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1. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients

Author

Cervera, R, Serrano, R, Pons-Estel, G J, Ceberio-Hualde, L, Shoenfeld, Y, de Ramón, E, Buonaiuto, V, Jacobsen, S, Zeher, M M, Tarr, T, Tincani, A, Taglietti, M, Theodossiades, G, Nomikou, E, Galeazzi, M, Bellisai, F, Meroni, P L, Derksen, R H W M, de Groot, P G D, Baleva, M, Mosca, M, Bombardieri, S, Houssiau, F, Gris, J-C, Quéré, I, Hachulla, E, Vasconcelos, C, Fernández-Nebro, A, Haro, M, Amoura, Z, Miyara, M, Tektonidou, M, Espinosa, G, Bertolaccini, M L, and Khamashta, M A

Published
2015
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17. Demographic and clinical data in acquired hemophilia A

Author

Knoebl, P, Marco, P, Baudo, F, Collins, P, Huth Kühne, A, Nemes, L, Pellegrini, F, Tengborn, L, Lévesque, H, Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, D'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lévesque H, Lifermann F, Marlu R, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Huth Kühne A, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Nemes L, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Baudo F, Caimi T, Contino L, Di Minno G, Cerbone AM, Di Minno D, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, POGLIANI, ENRICO MARIA, Carpenedo M, Remiddi C, Santagostino E, Santoro R, Papaleo G, Schinco P, Borchiellini A, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Sartori R, Tagariello G, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Brandolini B, Hamulyák K, Kamphuisen P, Laros van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez Yuste V, Jose Felix L, Pascual M, Mingot ME, Perez Garrido R, Perez Gonzale Nz, Prieto Garcia M, Rodriguez Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Tengborn L, Boehlen F, Korte W, Chowdary P, Collins P, Evans G, Pavord S, Rangarajan S, Wilde J., Knoebl, P, Marco, P, Baudo, F, Collins, P, Huth Kühne, A, Nemes, L, Pellegrini, F, Tengborn, L, Lévesque, H, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lifermann, F, Marlu, R, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Caimi, T, Contino, L, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, matteo nicola dario, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Sartori, R, Tagariello, G, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Pascual, M, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Boehlen, F, Korte, W, Chowdary, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., Aspoeck, G, Borg, JY, Huth-Kühne, A, Loreth, RM, Di Minno, G, Cerbone, AM, Di Minno, D, D'incà, M, Mazzucconi, MG, Scortechini, AR, Tagliaferri, AR, Rivolta, GF, Laros-van Gorkom, B, Leebeek, FW, van der Linden, PW, Gutiérrez Pimentel, MJ Jiménez-Yuste, V, Jose-Felix, L, Pascual, M, Mingot, ME, Rodriguez-Huerta, AM, Wilde, J, Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Huth Kühne, A, Lévesque, H, Borg, J, Loreth, R, Cerbone, A, Mazzucconi, M, Scortechini, A, Tagliaferri, A, Rivolta, G, Brandolini, B, Leebeek, F, van der Linden, P, Gutiérrez Pimentel, M, Mingot, M, Perez Gonzale, N, Rodriguez Huerta, A, and Other departments

Subjects
Registrie, Male, Pediatrics, diagnosis, medicine.medical_treatment, Hemostatic Technique, Kaplan-Meier Estimate, registry, THERAPY, Settore MED/15 - Malattie Del Sangue, Immunosuppressive Agent, IMMUNOADSORPTION, Risk Factors, Pregnancy, 80 and over, Prospective Studies, Registries, Prospective cohort study, health care economics and organizations, Aged, 80 and over, treatment, Immunosuppression, Hematology, Middle Aged, FACTOR-VIII INHIBITOR, Acquired hemophilia, Demographics, Diagnosis, Outcome, Registry, Treatment, Aged, Autoantibodies, Chi-Square Distribution, Europe, Factor VIII, Female, Hemostatic Techniques, Humans, Immunosuppressive Agents, Risk Assessment, Treatment Outcome, Hemophilia A, Hemorrhage, Autoantibodie, acquired hemophilia, demographics, outcome, INTRAVENOUS GAMMA-GLOBULIN, Human, medicine.medical_specialty, Malignancy, hemophilia, registry, medicine, METAANALYSIS, Autoimmune disease, business.industry, Risk Factor, Autoantibody, medicine.disease, Surgery, Prospective Studie, Hemostasis, business, Chi-squared distribution
Abstract

Summary. Background: 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. Objectives: 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. Results: 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. Conclusions: Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA.

Published
2012

18. The prothrombin time/international normalized ratio (PT/INR) Line: derivation of local INR with commercial thromboplastins and coagulometers – two independent studies

Author

POLLER L, IBRAHIM S, KEOWN M, PATTISON A, JESPERSEN J, EUROPEAN ACTION ON A.N.T.I.C.O.A.G.U.L.A.T.I.O.N. COLLABORATORS: MARUN S, MUNTEAN W, ASPÖCK G, BAILLEUL E, WIJNS W, MICHEL T, JOCHMANS K, CHATELAIN B, MARCELIS L, NIJS AN, JOHNSTON M, KYNDE K, SYRÄJLÄ M, SAVOLAINEN ER, IVASKA K, RAJAMÄKI A, VANHARANTA R, JUHAN I, AILLAUD MF, GUILLIN MC, HUISSE MG, SIE P, LECOMPTE T, SCHMITT Y, HARENBERG J, PLESCH W, ARONIS S, THEODOSSIADES G, TSOUKANAS B, MARKALA D, DITSA M, CAHILL M, MADDEN M, FITZGERALD H, MCCARTHY D, COLLINS B, ROONEY S, NAPARSTEK E, MARONGIU F, ERBA N, TESTA S, MARIANI G, POTÌ R, MANNUCCI PM, TRIPODI A, BADER R, PENGO V, GRESELE P, D'INCÀ M, AGENO W, TOSETTO A, HENSGENS HE, IDEMA RN, OOSTERHOUT DH, MULDER AB, HAMULYAK K, VD DUSSEN H, MUSIAL J, GAGO T, PALMEIRO A, CAMPOS M, MARQUES DIAS DA, CUNHA MONTEIRO Á, ANGELA CUNHA M, DE GAIA WN, PETERNEL P, STEGNAR M, FONTCUBERTA J, BORRELL M, REVERTER JC, SANTASUSANA PD, LOPEZ FERNANDEZ MF, MONTERO J, RIBERA CASADO C, VICENTE V, EDLUND B, EGBERG N, LÄMMLE B, ALBERIO L, DE MOERLOOSE P, REBER G, MACHIN SJ, MACKIE I, LAWRIE A, LUCKIT J, SHANKS D, DOLAN G, FLAHERTY T, LUDLAM CA, WALKER ID, LAWSON DE, TRISCOTT M, MARLAR RA, HEIT JA, WATZKE H, WEISSER B, GALLUS AS, OSMOND J, CORNET I, MUNSTER AM, LEED B, CHILLOU C, DEFARD M, HORELLOU MH, HALKIN H, LOEBSTEIN R, KIRGNER I, DENTALI F, TRAPANI LOMBARDO V, SOTTILOTTA G, CONSIGLIO P, DE MICHELE S, MOIA M, CARPENEDO M, OLIVIERO B, MANOTTI C, TASSONI MI, PALARETI G, BRUSI C, LEGNANI C, PEGORARO C, ANDRIANI C, GRAZIA CIRIGLIANO M, RIBALDI E, ABBATE R, POLI D, PERRICONE C, SCHIAVULI M, CASIERA C, LUPONE MR, ROSSI E, CRIVELLI S, BIROLINI A, PARENTE F, MIGLIETTA AM, CAMPOBASSO M, SYDOR W, KREVEL B, FERNANDEZ MA, LOZANO M, SHIACH C, BOWYER C, CHARLES F., PALARETI, GUALTIERO, COSMI, BENILDE, POLLER L, IBRAHIM S, KEOWN M, PATTISON A, JESPERSEN J, EUROPEAN ACTION ON ANTICOAGULATION. COLLABORATORS: MARUN S, MUNTEAN W, ASPÖCK G, BAILLEUL E, WIJNS W, MICHEL T, JOCHMANS K, CHATELAIN B, MARCELIS L, NIJS AN, JOHNSTON M, KYNDE K, SYRÄJLÄ M, SAVOLAINEN ER, IVASKA K, RAJAMÄKI A, VANHARANTA R, JUHAN I, AILLAUD MF, GUILLIN MC, HUISSE MG, SIE P, LECOMPTE T, SCHMITT Y, HARENBERG J, PLESCH W, ARONIS S, THEODOSSIADES G, TSOUKANAS B, MARKALA D, DITSA M, CAHILL M, MADDEN M, FITZGERALD H, MCCARTHY D, COLLINS B, ROONEY S, NAPARSTEK E, PALARETI G, MARONGIU F, ERBA N, TESTA S, MARIANI G, POTÌ R, MANNUCCI PM, TRIPODI A, BADER R, PENGO V, GRESELE P, D'INCÀ M, AGENO W, TOSETTO A, HENSGENS HE, IDEMA RN, OOSTERHOUT DH, MULDER AB, HAMULYAK K, VD DUSSEN H, MUSIAL J, GAGO T, PALMEIRO A, CAMPOS M, MARQUES-DIAS DA, CUNHA MONTEIRO Á, ANGELA CUNHA M, DE GAIA WN, PETERNEL P, STEGNAR M, FONTCUBERTA J, BORRELL M, REVERTER JC, SANTASUSANA PD, LOPEZ-FERNANDEZ MF, MONTERO J, RIBERA CASADO C, VICENTE V, EDLUND B, EGBERG N, LÄMMLE B, ALBERIO L, DE MOERLOOSE P, REBER G, MACHIN SJ, MACKIE I, LAWRIE A, LUCKIT J, SHANKS D, DOLAN G, FLAHERTY T, LUDLAM CA, WALKER ID, LAWSON DE, TRISCOTT M, MARLAR RA, HEIT JA, WATZKE H, WEISSER B, GALLUS AS, OSMOND J, CORNET I, MUNSTER AM, LEED B, CHILLOU C, DEFARD M, HORELLOU MH, HALKIN H, LOEBSTEIN R, KIRGNER I, DENTALI F, TRAPANI LOMBARDO V, SOTTILOTTA G, CONSIGLIO P, DE MICHELE S, MOIA M, CARPENEDO M, OLIVIERO B, MANOTTI C, TASSONI MI, COSMI B, BRUSI C, LEGNANI C, PEGORARO C, ANDRIANI C, GRAZIA CIRIGLIANO M, RIBALDI E, ABBATE R, POLI D, PERRICONE C, SCHIAVULI M, CASIERA C, LUPONE MR, ROSSI E, CRIVELLI S, BIROLINI A, PARENTE F, MIGLIETTA AM, CAMPOBASSO M, SYDOR W, KREVEL B, FERNANDEZ MA, LOZANO M, SHIACH C, BOWYER C, CHARLES F., Interne Geneeskunde, Biochemie, and RS: CARIM School for Cardiovascular Diseases

