P Knöbl

Medical University of Vienna, Linz, Upper Austria, Austria

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Publications (89)382.98 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: Please cite this paper as: Tengborn L, Baudo F, Huth-Kühne A, Knoebl P, Lévesque H, Marco P, Pellegrini F, Nemes L, Collins P on behalf of the EACH2 registry contributors. Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry. BJOG 2012;119:1529-1537. Objective  The European Acquired Haemophilia registry (EACH2) collected data on the demographics, diagnosis, underlying disorders, bleeding characteristics, treatment, and outcome of women with acquired haemophilia A (AHA), a rare and often severe bleeding disorder caused by autoantibodies directed against coagulation factor VIII. Design  Prospective, multi-centre, large-scale, pan-European registry. Setting  A total of 117 haemophilia centres in 13 European countries. Population  Pregnancy-associated AHA. Methods  Data were reported using a web-based electronic case report form. Diagnosis was based on the presence of a prolonged activated partial thromboplastin time, reduced coagulation Factor VIII level and positive inhibitor assay. Main outcome measures  Presenting characteristics, time to diagnosis, haemostatic treatment and outcome, immunosuppressive treatment and outcome. Results  The EACH2 registry (n = 501) documented 42 (8.4%) cases of AHA associated with the peripartum period, a median Factor VIII level at diagnosis of 2.5 (range 0-25) IU/dl and inhibitor titre of 7.8 (range 0.7-348) BU/ml. Antepartum inhibitors were evident in eight women. Time to diagnosis of AHA after delivery was 89 (range 21-120) days. First-line haemostatic treatment was successful in 20/23 (87%) women treated. Bleeding episodes resolved in 17/18 (94%) women treated with a bypassing agent and 29/39 (74%) women achieved complete remission with first-line immunosuppressive treatment. Two babies experienced postnatal bleeding, suggesting transplacental transfer of the antibody. All women were alive at last follow-up. Conclusions  Although rare, pregnancy-associated AHA may cause severe bleeding-related morbidity. Once diagnosed, women respond well to haemostatic treatment with bypassing agents and immunosuppression. Awareness of peripartum AHA requires improvement to facilitate rapid and appropriate management.
    BJOG An International Journal of Obstetrics & Gynaecology 08/2012; 119(12):1529-1537. · 3.76 Impact Factor
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    ABSTRACT:   Tissue factor pathway inhibitor (TFPI) is the major inhibitor of tissue factor-initiated coagulation, making it an interesting and novel therapeutic target in hemophilia treatment. The aptamer BAX499 (formerly ARC19499) is designed to improve hemostasis by specifically inhibiting TFPI. The aim of the study was to examine the concentration-dependent augmentation of clotting by BAX499. Whole blood clot formation was quantified by rotational thromboelastometry and thromboelastography, and thrombin generation in platelet-poor plasma was assessed with the calibrated automated thrombogram, in samples from patients with congenital hemophilia A (N=55) and B (N=11), patients with acquired hemophilia A (N=1), and healthy controls (N=37). BAX499 significantly improved clotting of samples from hemophilic patients in a concentration-dependent manner, resulting in clotting profiles in samples from patients with severe hemophilia that were similar to those of healthy controls. BAX499 improved ex vivo clotting parameters in blood and plasma from patients with hemophilia A and B with different severity of disease, and also in a patient with acquired hemophilia. These results further support the contention that anti TFPI strategies may be an effective treatment for hemophilic patients.
    Journal of Thrombosis and Haemostasis 05/2012; 10(8):1581-90. · 6.08 Impact Factor
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    ABSTRACT: Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).
