in reexposed patients (7.5% estimated reexposures). CONCLUSIONS: Lepirudin can cause fatal anaphylaxis, particularly in patients who are treated within 3 months of a previous exposure. The overall risk/benefit assessment of lepirudin as a treatment for heparin-induced thrombocytopenia remains favorable.
  •  
11.
  • Greinacher, A, et al. (författare)
  • Drug-induced and drug-dependent immune thrombocytopenias.
  • 2001
  • Ingår i: Reviews in Clinical and Experimental Hematology. - 1127-0020 .- 1825-151X. ; 5:3, s. 166-200; discussion 311
  • Tidskriftsartikel (refereegranskat)abstract
    • Thrombocytopenia is a frequent comorbid condition in many in hospital patients. In some patients, drugs are the cause of low platelet counts. While cytotoxic effects of anti-tumor therapy are the most frequent cause, immune mechanisms should also be considered. This review addresses thrombocytopenias in four groups. Heparin-dependent thrombocytopenia (HIT), by far the most frequent drug-induced immune-mediated type of thrombocytopenia, has a unique pathogenesis and clinical consequences. HIT is a clinicopathological syndrome in which antibodies mostly directed against a multimolecular complex of platelet factor 4 and heparin cause paradoxical thromboembolic complications. The mechanisms through which heparin can enhance thrombin generation are discussed and treatment alternatives for affected patients are presented in detail. It is of primary importance to recognize these patients as early as possible and to substitute heparin with a compatible anticoagulatory drug, such as hirudin, danaparoid or argatroban. Patients seem to benefit from therapeutic doses of alternative treatment rather than from low-dose prophylactic doses. With the increasing use of glycoprotein (GP) IIb/IIIa inhibitors in patients with acute coronary syndromes, thrombocytopenias are increasingly recognized as an adverse effect of these drugs. Up to 4% of treated patients are affected. Most important, pseudothrombocytopenia, a laboratory artefact, is as frequent as real drug-induced thrombocytopenia and must be excluded before changes in treatment are considered. The pathogenesis of these thrombocytopenias is still debated; an immune mechanism involving preformed antibodies is likely. However, since these antibodies are also detectable in a high percentage of normal controls and of patients not developing thrombocytopenia, their impact is still unclear. Patients with real thrombocytopenia are at an increased risk of bleeding; treatment consists of cessation of the GP IIb/IIIa inhibitor and platelet transfusions in cases of severe hemorrhage. Classic immune thrombocytopenia can be induced by some drugs, e.g. gold, which trigger anti-platelet antibodies indistinguishable from platelet autoantibodies found in autoimmune thrombocytopenia. Drug-induced and drug-dependent immune thrombocytopenia is induced by antibodies recognizing an epitope on platelet GP formed after binding of a drug to a platelet glycoprotein. Still unresolved is whether antibody binding is the consequence of a conformational change of the antigen, the antibody, or both. These antibodies typically react with monomorphic epitopes on platelet GP, but only in the presence of the drug or a metabolite. Although several platelet GP have been identified as antibody target (GPIb/IX, GPV, GP IIb/IIIa), antibodies in an individual patient are highly specific for a single GP. Clinically, these patients present with very low platelet counts and acute, sometimes severe, hemorrhage. Treatment is restricted to withdrawal of the drug and symptomatic treatment of bleeding.
  •  
12.
  • Greinacher, A, et al. (författare)
  • Heparin-induced thrombocytopenia : a prospective study on the incidence, platelet-activating capacity and clinical significance of antiplatelet factor 4/heparin antibodies of the IgG, IgM, and IgA classes.
  • 2007
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 5:8, s. 1666-73
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Platelet-activating antiplatelet factor 4/heparin (anti-PF4/heparin) antibodies are the major cause of heparin-induced thrombocytopenia (HIT). However, the relative utility of functional (platelet activation) vs. antigen [enzyme-immunoassay (EIA)] assays, and the significance of assay discrepancies remain unresolved. METHODS: Consecutive patient sera (n = 1650) referred for diagnostic HIT testing were screened prospectively by both the heparin-induced platelet activation (HIPA) test and anti-PF4/heparin EIA - including individual classes (IgG, IgA, IgM) - with clinical correlations studied. Platelet microparticle and annexin-V-binding properties of the sera were also investigated. RESULTS: Only 205 (12.4%) sera tested positive in either the HIPA and/or EIA: 95 (46.3%) were positive in both, 109 (53.1%) were only EIA-positive, and, notably, only one serum was HIPA-positive/EIA-negative. Of 185 EIA-positive sera, only 17.6% had detectable IgM and/or IgA without detectable IgG. Among sera positive for EIA IgG, optical density values were higher when the sera were HIPA-positive (1.117 vs. 0.768; P < 0.0001), with widely overlapping values. Two HIPA-positive but EIA-IgG-negative sera became HIPA-negative following IgG depletion, suggesting platelet-activating antibodies against non-PF4-dependent antigens. Clinical correlations showed that HIPA-negative/EIA-positive patients did not develop thrombosis and had reasons other than HIT to explain thrombocytopenia. IgM/A antibodies did not increase microparticle penetration, but increased annexin-V binding. CONCLUSIONS: The anti-PF4/heparin EIA has high ( approximately 99%) sensitivity for HIT. However, only about half of EIA-positive patients are likely to have HIT. Anti-PF4/heparin antibodies of IgM/A class and non-PF4-dependent antigens have only a minor role in HIT.
  •  
13.
  • Greinacher, A, et al. (författare)
  • Heparin-induced thrombocytopenia : towards standardization of platelet factor 4/heparin antigen tests.