Subjects
INR correction, endocrine system, medicine.medical_specialty, coagulometers, Prothrombin Time/*standard, Reproducibility of Result, PT, World Health Organization, International Normalized Ratio/*standard, Thromboplastin, Automation, Laboratory/standard, ECAA plasmas, Predictive Value of Tests, health services administration, medicine, Animals, Humans, heterocyclic compounds, International Normalized Ratio, cardiovascular diseases, thromboplastins, Blood Coagulation, Reference standards, Mathematics, Automation, Laboratory, Observer Variation, Prothrombin time, Analysis of Variance, medicine.diagnostic_test, business.industry, fungi, Reproducibility of Results, Hematology, Reference Standards, Surgery, INR Line, Multicenter study, Calibration, Linear Models, Prothrombin Time, Cattle, Rabbits, Observer variation, Nuclear medicine, business
Abstract

The WHO scheme for prothrombin time (PT) standardization has been limited in application, because of its difficulties in implementation, particularly the need for mandatory manual PT testing and for local provision of thromboplastin international reference preparations (IRP).The value of a new simpler procedure to derive international normalized ratio (INR), the PT/INR Line, based on only five European Concerted Action on Anticoagulation (ECAA) calibrant plasmas certified by experienced centres has been assessed in two independent exercises using a range of commercial thromboplastins and coagulometers. INRs were compared with manual certified values with thromboplastin IRP from expert centres and in the second study also with INRs from local ISI calibrations.In the first study with the PT/INR Line, 8.7% deviation from certified INRs was reduced to 1.1% with human reagents, and from 7.0% to 2.6% with rabbit reagents. In the second study, deviation was reduced from 11.2% to 0.4% with human reagents by both local ISI calibration and the PT/INR Line. With rabbit reagents, 10.4% deviation was reduced to 1.1% with both procedures; 4.9% deviation was reduced to 0.5% with bovine/combined reagents with local ISI calibrations and to 2.9% with the PT/INR Line. Mean INR dispersion was reduced with all thromboplastins and automated systems using the PT/INR Line.The procedure using the PT/INR Line provides reliable INR derivation without the need for WHO ISI calibration across the range of locally used commercial thromboplastins and automated PT systems included in two independent international studies.? 2010 International Society on Thrombosis and Haemostasis.

Published
2011

19. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients

Author

Cervera, R. Serrano, R. Pons-Estel, G. J. Ceberio-Hualde, L. and Shoenfeld, Y. de Ramon, E. Buonaiuto, V. Jacobsen, S. and Zeher, M. M. Tarr, T. Tincani, A. Taglietti, M. and Theodossiades, G. Nomikou, E. Galeazzi, M. Bellisai, F. and Meroni, P. L. Derksen, R. H. W. M. de Groot, P. G. D. and Baleva, M. Mosca, M. Bombardieri, S. Houssiau, F. Gris, J-C Quere, I. Hachulla, E. Vasconcelos, C. and Fernandez-Nebro, A. Haro, M. Amoura, Z. Miyara, M. and Tektonidou, M. Espinosa, G. Bertolaccini, M. L. Khamashta, M. A. Euro-Phospholipid Project Grp

Abstract

Objectives To assess the prevalence of the main causes of morbi-mortality in the antiphospholipid syndrome (APS) during a 10-year-follow-up period and to compare the frequency of early manifestations with those that appeared later. Methods In 1999, we started an observational study of 1000 APS patients from 13 European countries. All had medical histories documented when entered into the study and were followed prospectively during the ensuing 10years. Results 53.1% of the patients had primary APS, 36.2% had APS associated with systemic lupus erythematosus and 10.7% APS associated with other diseases. Thrombotic events appeared in 166 (16.6%) patients during the first 5-year period and in 115 (14.4%) during the second 5-year period. The most common events were strokes, transient ischaemic attacks, deep vein thromboses and pulmonary embolism. 127 (15.5%) women became pregnant (188 pregnancies) and 72.9% of pregnancies succeeded in having one or more live births. The most common obstetric complication was early pregnancy loss (16.5% of the pregnancies). Intrauterine growth restriction (26.3% of the total live births) and prematurity (48.2%) were the most frequent fetal morbidities. 93 (9.3%) patients died and the most frequent causes of death were severe thrombosis (36.5%) and infections (26.9%). Nine (0.9%) cases of catastrophic APS occurred and 5 (55.6%) of them died. The survival probability at 10years was 90.7%. Conclusions Patients with APS still develop significant morbidity and mortality despite current treatment. It is imperative to increase the efforts in determining optimal prognostic markers and therapeutic measures to prevent these complications.

Published
2015

20. Soluble CD146, a novel endothelial marker, is related to the severity of liver disease

Author

Nomikou, E. Alexopoulou, A. Vasilieva, L. Agiasotelli, D. Pavlou, E. Theodossiades, G. Dourakis, S.P.