    Blood 05/2012; 120(1):39-46. · 9.06 Impact Factor
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    ABSTRACT: Acquired hemophilia A (AHA) is an autoimmune disease caused by an autoantibody to factor VIII. Patients are at risk of severe and fatal hemorrhage until the inhibitor is eradicated, and guidelines recommend immunosuppression as soon as the diagnosis has been made. The optimal immunosuppressive regimen is unclear; therefore, data from 331 patients entered into the prospective EACH2 registry were analyzed. Steroids combined with cyclophosphamide resulted in more stable complete remission (70%), defined as inhibitor undetectable, factor VIII more than 70 IU/dL and immunosuppression stopped, than steroids alone (48%) or rituximab-based regimens (59%). Propensity score-matched analysis controlling for age, sex, factor VIII level, inhibitor titer, and underlying etiology confirmed that stable remission was more likely with steroids and cyclophosphamide than steroids alone (odds ratio = 3.25; 95% CI, 1.51-6.96; P < .003). The median time to complete remission was approximately 5 weeks for steroids with or without cyclophosphamide; rituximab-based regimens required approximately twice as long. Immunoglobulin administration did not improve outcome. Second-line therapy was successful in approximately 60% of cases that failed first-line therapy. Outcome was not affected by the choice of first-line therapy. The likelihood of achieving stable remission was not affected by underlying etiology but was influenced by the presenting inhibitor titer and FVIII level.
    Blood 04/2012; 120(1):47-55. · 9.06 Impact Factor
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    ABSTRACT: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA. The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large-scale, pan-European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients. Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty-seven per cent of the non-pregnancy-related cases were male. Four hundred and seventy-four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy-seven patients underwent immunosuppression, and 72.6% achieved complete remission. Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA.
    Journal of Thrombosis and Haemostasis 02/2012; 10(4):622-31. · 6.08 Impact Factor
  • Journal of Thrombosis and Haemostasis 11/2011; 10(1):156-8. · 6.08 Impact Factor
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    ABSTRACT: Although unfractionated heparin (UFH) is an effective antithrombotic agent in endovascular interventions for the treatment of peripheral occlusive arterial disease (PAOD), it produces a highly variable anticoagulant response. Intravenous (i.v.) enoxaparin might be an effective and safe alternative. In a prospective, open-label, randomized, single-center trial, 210 patients with PAOD (Fontaine stage IIb to IV) were randomly assigned in a 1 (UFH): 2 (enoxaparin) fashion to receive an i.v. bolus of 60 units UFH per kg body weight or 0.5 mg enoxaparin per kg body weight, respectively, before endovascular intervention. The primary composite endpoint assessed the clinical performance of enoxaparin by comparing the peri-interventional rate of thromboembolia/occlusion (efficacy) of endovascularly reconstructed areas, of bleeding according to the Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries (GUSTO) criteria (safety) and of any necessary re-intervention for any percutaneous transluminal angioplasty (PTA)-related bleeding. The secondary endpoint evaluated anti-factor (F)Xa levels during intervention. The primary composite endpoint showed a better performance of enoxaparin (10.5% vs. 2.5% absolute difference - 8.0%; P < 0.05). The concomitant use of acetylsalicylic acid (ASA) significantly (P < 0.05) increased the risk of a complication in the UFH group, but not in the enoxaparin group. Within 15 min, anti-Xa levels were reached by 63.7% of patients treated with enoxaparin and only by 39.1% with UFH. Enoxaparin has a better performance than UFH in endovascular interventions for the treatment of PAOD. In patients with concomitant use of ASA, the risk of complications with UFH increases significantly compared with enoxaparin.
    Journal of Thrombosis and Haemostasis 09/2011; 9(11):2159-67. · 6.08 Impact Factor
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    ABSTRACT: Paraneoplastic FVIII antibodies may occur concurrent with the diagnosis or at various times after diagnosis and treatment of cancer. Between 2002 and 2009, we observed two patients with acquired haemophilia A due to an FVIII auto-antibody, which appeared 4 and 5 months after uncomplicated cancer surgery. We aimed to evaluate if such an association of cancer surgery and FVIII antibody formation has been observed previously. We retrieved all published case reports of cancer-associated FVIII auto-antibodies from PubMed for the period 1950-2010. The search in the literature revealed 13 patients in whom a FVIII inhibitor developed after uncomplicated surgery for cancer and a bleeding-free time interval of up to 6 months; 11/15 patients had abdominal cancers (five colon cancer, four pancreatic cancer, gastric cancer and choledochus carcinoma one each). The median time period between surgery and antibody detection was 3 months (1 week-6 months). In most cases, the antibody titre was low (median: 14 BU mL⁻¹, range: 1.7-64 BU mL⁻¹). Immunosuppressive treatment was successful in most of the cases - nine of the treated patients reached a sustained CR of the antibody after a median time of 3 months. Postoperative paraneoplastic FVIII inhibitors may be regarded as a special, not yet recognized subgroup of acquired FVIII antibodies. They share some characteristics with postpartum FVIII inhibitors with regard to the latency period between the triggering event and the appearance of the antibody, and between the usually low antibody titres and their good response to immunosuppressive treatment.