  • 2010
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 8:9, s. 2025-31
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: Laboratory confirmation of heparin-induced thrombocytopenia (HIT) is based on detection of heparin-dependent platelet-activating antibodies. Platelet factor 4 (PF4)/heparin enzyme-immunoassays (EIA) are a widely available surrogate for platelet-activating antibodies. OBJECTIVE: Defining the optical density (OD) reactivity profiles of a PF4/heparin EIA in reference subject and patient populations and the correlation of the EIA results (expressed in OD units) with the prevalence of platelet-activating antibodies. PATIENTS/METHODS: Using quantile regression we determined the 97.5th percentile of PF4/heparin-immunoglobulin G (IgG) EIA reactivities in non-heparin-treated individuals [blood donors (n = 935)] and patients before heparin therapy (n = 1207). In patients with suspected HIT, we compared the correlation of EIA-IgG reactivities (Greifswald laboratory; n = 2821) and the heparin-induced platelet activation assay (HIPA) with the correlation of reactivities of another EIA-IgG (McMaster laboratory; n = 1956) with the serotonin-release assay (SRA). RESULTS: PF4/heparin-IgG EIA OD reactivities had a lower OD 97.5th percentile in blood donors compared with patient groups before heparin treatment (P < 0.001). The percentage of sera testing positive in the functional assays strongly correlated with PF4/heparin-IgG EIA OD reactivities in both laboratories with very similar results (correlation coefficient > 0.9) when normalized OD ranges (maximum OD divided by 10) were used instead of absolute OD values. CONCLUSIONS: Results of PF4/heparin-IgG EIA should not be reported as only positive or negative as there is no single acceptable cut-off value. Instead, reporting PF4/heparin-IgG EIA OD results in ranges allows for risk-stratified prediction for presence of platelet-activating antibodies. Use of normalized OD ranges permits a standardized approach for inter-laboratory comparisons.
  •  
14.
  • Greinacher, A, et al. (författare)
  • Heparin-induced thrombocytopenia with thromboembolic complications : meta-analysis of 2 prospective trials to assess the value of parenteral treatment with lepirudin and its therapeutic aPTT range.
  • 2000
  • Ingår i: Blood. - 0006-4971 .- 1528-0020. ; 96:3, s. 846-51
  • Tidskriftsartikel (refereegranskat)abstract
    • This meta-analysis focuses on 2 prospective studies in patients with heparin-induced thrombocytopenia (HIT) and thromboembolic complication (TEC) who were treated with lepirudin (n = 113). Data were compared with those of a historical control group (n = 91). The primary endpoint (combined incidence of death, new TEC, and limb amputation) occurred in 25 lepirudin-treated patients (22.1%; 95% CI, 14.5%-29.8%): 11 died (9.7%; 95% CI, 4.9%-16.8%), 7 underwent limb amputation (6.2%; 95% CI, 2.5%-12.3%), and 12 experienced new TEC (10.6%; 95% CI, 5.8%-18.3%). The risk was highest in the period between diagnosis of HIT and the start of lepirudin therapy (combined event rate per patient day 6.1%). It markedly decreased to 1.3% during lepirudin treatment and to 0.7% in the posttreatment period. From the start of lepirudin therapy to the end of follow-up, lepirudin-treated patients had consistently lower incidences of the combined endpoint than the historical control group (P =.004, log-rank test), primarily because of a reduced risk for new TEC (P =. 005). Thrombin-antithrombin levels in the pretreatment period (median, 43.9 microg/L) decreased after the initiation of lepirudin (at 24 hours +/- 6 hours; median, 9.18 microg/L.) During treatment with lepirudin, aPTT ratios of 1.5 to 2.5 produced optimal clinical efficacy with a moderate risk for bleeding, aPTT ratios lower than 1. 5 were subtherapeutic, and aPTT levels greater than 2.5 were associated with high bleeding risk. Bleeding events requiring transfusion were significantly more frequent in patients taking lepirudin than in historical control patients (P =.02). In conclusion, this meta-analysis provides further evidence that lepirudin is an effective and acceptably safe treatment for patients with HIT.
  •  
15.
  • Greinacher, A., et al. (författare)
  • Predonation finger lancet punctures : a potential risk factor for interdonor pathogen transmission in the blood donor clinic
  • 2016
  • Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 111:1, s. 3-7
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and Objectives: Point-of-care testing using capillary blood from a finger prick is widely used for predonation haemoglobin testing of blood donors. It is common practice to cover the finger prick with a cotton swab and to instruct the donor to press for few minutes. The finger prick can cause blood contamination of surfaces in contact with the lanced finger, especially door handles, risking infectious disease transmission, particularly if another person touching the contaminated door handle also has a punctured fingertip.Materials and Methods: First, we investigated contamination by blood (benzidine assay) of the door handles of our blood donor clinic, taking 175 samples 3 h after opening of the donation centre (baseline). We then introduced band-aids to cover the finger prick and started an information campaign using educational flyers to sensitize blood donors and staff to this problem (period-1). Thereafter, the staff was instructed to use the non-dominant hand for blood sampling and mandated to replace any discarded band-aids immediately (period-2).Results: At baseline, 82% of the nurse room door handles showed contamination with blood. This decreased somewhat (10-40%) after period-1, but only after immediate mandatory band-aid replacement on any donor finger without a band-aid (period-2), no further blood contaminations were detected.Conclusion: Blood contamination of shared surfaces can occur after finger prick for capillary blood sampling. Application of a band-aid and use of the non-dominant hand for fingertip incision are easy to apply and effective in reducing this iatrogenic health hazard.
  •  
16.
  • Greinacher, A, et al. (författare)
  • Recombinant hirudin in clinical practice : focus on lepirudin.
  • 2001
  • Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 103:10, s. 1479-84
  • Tidskriftsartikel (refereegranskat)abstract
    • Clinical applications for recombinant hirudins have been investigated for the past 10 years. The first indication for which a hirudin-lepirudin-has been approved is treatment of heparin-induced thrombocytopenia (HIT). Also, the recently completed trials for use of lepirudin in unstable angina indicate a potentially new indication. This review describes pharmacology and clinical applications of lepirudin with an emphasis on HIT and unstable angina. An overview of usage of lepirudin in acute coronary syndromes is given, as well as a summary of rare indications for lepirudin, such as extracorporeal circulation, for which comprehensive data are lacking.
  •  
17.
  • Greiser, Anne, et al. (författare)
  • The 99th percentile and imprecision of point-of-care cardiac troponin I in comparison to central laboratory tests in a large reference population
  • 2017
  • Ingår i: Clinical Biochemistry. - : Elsevier BV. - 0009-9120 .- 1873-2933. ; 50:18, s. 1198-1202
  • 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.
  •  
18.
  • Hartmann, Gunther, et al. (författare)
  • Rational design of new CpG oligonucleotides that combine B cell activation with high IFN-alpha induction in plasmacytoid dendritic cells.