Abstract

Objectives. Angiogenesis and inflammation have been involved in the progression of fibrosis in patients with chronic liver disease (CLD). Soluble CD146 (sCD146), a biomarker that was recently characterized as a novel component of the endothelial junction is implicated in endothelial proliferation. Our study evaluates the performance of sCD146 in assessing liver fibrosis and cirrhosis, and determines if its levels are related to the severity of liver disease in patients with cirrhosis. Material and methods. sCD146 levels were determined by a commercially available immunoenzymatic technique in 62 consecutive patients with cirrhosis, 43 patients with CLD and 27 healthy controls. Results. Patients with cirrhosis compared to non-cirrhotics with CLD had a higher median sCD146 concentration (639 vs. 317 ng/ml). In receiver operating characteristic (ROC) curve analysis, the cut-off of 412 ng/ml showed a sensitivity of 78% and a specificity of 75% for diagnosis of cirrhosis, offering good diagnostic accuracy (area under the ROC curve [AUROC: 0.838]). Patients with compensated compared to those with decompensated cirrhosis had a lower median sCD146 concentration (399 vs. 848 ng/ml, respectively). A cut-off of 534 ng/ml offered a sensitivity of 83% and a specificity of 78% for differentiating compensated from decompensated cirrhosis (AUROC: 0.866). Furthermore, in cirrhotics, sCD146 correlated positively with AST, bilirubin levels and most importantly with international normalized ratio and model for end-stage liver disease (r = 0.648, p < 0.001 and r = 0.567, p < 0.001, respectively). Conclusion. sCD146 can be used as a surrogate, inexpensive biomarker for the diagnosis of cirrhosis. It is also well correlated with severity of liver disease in cirrhotic patients. Further studies are needed to define its role in clinical practice. © 2015 Informa Healthcare.

Published
2015

21. Immunosuppression for acquired hemophilia A: results from the European Acquired Haemophilia Registry (EACH2)

Author

Collins, Peter, Baudo, Francesco, Knoebl, Paul, Lévesque, Hervé, Nemes, László, Pellegrini, Fabio, Marco, Pascual, Tengborn, Lilian, Huth Kühne, Angela, Group Author: Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, d'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lévesque H, Lifermann F, Marlu R, Ninet J, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Huth Kühne A, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Nemes L, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Baudo F, Caimi T, Contino L, D'Angelo Armando CL, Fattorini A, Cerbone AM, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, Pogliani E, Carpenedo M, Remiddi C, Santagostino E, Mancuso ME, Santoro R, Papaleo G, Schinco P, Borchiellini A, Valeri F, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Tagariello G, Sartori R, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Brandolin B, Hamulyák K, Kamphuisen P, Laros van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez Yuste V, Jose Felix L, Marco P, Mingot ME, Perez Garrido R, Perez Gonzale NZ, Prieto Garcia M, Rodriguez Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Tengborn L, Boehlen F, Korte W, Chowdary P, Collins P, Evans G, Pavord S, Rangarajan S, Wilde J., DI MINNO, GIOVANNI, DI MINNO, MATTEO, Interne Geneeskunde, Foundations and methods of Law, RS: CARIM School for Cardiovascular Diseases, Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Collins, Peter, Baudo, Francesco, Knoebl, Paul, Lévesque, Hervé, Nemes, László, Pellegrini, Fabio, Marco, Pascual, Tengborn, Lilian, Huth Kühne, Angela, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, Matteo, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Brandolin, B, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Tengborn, L, Boehlen, F, Korte, W, Chowdary, P, Collins, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., and Other departments

Subjects
Registrie, Male, Clinical Trials and Observations, medicine.medical_treatment, THERAPY, Biochemistry, Gastroenterology, Immunosuppressive Agent, Antibodies, Monoclonal, Murine-Derived, Adult, Aged, Aged, 80 and over, Autoantibodies, Cyclophosphamide, Cyclosporine, Europe, Factor VIII, Female, Follow-Up Studies, Hemophilia A, Humans, Immunosuppressive Agents, Middle Aged, Registries, Rituximab, Secondary Prevention, Steroids, Treatment Outcome, FACTOR-VIII INHIBITORS, Monoclonal, 80 and over, UNITED-KINGDOM, Hematology, RECLASSIFICATION, Immunosuppression, Autoantibodie, Human, medicine.drug, Murine-Derived, medicine.medical_specialty, Immunology, DIAGNOSIS, Antibodies, Follow-Up Studie, Internal medicine, MANAGEMENT, medicine, Steroid, Autoimmune disease, business.industry, Settore MED/09 - MEDICINA INTERNA, Autoantibody, Cell Biology, Odds ratio, CENTER DOCTORS ORGANIZATION, medicine.disease, Surgery, DISCRIMINATION, Etiology, business
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.

Published
2012

22. Management of bleeding in acquired hemophilia A: results from the European Acquired Haemophilia (EACH2) Registry

Author

Baudo, Francesco, Collins, Peter, Huth Kühne, Angela, Lévesque, Hervé, Marco, Pascual, Nemes, László, Pellegrini, Fabio, Tengborn, Lilian, Knoebl, Paul, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, Cerbone, Am, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Brandolin, B, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Tengborn, L, Boehlen, F, Korte, W, Chowdary, P, Collins, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., DI MINNO, GIOVANNI, DI MINNO, MATTEO, Other departments, Baudo, Francesco, Collins, Peter, Huth Kühne, Angela, Lévesque, Hervé, Marco, Pascual, Nemes, László, Pellegrini, Fabio, Tengborn, Lilian, Knoebl, Paul, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, Matteo, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Brandolin, B, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Tengborn, L, Boehlen, F, Korte, W, Chowdary, P, Collins, P, Evans, G, Pavord, S, Rangarajan, S, Wilde, J., Faculteit Medische Wetenschappen/UMCG, Cardiovascular Centre (CVC), Vascular Ageing Programme (VAP), Huth Kühne, A, Lévesque, H, Pellegrini, F, Knoebl, P, Aspoeck, G, Borg, J, Loreth, R, D'Angelo Armando, C, Di Minno, G, Cerbone, A, Di Minno, D, Mazzucconi, M, Mancuso, M, Scortechini, A, Tagliaferri, A, Rivolta, G, Leebeek, F, van der Linden, P, Gutiérrez Pimentel, M, Mingot, M, Perez Gonzale, N, Rodriguez Huerta, A, and Wilde, J

Subjects
Registrie, Male, SURGERY, Biochemistry, THERAPY, Hemostatics, Hemostatic, FACTOR-VIII INHIBITORS, 80 and over, Deamino Arginine Vasopressin, Registries, Desmopressin, UNITED-KINGDOM, Factor IX, Aged, 80 and over, Hematology, biology, Incidence, FEIBA, Recombinant Protein, Middle Aged, Blood Coagulation Factors, Recombinant Proteins, Europe, Treatment Outcome, Coagulation, Female, medicine.drug, Blood Coagulation Factor, Human, Adult, medicine.medical_specialty, Adolescent, Immunology, Aged, Factor VIII, Factor VIIa, Hemophilia A, Hemorrhage, Humans, Young Adult, DIAGNOSIS, Internal medicine, BYPASSING ACTIVITY, medicine, business.industry, Settore MED/09 - MEDICINA INTERNA, RECOMBINANT FACTOR VIIA, Retrospective cohort study, Cell Biology, FACTOR-IX, CENTER DOCTORS ORGANIZATION, Surgery, Recombinant factor VIIa, Propensity score matching, biology.protein, business
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%).

Published
2012

23. Pregnancy-associated acquired haemophilia A: results from the European Acquired Haemophilia (EACH2) registry

Author

Tengborn L, Baudo F, Huth-Kühne A, Knoebl P, Lévesque H, Marco P, Pellegrini F, Nemes L, Collins P, EACH2 registry contributors, Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, d'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lifermann F, Marlu R, Ninet J, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Caimi T, Contino L, D'Angelo Armando CL, Fattorini A, Di Minno G, Cerbone AM, Di Minno D, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, Pogliani E, Carpenedo M, Remiddi C, Santagostino E, Mancuso ME, Santoro R, Papaleo G, Schinco P, Borchiellini A, Valeri F, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Tagariello G, Sartori R, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Hamulyák K, Kamphuisen P, Laros-van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez-Yuste V, Jose-Felix L, Mingot ME, Perez Garrido R, Perez Gonzale NZ, Prieto Garcia M, Rodriguez-Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Boehlen F, Korte W, Chowdary P, Evans G, Pavord S, Rangarajan S, Wilde J, Tengborn, L, Baudo, F, Huth-Kühne, A, Knoebl, P, Lévesque, H, Marco, P, Pellegrini, F, Nemes, L, Collins, P, EACH2 registry, C, Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, J, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Loreth, R, Steigerwald, U, Tiede, A, Theodossiades, G, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Caimi, T, Contino, L, D'Angelo Armando, C, Fattorini, A, Di Minno, G, Cerbone, A, Di Minno, D, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, M, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, M, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, A, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, A, Di Perna, C, Rivolta, G, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Hamulyák, K, Kamphuisen, P, Laros-van Gorkom, B, Leebeek, F, Marten, N, Novakova, I, Schutgens, R, van der Linden, P, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, M, Jiménez-Yuste, V, Jose-Felix, L, Mingot, M, Perez Garrido, R, Perez Gonzale, N, Prieto Garcia, M, Rodriguez-Huerta, A, Sedano, C, Tolosa Munoz, A, Baghaei, F, Boehlen, F, Korte, W, Chowdary, P, Evans, G, Pavord, S, Rangarajan, S, and Wilde, J

Subjects
Adult, Acquired haemophilia A, diagnosis, pregnancy, treatment, Antifibrinolytic Agents, Blood Coagulation Factors, Drug Therapy, Combination, Europe, Factor VIIa, Female, Follow-Up Studies, Hemostatics, Humans, Immunosuppressive Agents, Kaplan-Meier Estimate, Pregnancy, Prospective Studies, Recombinant Proteins, Registries, Treatment Outcome, Hemophilia A, Pregnancy Complications, Hematologic, Drug Therapy, Hematologic, Acquired Haemophilia, Pregnancy, Pregnancy Complications, Combination
Abstract

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.

Published
2012

24. Pregnancy-associated acquired haemophilia A: Results from the European Acquired Haemophilia (EACH2) registry

Author

Tengborn, L, Baudo, F., Huth Kühne, A., Knoebl, P., Lévesque, H., Marco, P., Pellegrini, F., Nemes, L., Collins, P, Group Author: Aspoeck G, Heistinger M, Knöbl P, Makipernaa A, André H, Aouba A, Bellucci S, Beurrier P, Borg JY, Darnige L, Devignes J, d'Oiron R, Gautier P, Gay V, Girault S, Gruel Y, Guerin V, Hézard N, Khellaf M, Koenig M, Lévesque H, Lifermann F, Marlu R, Ninet J, Peynet J, Quéméneur T, Rothschild C, Schleinitz N, Sigaud M, Trouillier S, Voisin S, Giebl A, Holstein K, Huth Kühne A, Loreth RM, Steigerwald U, Tiede A, Theodossiades G, Nemes L, Radvanyi G, Schlammadinger A, Barillari G, Pasca S, Baudo F, Caimi T, Contino L, D'Angelo Armando CL, Fattorini A, Cerbone AM, D'incà M, Falanga A, Maggioni A, Lerede T, Franchini M, Gaidano G, De Paoli L, Gamba G, Ghirardi R, Girotto M, Tasca D, Grandone E, Tiscia G, Imberti D, Iorio A, Landolfi R, Di Gennaro L, Novarese L, Mariani G, Lapecorella M, Marietta M, Pedrazzi P, Mazzucconi MG, Santoro C, Morfini M, Linari S, Moratelli S, Paolini R, Piseddu G, Poggio R, Pogliani E, Carpenedo M, Remiddi C, Santagostino E, Mancuso ME, Santoro R, Papaleo G, Schinco P, Borchiellini A, Valeri F, Scortechini AR, Siragusa S, Sottilotta G, Squizzato A, Tagariello G, Sartori R, Tagliaferri AR, Di Perna C, Rivolta GF, Testa S, Paoletti O, Toschi V, Zanon E, Hamulyák K, Kamphuisen P, Laros van Gorkom B, Leebeek FW, Marten N, Novakova I, Schutgens R, van der Linden PW, van Esser J, van der Meer J, Ypma P, Campos M, Aguilar C, Altisent C, Bermejo N, Del Campo R, Ferreiro Argüelles M, González Boullosa R, Gutiérrez Pimentel MJ, Jiménez Yuste V, Jose Felix L, Marco P, Mingot ME, Perez Garrido R, Perez Gonzale NZ, Prieto Garcia M, Rodriguez Huerta AM, Sedano C, Tolosa Munoz A, Baghaei F, Tengborn L, Boehlen F, Korte W, Chowdary P, Collins P, Evans G, Pavord S, Rangarajan S, Wilde J., DI MINNO, GIOVANNI, DI MINNO, MATTEO, Tengborn, L, Baudo, F., Huth Kühne, A., Knoebl, P., Lévesque, H., Marco, P., Pellegrini, F., Nemes, L., Collins, P, Group Author: Aspoeck, G, Heistinger, M, Knöbl, P, Makipernaa, A, André, H, Aouba, A, Bellucci, S, Beurrier, P, Borg, Jy, Darnige, L, Devignes, J, D'Oiron, R, Gautier, P, Gay, V, Girault, S, Gruel, Y, Guerin, V, Hézard, N, Khellaf, M, Koenig, M, Lévesque, H, Lifermann, F, Marlu, R, Ninet, J, Peynet, J, Quéméneur, T, Rothschild, C, Schleinitz, N, Sigaud, M, Trouillier, S, Voisin, S, Giebl, A, Holstein, K, Huth Kühne, A, Loreth, Rm, Steigerwald, U, Tiede, A, Theodossiades, G, Nemes, L, Radvanyi, G, Schlammadinger, A, Barillari, G, Pasca, S, Baudo, F, Caimi, T, Contino, L, D'Angelo Armando, Cl, Fattorini, A, DI MINNO, Giovanni, Cerbone, Am, DI MINNO, Matteo, D'Incà, M, Falanga, A, Maggioni, A, Lerede, T, Franchini, M, Gaidano, G, De Paoli, L, Gamba, G, Ghirardi, R, Girotto, M, Tasca, D, Grandone, E, Tiscia, G, Imberti, D, Iorio, A, Landolfi, R, Di Gennaro, L, Novarese, L, Mariani, G, Lapecorella, M, Marietta, M, Pedrazzi, P, Mazzucconi, Mg, Santoro, C, Morfini, M, Linari, S, Moratelli, S, Paolini, R, Piseddu, G, Poggio, R, Pogliani, E, Carpenedo, M, Remiddi, C, Santagostino, E, Mancuso, Me, Santoro, R, Papaleo, G, Schinco, P, Borchiellini, A, Valeri, F, Scortechini, Ar, Siragusa, S, Sottilotta, G, Squizzato, A, Tagariello, G, Sartori, R, Tagliaferri, Ar, Di Perna, C, Rivolta, Gf, Testa, S, Paoletti, O, Toschi, V, Zanon, E, Hamulyák, K, Kamphuisen, P, Laros van Gorkom, B, Leebeek, Fw, Marten, N, Novakova, I, Schutgens, R, van der Linden, Pw, van Esser, J, van der Meer, J, Ypma, P, Campos, M, Aguilar, C, Altisent, C, Bermejo, N, Del Campo, R, Ferreiro Argüelles, M, González Boullosa, R, Gutiérrez Pimentel, Mj, Jiménez Yuste, V, Jose Felix, L, Marco, P, Mingot, Me, Perez Garrido, R, Perez Gonzale, Nz, Prieto Garcia, M, Rodriguez Huerta, Am, Sedano, C, Tolosa Munoz, A, Baghaei, F, Boehlen, F, Korte, W, Chowdary, P, Evans, G, Pavord, S, Rangarajan, S, and Wilde, J.

Subjects
Adult, Registrie, treatment, Pregnancy Complications, Hematologic, Obstetrics and Gynecology, Factor VIIa, Kaplan-Meier Estimate, Recombinant Protein, Antifibrinolytic Agent, Hemophilia A, Follow-Up Studie, Europe, diagnosi, Immunosuppressive Agent, Prospective Studie, Hemostatic, Treatment Outcome, Pregnancy, Drug Therapy, Combination, Female, Acquired haemophilia A, Blood Coagulation Factor, Human
Published
2012

25. Pylephlebitis: An overview of non-cirrhotic cases and factors related to outcome

Author

Kanellopoulou, T. Alexopoulou, A. Theodossiades, G. Koskinas, J. Archimandritis, A.J.

Abstract

Pylephlebitis is a condition with significant morbidity and mortality. We review herein 100 relevant case reports published since 1971. Eighty-one patients were reported with acute pylephlebitis, while the remaining patients had chronic pylephlebitis. The most common predisposing infections leading to pylephlebitis were diverticulitis and appendicitis. Cultures from blood or other tissues were positive in 77%. The infection was polymicrobial in half of the patients and the most common isolates were Bacteroides spp, Escherichia coli and Streptococcus spp. Thrombosis was extended to the superior mesenteric vein (SMV), splenic vein, and intrahepatic branches of the portal vein (PV) in 42%, 12%, and 39%, respectively. Antibiotics were administered in all and anticoagulation in 35 cases. Patients who received anticoagulation had a favourable outcome compared to those who received antibiotics alone (complete recanalization 25.7% vs 14.8% (p > 0.05), no recanalization 5.7% vs 22.2% (p < 0.05), and death 5.7% vs 22.2% (p < 0.01)). Cases with complete recanalization had prompt diagnosis and management and two-thirds were recently published. Nineteen patients died; the majority of these (73.7%) died over the period 1971-1990. In conclusion, pylephlebitis remains an entity with high morbidity and mortality, but modern imaging modalities have facilitated an earlier diagnosis and have improved the prognosis. Anticoagulation has a rather beneficial effect on patients with pylephlebitis. © 2010 Informa Healthcare.

Published
2010

26. Administration of human protein C improves survival in an experimental model of sepsis

Author

Messaris, E. Betrosian, A.P. Memos, N. Chatzigianni, E. Boutsikou, M. Economou, V. Dontas, I. Theodossiades, G. Konstadoulakis, M.M. Douzinas, E.E.

Subjects
bacterial infections and mycoses
Abstract

OBJECTIVE: Study the effect of human protein C (PC) concentrate administration on organ damage and survival in septic rats. DESIGN: Animal study. SETTING: University laboratory. SUBJECTS: Male Wistar rats. INTERVENTIONS: Cecal ligation and puncture (CLP) was performed in 210 rats. Rats were randomly assigned to receive either human protein C (PC) IV 1, 7, and 13 hrs after CLP (CLP+PC) or placebo (CLP). Septic animals were again randomized in a survival group (CLP: n = 50 and CLP+PC: n = 40) that was monitored for 60 hrs and time groups (CLP: n = 60 and CLP+PC: n = 60) that were killed at 6, 12, 24, 36, 48, and 60 hrs after CLP. Brain, heart, lung, liver, kidney, gastric, and colon tissue were removed and postfixed in paraffin sections. MEASUREMENTS AND MAIN RESULTS: PC infusion increased PC serum levels in early sepsis (median 7.25) compared with late sepsis (median 2, p =.001). Activated protein C/a1-antitrypsin complex levels in the CLP+PC group were significantly increased in late sepsis (60 hrs after CLP) compared with early sepsis (6, 12, and 24 hrs after CLP, p =.009, p =.004, and p =.008, respectively) and to late septic CLP and normal rats (p =.005 and p =.007, respectively). Their IL-6 and tumor necrosis factor a plasma levels were decreased (by 27% and 25%, respectively) at 6 hrs compared with placebo (p =.008 and p =.016). Their serum PC levels were also decreased in CLP+PC survivors compared with nonsurvivors of the same group (median = 1.5 vs. median = 7, p =.001). Apoptosis was reduced in brain (10% vs. 77.8%, p

Published
2010

27. Thrombotic risk factors and liver histologic lesions in non-alcoholic fatty liver disease

Author

Papatheodoridis, G.V. Chrysanthos, N. Cholongitas, E. Pavlou, E. Apergis, G. Tiniakos, D.G. Andrioti, E. Theodossiades, G. Archimandritis, A.J.

Subjects
nutritional and metabolic diseases, digestive system, digestive system diseases
Abstract

Background/Aims: The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH. Methods: We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n = 39) or C (n = 51). Thrombophilic factors were evaluated on the day of the liver biopsy. Results: One or more thrombotic RFs were detected in 37% of NAFLD patients, and ≥ 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; P ≤ 0.001). Among NAFLD cases, one or more thrombotic RFs were significantly more frequently present in NASH than simple fatty liver (56% vs. 8%; odds ratio [OR]: 13.8, 2.8-67.4, P < 0.001). In multivariate analysis, NASH was independently associated with moderate to severe steatosis (adjusted OR: 24.3; P = 0.001) and the presence of one or more thrombotic RFs (adjusted OR: 38.7; P = 0.002). Fibrosis stage was worse in NASH patients with than without thrombotic RFs (2.5 ± 1.1 vs. 1.3 ± 1.1; P = 0.002). Conclusions: Thrombotic RFs are frequently present in patients with NAFLD and are associated with NASH and more advanced fibrosis. Such an association may have significant clinical implications, even though it is not clear yet whether it represents a primary or secondary phenomenon. © 2009 European Association for the Study of the Liver.

Published
2009

28. Modification of nursing students' performance in blood pressure measurement: An educational retraining programme

Author

Brokalaki, H. Matziou, V. Gymnopoulou, E. Galanis, P. Brokalaki, E. Theodossiades, G.

Subjects
education
Abstract

Aim: To assess the procedure for measuring blood pressure (BP) among nursing students after the basic educational programme and after further supplementary training. Methods: One hundred and fifty nursing students participated in the study, which was divided into two phases. During the first phase, students attended the routine educational programme in respect of the technique of measuring BP in the course of the lesson 'Basic Nursing'. During the next semester (second phase), the same students attended the lesson of 'Internal Medicine Nursing'. In the course of this lesson, a supplementary educational intervention for BP measurement was introduced for the purpose of this study. In order to perform our study, the university's written approval was given. At the end of the second phase, the 150 participants (volunteers) gave their oral consent for the anonymous publication of the results. Results: The results showed an inadequate performance after the basic educational programme, but a significant improvement in the technique of measuring BP after supplementary educational intervention was achieved. This improvement was significant for all the parameters examined. Conclusion: Supplementary education of students may be required, as this could significantly improve their technique for the accurate measurement of BP. © 2008 International Council of Nurses.

Published
2008

29. Prophylactic and therapeutic use of recombinant activated factor VII in patients with cirrhosis and coagulation impairment

Author

Tsochatzis, E. Papatheodoridis, G. V. Elefsiniotis, I. and Thanelas, S. Theodossiades, G. Moulakakis, A. and Archimandritis, A. J.

Abstract

Patients with cirrhosis and impaired coagulation often pose major therapeutic problems during bleeding episodes or invasive procedures. Recombinant activated factor VII (rFVIIa), which has been licensed for the treatment of haemophilia patients with factor VIII or IX inhibitors, has been occasionally used in cirrhotic patients. We present five patients with cirrhosis and coagulopathy who received 1-4 recombinant activated factor VII infusions either prophylactically in order to safely undergo an invasive procedure or therapeutically in order to control a severe bleeding episode which did not respond to standard supportive care. In particular, recombinant activated factor VII infusions were given in two patients before a percutaneous liver biopsy, in one patient before teeth extraction and in two patients with haemoperitoneum after an invasive procedure. Infusions of recombinant activated factor VII achieved rapid correction of prothrombin time in all cases allowing the safe performance of invasive procedures or resulting in efficient control of the bleeding episode. In conclusion, recombinant activated factor VII seems to be a rather promising agent for the prevention or treatment of complications of haemostasis impairment in cirrhotic patients. However, its exact role in this setting needs to be evaluated within well-designed, controlled clinical trials. (C) 2006 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Published
2007

31. Pseudohyperkalemia in patients with increased cellular components of blood

Author

Sevastos, N Theodossiades, G Savvas, SP Tsilidis, K and Efstathiou, S Archimandritis, AJ

Subjects
hemic and lymphatic diseases
Abstract

Objective: We performed a study to investigate the difference between serum and plasma potassium concentration in patients with increase in one or more of the cellular components of blood. Design and Methods: This study was performed in two phases. During the first phase, we performed a cross-sectional comparison of the difference between serum and plasma potassium concentration (Dk) in 341 patients with the various clinical conditions where pseuclohyperkalemia has been described, as well as with secondary or spurious erythrocytosis and in 30 normal controls. A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated. In the second phase we studied the significance of this cut-off value as predictor of polycythemia vera in 90 naive patients who were referred with an elevated hematocrit. Results: Dk was significantly increased in the groups with platelet, erythrocyte or with a mixed type disorder compared to the controls (P < 0.01). Among these groups, Dk was significantly increased in the groups with thrombocytosis and mixed type disorder, compared to the group with erythrocytosis (both P < 0.01). A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated (0.70 mmol/L). Dk (>= 0.70 mmol/L), platelet and white blood cell count were identified as significant independent predictors of polycythemia vera. Conclusions: The Dk is increased in patients with erythrocytoses, thrombocytoses or both. This phenomenon is more profound in patients with a mixed type disorder, such as polycythemia vera patients, compared to those with erythrocytoses alone.

Published
2006

32. Pseudohyperkalemia in serum: the phenomenon and its clinical magnitude

Author

Sevastos, N Theodossiades, G Efstathiou, S Papatheodoridis, GV Manesis, E Archimandritis, AJ

Abstract

We investigated in detail the difference between serum and plasma potassium levels in patients with several conditions associated with pseudohyperkalemia. In total, 435 patients with either thrombocytoses, erythrocytoses, leucocytoses, or a mixed-type disorder and 30 healthy controls were included. In each case, the index Dk (serum potassium minus plasma potassium) and the index Dk100 (Dk x 100,000/platelets), which indicates the Dk value that corresponds to platelets of 100,000/mm(3) were estimated. Median Dk was significantly higher in the groups with platelet, erythrocyte, or mixed-type disorders than in the controls (P = 0.001). Among these groups, Dk values were significantly higher in patients with thrombocytosis or mixed-type disorders compared with those with erythrocytosis (P < 0.001, for both). Furthermore, no significant difference was observed in Dk values between controls and patients with white blood cell disorders (P = 0.74). Dk values did not exceed 2.61 mmol/L, whereas Dk100 values were inversely related to platelet counts (r = - 0.351, P < 0.01). In conclusion, pseudohyperkalemia is mainly present in patients with thrombocytosis or mixed-type disorders, probably as a result of the degranulation of platelets, which offers a potassium load to the surrounding plasma at the time of clot formation in vitro. However, the degree of pseudohyperkalemia does not increase proportionally with the increase of platelet counts, which may be associated with transfer of part of potassium load from the plasma back into red and white blood cells.

Published
2006

34. Morbidity and mortality in the antiphospholipid syndrome during a 10-year period: a multicentre prospective study of 1000 patients

Author

Cervera, R, primary, Serrano, R, additional, Pons-Estel, G J, additional, Ceberio-Hualde, L, additional, Shoenfeld, Y, additional, de Ramón, E, additional, Buonaiuto, V, additional, Jacobsen, S, additional, Zeher, M M, additional, Tarr, T, additional, Tincani, A, additional, Taglietti, M, additional, Theodossiades, G, additional, Nomikou, E, additional, Galeazzi, M, additional, Bellisai, F, additional, Meroni, P L, additional, Derksen, R H W M, additional, de Groot, P G D, additional, Baleva, M, additional, Mosca, M, additional, Bombardieri, S, additional, Houssiau, F, additional, Gris, J-C, additional, Quéré, I, additional, Hachulla, E, additional, Vasconcelos, C, additional, Fernández-Nebro, A, additional, Haro, M, additional, Amoura, Z, additional, Miyara, M, additional, Tektonidou, M, additional, Espinosa, G, additional, Bertolaccini, M L, additional, and Khamashta, M A, additional

Published
2014
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36. Soluble CD146, a novel endothelial marker, is related to the severity of liver disease.

Author

Nomikou E, Alexopoulou A, Vasilieva L, Agiasotelli D, Pavlou E, Theodossiades G, and Dourakis SP

Subjects
Aged, Biomarkers blood, Biopsy, CD146 Antigen blood, Disease Progression, Female, Humans, Liver Cirrhosis pathology, Male, Middle Aged, ROC Curve, Liver pathology, Liver Cirrhosis diagnosis
Abstract

Objectives: Angiogenesis and inflammation have been involved in the progression of fibrosis in patients with chronic liver disease (CLD). Soluble CD146 (sCD146), a biomarker that was recently characterized as a novel component of the endothelial junction is implicated in endothelial proliferation. Our study evaluates the performance of sCD146 in assessing liver fibrosis and cirrhosis, and determines if its levels are related to the severity of liver disease in patients with cirrhosis., Material and Methods: sCD146 levels were determined by a commercially available immunoenzymatic technique in 62 consecutive patients with cirrhosis, 43 patients with CLD and 27 healthy controls., Results: Patients with cirrhosis compared to non-cirrhotics with CLD had a higher median sCD146 concentration (639 vs. 317 ng/ml). In receiver operating characteristic (ROC) curve analysis, the cut-off of 412 ng/ml showed a sensitivity of 78% and a specificity of 75% for diagnosis of cirrhosis, offering good diagnostic accuracy (area under the ROC curve [AUROC: 0.838]). Patients with compensated compared to those with decompensated cirrhosis had a lower median sCD146 concentration (399 vs. 848 ng/ml, respectively). A cut-off of 534 ng/ml offered a sensitivity of 83% and a specificity of 78% for differentiating compensated from decompensated cirrhosis (AUROC: 0.866). Furthermore, in cirrhotics, sCD146 correlated positively with AST, bilirubin levels and most importantly with international normalized ratio and model for end-stage liver disease (r = 0.648, p < 0.001 and r = 0.567, p < 0.001, respectively)., Conclusion: sCD146 can be used as a surrogate, inexpensive biomarker for the diagnosis of cirrhosis. It is also well correlated with severity of liver disease in cirrhotic patients. Further studies are needed to define its role in clinical practice.

Published
2015
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37. Effect of titanium maxillofacial implants and osteosynthesis materials on platelet function.

Author

Stathopoulos P, Theodossiades G, Mourouzis C, and Evangelou A

Subjects
Adenosine Diphosphate pharmacology, Adolescent, Adult, Blood Platelets physiology, Collagen pharmacology, Epinephrine pharmacology, Female, Hemostasis drug effects, Humans, Male, Middle Aged, Platelet Activation drug effects, Platelet Count, Young Adult, Biocompatible Materials pharmacology, Blood Platelets drug effects, Dental Implants, Dental Materials pharmacology, Orthopedic Fixation Devices, Titanium pharmacology
Abstract

The use of titanium implants and osteosynthesis materials in orthopaedics, neurosurgery, and maxillofacial surgery has increased considerably, and they may be retained in patients for a long time. We could find no papers in English that provided data about the effect of titanium osteosynthesis materials on platelet function, and the purpose of this study was to evaluate those effects. Platelet function was tested in 33 patients with titanium maxillofacial implants using the PFA-100 (platelet function analyser) system and these results were compared with those of a control group of 34 healthy volunteer blood donors. Platelet function was measured in each group using collagen/adrenaline and collagen/adenosine diphosphate (ADP) as agonists for assessment of platelet function. There were no significant differences between the groups (collagen/adrenaline p=0.1, collagen/ADP p=0.09). Titanium maxillofacial osteosynthesis materials have no significant effect on platelet function as assessed by the PFA-100 system., (Copyright © 2010 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.)

Published
2011
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38. Pylephlebitis: an overview of non-cirrhotic cases and factors related to outcome.

Author

Kanellopoulou T, Alexopoulou A, Theodossiades G, Koskinas J, and Archimandritis AJ

Subjects
Anti-Bacterial Agents therapeutic use, Bacteria classification, Bacteria isolation & purification, Bacterial Infections drug therapy, Bacterial Infections microbiology, Bacterial Infections mortality, Humans, Portal Vein microbiology, Treatment Outcome, Venous Thrombosis drug therapy, Venous Thrombosis microbiology, Venous Thrombosis mortality, Appendicitis complications, Bacterial Infections pathology, Diverticulitis complications, Portal Vein pathology, Venous Thrombosis pathology
Abstract

Pylephlebitis is a condition with significant morbidity and mortality. We review herein 100 relevant case reports published since 1971. Eighty-one patients were reported with acute pylephlebitis, while the remaining patients had chronic pylephlebitis. The most common predisposing infections leading to pylephlebitis were diverticulitis and appendicitis. Cultures from blood or other tissues were positive in 77%. The infection was polymicrobial in half of the patients and the most common isolates were Bacteroides spp, Escherichia coli and Streptococcus spp. Thrombosis was extended to the superior mesenteric vein (SMV), splenic vein, and intrahepatic branches of the portal vein (PV) in 42%, 12%, and 39%, respectively. Antibiotics were administered in all and anticoagulation in 35 cases. Patients who received anticoagulation had a favourable outcome compared to those who received antibiotics alone (complete recanalization 25.7% vs 14.8% (p > 0.05), no recanalization 5.7% vs 22.2% (p < 0.05), and death 5.7% vs 22.2% (p < 0.01)). Cases with complete recanalization had prompt diagnosis and management and two-thirds were recently published. Nineteen patients died; the majority of these (73.7%) died over the period 1971-1990. In conclusion, pylephlebitis remains an entity with high morbidity and mortality, but modern imaging modalities have facilitated an earlier diagnosis and have improved the prognosis. Anticoagulation has a rather beneficial effect on patients with pylephlebitis.

Published
2010
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39. Administration of human protein C improves survival in an experimental model of sepsis.

Author

Messaris E, Betrosian AP, Memos N, Chatzigianni E, Boutsikou M, Economou V, Dontas I, Theodossiades G, Konstadoulakis MM, and Douzinas EE

Subjects
Animals, Cecum surgery, Chi-Square Distribution, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Flow Cytometry, Humans, Immunohistochemistry, In Situ Nick-End Labeling, Kaplan-Meier Estimate, Ligation, Male, Probability, Random Allocation, Rats, Rats, Wistar, Sepsis pathology, Statistics, Nonparametric, Survival Rate, Cytokines blood, Protein C pharmacology, Sepsis drug therapy, Sepsis mortality
Abstract

Objective: Study the effect of human protein C (PC) concentrate administration on organ damage and survival in septic rats., Design: Animal study., Setting: University laboratory., Subjects: Male Wistar rats., Interventions: Cecal ligation and puncture (CLP) was performed in 210 rats. Rats were randomly assigned to receive either human protein C (PC) IV 1, 7, and 13 hrs after CLP (CLP+PC) or placebo (CLP). Septic animals were again randomized in a survival group (CLP: n = 50 and CLP+PC: n = 40) that was monitored for 60 hrs and time groups (CLP: n = 60 and CLP+PC: n = 60) that were killed at 6, 12, 24, 36, 48, and 60 hrs after CLP. Brain, heart, lung, liver, kidney, gastric, and colon tissue were removed and postfixed in paraffin sections., Measurements and Main Results: PC infusion increased PC serum levels in early sepsis (median 7.25) compared with late sepsis (median 2, p = .001). Activated protein C/a1-antitrypsin complex levels in the CLP+PC group were significantly increased in late sepsis (60 hrs after CLP) compared with early sepsis (6, 12, and 24 hrs after CLP, p = .009, p = .004, and p = .008, respectively) and to late septic CLP and normal rats (p = .005 and p = .007, respectively). Their IL-6 and tumor necrosis factor a plasma levels were decreased (by 27% and 25%, respectively) at 6 hrs compared with placebo (p = .008 and p = .016). Their serum PC levels were also decreased in CLP+PC survivors compared with nonsurvivors of the same group (median = 1.5 vs. median = 7, p = .001). Apoptosis was reduced in brain (10% vs. 77.8%, p < .001), stomach (66.7% vs. 100%, p < .002) and intestine (33.3% vs. 85.2%, p < .001) compared with placebo. Finally, the survival of septic rats treated with human PC was significantly increased compared with placebo (75% vs. 54%, p = .033)., Conclusions: Human Protein C administration increased survival in septic rats, decreased plasma inflammatory cytokines levels and tissue injury in vital organs.

Published
2010
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40. Thrombotic risk factors and liver histologic lesions in non-alcoholic fatty liver disease.

Author

Papatheodoridis GV, Chrysanthos N, Cholongitas E, Pavlou E, Apergis G, Tiniakos DG, Andrioti E, Theodossiades G, and Archimandritis AJ

Subjects
Adult, Antibodies, Anticardiolipin blood, Cohort Studies, Factor V genetics, Fatty Liver blood, Fatty Liver etiology, Female, Hepatitis B, Chronic blood, Hepatitis B, Chronic complications, Hepatitis B, Chronic pathology, Hepatitis C, Chronic blood, Hepatitis C, Chronic complications, Hepatitis C, Chronic pathology, Humans, Liver pathology, Liver Cirrhosis complications, Liver Cirrhosis pathology, Male, Middle Aged, Prothrombin genetics, Risk Factors, Thrombosis blood, Thrombosis genetics, Fatty Liver complications, Fatty Liver pathology, Thrombosis complications
Abstract

Background/aims: The pathogenetic mechanisms of development of non-alcoholic steatohepatitis (NASH) and fibrosis are not clear, although thrombosis of small intrahepatic veins has been suggested to trigger liver tissue remodelling and thrombotic risk factors have been associated with more advanced fibrosis in chronic viral hepatitis (CVH). We evaluated the prevalence of thrombotic risk factors (RFs) in non-alcoholic fatty liver disease (NAFLD) and their possible association with fatty liver or NASH., Methods: We included 60 patients with histologically documented NAFLD and a historical cohort of 90 patients with chronic hepatitis B (n=39) or C (n=51). Thrombophilic factors were evaluated on the day of the liver biopsy., Results: One or more thrombotic RFs were detected in 37% of NAFLD patients, and >or= 2 RFs were detected in 12% of NAFLD patients, being less frequently present than in CVH patients (37% and 68%, respectively; P

Published
2009
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42. Pseudohyperkalemia in serum: the phenomenon and its clinical magnitude.

Author

Sevastos N, Theodossiades G, Efstathiou S, Papatheodoridis GV, Manesis E, and Archimandritis AJ

Subjects
Adult, Aged, Blood Chemical Analysis, Case-Control Studies, Female, Humans, Male, Middle Aged, Platelet Count, Potassium blood, Thrombocytosis, Hyperkalemia blood
Abstract

We investigated in detail the difference between serum and plasma potassium levels in patients with several conditions associated with pseudohyperkalemia. In total, 435 patients with either thrombocytoses, erythrocytoses, leucocytoses, or a mixed-type disorder and 30 healthy controls were included. In each case, the index Dk [serum potassium minus plasma potassium] and the index Dk100 (Dk x 100,000/platelets), which indicates the Dk value that corresponds to platelets of 100,000/mm(3), were estimated. Median Dk was significantly higher in the groups with platelet, erythrocyte, or mixed-type disorders than in the controls (P=0.001). Among these groups, Dk values were significantly higher in patients with thrombocytosis or mixed-type disorders compared with those with erythrocytosis (P<0.001, for both). Furthermore, no significant difference was observed in Dk values between controls and patients with white blood cell disorders (P=0.74). Dk values did not exceed 2.61 mmol/L, whereas Dk100 values were inversely related to platelet counts (r=-0.351, P<0.01). In conclusion, pseudohyperkalemia is mainly present in patients with thrombocytosis or mixed-type disorders, probably as a result of the degranulation of platelets, which offers a potassium load to the surrounding plasma at the time of clot formation in vitro. However, the degree of pseudohyperkalemia does not increase proportionally with the increase of platelet counts, which may be associated with transfer of part of potassium load from the plasma back into red and white blood cells.

Published
2006
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43. Pseudohyperkalemia in patients with increased cellular components of blood.

Author

Sevastos N, Theodossiades G, Savvas SP, Tsilidis K, Efstathiou S, and Archimandritis AJ

Subjects
Case-Control Studies, Cross-Sectional Studies, Humans, Potassium blood, Blood Cell Count, Hyperkalemia blood
Abstract

Objective: We performed a study to investigate the difference between serum and plasma potassium concentration in patients with increase in one or more of the cellular components of blood., Design and Methods: This study was performed in two phases. During the first phase, we performed a cross-sectional comparison of the difference between serum and plasma potassium concentration (Dk) in 341 patients with the various clinical conditions where pseudohyperkalemia has been described, as well as with secondary or spurious erythrocytosis and in 30 normal controls. A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated. In the second phase we studied the significance of this cut-off value as predictor of polycythemia vera in 90 naive patients who were referred with an elevated hematocrit., Results: Dk was significantly increased in the groups with platelet, erythrocyte or with a mixed type disorder compared to the controls (P < 0.01). Among these groups, Dk was significantly increased in the groups with thrombocytosis and mixed type disorder, compared to the group with erythrocytosis (both P < 0.01). A cut-off value of Dk discriminating polycythemia vera from other erythrocytoses was estimated (0.70 mmol/L). Dk (> or = 0.70 mmol/L), platelet and white blood cell count were identified as significant independent predictors of polycythemia vera., Conclusions: The Dk is increased in patients with erythrocytoses, thrombocytoses or both. This phenomenon is more profound in patients with a mixed type disorder, such as polycythemia vera patients, compared to those with erythrocytoses alone.

Published
2006
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45. Heparin-induced thrombocytopenia with pulmonary embolism and disseminated intravascular coagulation associated with low-molecular-weight heparin.

Author

Betrosian AP, Theodossiades G, Lambroulis G, Kostantonis D, Balla M, Papanikolaou M, and Georgiades G

Subjects
Arthroplasty, Replacement, Hip, Disseminated Intravascular Coagulation diagnosis, Female, Humans, Immunoglobulin G immunology, Middle Aged, Nadroparin immunology, Platelet Activation, Postoperative Complications, Pulmonary Embolism diagnosis, Thrombocytopenia immunology, Thrombosis prevention & control, Tomography, Spiral Computed, Ultrasonography, Venous Thrombosis diagnosis, Venous Thrombosis etiology, Disseminated Intravascular Coagulation etiology, Nadroparin adverse effects, Pulmonary Embolism etiology, Thrombocytopenia chemically induced
Abstract

Heparin-induced thrombocytopenia (HIT) is a severe adverse effect of heparin therapy. Although most cases occur in patients receiving unfractionated heparin, HIT can arise in venous thrombosis prophylaxis with a low-molecular-weight heparin (LMWH). We report an uncommon case of HIT in a postoperative orthopedic patient associated with LMWH (nadroparin), complicated by deep venous thrombosis, pulmonary embolism, and disseminated intravascular coagulation, treated successfully with recombinant hirudin and immunoglobulin therapy.

Published
2003
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46. Cardiac tamponade due to post-cardiac injury syndrome in a patient with severe haemophilia A and HIV-1 infection.

Author

Theodossiades G, Tsevrenis V, Bellia M, Avgeropoulou A, Nomikos J, and Kontopoulou-Griva I

Subjects
Adolescent, Cardiac Tamponade therapy, Fractures, Bone complications, HIV-1, Hemophilia A virology, Hemorrhage drug therapy, Hemorrhage prevention & control, Humans, Male, Nasal Bone injuries, Pericardial Effusion virology, Syndrome, Cardiac Tamponade etiology, HIV Infections complications, Hemophilia A complications, Pericardial Effusion complications
Abstract

An 18-year-old man with severe haemophilia A (FVIII:C < 1%) and human immunodeficiency virus 1 (HIV-1) infection was admitted to the hospital with fever and chest pain for 7 days. Eight weeks prior to his admission he had an accident for which he underwent, at another hospital, clinical and laboratory examination that revealed bone fractures of the nose cavity, and he was given factor VIII concentrates for seven days due to nasal bleeding. On admission, chest roentgenogram showed a large cardiac silhouette and echocardiography confirmed the presence of a large quantity of pericardial fluid. A presumptive diagnosis of the post-cardiac injury syndrome was made and he was given anti-inflammatory drugs plus infusion of recombinant factor VIII concentrate (35 units kg-1 b.i.d.). On the seventh day he exhibited cardiac tamponade for which he underwent subxiphoid pericardiotomy with drainage of approximately 1500 mL of bloody exudate. He had an uncomplicated recovery and 10 days later he left hospital. He was given a continuous prophylactic treatment of 15 units kg-1 of recombinant FVIII every 2 days for 6 months, and 30 months after this episode the patient is free of any symptom.

Published
2000
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47. [The macula in Adamantiades-Behçet disease].

Author

Palimeris G, Theodossiades G, Constantinidou B, and Chimonidou E

Subjects
Behcet Syndrome drug therapy, Behcet Syndrome surgery, Cyclosporins therapeutic use, Female, Humans, Immunosuppressive Agents therapeutic use, Laser Therapy, Macula Lutea pathology, Male, Retinal Diseases drug therapy, Retinal Diseases surgery, Steroids therapeutic use, Behcet Syndrome complications, Macula Lutea physiopathology, Retinal Diseases etiology
Abstract

Adamantiades-Behçet disease is a well known clinical entity in the Mediterranean area. Signs and complications in these patients, arising from the macular area, are often overlooked for a prolonged period of time, because they are masked by the inflammatory signs of the anterior segment and/or the vitreous. Although blindness, in most cases, is the result of the optic disc atrophy, the macular alterations--as a sequelae of inflammation--are responsible for the low visual acuity. The authors in a retrospective clinical study of the last 100 consecutive cases of A-B disease, studied these macular alterations in detail. Their findings are also described in detail. Therapeutic modalities center around treatment with steroids, Cyclosporine A, and argon laser application. The results obtained from a long follow-up period are discussed.

Published
1989

49. [Antibiotics and blood cholesterol in the pig].

Author

FERRANDO R, THEODOSSIADES G, and VAN OSS C

Subjects
Animals, Humans, Swine, Anti-Bacterial Agents pharmacology, Cholesterol blood, Diet, Meat, Nutrition Assessment, Nutritional Status, Poultry
Published
1960

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