    Haemophilia 04/2011; 17(5):e889-94. · 3.17 Impact Factor
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    ABSTRACT: Severe deficiency of the von Willebrand factor (VWF)-cleaving protease ADAMTS13 as observed in acquired thrombotic thrombocytopenic purpura (TTP) is caused by inhibitory and non-inhibitory autoantibodies directed against the protease. Current treatment with plasma exchange is considered to remove circulating antibodies and to concurrently replenish the deficient enzyme. To explore the use of recombinant ADAMTS13 (rADAMTS13) as a potential therapeutic agent in acquired TTP, we investigated its efficacy in normalizing VWF-cleaving activity in the presence of ADAMTS13 inhibitors. Thirty-six plasma samples from TTP patients were adjusted to predefined inhibitor titers, and recovery of ADAMTS13 activity was analyzed following supplementation with rADAMTS13. We showed a linear relation between the inhibitor titer measured and effective rADAMTS13 concentration necessary for reconstitution of VWF-cleaving activity in the presence of neutralizing autoantibodies. Our results support the further investigation of the potential therapeutic applicability of rADAMTS13 as an adjunctive therapy in acquired TTP.
    Journal of Thrombosis and Haemostasis 02/2011; 9(5):936-44. · 6.08 Impact Factor
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    ABSTRACT: A prospective, observational, multicentre study was performed to assess the incidence, diagnosis, epidemiology and outcome of invasive mould infections (IMIs) reported to the Nationwide Austrian Aspergillus Registry. In total, 186 cases were recorded, corresponding to an annual incidence of 42 cases/1000 patients at risk or 2.36 cases/100000 inhabitants. Patients with acute myelogenous leukaemia (34%) and lung transplant recipients (17%) are currently at highest risk for IMI, followed by a mixed population with impaired immunity (14%). In total, 34%, 30% and 36% were proven, probable and possible cases of IMI. Predominant pathogens were Aspergillus spp. (67%), followed by the zygomycetes (28%). Voriconazole was the most frequently administered agent (38%), followed by caspofungin (20%) and posaconazole (19%). Eighty patients (43%) received antifungal prophylaxis for ≥7 days, 30% of whom (24 patients) suffered from a breakthrough infection. The overall crude 12-week mortality was 34%. Multivariate analysis showed that outcome and survival did not correlate with the status of fungal disease, breakthrough infection, fungal species or age (P>0.05). Aspergillosis remains the most commonly identified IMI amongst immunocompromised and/or immunosuppressed patients, but other moulds constitute a significant problem. Survival from IMIs appears to have improved and the main challenge is to overcome breakthrough fungal infections.
    International journal of antimicrobial agents 10/2010; 36(6):531-6. · 3.03 Impact Factor
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    ABSTRACT: Acquired haemophilia is an autoimmune disorder characterised by autoantibody formation against coagulation factor VIII. Immunosuppressive treatments including steroids, cytotoxic drugs, rituximab or combinations thereof have been used to eradicate autoantibodies. Very few prospective studies exist evaluating the use of these treatments. Here, we performed a survey among 73 physicians from 57 haemophilia treatment centres in order to describe current practice patterns and critical issues for future research in acquired haemophilia. The results demonstrate a high diversity of first- and second-line treatments. Factors influencing treatment decision were underlying disorder, severity of bleeding and inhibitor titre. Frequently used first-line treatments were steroids plus cyclophosphamide (44%) and steroids alone (11%). Second-line treatment was most often rituximab (30%), with or without steroids and/or cyclophosphamide. Most participants indicated to change from first- to second-line treatment after 4 weeks in case of failure to obtain partial remission (31%), continued bleeding (40%) or continued severe bleeding requiring bypass treatment (59%). Immunoadsorption was preferred for first- and second-line treatment by 10% and 9% of participants, respectively. These results highlight critical issues in the field. Open questions and directions for future research are discussed.