  • 2003
  • Ingår i: European Journal of Immunology. - : Wiley. - 0014-2980 .- 1521-4141. ; 33:6, s. 1633-41
  • Tidskriftsartikel (refereegranskat)abstract
    • Two different types of CpG motif-containing oligonucleotides (CpG ODN) have been described: CpG-A with high induction of IFN-alpha in plasmacytoid dendritic cells; and CpG-B with little induction of IFN-alpha, but potent activation of B cells. In this study, we demonstrate that CpG-A fail to activate B cells unless plasmacytoid dendritic cells are present. We identified a new set of CpG ODN sequences which induces high levels of IFN-alpha in plasmacytoid dendritic cells but remains capable of directly activating B cells. These new CpG ODN (termed CpG-C) are more potent stimulants of B cells than CpG-B due to their ability of directly and indirectly (via plasmacytoid dendritic cells) activating B cells. The sequence of CpG-C combines structural elements of both CpG-A and CpG-B. The most potent sequence, M362, contains a 5'-end 'TCGTCG-motif' and a 'GTCGTT-motif', both of which are present in CpG-B (ODN 2006); a palindromic sequence characteristic for CpG-A (ODN 2216); but no poly G motif required for CpG-A. In conclusion, we defined the first CpG-containing sequences that potently activate both TLR9-expressing immune cell subsets in humans, the plasmacytoid dendritic cell and the B cell. CpG-C may allow for improved therapeutic immuno-modulation in vivo.
  •  
19.
  • Hellberg, Åsa, et al. (författare)
  • A novel nonsense variant in RHAG underlies a Nordic Rhnull phenotype
  • 2023
  • Ingår i: Vox Sanguinis. - : John Wiley & Sons. - 0042-9007 .- 1423-0410. ; 118:8, s. 690-694
  • Tidskriftsartikel (refereegranskat)abstract
    • Background and ObjectivesThe extremely rare Rhnull phenotype is characterized by the absence of all Rh antigens on erythrocytes. It is divided into the regulator and amorph types based on the underlying genetic background. The more common regulator type depends on critical variants silencing RHAG, which encodes RhAG glycoprotein, necessary for RhD/RhCE expression. Rhnull cells have altered expression of glycophorin B and LW glycoprotein.Materials and MethodsFour unrelated Rhnull individuals were investigated. Serological testing was performed according to standard blood bank practice. RHD/RHCE and S/s allele-specific Polymerase chain reaction (PCR) genotyping was done on genomic DNA using in-house PCR assays. RHAG, and in some cases also RHD/RHCE, were sequenced. Initial s phenotyping results triggered additional serological investigation.ResultsAnti-Rh29 was identified in all four individuals. Extended typing with anti-S and anti-s showed that the three samples predicted to type as s+ failed to react with 2 of 5 anti-s. Sequence analysis of all 10 RHAG exons and the immediate intron/exon boundaries revealed a single nucleotide variant in the 3′-end of intron 6, c.946 −2a>g in all samples. RHD/RHCE showed no alterations.ConclusionA novel Nordic Rhnull allele was identified. In addition, it was shown that s+ Rhnull red blood cells are not only U− but also have qualitative changes in their s antigen expression.
  •  
20.
  • Hinz, P, et al. (författare)
  • [Current recommendations for diagnosis and therapy of heparin-induced thrombocytopenia].
  • 2002
  • Ingår i: Der Unfallchirurg (Berlin. Print). - : Springer Science and Business Media LLC. - 0177-5537 .- 1433-044X. ; 105:9, s. 845-50
  • Tidskriftsartikel (refereegranskat)abstract
    • Thrombosis prophylaxis using heparins is mandatory in most trauma patients. However, heparins can induce heparin-induced thrombocytopenia (HIT), the most common and clinically important immune-mediated drug-dependent thrombocytopenia. Affected patients are at risk of developing new thromboembolic complications. HIT has to be considered if platelet counts decrease >50% between day 5-10 of heparin therapy that cannot be explained alternatively or if new thromboses occur in a sufficiently heparinised patient. Immediately changing the anticoagulant to danaparoid or lepirudin is most important. Proof of anti-platelet-factor-4/heparin antibodies secures the diagnosis, usually retrospectively. Diagnosis and therapy are demonstrated in a typical HIT patient. HIT usually occurs in the second week of heparin administration. Heparin-reexposure within 100 days can lead to HIT before day 5. For early recognition of HIT, platelet counts should be monitored regularly. Because of earlier discharge of patients to rehabilitation or outpatient care, the problem of HIT-diagnosis and therapy gains increasing relevance in these sectors.
  •  
21.
  • Hinz, P, et al. (författare)
  • [Informed consent on heparin-induced thrombocytopenia during thrombosis prophylaxis. A pilot study including 460 patients].
  • 2003
  • Ingår i: Deutsche Medizinische Wochenschrift. - : Georg Thieme Verlag KG. - 0012-0472 .- 1439-4413. ; 128:42, s. 2184-8
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: The practicability and acceptance of written information about heparin thrombosis prophylaxis and the associated risk of heparin-induced thrombocytopenia (HIT) was evaluated in a pilot study. PATIENTS AND METHODS: All patients consecutively admitted to the department of trauma- and reconstructive surgery at the Ernst-Moritz-Arndt-University, Greifswald, Germany, with an indication for heparin thrombosis prophylaxis were give written information about thrombosis prophylaxis and the undesired drug effect HIT. After this, acceptance was evaluated using a standardized questionnaire. Primary endpoint was refusal of heparin for thrombosis prophylaxis, secondary endpoint acceptance and comprehensibility of the information. RESULTS: None of the 460 patients included in the study subsequently refused thrombosis prophylaxis with heparin. The majority welcomed the information and thought it should be given to all patients that are about to be treated with heparin. Only 0.9 % of patients judged comprehensibility of the information to be insufficient. Anticipation of imminent heparin therapy (good/very good in 90 %) and appreciation of the quality of care was not judged to be unacceptable by any patient. CONCLUSIONS: The present study demonstrates that giving information about heparin-induced thrombocytopenia during explanation of the risks and benefits of heparin thrombosis prophylaxis is feasible. This information--given in writing in our pilot study--was judged by patients to be comprehensible and necessary and did not lead to refusal of treatment. Lower incidence of HIT with use of low molecular weight heparins should be considered in the choice of drug for thrombosis prophylaxis.
  •  
22.
  • Hinz, P, et al. (författare)
  • [Thrombosis prophylaxis in trauma surgery units in Germany : a survey].
  • 2009
  • Ingår i: Der Unfallchirurg. - : Springer Science and Business Media LLC. - 1433-044X .- 0177-5537. ; 112:12, s. 1029-33
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: A questionnaire study was conducted to ask trauma surgery centers about thrombosis prophylaxis methods and strategies for the diagnosis and therapy of heparin-induced thrombocytopenia (HIT). METHODS: Questionnaires were sent by post to German hospitals with trauma surgery units inquiring about the use of unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH), the duration of medication, and the HIT diagnosis. Questionnaires were evaluated descriptively. RESULTS: 314 of 685 questionnaires sent out were evaluable (46%): half were from general hospitals, 96 (31%) from specialized hospitals, and 53 (17%) from tertiary care hospitals (others: 8). In more than 90%, only LMWH was used. The mean duration of pharmacological thrombosis prophylaxis was 16.6+/-10.4 days (inpatient/outpatient). Only 10% adhered to the recommended platelet count controls every 2 days (days 5-14) for early detection of HIT. CONCLUSIONS: While pharmacological thrombosis prophylaxis following trauma surgery seems to be generally performed according to guidelines, diagnosis and treatment of HIT need to be systematized.
  •  
23.
  • Hron, Gregor, et al. (författare)
  • Alternative diagnosis to heparin-induced thrombocytopenia in two critically ill patients despite a positive PF4/heparin-antibody test
  • 2013
  • Ingår i: Upsala Journal of Medical Sciences. - : Uppsala Medical Society. - 0300-9734 .- 2000-1967. ; 118:4, s. 279-284
  • 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.
  •  
24.
  • Juhl, David, et al. (författare)
  • 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
  • Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 76:5, s. 420-6
  • 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.
  •  
25.
  • Klenner, Anne F, et al. (författare)
  • Heparin-induced thrombocytopenia in children : 12 new cases and review of the literature.
  • 2004
  • Ingår i: Thrombosis and Haemostasis. - 0340-6245 .- 2567-689X. ; 91:4, s. 719-24
  • 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.
  •  
26.
  •  
27.
  • Lubenow, Norbert, et al. (författare)
  • Drugs for the prevention and treatment of thrombosis in patients with heparin-induced thrombocytopenia.
  • 2001
  • Ingår i: American Journal of Cardiovascular Drugs. - 1175-3277 .- 1179-187X. ; 1:6, s. 429-43
  • Tidskriftsartikel (refereegranskat)abstract
    • Most patients with heparin-induced thrombocytopenia (HIT), a serious adverse effect of heparin mediated by platelet-activating heparin-dependent antibodies, require alternative anticoagulation. This is because HIT is highly prothrombotic and is characterized by markedly increased thrombin generation. Unfractionated heparins seem to induce HIT more often than low molecular weight heparins. There are three anticoagulants for which there is an emerging consensus for their efficacy in management of HIT, and which are currently approved for treatment of HIT in several countries: the recombinant hirudin, lepirudin, a direct thrombin inhibitor; the synthetic direct thrombin inhibitor, argatroban; and the heparinoid, danaparoid sodium, mainly exhibiting antifactor-Xa activity. Recommendations for optimal use of these drugs in HIT are given in this review stressing the need for immediate treatment of patients with HIT without awaiting laboratory diagnosis. Hirudin, the drug for which most data from prospective trials exists, can be safely and effectively used in patients with HIT, its dramatically increased elimination half-life in patients with renal failure being the most important drawback. Argatroban, which is mainly eliminated by the liver, could be used preferentially in such patients with renal impairment. Interference with the international normalized ratio makes oral anticoagulation, which is necessary in many patients with HIT, problematic. Activated partial thromboplastin time is sufficient to monitor lepirudin and argatroban treatment in most cases. Danaparoid sodium, with an antifactor-X activity half-life of about 24 hours seems to be best suited for thrombosis prophylaxis in patients with HIT. In some patients monitoring by determining antifactor-Xa activity is necessary. No antidote is available for any of the drugs discussed, and bleeding complications are the most important adverse effects. In situations such as hemodialysis or cardiopulmonary bypass, not only the characteristics of the drug in use itself, but also availability of monitoring methods play an important role. Adjunctive treatments have not been systematically evaluated and should be used cautiously. Recent data suggest that re-exposure of patients with a history of HIT with heparin, for example during cardiopulmonary bypass, can be well tolerated provided no circulating HIT antibodies are detectable at the time of re-exposure, and heparin is strictly avoided pre- and postoperatively.
  •  
28.
  • Lubenow, Norbert, et al. (författare)
  • Heparin-induced thrombocytopenia : recommendations for optimal use of recombinant hirudin.
  • 2000
  • Ingår i: BioDrugs. - 1173-8804 .- 1179-190X. ; 14:2, s. 109-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Recombinant hirudins have a definite role in the treatment of patients with heparin-induced thrombocytopenia (HIT). The most important adverse effects are haemorrhages and the induction of antihirudin antibodies. Major haemorrhages were not significantly increased in patients with HIT compared with a historical control group, but prospective data comparing hirudin and heparinoids such as danaparoid are lacking. The definition of the optimal method for monitoring and the availability of an antidote for hirudin would probably increase safety with this drug. To date, haemofiltration using high-flux filter systems is the only way to remove an overdosage of hirudin from the circulation. In patients with renal impairment requiring hirudin treatment, it therefore seems safer to start with a low dose that is subsequently adjusted according to the activated partial prothromboplastin time or ecarin clotting time. Even in special circumstances, such as cardiopulmonary bypass or dialysis, hirudins can be applied successfully if care is taken to monitor their effects meticulously. There are many other indications in which hirudins have shown feasibility (e.g. acute coronary syndromes) but available data preclude definite conclusions.
  •  
29.
  • Lubenow, Norbert, et al. (författare)
  • Heparin-induced thrombocytopenia : temporal pattern of thrombocytopenia in relation to initial use or reexposure to heparin.