    Annals of Hematology 01/2009; 88(4):365-70. · 2.87 Impact Factor
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    ABSTRACT: This prospective, randomized, single-center, open-label pilot study evaluated the safety and efficacy in carotid surgery of a single intraoperative bolus of body weight-adjusted enoxaparin compared with unfractionated heparin. Symptomatic and asymptomatic patients with high-grade internal carotid artery stenosis were included. The primary objective was to evaluate perioperative efficacy (incidence of thromboembolic ischemic stroke). The secondary objective was to evaluate safety, including avoidance of hematoma at the site of surgery, gastrointestinal bleeding, rate of blood transfusions, and occurrence of heparin-induced thrombocytopenia. From July 2005 to June 2006, 338 consecutive patients undergoing carotid endarterectomy were enrolled; of these, 115 patients did not fulfill inclusion criteria, and 63 patients refused to participate. The remaining 160 patients were assigned in a 3:1 randomization to receive enoxaparin (0.5 mg/kg) or unfractionated heparin (5000 IU) intraoperatively as an intravenous bolus (120 and 40 patients, respectively). The mean patient age was 70.3 years (range, 43.3-94.7 years), and 54 were women. Internal carotid artery stenosis was asymptomatic in 55% and symptomatic in 45%. The difference in baseline characteristics between these groups was not significant. The rate of cerebral embolic events was 0.8% in the enoxaparin group (n = 1) and 2.5% in the unfractionated heparin group (n = 1). The rate of severe bleeding complications was 1.7% in the enoxaparin group (n = 2) and 5% in the unfractionated heparin group (n = 2; P > .05). No case of heparin-induced thrombocytopenia was observed. This pilot study found no difference between enoxaparin and unfractionated heparin during carotid endarterectomy in perioperative bleeding or embolic events. A large multicenter trial seems to be warranted.
    Journal of Vascular Surgery 04/2008; 47(3):537-42. · 2.88 Impact Factor
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    ABSTRACT: Central nervous system (CNS) relapse in chronic myeloid leukaemia (CML) is rare and if recorded is usually found to occur in patients with lymphoblastic transformation. The BCR/ABL tyrosine kinase inhibitor imatinib is highly effective in patients with CML, but hardly crosses the blood-brain barrier. We report on two CML patients who developed a myeloid CNS relapse during treatment with imatinib. One patient was in major cytogenetic response at the time of CNS relapse. In both cases, the myeloid origin of neoplastic cells in the cerebrospinal fluid (CSF) was demonstrable by immunophenotyping, and their leukaemic origin by detection of the BCR/ABL oncoprotein. No BCR/ABL kinase domain mutations were found. Both patients received intrathecal liposomal cytarabine (50 mg each cycle; 6 cycles). In one patient, additional CNS radiation was performed, whereas in the other, consecutive treatment with dasatinib (70 mg per os twice daily) was started. In response to therapy, the clinical symptoms resolved, and the leukaemic cells in the CSF disappeared in both cases. After three months of observation, both patients are in complete cytogenetic and major molecular response, without evidence for a systemic or a CNS relapse. 'Anatomic' resistance against imatinib in the CNS can lead to a myeloid CNS relapse. Liposomal cytarabine with or without radiation is effective as local therapy in these patients. For systemic treatment and prophylaxis, BCR/ABL kinase inhibitors crossing the blood-brain barrier such as dasatinib should be considered in patients with CNS relapse.
    European Journal of Clinical Investigation 11/2007; 37(10):808-13. · 3.37 Impact Factor
  • P Knöbl
    Journal of Thrombosis and Haemostasis 12/2006; 4(11):2352-4. · 6.08 Impact Factor
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    ABSTRACT: Antiplatelet therapy is one of the most important modalities for secondary prevention of ischemic events. The aim of this prospective study was to evaluate the current practice of antiplatelet therapy in patients with high grade stenosis of the internal carotid artery (ICA), who were referred by neurologists, stroke physicians and cardiologists for carotid endarterectomy. Patients referred to our department for carotid endarterectomy with ICA stenosis (> 70% according to NASCET criteria) were prospectively evaluated regarding atherosclerosis risk factors and current antiplatelet therapy. During a 7 month period, 235 patients were scheduled for carotid endarterectomy. Their mean age was 70 years (range 42 years to 95 years), 91 patients were female (39%), 144 male (61%). 122 patients (52%) had a symptomatic ICA stenosis, 113 (48%) an asymptomatic ICA stenosis. Of the 235 patients, 29 were either on low molecular weight heparin or vitamin K antagonists for reasons other than ICA stenosis and were therefore excluded from analysis. Therefore, 206 patients (88%) were evaluated for antiplatelet therapy prescribed by their admitting physicians. Of these patients, 77 (37%) (42 (41%) symptomatic and 35 (34%) asymptomatic patients) did not receive any antithrombotic therapy prior to admission for surgery. The majority of patients received aspirin preoperatively (106 patients, 51.5%) 13 (6%) patients were on clopidogrel and 10 (5%) on dual therapy with Aspirin and clopidogrel. More than one third of patients awaiting carotid endarterectomy did not receive any antiplatelet therapy, despite high grade ICA stenosis. Since this practice does not meet the current guidelines, campaigns to increase the awareness of this problem are urgently needed.
    VASA.: Zeitschrift für Gefässkrankheiten. Journal for vascular diseases 06/2006; 35(2):96-100. · 1.01 Impact Factor
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    ABSTRACT: The aim of this study was to evaluate the current practice of peri and postoperative antithrombotic therapy in vascular surgery in Austria and to compare this with the results of randomised prospective clinical trials. A questionnaire assessing intra, postoperative and long-term antithrombotic treatment in 13 different surgical procedures (three supra-aortic, three aorto-iliac reconstructions and seven inguinal and infra-inguinal arterial reconstructions) was sent to all 22 institutions training vascular surgical fellows in Austria. Intraoperative antithrombotic therapy was quite consistently performed with unfractionated heparin (UFH) with or without acetylsalicylic acid (ASA). Early and long-term postoperative therapy differed considerably. Most centres used low molecular weight heparin (LMWH) for early postoperative therapy after vascular reconstructions, in > 75% combined with ASA and/or clopidogrel. Long-term therapy consisted of antiplatelet agents in all centres. Vascular grafts were anticoagulated with UFH in 25% of the centres in the early postoperative period, the remaining institutions used LMWH +/- antiplatelet agents. For long-term antithrombotic therapy cumarins were used in 75% of the centres, predominantly for venous grafts. Distal prosthetic grafts were mainly treated with antiplatelet agents. Intraoperative antithrombotic therapy was in accordance to present guidelines, postoperative antithrombotic therapy, however, differed considerably between the participating institutions and the results of available controlled studies. Optimal antithrombotic strategies during and after vascular surgery are still under debate, and current practice often differs from available evidence. Vascular surgical societies should be encouraged to define recommendations on antiplatelet therapy and anticoagulation for different vascular interventions.