  • 2002
  • Ingår i: Chest. - 0012-3692 .- 1931-3543. ; 122:1, s. 37-42
  • Tidskriftsartikel (refereegranskat)abstract
    • STUDY OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse drug reaction associated with a decrease of platelet counts that usually begins after at least 5 days of heparin treatment. Uncertainty exists about the risk of early onset of HIT (ie, < 5 days) in relation to previous heparin exposure. We therefore analyzed the temporal pattern of thrombocytopenia in patients with laboratory-confirmed HIT to assess whether patients with previous heparin exposure have an increased risk of early onset of HIT. DESIGN: Platelet count patterns in patients with a laboratory-confirmed diagnosis of HIT were examined in a retrospective chart review of a clinical study database. The onset of thrombocytopenia < 100 x 10(9)/L associated with the current heparin treatment (mainly unfractionated heparin) was analyzed using nonparametric maximum likelihood estimation. RESULTS: A total of 119 patients with 125 treatment episodes were assessed: HIT developed in 79 patients during initial exposure to heparin, and in 46 patients during reexposure. Early onset (< 5 days) of thrombocytopenia was associated with very recent heparin exposure. Patients reexposed to heparin within 3 months had an earlier onset of thrombocytopenia as compared to patients reexposed to heparin after 3 months (4.9 +/- 4.4 days vs 11.5 +/- 5.5 days [mean +/- SD], p = 0.001). There was no difference between onset on thrombocytopenia < 100 x 10(9)/L in patients reexposed to heparin within 3 to 12 months and after 1 year (9.7 +/- 6.4 days vs 12.3 +/- 5.2 days, p = 0.41). Whether platelet counts were obtained daily or less regularly did not affect the analysis. CONCLUSION: Early onset of thrombocytopenia in HIT is associated with recent heparin treatment (< 3 months). In contrast, for patients who did not receive heparin within the previous 3 months, HIT is an unlikely explanation for thrombocytopenia that occurs within the first 5 days.
  •  
30.
  • Lubenow, Norbert, et al. (författare)
  • Heparin-induced thrombocytopenia and cardiopulmonary bypass : perioperative argatroban use.
  • 2003
  • Ingår i: Annals of Thoracic Surgery. - 0003-4975 .- 1552-6259. ; 75:2, s. 577-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparin-induced thrombocytopenia (HIT), a serious complication of heparin therapy, mandates heparin cessation and alternative anticoagulation. We report a patient with a history of HIT who successfully underwent cardiopulmonary bypass (CPB) using short-term reexposure to heparin and perioperative therapy with argatroban. No bleeding complications or HIT-related problems occurred. The pharmacokinetics of argatroban, especially its hepatic rather than renal elimination, makes it the drug of choice for some HIT patients in whom other alternative anticoagulants (eg, danaparoid and hirudin) are less well suited. Because of interference with the international normalized ratio (INR), switching from argatroban to oral anticoagulants is not straightforward.
  •  
31.
  • Lubenow, Norbert, et al. (författare)
  • Hirudin in heparin-induced thrombocytopenia.
  • 2002
  • Ingår i: Seminars in Thrombosis and Hemostasis. - : Georg Thieme Verlag KG. - 0094-6176 .- 1098-9064. ; 28:5, s. 431-8
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparin-induced thrombocytopenia (HIT), a serious side effect of heparin treatment, requires alternative anticoagulation in most affected patients. The recombinant hirudin (r-hirudin) lepirudin has been approved for this purpose after two prospective trials in laboratory-confirmed HIT patients. Other drugs available for this purpose are danaparoid sodium (a heparinoid) and argatroban, a synthetic direct thrombin inhibitor. In this article, recommendations for optimal use of r-hirudin in HIT are given, covering therapy in uncomplicated patients as well as in special situations such as heparin reexposure of HIT patients. Because lepirudin's half-life depends on renal function, it may vary between 1 and 200 hours, which requires individual dose adjustments. Lepirudin compares favorably with danaparoid, based on retrospective data. No direct comparisons of lepirudin with argatroban are available, but argatroban might offer advantages in patients with renal failure, because it is mainly eliminated hepatically. Major hemorrhage, the main risk of lepirudin treatment, occurring in about 15% of patients, makes close monitoring important. New monitoring tools, such as the ecarin clotting time (ECT), might further reduce bleeding risks. Antihirudin antibodies, which can alter the pharmacokinetics as well as the pharmacodynamics of hirudin, can also be countered by close monitoring and appropriate dose adjustments. Whereas hirudins have not yet managed to gain importance in non-HIT indications such as unstable coronary syndromes, they have a major role to play in the treatment of HIT. The choice between the available drugs for HIT, namely lepirudin, danaparoid, and argatroban, has to be made according to the clinical presentation of the patient.
  •  
32.
  • Lubenow, Norbert, et al. (författare)
  • [Hirudins in the treatment of heparin-induced thrombocytopenia and in thrombosis prophylaxis].
  • 2002
  • Ingår i: Hämostaseologie. - 0720-9355. ; 22:3, s. 44-54
  • Tidskriftsartikel (refereegranskat)abstract
    • Approved indications for the recombinant hirudins lepirudin (Refludan(R)) und desirudin (Revasc(R)) are therapy of heparin-induced thrombocytopenia (HIT) and thrombosis prophylaxis following knee or hip replacement surgery. Kidney function dependent pharmacokinetics and their capability of inducing antibodies directed against hirudin are characteristic of this class of drugs. However, close dose-monitoring allows safe and effective use of both compounds. While lepirudin is used widely, besides danaparoid, for treatment of HIT, desirudin has not yet been widely accepted for thrombosis prophylaxis following knee or hip replacement surgery.
  •  
33.
  • Lubenow, Norbert, et al. (författare)
  • Lepirudin for prophylaxis of thrombosis in patients with acute isolated heparin-induced thrombocytopenia : an analysis of 3 prospective studies.
  • 2004
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 104:10, s. 3072-7
  • Tidskriftsartikel (refereegranskat)abstract
    • This analysis of 3 prospective multicenter trials in patients with laboratory-confirmed acute heparin-induced thrombocytopenia (HIT) without clinically evident thromboembolic complications (TECs), isolated HIT, assessed the combined individual end points of death, new TECs, and limb amputation. Patients with the same inclusion criteria who did not receive lepirudin or danaparoid served as a contemporaneous control group. Ninety-one patients were treated with lepirudin (intravenous infusion 0.10 mg/kg/h, no bolus, activated partial thromboplastin time [aPTT]-adjusted to 1.5-2.5 times baseline) for a median of 11.0 days (range, 1-68 days). During the observation period (median 24 days), 13 (14.3%) deaths, 4 (4.4%) new TECs, 3 (3.3%) limb amputations (combined 18 [19.8%]), and 13 (14.3%) major bleeding events occurred. In comparison to the control group (N = 47), the combined end point (P = .0281) and new TECs (P = .02) were reduced, and major bleeding was not significantly different between groups (P = .5419). In renal impairment, lepirudin did not reach its steady state within 4 hours, and additional monitoring every 4 hours after start of lepirudin until steady state is reached is recommended. Lepirudin seems to be effective in patients with isolated HIT. Dose reductions in renal impairment are important. Keeping the aPTT in the range corresponding to 600 to 700 microg/L lepirudin during treatment may minimize bleeding complications.
  •  
34.