    European Journal of Vascular and Endovascular Surgery 06/2005; 29(5):516-21. · 2.82 Impact Factor
  • 12/2004: pages 79-88;
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    ABSTRACT: Transfusion of fresh-frozen plasma is still a pillar in emergency medicine for using to prevent dilutional coagulopathy or disseminated intravascular coagulation after severe blood loss, but thawing procedures can delay its availability. On the other hand, the wastage of plasma, once thawed and not transfused within a defined time-period, represents an inefficient handling of economic resources and is contradictory to blood donor intentions. In this study we investigated the stability of coagulation factor activities and plasma protein levels during 6 days of storage of thawed solvent/detergent (S/D)-treated plasma at +4 degrees C. Our results may form the basis for reconsideration of expiry times of thawed S/D-treated plasma. Five units of S/D-treated plasma (Octaplas) were thawed and warmed to 20 degrees C, then recooled and stored at +4 degrees C for 6 days. The activities of coagulation factors II, V, VII, VIII, IX, X, XI and XII, fibrinogen, antithrombin (AT), protein C, protein S and von Willebrand factor antigen (vWF:Ag) were measured on days 0, 1, 2, 3 and 6. Except for protein S, the activities of all coagulation factors and inhibitors were at least 0.5 U/ml during storage at 4 degrees C for 6 days. The mean levels, during storage, of factors IX, X, XI and XII, vWF:Ag, fibrinogen and protein C were at least 94%, and of factors II, V and VIII, and AT at least 78%, of the levels immediately after thawing; the activity of factor VII decreased to 83% and of protein S to 43% of the baseline values. Thawed S/D-treated plasma stored at +4 degrees C for up to 6 days still contains sufficient coagulation activities and plasma proteins to be regarded as suitable for transfusion in the established indications.
    Vox Sanguinis 11/2004; 87(3):182-6. · 2.85 Impact Factor
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    ABSTRACT: The CryoSeal FS has been introduced as an automated device for the production of fibrin sealant from small volumes of plasma. We tested this device and compared the product with commercially available fibrin sealants and with the requirements of the European Pharmacopoeia. The CP3 program and disposables required were used to manufacture fibrin sealant. The chemistry and mechanical properties of the product were investigated. The cryoprecipitate generated with CryoSeal contains concentrated fibrinogen and critical clotting factors. The efficiency of the production process is poor, but the production procedure itself is simple and not time-consuming. The volume of plasma required allows application in the preoperative autologous setting. The CryoSeal FS is an automated device for cryoprecipitation and production of thrombin. It can be implemented easily in the clinical routine, although, owing to product specifications, the efficacy of the CryoSeal fibrin sealant requires further clinical trials.
    Vox Sanguinis 06/2004; 86(4):257-62. · 2.85 Impact Factor
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    ABSTRACT: Karyotype is an important prognostic factor in patients with newly diagnosed acute myeloblastic leukaemia (AML). The prognostic value of cytogenetics on the outcome of patients with AML in relapse has not yet been well defined. We analysed the clinical outcome of 152 patients with de novo, chemotherapy-treated AML in first relapse according to the cytogenetic classification of the United Kingdom Medical Research Council. The rate of second complete remission (CR) (88, 64 and 36%) and the probability of survival at 3 years (43, 18 and 0%) were significantly different between the favourable, intermediate and adverse cytogenetic risk groups, respectively. Compared to the favourable group, the relative risk (RR) of death (multivariate analyses) was 2.6 (confidence interval (CI): 1.5-4.4, P<0.001) for the intermediate and 3.7 (CI: 1.7-7.9, P=0.001) for the adverse group. The prognostic value of the duration of first CR was confirmed (RR of death: 2.0 (CI: 1.0-4.0) for each additional year in first CR), whereas the FLT3 mutation obtained at diagnosis did not markedly influence the outcome of patients with AML in relapse. In conclusion, our results indicate that both karyotype and the duration of first CR are independent prognostic factors for patients with de novo AML in first relapse.
    Leukemia 03/2004; 18(2):293-302. · 10.16 Impact Factor

Publication Stats

1k Citations
382.98 Total Impact Points


  • 1999–2012
    • Medical University of Vienna
      • • Universitätsklinik für Innere Medizin I
      • • Universitätsklinik für Klinische Pharmakologie
      • • Station für Intensivmedizin
      Linz, Upper Austria, Austria
  • 2009
    • Hannover Medical School
      • Clinic for Hematology, Hemostasis, Oncology and Stem Cell Transplantation
      Hanover, Lower Saxony, Germany
  • 1992–2009
    • University of Vienna
      • • Institute of Social Medicine
      • • Universitätsklinik für Innere Medizin I
      Wien, Vienna, Austria
  • 2004
    • Vienna General Hospital
      Wien, Vienna, Austria
  • 2000
    • St Anna's Kinderspital
      Wien, Vienna, Austria