  • Lubenow, Norbert, et al. (författare)
  • Lepirudin in patients with heparin-induced thrombocytopenia - results of the third prospective study (HAT-3) and a combined analysis of HAT-1, HAT-2, and HAT-3.
  • 2005
  • Ingår i: Journal of Thrombosis and Haemostasis. - : Elsevier BV. - 1538-7933 .- 1538-7836. ; 3:11, s. 2428-36
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: To assess efficacy and safety of lepirudin in patients with heparin-induced thrombocytopenia (HIT) in a prospective study (HAT-3) as well as in a combined analysis of all HAT study data. PATIENTS/METHODS: Patients with laboratory-confirmed HIT were treated with lepirudin in three different aPTT-adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison. RESULTS: After start of lepirudin in 205 patients treated in HAT-3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log-rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg(-1) h(-1). Major bleeding was more frequent in the lepirudin-treated patients (29.4% vs. 9.1%, P = 0.0148). CONCLUSIONS: The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg(-1) h(-1).
  •  
35.
  •  
36.
  • Lubenow, Norbert (författare)
  • New developments in diagnosis and treatment of heparin-induced thrombocytopenia.
  • 2003
  • Ingår i: Pathophysiology of Haemostasis and Thrombosis. - : S. Karger AG. - 1424-8832 .- 1424-8840. ; 33:5-6, s. 407-12
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparin-induced thrombocytopenia (HIT) is a drug induced immune mediated thrombocytopenia that affects up to 3% of patients treated with unfractionated heparin (UFH). It is less frequent when low molecular weight heparins (LMWH) are used. Fondaparinux does not seem to induce HIT. A functional and an antigen assay should be performed to confirm the clinical diagnosis of HIT. Immediate cessation of heparin and start of compatible anticoagulant is mandatory when HIT is suspected clinically. Danaparoid (a heparinoid)and the direct thrombin inhibitors lepirudin and argatroban are available for this purpose. Short-term reexposure with heparin, for example during cardiopulmonary bypass, is possible in patients with history of HIT, provided HIT antiodies are no longer detectable. In children systematic data on treatment of HIT are lacking.
  •  
37.
  •  
38.
  • Lubenow, Norbert, et al. (författare)
  • Phenylketonuria screening with a fluorometric microplate assay.
  • 1994
  • Ingår i: European journal of clinical chemistry and clinical biochemistry : journal of the Forum of European Clinical Chemistry Societies. - 0939-4974. ; 32:7, s. 525-8
  • Tidskriftsartikel (refereegranskat)abstract
    • A fluorometric assay in microtitre plates for the screening of phenylketonuria was evaluated and adapted to a neonatal screening programme. Using this assay, it is possible to determine quantitatively the phenylalanine concentration in dried blood spots on filter paper. The test exhibited a linear calibration curve with a good slope as well as sufficient precision and accuracy in the statistical analysis. Interference by other amino acids and antibiotics was not observed. Only elevated concentrations of leucine interfered to a small degree. The phenylalanine concentration in dried blood spots of 13 phenylketonuria patients correlated to that in serum. 7381 dried blood samples of newborn infants were tested simultaneously by both the fluorometric and the Guthrie test. The results did not show significant differences. We screened 29,182 newborns using the fluorometric assay and an online data processing programme. The internal repetition rate was 0.64%, the external recall rate 0.15%. False negative results were not observed. In December 1991 the fluorometric method replaced the Guthrie test in our routine programme for phenylketonuria screening, and was introduced as a follow up test for phenylketonuria patients.
  •  
39.
  • Lubenow, Norbert, et al. (författare)
  • Results of a systematic evaluation of treatment outcomes for heparin-induced thrombocytopenia in patients receiving danaparoid, ancrod, and/or coumarin explain the rapid shift in clinical practice during the 1990s.
  • 2006
  • Ingår i: Thrombosis Research. - : Elsevier BV. - 0049-3848 .- 1879-2472. ; 117:5, s. 507-15
  • Tidskriftsartikel (refereegranskat)abstract
    • INTRODUCTION: Randomized controlled trials evaluating treatment of acute, transient, but uncommon diseases are difficult to perform. The prothrombotic adverse drug reaction, heparin-induced thrombocytopenia (HIT), is such an example. During the mid-1980s, the defibrinogenating snake venom, ancrod (+/-warfarin, Canada), or coumarin (warfarin, Canada; phenprocoumon, Germany) alone, were often used to treat HIT. During the 1990s, danaparoid+/-coumarin began to replace ancrod (+/-coumarin), or coumarin alone, for treating HIT, despite danaparoid not being approved for treatment of HIT. METHODS: We performed a retrospective evaluation of treatment outcomes from 1986 to 1999, comparing danaparoid+/-coumarin (n=62) versus ancrod+/-coumarin or coumarin alone (controls, n=56). RESULTS: The predefined composite endpoint of adjudicated new, progressive, or recurrent thrombosis (including thrombotic death), or limb amputation, at day 7 (maximum, one event per patient) was significantly lower in danaparoid-treated patients, compared with controls: 8/62=12.9% (95% CI, 4.3-21.5) vs. 22/56=39.3% (95% CI, 26.1-52.5); p=0.0014. We also found a lower frequency of the composite endpoint at end of study (day 35) in danaparoid-treated patients: 12/62=19.4% vs. 24/56=42.9% (p=0.0088). Major bleeding (by day 7) occurred in 7/62 (11.3%) and 16/56 (28.6%) of danaparoid-treated and control patients, respectively (p=0.0211). CONCLUSIONS: The replacement of ancrod+/-coumarin, or coumarin alone, by danaparoid (+/-coumarin) in the mid-1990s for the treatment of HIT was justified by improved efficacy and safety.
  •  
40.
  • Lubenow, Norbert, et al. (författare)
  • Should patients be informed about the risk of heparin-induced thrombocytopenia before prolonged low-molecular-weight heparin thromboprophylaxis post-trauma/orthopedic surgery?
  • 2007
  • Ingår i: European Journal of Haematology. - : Wiley. - 0902-4441 .- 1600-0609. ; 79:3, s. 187-90
  • Tidskriftsartikel (refereegranskat)abstract
    • OBJECTIVES: Heparin-induced thrombocytopenia (HIT) is an immune-mediated prothrombotic adverse drug effect that occurs less frequently with low-molecular-weight heparin (LMWH) than with unfractionated heparin (UFH) in post-trauma/orthopedic surgery patients. The life-threatening nature of HIT raises the question whether informed consent for this treatment-induced adverse effect should be obtained, particularly as LMWH is often continued during the outpatient period when clinical and platelet count monitoring become problematic. Paradoxically, refusal of thromboprophylaxis as a result of seeking informed consent could increase risk for thrombosis. METHODS: We evaluated in patients undergoing routine LMWH thromboprophylaxis post-trauma/orthopedic surgery the feasibility of obtaining informed consent, using a standardized questionnaire to determine patient preferences. We also identified the proportion of HIT patients in our laboratory comprised of trauma/orthopedic surgery patients from 1995-1997 and 2002-2004 (time periods characterized, respectively, by UFH and LMWH thromboprophylaxis for this patient population). RESULTS: None of 460 patients in whom informed consent was administered rejected LMWH thromboprophylaxis. The patients' perception of the informed consent process and the written information provided about the risk of HIT and its risk due to clinical consequences were highly favorable. From 1995-1997 to 2002-2004, the proportion of HIT identified among trauma/orthopedic surgery patients declined from 30.3% to 1.2% (P < 0.0001). CONCLUSIONS: Obtaining informed consent about HIT is feasible in written form and does not cause refusal of LMWH thromboprophylaxis. Despite the uncommon occurrence of HIT during LMWH thromboprophylaxis, informed consent increases patient's awareness of this potentially life-threatening adverse drug effect, an outcome that could increase outpatient recognition of the diagnosis.
  •  
41.
  • Lubenow, Norbert, et al. (författare)
  • The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia.
  • 2010
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 115:9, s. 1797-803
  • Tidskriftsartikel (refereegranskat)abstract
    • Heparin can induce heparin-induced thrombocytopenia (HIT). The combined effect of type of surgery (major vs minor) and heparin on this prothrombotic immune reaction to platelet factor 4 (PF4)/heparin was analyzed. In a randomized, double-blind study, trauma patients receiving low-molecular-weight (LMWH) or unfractionated heparin (UFH) for thrombosis prophylaxis were assessed for PF4/heparin-antibody seroconversion, HIT, and thrombosis according to type of surgery. The risk for seroconversion was higher than major versus minor surgery odds ratio, 7.98 [95% confidence interval, 2.06-31.00], P = .003, controlled for potential confounders, as was the risk for HIT (2.2% [95% confidence interval, 0.3%-4.1%] vs 0.0%, P = .010). During LMWH compared with UFH thromboprophylaxis, HIT (1 of 298 vs 4 of 316; P = .370) and PF4/heparin seroconversion (1.7% vs 6.6%; P = .002) were less frequent, driven by differences in patients undergoing major surgery (incidence of HIT: LMWH 0.8% vs UFH 4.0%; P = .180; seroconversion rates: 4.0% vs 17.0%; P = .001). After minor surgery, no case of HIT occurred. The severity of trauma and the need for major surgery strongly influence the risk of an anti-PF4/heparin immune response, which is then increased by UFH. In major trauma certoparin may be safer than UFH because it induces HIT-antibody seroconversion, and the corresponding risk of HIT, less frequently.
  •  
42.
  • Lubenow, Norbert, et al. (författare)
  • Very low platelet counts in post-transfusion purpura falsely diagnosed as heparin-induced thrombocytopenia. Report of four cases and review of literature.
  • 2000
  • Ingår i: Thrombosis Research. - 0049-3848 .- 1879-2472. ; 100:3, s. 115-25
  • Tidskriftsartikel (refereegranskat)abstract
    • Differential diagnosis between post-transfusion purpura (PTP) and heparin-induced thrombocytopenia (HIT) can be difficult in the initial stages of thrombocytopenia, as the early clinical presentations are often similar. Four patients are described who were suspected clinically of suffering from HIT. All four patients had recent blood transfusions and platelet alloantibodies, thus the diagnosis of PTP was made. One lethal gastrointestinal and one retroperitoneal hemorrhage developed in two of the four patients. Unusually, one patient was male and two different platelet alloantibodies were present in his serum; in another patient platelet alloantibodies and HIT-antibodies were detectable. To arrive at the right diagnosis as quickly as possible is vitally important since treatment, which has to be initiated promptly, is very different for the two syndromes. Thus, we suggest that in patients where HIT is suspected, additional information should be sought. If features consistent with PTP (such as a recent blood transfusion or a marked drop in platelet count to below 15 Gpt/L) are present, we recommend parallel testing for platelet alloantibodies to rule out PTP.
  •  
43.
  •  
44.
  • Mogensen, Stefan, et al. (författare)
  • An evaluation of the mixed pediatric unit for blood loss replacement in pediatric craniofacial surgery
  • 2017
  • Ingår i: Pediatric Anaesthesia. - : Wiley. - 1155-5645 .- 1460-9592. ; 27:7, s. 711-717
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Surgical correction for craniosynostosis is often associated with significant perioperative hemorrhage. We implemented a transfusion strategy with a strict protocol including transfusion triggers, frequent assessment of coagulation tests, and the use of a novel transfusion unit, the mixed pediatric unit. Aim: The aim of the study was to evaluate if the applied transfusion strategy could reduce total blood loss and number of blood donors. Methods: Children <1 year old admitted for craniosynostosis surgery were included for the study. On the day before surgery, an adult red blood cell unit was mixed with plasma and split into two mixed pediatric units-one intended for intraoperative use and the other saved for the postoperative period. A series of blood samples were obtained for standard coagulation parameters as well as thromboelastography to evaluate potential coagulopathy. Estimated blood loss, the number of additional standard packed red cell units opened in the first 24 h after surgery, the volume of fluid administered, and the total transfusion volumes were compared to a historical control group with similar age and characteristics. Results: Nineteen infants were included in the study group, and were compared to 21 historical controls. There was a significant reduction of intraoperative transfusion volume. Twelve patients were transfused postoperatively, but in 8 of these additional exposure to packed red cell donor blood was avoided by using the saved mixed pediatric unit. In the historical controls, a total of 10 packed red cell units were used in nine patients postoperatively. No additional transfusions of plasma, platelets, fibrinogen, or tranexamic acid were needed in either group, and the coagulation parameters including thromboelastography remained within their respective normal ranges in the study group. Conclusion: For craniofacial surgery in infants, moderate perioperative blood loss and avoidance of coagulopathy is possible when a multifactorial approach is implemented. In this setting, intraoperative, but not total perioperative blood loss was reduced with the studied protocol. The study indicates that there may be a role for mixed pediatric units to reduce exposure to multiple donors although the reduction in total donor exposure was not significant.
  •  
45.
  •  
46.
  •  
47.
  • Petersmann, Astrid, et al. (författare)
  • Impact of physical activity of individuals and creatine kinase on 99th percentiles of troponin I assays
  • 2016
  • Ingår i: Clinica Chimica Acta. - : Elsevier BV. - 0009-8981 .- 1873-3492. ; 462, s. 187-192
  • Tidskriftsartikel (refereegranskat)abstract
    • Determination of cardiac troponin I (cTnI) is one central means for diagnosis of myocardial infarction. Assay performance of three troponin I assays was compared previously in a large reference population detecting sex-differences in the 99th percentile only for the Dimension Vista cTnI assay. The present study examined the underlying effects. Values for cTnI were reused. Creatine kinase (CK) activity was determined in 2358 samples from blood donors. Information on physical activity was evaluated from health questionnaires. Using quantile regression data were analysed to investigate the impact of sex, physical activity, and CK on the 99th percentile of the cTnI assay. We report significant sex-differences for the 99th percentile of cTnI. Physical activity was significantly associated with cTnI values. Strong association of CK activity with cTnI values was detected only in men. Adjustment for CK in quantile regression abolished sex -differences in the 99th percentile. Two other contemporary sensitive cTnI assays were not relevantly affected by physical activity or CK. Sex -differences in the 99th percentile for the Dimension Vista cTnI assay arise from a positive association between cTnI and physical activity and were abrogated when data were adjusted for CK activity. These findings should be taken into account when using this assay.
  •  
48.
  • Pietersz, R. N. I., et al. (författare)
  • Prophylactic platelet transfusions
  • 2012
  • Ingår i: Vox Sanguinis. - : Wiley. - 0042-9007 .- 1423-0410. ; 103:2, s. 159-176
  • Tidskriftsartikel (refereegranskat)
  •  
49.
  • Puuvuori, Emmi, et al. (författare)
  • PET imaging of neutrophil elastase with 11C-GW457427 in Acute Respiratory Distress Syndrome in pigs
  • 2023
  • Ingår i: Journal of Nuclear Medicine. - : Society of Nuclear Medicine and Molecular Imaging. - 0161-5505 .- 1535-5667 .- 2159-662X. ; 64:3, s. 423-429
  • Tidskriftsartikel (refereegranskat)abstract
    • Today, there is a lack of clinically available imaging techniques to detect and quantify specific immune cell populations. Neutrophils are one of the first immune cells at the site of inflammation, and they secrete the serine protease neutrophil elastase (NE), which is crucial in the fight against pathogens. However, the prolonged lifespan of neutrophils increases the risk that patients will develop severe complications, such as acute respiratory distress syndrome (ARDS). Here, we evaluated the novel radiolabeled NE inhibitor 11C-GW457427 in a pig model of ARDS, for detection and quantification of neutrophil activity in the lungs. Methods: ARDS was induced by intravenous administration of oleic acid to 5 farm pigs, and 4 were considered healthy controls. The severity of ARDS was monitored by clinical parameters of lung function and plasma biomarkers. Each pig was studied with 11C-GW457427 and PET/CT, before and after pretreatment with the NE inhibitor GW311616 to determine in vivo binding specificity. PET image data were analyzed as SUVs and correlated with immunohistochemical staining for NE in biopsies. Results: The binding of 11C-GW457427 was increased in pig lungs with induced ARDS (median SUVmean, 1.91; interquartile range [IQR], 1.67-2.55) compared with healthy control pigs (P < 0.05 and P = 0.03, respectively; median SUVmean, 1.04; IQR, 0.66-1.47). The binding was especially strong in lung regions with high levels of NE and ongoing inflammation, as verified by immunohisto-chemistry. The binding was successfully blocked by pretreatment of an NE inhibitor drug, which demonstrated the in vivo specificity of 11C-GW457427 (P < 0.05 and P = 0.04, respectively; median SUVmean, 0.60; IQR, 0.58-0.77). The binding in neutrophil-rich tissues such as bone marrow (P < 0.05 and P = 0.04, respectively; baseline median SUVmean, 5.01; IQR, 4.48-5.49; block median SUVmean, 1.57; IQR, 0.95-1.85) and spleen (median SUVmean, 2.14; IQR, 1.19-2.36) was also high in all pigs. Conclusion: 11C-GW457427 binds to NE in a porcine model of oleic acid-induced lung inflammation in vivo, with a specific increase in regional lung, bone marrow, and spleen SUV. 11C-GW457427 is a promising tool for localizing, tracking, and quantifying neutrophil-facilitated inflammation in clinical diagnostics and drug development.
  •  
50.
  • Rothenfusser, Simon, et al. (författare)
  • CpG-A and CpG-B oligonucleotides differentially enhance human peptide-specific primary and memory CD8+ T-cell responses in vitro.
  • 2004
  • Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 103:6, s. 2162-9
  • Tidskriftsartikel (refereegranskat)abstract
    • Two distinct types of CpG oligodeoxynucleotide (ODN) have been identified that differ in their capacity to stimulate antigen-presenting cells: CpG-A induces high amounts of interferon-alpha (IFN-alpha) and IFN-beta in plasmacytoid dendritic cells (PDCs), whereas CpG-B induces PDC maturation and is a potent activator of B cells but stimulates only small amounts of IFN-alpha and IFN-beta. Here we examined the ability of these CpG ODNs to enhance peptide-specific CD8+ T-cell responses in human peripheral blood mononuclear cells (PBMCs). The frequency of influenza matrix-specific "memory" CD8+ T cells was increased by both types of CpG ODN, whereas the frequency of Melan-A specific "naive" CD8+ T cells increased on stimulation with CpG-B but not with CpG-A. The presence of PDCs in PBMCs was required for this CpG ODN-mediated effect. The expanded cells were cytotoxic and produced IFN- on peptide restimulation. Soluble factors induced by CpG-A but not CpG-B increased the granzyme-B content and cytotoxicity of established CD8+ T-cell clones, each of which was IFN-alpha/-beta dependent. In conclusion, CpG-B seems to be superior for priming CD8+ T-cell responses, and CpG-A selectively enhances memory CD8+ T-cell responses and induces cytotoxicity. These results demonstrate distinct functional properties of CpG-A and CpG-B with regard to CD8 T cells.
  •  
Skapa referenser, mejla, bekava och länka
  • Resultat 1-50 av 64

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy