160 results on '"Manotti C"'
Search Results
52. Platelet Activation in Migraine
- Author
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Manotti, C, additional, Quintavalla, R, additional, and Manzoni, G C, additional
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- 1983
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53. Normal Prostacyclin-Like Activity in Thrombotic Thrombocytopenic Purpura
- Author
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Pini, M, additional, Manotti, C, additional, Quintavalla, R, additional, and Dettori, A G, additional
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- 1981
- Full Text
- View/download PDF
54. Inherited Deficiency Of Antithrombin III In Two Italian Families. Different Behaviour After Long-Term Anticoagulant Treatment
- Author
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Manotti, C, additional, Pini, M, additional, Poti, R, additional, and Quintavalia, R, additional
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- 1981
- Full Text
- View/download PDF
55. Inherited Deficiency of Antithrombin III in Two Italian Families
- Author
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Manotti, C., primary, Quintavalla, R., additional, Megha, A., additional, Ponari, O., additional, and Dettori, A.G., additional
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- 1982
- Full Text
- View/download PDF
56. ‘In Vivo’ and ‘In Vitro’ Effects of Some Vasoactive Drugs on Platelet Function and on Coagulation/Fibrinolysis System
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Dettori, A.G., additional, Ponari, O., additional, Manotti, C., additional, Megha, A., additional, and Pini, M., additional
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- 1977
- Full Text
- View/download PDF
57. Awareness of Teratogenic Effect of Oral Anticoagulants in Fertile Women
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Pattacini, C., Tagliaferri, A., and Manotti, C.
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- 2002
- Full Text
- View/download PDF
58. Normal Prostacyclin-Like Activity In A Patient With Thrombotic Thrombocytopenic Purpura
- Author
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Pini, M, Manotti, C, Quintavalla, R, and Dettori, A G
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- 1981
- Full Text
- View/download PDF
59. Changes Induced by Venous Stasis on Factor VIII Activities (VIII:C; VIIIR.AG; VIIIR:WF) in Different Clinical Conditions
- Author
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Ponari, O., Pini, M., Manotti, C., and Dettori, A.G.
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- 1979
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60. PROTHROMBIN TIME MONITORING OF ORAL ANTICOAGULANT TREATMENT: COMPARISON OF INSTRUMENTS AND THROMBOPLASTINS
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Seveso, M P, Macagni, A, Viganò D'Angelo, S, Manotti, C, Bonini, P A, and D'Angelo, A
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- 1987
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61. ANTICOAGULANT AND ANTIGENIC LEVELS OF PROTEIN C AND PROTEIN S IN PATIENTS ON STABILIZED ORAL ANTICOAGULANT TREATMENT
- Author
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D'Angelo, A, Gilardoni, F, Seveso, M P, Poli, P, Quintavalle, R, and Manotti, C
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- 1987
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62. ‘In Vivo’ and ‘In Vitro’ Effects of Some Vasoactive Drugs on Platelet Function and on Coagulation/Fibrinolysis System
- Author
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Dettori, A.G., Ponari, O., Manotti, C., Megha, A., and Pini, M.
- Published
- 1977
- Full Text
- View/download PDF
63. Inherited Deficiency Of Antithrombin III In Two Italian Families. Different Behaviour After Long-Term Anticoagulant Treatment
- Author
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Manotti, C, Pini, M, Poti, R, and Quintavalia, R
- Published
- 1981
- Full Text
- View/download PDF
64. Cerebral venous sinus thrombosis in childhood: clinical aspects and neurological and cognitive long-term outcome in three cases
- Author
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A. De Fanti, G. Cossu, Giovanni Buccino, G. C. Izzi, Domenico Mancia, C. Manotti, Buccino, G, Cossu, G, DE FANTI, A, Manotti, C, Izzi, Gc, and Mancia, D.
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Neurology ,Fever ,Neurological examination ,Dermatology ,Neuropsychological Tests ,Dyslexia ,Sinus Thrombosis, Intracranial ,Cognition ,Protein C deficiency ,medicine ,Humans ,Neuropsychological assessment ,Cerebral venous sinus thrombosis ,Child ,Neuroradiology ,Paresis ,Neurologic Examination ,Diplopia ,medicine.diagnostic_test ,General Medicine ,medicine.disease ,Magnetic Resonance Imaging ,Psychiatry and Mental health ,Child, Preschool ,Anesthesia ,Neurology (clinical) ,Nervous System Diseases ,medicine.symptom ,Psychology ,Protein C - Abstract
We report clinical findings, risk factors and neurological and cognitive long-term outcome in three Italian children aged 7, 8 and 5, respectively, who experienced cerebral venous sinus thrombosis (CVST). All children presented with headache, associated to nausea, vomiting and papilloedema. None suffered from epileptic seizures. In two of them a paresis of the sixth cranial nerve with diplopia was found. Diagnosis was confirmed by magnetic resonance imaging angiography (angio MRI) in all cases. In all patients plasma levels of protein C, protein S, antithrombin III (AT III), antiphospholipid antibodies (ApA) and homocysteine were detected. Furthermore, factor V Leiden mutation, prothrombin mutation G20210A and MTHFR mutation were searched for. A Protein C reduction was detected in all patients at onset; this finding, however, was not confirmed at follow-up in all of them. At one-year follow-up, neurological examination was normal in all children and neuropsychological assessment, aimed at excluding linguistic and non-linguistic cognitive deficits, revealed normal performances in two of them. In the third child, cognitive assessment confirmed a previously diagnosed developmental dyslexia.
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- 2004
65. The expert in hemostasis and thrombosis in the Italian health system: Role and requirements for a specific clinical and laboratory expertise
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Francesco Rodeghiero, Massimo Morfini, Carlo Nozzoli, Cesare Manotti, Francesco Violi, Giuseppe Castaldo, Fabrizio Pane, Bruno Biasioli, Claudio Velati, On behalf of SISET, AICE, FADOI, FCSA, SIBioC, SIE, SIMeL, SIMI, SIMTI, Rodeghiero, F., Morfini, M., Nozzoli, C., Manotti, C., Violi, F., Castaldo, G., Pane, F., Biasioli, B., and Velati, C.
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Blood coagulation disorder ,medicine.medical_specialty ,Epidemiology ,media_common.quotation_subject ,Population ,lcsh:Medicine ,Laboratory diagnosi ,Excellence ,Medicine ,education ,media_common ,education.field_of_study ,blood coagulation disorders, laboratory diagnosis, treatment, epidemiology ,business.industry ,Professional development ,lcsh:R ,General Medicine ,medicine.disease ,Thrombosis ,Treatment ,Hemostasis ,Scale (social sciences) ,Physical therapy ,Medical emergency ,business ,Healthcare system - Abstract
Hemorrhagic and thrombotic diseases are highly heterogeneous disorders that may affect a large proportion of the population, as in the case of patients taking antithrombotic drugs. The appropriate management of such conditions requires the availability of specific diagnostic assays, together with knowledge of the possible clinical syndromes and of their appropriate treatment. This can only be achieved through second-level specialized laboratories supervised by trained personnel. Such diagnostic and therapeutic organization is not widely available in Italy except in a very limited number of those large hospitals that are centers of excellence on a national scale. Increasing the availability of such resources would be of great benefit to patients, and could also be cost-effective for the national healthcare system. This document is promoted by the Italian Society for the Study on Hemostasis and Thrombosis (SISET) and by the main Italian scientific societies involved in the field during the years 2011-2012. It aims to identify the level of scientific and professional training required to define a physician as a Hemostasis and Thrombosis Expert, graded according to the levels of skill required for different clinical settings.
- Published
- 2013
66. Phase III studies on novel oral anticoagulants for stroke prevention in atrial fibrillation: a look beyond the excellent results
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Marco Moia, Guido Finazzi, Francesco Marongiu, Daniela Poli, Gualtiero Palareti, Cesare Manotti, Vittorio Pengo, Sophie Testa, E. Tiraferri, L. Crippa, Anna Falanga, A. Tosetto, Armando Tripodi, Sergio Siragusa, Pengo, V, Crippa, L, Falanga, A, Finazzi, G, Marongiu, F, Moia, M, Palareti, G, Poli, D, Testa, S, Tiraferri, E, Tosetto, A, Tripodi, A, Siragusa, S, and Manotti, C
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Male ,medicine.medical_specialty ,Pyridones ,Morpholines ,Administration, Oral ,Hemorrhage ,Thiophenes ,Dabigatran ,novel oral anticoagulants, atrial fibrillation ,Rivaroxaban ,Internal medicine ,Atrial Fibrillation ,Preventive Health Services ,medicine ,Humans ,Stroke ,Aged ,Randomized Controlled Trials as Topic ,Aged, 80 and over ,Evidence-Based Medicine ,business.industry ,Warfarin ,Anticoagulants ,Atrial fibrillation ,Hematology ,Middle Aged ,medicine.disease ,Treatment Outcome ,Clinical Trials, Phase III as Topic ,Heart failure ,Inclusion and exclusion criteria ,Cardiology ,beta-Alanine ,Pyrazoles ,Apixaban ,Benzimidazoles ,Female ,Patient Safety ,business ,medicine.drug - Abstract
Summary. In this overview we address the three phase III studies that compared new oral anticoagulants (dabigatran, rivaroxaban and apixaban) with warfarin in the setting of stroke prevention in atrial fibrillation. Strengths and weaknesses of the studies were examined in detail through indirect comparison. We analyze and comment the inclusion and exclusion criteria, the characteristics of randomized patients, the primary efficacy and safety end points and side effects. All new oral anticoagulants resulted in being non-inferior to vitamin K antagonists in reducing stroke or systemic embolism in patients with atrial fibrillation. Dabigatran 150 mg and apixaban were superior to vitamin K antagonists. Importantly, new oral anticoagulants significantly reduced hemorrhagic stroke in all three studies. Major differences among new oral anticoagulants include the way they are eliminated and side effects. Both dabigatran and apixaban were tested in low- to moderate-risk patients (mean CHADS2 [Congestive heart failure, Hypertension, Age, Diabetes, Stroke] score = 2.1–2.2) whereas rivaroxaban was tested in high-risk patients (mean CHADS2 score = 3.48) and at variance with dabigatran and apixaban was administered once daily. Apixaban significantly reduced mortality from any cause. The choice of a new oral anticoagulant should take into account these and other differences between the new drugs.
- Published
- 2012
67. Low oestrogen oral contraceptives as a major risk factor for cerebral venous and sinus thrombosis: evidence from a clinical series
- Author
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U. Scoditti, Giovanni Buccino, Domenico Mancia, C. Manotti, A.R. Tagliaferri, M. Pini, Buccino, G, Scoditti, U, Pini, M, Tagliaferri, Ar, Manotti, C, and Mancia, D.
- Subjects
Cerebral veins ,Adult ,Male ,medicine.medical_specialty ,Neurology ,Sinus Thrombosis, Intracranial ,Risk Factors ,medicine ,Sinus thrombosis ,Humans ,Risk factor ,Neuroradiology ,Venous Thrombosis ,medicine.diagnostic_test ,Dose-Response Relationship, Drug ,business.industry ,General Neuroscience ,Factor V ,Magnetic resonance imaging ,Estrogens ,Middle Aged ,Cerebral Veins ,Mutation ,Female ,Neurology (clinical) ,Neurosurgery ,Radiology ,business ,Cerebral angiography ,Contraceptives, Oral - Abstract
Cerebral venous and sinus thrombosis (CVST) is still considered a severe clinical problem that is difficult to diagnose and manage and is linked to a poor prognosis. Nonetheless, conventional cerebral angiography and magnetic resonance imaging (MRI), or more recently, MR angiography allow a more rapid and precise diagnosis, and prognosis has improved with the use of anticoagulant treatment. We report 23 cases of CVST consecutively admitted to the Institute of Neurology of the University of Parma during the period 1990-1997. In all cases diagnosis was confirmed by means of MRI or conventional angiography of brain vessels. Among the patients, 22 were female and 1 was male. In all patients, plasma levels of protein C, protein S, antithrombin III (ATIII) and antiphospholipid antibodies (APA) were evaluated. In 15 of 23 patients, the presence of factor V Leiden mutation was also determined, and found positive in 3 patients (20%). Of the 22 female patients, 15 (68%) were on low-oestrogen (containing less than 50 microg oestrogen) oral contraceptive (OC) treatment. This percentage of OC use by patients with CVST is much higher than that of the rest of the female Italian population. OC use was associated with the presence of factor V Leiden mutation in two cases, with a deficiency of protein C in 1 case and a deficiency of protein S in another.Whether low-oestrogen Ocs may induce cerebral thromboembolic events is an open matter. According to our data, it may be argued that Ocs, even if at low oestrogen content, represent a major risk factor for CVST. The use of Ocs, as is the case for systemic venous thromboembolic events, may further increase the risk of CVST in women carrying the factor V Leiden mutation or other inherited hyperthrombotic conditions.
- Published
- 1999
68. Management of DOAC in Patients Undergoing Planned Surgery or Invasive Procedure: Italian Federation of Centers for the Diagnosis of Thrombotic Disorders and the Surveillance of the Antithrombotic Therapies (FCSA) Position Paper.
- Author
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Squizzato A, Poli D, Barcellona D, Ciampa A, Grandone E, Manotti C, Moia M, Toschi V, Tosetto A, and Testa S
- Subjects
- Elective Surgical Procedures methods, Humans, Italy, Patient Care Management methods, Patient Care Management standards, Perioperative Care methods, Perioperative Care standards, Risk Adjustment methods, Risk Adjustment organization & administration, Vitamin K antagonists & inhibitors, Anticoagulants administration & dosage, Anticoagulants adverse effects, Antithrombins administration & dosage, Antithrombins adverse effects, Elective Surgical Procedures adverse effects, Hematologic Tests methods, Postoperative Hemorrhage etiology, Postoperative Hemorrhage prevention & control, Thrombosis diagnosis, Thrombosis prevention & control
- Abstract
Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. About a quarter of the anticoagulated patients require temporary cessation of direct oral anticoagulants (DOACs) or vitamin K antagonists for a planned intervention within 2 years from anticoagulation inception. Several clinical issues about DOAC interruption remain unanswered: many questions are tentatively addressed daily by thousands of physicians worldwide through an experience-based balancing of thrombotic and bleeding risks. Among possible valuable answers, the Italian Federation of Centers for the diagnosis of thrombotic disorders and the Surveillance of the Antithrombotic therapies (FCSA) proposes some experience-based suggestions and expert opinions. In particular, FCSA provides practical guidance on the following issues: (1) multiparametric assessment of thrombotic and bleeding risks based on patients' individual and surgical risk factor, (2) testing of prothrombin time, activated partial thromboplastin time, and DOAC plasma levels before surgery or invasive procedure, (3) use of heparin, (4) restarting of full-dose DOAC after high risk bleeding surgery, (5) practical nonpharmacological suggestions to manage patients perioperatively. Finally, FCSA suggests creating a multidisciplinary "anticoagulation team" with the aim to define the optimal perioperative management of anticoagulation., Competing Interests: A.S.: Honoraria for lectures, manuscript writing, and/or participation on advisory board from Daiichi Sankyo, Bayer, Pfizer, Bristol-Myers Squibb, Sanofi, Werfen, Alexion, and Roche. D.P.: Honoraria for a webinar from Daiichi Sankyo. D.B.: Honoraria for lectures from Aspen and Werfen. A.C.: Honoraria for lectures from Bayer. E.G.: Honoraria for lectures from Sanofi and Italfarmaco, and for participation on advisory board from Roche, Sanofi Genzyme, and Novo Nordisk. C.M.: None. M.M.: Honoraria for lectures and manuscript writing from Daiichi-Sankyo. V.T.: Honoraria for lectures from Bayer and Novo Nordisk. A.T.: Honoraria for lectures from Werfen, Stago, and Roche; support for attending meetings from Novo Nordisk; honoraria for participation on advisory board from Bayer and Novo Nordisk. S.T.: Honoraria for lectures and for participation on advisory board from Werfen, Stago, Italfarmaco, Pfizer, Bristol-Myers Squibb, and Sanofi., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)
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- 2022
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69. MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study.
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Rossetti P, Goldoni M, Pengo V, Vescovini R, Mozzoni P, Tassoni MI, Lombardi M, Rubino P, Bernuzzi G, Verzicco I, Manotti C, and Quintavalla R
- Subjects
- Animals, Biomarkers, Case-Control Studies, Humans, Pilot Projects, MicroRNAs genetics, Venous Thromboembolism genetics
- Abstract
Venous thromboembolism (VTE) is the third most common cardiovascular disease. Interleukins (ILs) and micro-ribonucleic acids (miRNAs) have been proposed as molecules able to modulate endothelial inflammation and platelet hyperactivity. At present, no early biomarkers are available to predict the outcome of VTE. We investigated in a pilot study a selected number of miRNAs and ILs as prognostic VTE biomarkers and reviewed literature in this setting. Twenty-three patients (aged 18-65) with a new diagnosis of non-oncological VTE and free from chronic inflammatory diseases were enrolled. Twenty-three age- and sex-matched healthy blood donors were evaluated as control subjects. Serum miRNAs (MiRNA 126, 155, 17.92, 195), inflammatory cytokines (IL-6, tumor necrosis factor-α, IL-8), and lymphocyte subsets were evaluated in patients at enrolment (T0) and in controls. In VTE patients, clinical and instrumental follow-up were performed assessing residual vein obstruction, miRNA and ILs evaluation at 3 months' follow-up (T1). At T0, IL-8, activated T lymphocytes, Treg lymphocytes, and monocytes were higher in patients compared with healthy controls, as were miRNA 126 levels. Moreover, miRNA 126 and IL-6 were significantly increased at T0 compared with T1 evaluation in VTE patients. Higher levels of MiR126 at T0 correlated with a significant overall thrombotic residual at follow-up. In recent years an increasing number of studies (case-control studies, in vivo studies in animal models, in vitro studies) have suggested the potential role of miRNAs in modulating the cellular and biohumoral responses involved in VTE. In the frame of epidemiological evidence, this pilot study with a novel observational approach supports the notion that miRNA can be diagnostic biomarkers of VTE and first identifies miRNA 126 as a predictor of outcome, being associated with poor early recanalization., Competing Interests: None declared., (Thieme. All rights reserved.)
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- 2021
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70. Managing anticoagulation in the COVID-19 era between lockdown and reopening phases.
- Author
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Poli D, Tosetto A, Palareti G, Barcellona D, Ciampa A, Grandone E, Manotti C, Moia M, Squizzato A, Toschi V, and Testa S
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- Anticoagulants adverse effects, Betacoronavirus, COVID-19, Coronavirus Infections epidemiology, Humans, Italy epidemiology, Pandemics, Pneumonia, Viral epidemiology, Quarantine, Risk Factors, SARS-CoV-2, Ambulatory Care Facilities, Anticoagulants administration & dosage, Coronavirus Infections complications, Pneumonia, Viral complications
- Abstract
Patients on anticoagulant treatment are constantly increasing, with an estimated prevalence in Italy of 2% of the total population. The recent spreadout of the COVID-19 pandemic requires a re-organization of Anticoagulation Clinics to prevent person-to-person viral diffusion and continue to offer the highest possible quality of assistance to patients. In this paper, based on the Italian Federation of Anticoagulation Clinics statements, we offer some advice aimed at improving patient care during COVID-19 pandemic, with particular regard to the lockdown and reopening periods. We give practical guidance regarding the following points: (1) re-thinking the AC organization, (2) managing patients on anticoagulants when they become infected by the virus, (3) managing anticoagulation surveillance in non-infected patients during the lockdown period, and (4) organizing the activities during the reopening phases.
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- 2020
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71. Direct oral anticoagulants vs non-vitamin K antagonist in atrial fibrillation: A prospective, propensity score adjusted cohort study.
- Author
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Marietta M, Banchelli F, Pavesi P, Manotti C, Quintavalla R, Sinigaglia T, Guazzaloca G, Pattacini C, Urbinati S, Malavasi VL, Boriani G, Voci C, D'Amico R, and Magrini N
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- Aged, Aged, 80 and over, Anticoagulants adverse effects, Dabigatran administration & dosage, Dabigatran adverse effects, Female, Humans, Italy epidemiology, Male, Propensity Score, Prospective Studies, Pyrazoles administration & dosage, Pyrazoles adverse effects, Pyridones administration & dosage, Pyridones adverse effects, Rivaroxaban administration & dosage, Rivaroxaban adverse effects, Stroke prevention & control, Anticoagulants administration & dosage, Atrial Fibrillation drug therapy, Stroke epidemiology
- Published
- 2019
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72. Position Paper on laboratory testing for patients on direct oral anticoagulants. A Consensus Document from the SISET, FCSA, SIBioC and SIPMeL.
- Author
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Tripodi A, Ageno W, Ciaccio M, Legnani C, Lippi G, Manotti C, Marcucci R, Moia M, Morelli B, Poli D, Steffan A, and Testa S
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- Administration, Oral, Anticoagulants administration & dosage, Anticoagulants adverse effects, Humans, Italy, Societies, Scientific, Anticoagulants pharmacokinetics, Drug Monitoring methods, Drug Monitoring standards
- Abstract
Although direct oral anticoagulants (DOAC) do not require dose-adjustment on the basis of laboratory test results, the measurement of their anticoagulant effect is useful in special situations. This position paper issued by the Italian Scientific Societies that are mainly involved in the management of patients on DOAC is aimed at providing guidance to care-givers on which tests should be used and the situations in which testing is useful. The guidance is based on the data from the literature so far available and/or on consensus among experts.
- Published
- 2018
- Full Text
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73. Position paper on laboratory testing for patients taking new oral anticoagulants. Consensus document of FCSA, SIMeL, SIBioC and CISMEL1).
- Author
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Tripodi A, Di Iorio G, Lippi G, Testa S, and Manotti C
- Subjects
- Administration, Oral, Hemostasis, Humans, Thrombosis prevention & control, Anticoagulants administration & dosage, Consensus
- Abstract
At variance with vitamin K antagonists, the new oral anticoagulants(NOAs) can be prescribed at fixed dosage without adjustment by laboratory testing. However, this does not necessarily mean that the laboratory does not play a role for their management. This position paper represents the consensus document of three Italian scientific societies dealing with laboratory issues in thrombosis and hemostasis. It is aimed at reviewing: 1) which test(s) should be used to evaluate the anticoagulant effect of each of the NOAs presently available(i.e., dabigatran, rivaroxaban and apixaban); 2) the patients to be investigated; and 3) the timing of investigation.
- Published
- 2012
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74. Questions and answers on the use of dabigatran and perspectives on the use of other new oral anticoagulants in patients with atrial fibrillation. A consensus document of the Italian Federation of Thrombosis Centers (FCSA).
- Author
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Pengo V, Crippa L, Falanga A, Finazzi G, Marongiu F, Palareti G, Poli D, Testa S, Tiraferri E, Tosetto A, Tripodi A, and Manotti C
- Subjects
- Administration, Oral, Anticoagulants adverse effects, Atrial Fibrillation complications, Benzimidazoles adverse effects, Dabigatran, Drug Substitution, Evidence-Based Medicine, Hemorrhage chemically induced, Humans, Italy, Patient Selection, Risk Assessment, Risk Factors, Stroke etiology, Treatment Outcome, Warfarin adverse effects, beta-Alanine administration & dosage, beta-Alanine adverse effects, Anticoagulants administration & dosage, Atrial Fibrillation drug therapy, Benzimidazoles administration & dosage, Primary Prevention, Stroke prevention & control, Warfarin administration & dosage, beta-Alanine analogs & derivatives
- Abstract
Dabigatran and other new oral anticoagulants (OAC) represent a step forward in stroke prevention in patients with atrial fibrillation (AF). They indeed have been shown to be an alternative to vitamin K antagonists (VKAs) without the burden of laboratory control. However, these new drugs compete with an effective and well-established therapy, thus bringing about a series of questions and doubts. In this report members of the board of the Italian Federation of Thrombosis Centers (FCSA) answer some questions every clinician might be confronted with.
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- 2011
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75. Effects of raloxifene and continuous combined hormone therapy on haemostasis variables: a multicenter, randomized, double-blind study.
- Author
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Sgarabotto M, Baldini M, Dei Cas A, Manotti C, Luciana Barilli A, Rinaldi M, Benassi L, and Bacchi Modena A
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- Aged, Body Mass Index, Contraceptives, Oral, Synthetic therapeutic use, Double-Blind Method, Drug Combinations, Estriol therapeutic use, Female, Hemostasis drug effects, Humans, Middle Aged, Norethindrone therapeutic use, Norethindrone Acetate, Postmenopause, Time Factors, Estradiol therapeutic use, Norethindrone analogs & derivatives, Raloxifene Hydrochloride therapeutic use, Selective Estrogen Receptor Modulators therapeutic use
- Abstract
Introduction: Hormone replacement therapy is known to increase the risk of thromboembolic events. We compared the effects of HRT and raloxifene on some haemostasis variables., Materials and Methods: In a multicenter, double-blind study, 54 healthy postmenopausal women were randomized to receive either continuous treatment with 2 mg 17beta-estradiol plus 1 mg norethisterone acetate (n=30) or 60 mg raloxifene (n=24) daily for 12 months. Blood samples were collected at baseline and at 3, 6 and 12 months to evaluate therapy effects on some haemostasis variables (factor VII, factor VIII, prothrombin fragments 1 and 2, protein C, protein C activity, protein S, thrombin-antithrombin complex, D-dimer, antithrombin, fibrinogen and plasminogen activator inhibitor)., Results: Both raloxifene and continuous combined hormone therapy modified the haemostasis variables toward a more prothrombotic profile. Factor VIII (p<0.01) and fibrinogen (p<0.05) plasma levels significantly increased at 6 months, prothrombin fragments 1 and 2 (p<0.05) significantly increased at 12 months, whereas protein C activity (p<0.001) and antithrombin (p<0.01) significantly decreased at 12 months in both groups., Conclusions: Our results demonstrate that raloxifene and continuous combined hormone therapy exhibit the same prothrombotic profile. Both treatments induced an increase in procoagulant parameters at 6 months and a decrease in anticoagulant parameters at 12 months.
- Published
- 2007
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76. Effects of subacute treatment with benzopyranopyrimidines in hemostasis and experimental thrombosis in mice.
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Ballabeni V, Calcina F, Tognolini M, Bruno O, Manotti C, and Barocelli E
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- Animals, Mice, Paralysis drug therapy, Peptic Ulcer drug therapy, Platelet Aggregation Inhibitors therapeutic use, Pyrimidines therapeutic use, Rats, Rats, Wistar, Hemostasis drug effects, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors pharmacology, Pulmonary Embolism drug therapy, Pyrimidines pharmacology
- Abstract
The antithrombotic activity of a series of benzopyranopyrimidine derivatives was investigated in platelet-dependent and independent pulmonary thromboembolism in mice. Intraperitoneal subacute treatment with 2-morpholino derivative 3c significantly prevented paralysis due to collagen plus epinephrine-induced pulmonary thrombosis while 2-piperidino substituted derivative 3h significantly protected mice from paralysis caused by thrombin-induced intravascular fibrin formation at dosage not affecting bleeding time. These compounds, previously proved to be effective as antiplatelet agents in vitro, were in vivo more potent as antithrombotics than lysine acetylsalicylate and possessed lower prohemorrhagic activity than the reference drug. Although their ineffectiveness on clotting times, PT and APTT, allows the involvement of coagulation pathways to be ruled out, the mechanisms underlying the favourable benefit risk ratio for these two compounds remain to be further clarified.
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- 2004
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77. Intron factor VIII gene inversion in a population of Italian hemophilia A patients.
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Riccardi F, Tagliaferri A, Manotti C, Pattacini C, and Neri TM
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- Gene Frequency, Hemophilia A epidemiology, Humans, Italy epidemiology, Male, Chromosome Inversion, DNA Mutational Analysis, Factor VIII genetics, Hemophilia A genetics, Introns genetics, Polymerase Chain Reaction methods
- Published
- 2002
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78. Doppler velocimetry and thrombophilic screening at middle trimester of gestation: preliminary data.
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Delle Chiaie L, Gramellini D, Piantelli G, Manotti C, Fieni S, and Vadora E
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- Adult, Arteries diagnostic imaging, Arteries physiology, Blood Flow Velocity, Female, Fetal Growth Retardation diagnostic imaging, Gestational Age, Humans, Pre-Eclampsia diagnostic imaging, Predictive Value of Tests, Pregnancy, Pregnancy Outcome, Pregnancy Trimester, Second, Prospective Studies, Reference Values, Thrombophilia complications, Uterus diagnostic imaging, Pregnancy Complications, Hematologic diagnostic imaging, Thrombophilia diagnostic imaging, Ultrasonography, Doppler methods, Uterus blood supply
- Abstract
Objective: To establish whether asymptomatic normotensive pregnant women with an abnormal uterine Doppler velocimetry, have haematological changes characteristic of congenital or acquired thrombophilia, and whether this information improve predict in pregnancy complications., Study Design: A prospective study involved the enrolment of 30 healthy normotensive pregnant women between the 23rd and 27th week of gestation, subdivided into group A (normal uterine Doppler velocimetry) and group B (abnormal uterine Doppler velocimetry). Besides uterine velocimetry (resistence index and presence/absence of notch), at enrolment in the study the PI of the umbilical artery and of the middle cerebral artery were measured, in addition to the usual foetal biometric parameters (biparietal diameter and abdominal circumference). Contemporaneously, a 20 ml blood sample was taken for the dosage of protein C, protein S, antithrombin III, activated protein C resistance, antiphospholipid antibodies and platelet functionality. Subsequently, for all the remaining period of the pregnancy, data were collected relating to the onset of any materno-foetal complications and modality of delivery, as well as neonatal data up to the first 20 days of life., Results: The incidence of adverse perinatal outcomes (pre-eclampsia, gestational hypertension, abruptio placentae, endouterine foetal death, preterm birth, caesarean section because of maternal or foetal problems, APGAR score lower than 7 at the 5th minute of life, small for gestational age) resulted as being 75% in group B versus 11% in group A (P<0.001). The mean gestational age at delivery was 34 weeks (range 27-41) in group A versus 39 weeks (range 37-42) in group B (P<0.001). No difference emerged as to either the mean activity in the plasma levels of the coagulation protein studied in patients with normal and abnormal uterine velocimetry. The same consideration is also true if the population is analysed in relation to the lesser or greater seriousness of the Doppler velocimetry abnormalities. Subdividing the patients in relation to the absence and to the presence of unfavourable perinatal outcomes, the thrombophilic indices appear to be substantially comparable., Conclusion: Uterine Doppler velocimetry, carried out between the 24th and the 26th week of pregnancy, proves its validity by identifying a population at high risk of adverse perinatal outcomes. In contrast, the investigations carried out on the haematological abnormalities characteristic of thrombophilia do not reveal any significant differences, either between patients with normal and those with abnormal velocimetry, or between patients with adverse perinatal outcomes and those without. It is thus unlikely that these preliminary data will lead to an improvement in the clinical reliability of uterine velocimetry.
- Published
- 2001
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79. Effect of computer-aided management on the quality of treatment in anticoagulated patients: a prospective, randomized, multicenter trial of APROAT (Automated PRogram for Oral Anticoagulant Treatment).
- Author
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Manotti C, Moia M, Palareti G, Pengo V, Ria L, and Dettori AG
- Subjects
- Disease Management, Drug Administration Schedule, Drug Monitoring, Humans, International Normalized Ratio, Prospective Studies, Treatment Outcome, Algorithms, Anticoagulants administration & dosage, Decision Making, Computer-Assisted
- Abstract
Background and Objectives: We carried out a prospective, randomized trial to test whether a computer-based decision support system to initiate and maintain oral anticoagulant (OA) treatment can improve the laboratory quality of therapy., Design and Methods: Two separate sets of patients on oral anticoagulants, in five Italian anticoagulant clinics, were studied: 335 patients in the first three months of treatment (stabilization phase), 916 patients (775 patient-years) beyond the third month of treatment (maintenance phase). Patients were randomized to a computerized system, which included algorithms able to suggest OA dosing and to schedule appointments (computer-aided dosing) or to an arm in which OA were prescribed by the same teams of expert physicians without such algorithms (control group). Primary outcomes were: A) the percentage of patients reaching a stable state of anticoagulation during each of the first three months of treatment; B) the percentage of time individuals spent within the aimed therapeutic range (maintenance phase)., Results: Patients in the computer-aided dosing group achieved a stable state significantly faster (p<0.01) and they spent more time within the therapeutic range during maintenance (p<0.001) than controls. The favorable effect of computer-aided dosing was mainly due to a reduction of the time spent below the therapeutic range and was associated with an increase of mean INR value, of anticoagulant drug dosage, and with a reduction of the number of appointments per patient (all changes significant: p<0.001)., Interpretation and Conclusions: The computer decision-aided support improves the laboratory quality of anticoagulant treatment, both during long-term maintenance and in the early, highly unstable phase of treatment, and it also significantly reduces the number of scheduled laboratory controls.
- Published
- 2001
80. A comparison of the safety and efficacy of oral anticoagulation for the treatment of venous thromboembolic disease in patients with or without malignancy.
- Author
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Palareti G, Legnani C, Lee A, Manotti C, Hirsh J, D'Angelo A, Pengo V, Moia M, and Coccheri S
- Subjects
- Administration, Oral, Adolescent, Adult, Aged, Aged, 80 and over, Anticoagulants adverse effects, Female, Humans, Male, Middle Aged, Neoplasms complications, Prospective Studies, Treatment Outcome, Venous Thrombosis complications, Anticoagulants administration & dosage, Venous Thrombosis drug therapy
- Abstract
The optimal long-term treatment of acute venous thromboembolism (VTE) in patients with malignancy remains undefined. In particular, based on current evidence, it is uncertain whether secondary prophylaxis using standard intensity oral anticoagulant therapy is associated with higher risks of bleeding and recurrent thrombosis in patients with cancer than in those without cancer. This study compared the outcome of anticoagulation courses in 95 patients with malignancy with those of 733 patients without malignancy. All patients were participants in a large, nation-wide population study and were prospectively followed from the initiation of their oral anticoagulant therapy. Based on 744 patient-years of treatment and follow-up, the rates of major (5.4% vs 0.9%), minor (16.2% vs 3.6%) and total (21.6% vs 4.5%) bleeding were statistically significantly higher in cancer patients compared with patients without cancer. Bleeding was also a more frequent cause of early anticoagulation withdrawal in patients with malignancy (4.2% vs. 0.7%; p <0.01; RR 6.2 (95% CI 1.95-19.4). There was a trend towards a higher rate of thrombotic complications in cancer patients (6.8% vs. 2.5%; p = 0.058; RR 2.5 [CI 0.96-6.5]) but this did not achieve statistical significance. In the group of patients with cancer, the bleeding rate was high across the different INR categories and was independent of the temporally associated International Normalized Ratio (INR). In contrast, the bleeding rate was increased only with INR values greater than 4.5 in the group of patients without cancer. The rate of thrombotic events was significantly higher in both cohorts when the INR was less than 2.0. In conclusion, patients with malignancy treated with oral anticoagulants have a higher rate of bleeding and possibly an increased risk of recurrent thrombosis compared with patients without malignancy. Safer and more effective anticoagulant therapy is needed for this challenging group of patients.
- Published
- 2000
81. Oral anticoagulation treatment in the elderly: a nested, prospective, case-control study.
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Palareti G, Hirsh J, Legnani C, Manotti C, D'Angelo A, Pengo V, Moia M, Guazzaloca G, Musolesi S, and Coccheri S
- Subjects
- Administration, Oral, Age Factors, Aged, Aged, 80 and over, Anticoagulants administration & dosage, Anticoagulants adverse effects, Blood Coagulation drug effects, Case-Control Studies, Female, Humans, International Normalized Ratio, Italy, Male, Multivariate Analysis, Poisson Distribution, Prospective Studies, Risk, Anticoagulants therapeutic use, Hemorrhage chemically induced, Thrombosis prevention & control
- Abstract
Background: Whether elderly patients are at increased risk of complications during oral anticoagulant treatment (OAT) is still a matter of debate., Method: Bleeding and thrombotic events occurring during OAT in 461 patients, aged 75 years or older when they started OAT, and in 461 patients younger than 70 years, matched for sex, OAT indication, and treating center, were examined in a prospective, multicenter, inception-cohort study., Results: Bleeding rate was 9.9% and 6.6% patient-years in elderly and young patients, respectively (P = .07), and 2.1% and 1.1% for major bleeding (P = .19); 6 and 1 events, respectively, were fatal (all intracranial, relative risk, 6.4; P = .05). In the elderly, bleeding rate was lower (4.5%) for international normalized ratios (INRs) between 2.0 and 2.9; it was higher during the first 90 treatment days (P = .05) and when arterial vascular disease was the indication for OAT (P = .03). Thrombosis rate was 4.2% and 2.5% patient-years in elderly and young patients, respectively (P = .10); however, 13 and 5 events were fatal (relative risk, 2.8; P = .04). Thrombosis rate was lower (1.5%) for INRs between 2.0 and 2.9; it was higher during the first 90 treatment days (P<.001) and 6 of 7 venous events occurred at lower than 2.0 INRs., Conclusions: A nonsignificant trend was noted toward a higher rate of both bleeding and thrombotic complications in elderly vs matched younger patients. Intracranial bleeding and fatal thrombotic events were significantly more frequent in the elderly. Our results also indicate that lower than 2.0 INRs do not preclude bleeding in the elderly nor offer adequate protection from thrombotic events. Moderate anticoagulation (2.0-3.0 INRs) in elderly patients seems the safest and most effective.
- Published
- 2000
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82. [Recurrences and new vein thrombotic events during oral anticoagulant therapy in patients treated for previous vein thromboembolism. Data from the literature and results of the ISCOAT study].
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Palareti G, Manotti C, Legnani C, Poggi M, Guazzaloca G, and Coccheri S
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- Administration, Oral, Humans, Recurrence, Thromboembolism complications, Venous Thrombosis complications, Anticoagulants administration & dosage, Heparin administration & dosage, Thromboembolism drug therapy, Venous Thrombosis drug therapy
- Published
- 1999
83. Comparison of in vitro and ex vivo antiplatelet effects of 1,2-benzisothiazolin-3-one and its 2-amino derivative.
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Vicini P, Manotti C, Caretta A, and Amoretti L
- Subjects
- Adenosine Diphosphate pharmacology, Adolescent, Adult, Animals, Arachidonic Acid pharmacology, Collagen pharmacology, Female, Humans, In Vitro Techniques, Indicators and Reagents, Male, Middle Aged, Platelet Aggregation drug effects, Rabbits, Platelet Aggregation Inhibitors pharmacology, Thiazoles pharmacology
- Abstract
The in vitro and ex vivo antiplatelet effects of 2-amino-1,2-benzisothiazolin-3-one (1) are compared with those of its parent compound 1,2-benzisothiazolin-3-one (2) and with acetylsalicylic acid (ASA) against different agonists. 2-Amino-1,2-benzisothiazolin-3-one inhibits adenosine diphosphate (ADP)-, arachidonic acid (AA)- and collagen-induced human platelet aggregation in vitro, with IC50 values of 8.90 x 10(-5), 1.50 x 10(-6) and 5.11 x 10(-8) mol/l, respectively. The strong inhibitory activity is significant not only for collagen but also for AA-induced aggregation. The same compound inhibits ex vivo collagen- and particularly AA-induced rabbit platelet aggregation at the tested dose of 10 mg/kg i.m. In view of the potential use of 2-amino-1,2-benzisothiazolin-3-one as antithrombotic agent, the log P values for both 1,2-benzisothiazolin-3-one derivatives 1 and 2 are determined, to gain an understanding of the significance of the 2-amino group in the 1,2-benzisothiazolin-3-one moiety with respect to the biological activity under study.
- Published
- 1999
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84. Thrombotic events during oral anticoagulant treatment: results of the inception-cohort, prospective, collaborative ISCOAT study: ISCOAT study group (Italian Study on Complications of Oral Anticoagulant Therapy).
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Palareti G, Manotti C, DAngelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, Leali N, Poggi M, Legnani C, Musolesi S, and Coccheri S
- Subjects
- Administration, Oral, Age Factors, Aged, Anticoagulants administration & dosage, Cohort Studies, Dose-Response Relationship, Drug, Female, Follow-Up Studies, Hemorrhage chemically induced, Humans, Italy epidemiology, Male, Middle Aged, Prospective Studies, Thromboembolism drug therapy, Thrombosis epidemiology, Anticoagulants adverse effects, Anticoagulants therapeutic use, Thrombosis etiology
- Abstract
The paper reports on rate and type of thrombotic events occurring during the observational, prospective, inception-cohort, multicenter ISCOAT study. 2,745 unselected, daily practice patients, consecutively referring to 34 Italian anticoagulation clinics to monitor the oral anticoagulant treatment, were included in the study from beginning of their first anticoagulant course. During a total follow-up of 2,011 patient-years of treatment 70 thrombotic events (3.5 per 100 patient years) were recorded in 67 patients: 20 fatal (1%), 39 major (1.9%) and 11 minor (0.6%). 34/70 events occurred within the first 90 days of treatment (relative risk - at multivariate analysis - of < or =90 days vs. >90 = 20.6, C.I. 12.7-33.5; p <0.0001). The risk was higher in patients aged > or =70 y (1.62, C.I. 1.0-2.61; p <0.05), and when indication for anticoagulant treatment was peripheral/cerebral arterial disease (1.84, C.I. 1.01-3.36; p <0.05). The frequency of thrombotic events was 17.5% when international normalised ratio (INR) levels were < 1.5, decreasing to 2.3% for INRs within the 2-2.99 category (relative risk of INRs <2.0 vs. > or =2 = 1.88, C.I. 1.16-3.07; p <0.05). The recorded rate of thrombotic events was lower than that reported in the few available studies. A greater risk should be expected during the first 90 days of treatment, when anticoagulation levels are <2.0 INR, in patients > 70 years and in those with cerebrovascular/peripheral arterial disease.
- Published
- 1997
85. Synthesis and antiplatelet effects of 2-amino-1,2-benzisothiazolin-3-one.
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Vicini P, Manotti C, Caretta A, and Amoretti L
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- Animals, Bleeding Time, Female, Humans, In Vitro Techniques, Male, Mice, Platelet Aggregation drug effects, Platelet Aggregation Inhibitors pharmacology, Rabbits, Platelet Aggregation Inhibitors chemical synthesis
- Abstract
The synthesis of a new compound, 2-amino-1,2-benzisothiazolin-3-one, is described and its antiplatelet activity was studied. A good platelet aggregation inhibitory activity of the tested drug was clearly demonstrated both in vitro and ex vivo, presumably through an effect on arachidonic acid cascade or directly on thromboxane A2 (TXA2) receptors. An early and long lasting effect on bleeding time has also been observed. The results suggest that 2-amino-1,2-benzisothiazolin-3-one could be a potential antithrombotic agent.
- Published
- 1997
86. [Hemorrhagic complications of oral anticoagulant therapy: results of a prospective multicenter study ISCOAT (Italian Study on Complications of Oral Anticoagulant Therapy)].
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Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berretini M, and Musolesi S
- Subjects
- Aged, Female, Hemorrhage epidemiology, Humans, Italy epidemiology, Male, Middle Aged, Prospective Studies, Risk Factors, Warfarin adverse effects, Anticoagulants adverse effects, Hemorrhage chemically induced
- Abstract
Background: To assess the incidence of bleeding complications during oral anticoagulant therapy (OAT) in a population of patients representative of daily practice in Italian anticoagulation clinics., Design: prospective, inception-cohort, multicentre., Setting: Thirty-four anticoagulation clinics federated in the Italian Federation of Anticoagulation Clinics., Patients: 2745 consecutive patients, included from beginning of their first OAT course. Most patients were aged between 60 and 79 y (57.8%), with 8% being > or = 80 y. Venous thromboembolism was the most frequent indication for OAT (one third of all the patients), followed by non ischemic heart disease which mainly included atrial fibrillation (16.8% of patients). Warfarin (in 63.8% of patients) and acenocoumarol were the only anticoagulant drugs used. The targeted anticoagulation intensity was low (INR < or = 2.8) in 71% of patients and high (INR > 2.8) in the remainder., Outcomes: Fatal, major and minor bleeding events. Thrombotic events were also recorded, though not analyzed in the present report., Findings: During the 2011 patient-years (pt-y) of follow-up, 153 bleeding complications (7.6% pt-y) were recorded--5 fatal (all cerebral haemorrhages, 0.25% pt-y), 23 major (1.1% pt-y) and 125 minor (6.2% pt-y). The rate of events did not vary according to sex, coumarin type, size of enrolling centre or targeted therapeutic range; it was higher in older patients (10.5% pt-y in those aged > or = 70 y, relative risk--RR--1.75, p < 0.001), in cases where indication for anti-coagulant treatment was peripheral and/or cerebrovascular disease (12.5% pt-y; RR 1.80, p < 0.01) and during the first 90 days of treatment (11% pt-y, RR 1.75, p < 0.001). One fifth of bleeding events occurred at a very low anticoagulation intensity (INR < 2; the category rate being 7.7% pt-y); the rate was 4.8% pt-y in the 2.0-2.9 INR category, reaching 9.5% pt-y, 40.5% pt-y and 200% pt-y in the 3-4.4, 4.5-6.9 and > or = 7 INR categories respectively (RR for INR levels > 4.5 = 7.91, p < 0.0001)., Conclusions: The overall rate of bleeding events recorded in the present study was much lower than that recorded in other (including recent) observational and experimental studies. The risk of bleeding increased in the following cases: age > 70 y; arterial vascular disease as indication for OAT; first 3 months of treatment; INR values > or = 4.5. OAT has become safer in recent years, particularly if monitored in special anticoagulation clinics. Caution should be exercised when prescribing OAT in elderly patients and the intensity anticoagulation levels should be closely monitored to minimize incidental periods of overanticoagulation.
- Published
- 1997
87. Bleeding complications of oral anticoagulant treatment: an inception-cohort, prospective collaborative study (ISCOAT). Italian Study on Complications of Oral Anticoagulant Therapy.
- Author
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Palareti G, Leali N, Coccheri S, Poggi M, Manotti C, D'Angelo A, Pengo V, Erba N, Moia M, Ciavarella N, Devoto G, Berrettini M, and Musolesi S
- Subjects
- Acenocoumarol adverse effects, Administration, Oral, Adult, Aged, Aged, 80 and over, Anticoagulants administration & dosage, Cardiovascular Diseases drug therapy, Cohort Studies, Female, Hemorrhage mortality, Humans, Italy, Male, Middle Aged, Prospective Studies, Risk Factors, Warfarin adverse effects, Anticoagulants adverse effects, Hemorrhage chemically induced
- Abstract
Background: Bleeding is the most serious complication of the use of oral anticoagulation in the prevention and treatment of thromoboembolic complications. We studied the frequency of bleeding complications in outpatients treated routinely in anticoagulation clinics., Methods: In a prospective cohort from thirty-four Italian anticoagulation clinics, 2745 consecutive patients were studied from the start of their oral anticoagulation (warfarin in 64%, acenocourmarol in the rest). The target anticoagulation-intensity was low (international normalised ratio [INR] < or = 2.8) in 71% of the patients and high (> 2.8) in the remainder. We recorded demographic details and the main indication for treatment and, every 3-4 months, INR and outcome events. Such events included all complications (bleeding, thrombosis, other), although only bleeding events are reported here, and deaths. We divided bleeding into major and minor categories., Findings: 43% of the patients were women. Nearly three-fifths of the patients were aged 60-79; 8% were over 80. The main indication for treatment was venous thrombolism (33%), followed by non-ischaemic heart disease (17%). Mean follow-up was 267 days. Over 2011 patient-years of follow-up, 153 bleeding complications occurred (7.6 per 100 patient-years). 5 were fatal (all cerebral haemorrhages, 0.25 per 100 patient-years), 23 were major (1.1), and 125 were minor (6.2). The rate of events was similar between sexes, coumarin type, size of enrolling centre, and target INR. The rate was higher in older patients: 10.5 per 100 patient-years in those aged 70 or over, 6.0 in those aged under 70 (relative risk 1.75, 95% Cl 1.29-2.39, p < 0.001). The rate was also higher when the indication was peripheral and/or cerebrovascular disease than venous thromboembolism plus other indications (12.5 vs 6.0 per 100 patient-years) (1.80, 1.2-2.7, p < 0.01), and during the first 90 days of treatment compared with later (11.0 vs 6.3, 1.75, 1.27-2.44, p < 0.001). A fifth of the bleeding events occurred at low anticoagulation intensity (INR < 2, rate 7.7 per 100 patient-years of follow-up). The rates were 4.8, 9.5, 40.5, and 200 at INRs 2.0-2.9, 3-4.4, 4.5-6.9, and over 7, respectively (relative risks for INR > 4.5, 7.91, 5.44-11.5, p < 0.0001)., Interpretation: We saw fewer bleeding events than those recorded in other observational and experimental studies. Oral anticoagulation has become safer in recent years, especially if monitored in anticoagulation clinics. Caution is required in elderly patients and anticoagulation intensity should be closely monitored to reduce periods of overdosing.
- Published
- 1996
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88. Risk of venous thromboembolism and stroke associated with oral contraceptives. Role of congenital thrombophilias.
- Author
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Pini M, Scoditti U, Caliumi F, Manotti C, Quintavalla R, Pattacini C, Poli T, Tagliaferri A, di Iasio MG, and Bernardi F
- Subjects
- Adolescent, Adult, Cerebrovascular Disorders epidemiology, Female, Humans, Italy, Risk Factors, Thromboembolism epidemiology, Cerebrovascular Disorders etiology, Contraceptives, Oral adverse effects, Thromboembolism etiology, Thrombosis complications, Thrombosis congenital
- Abstract
To assess the risk of thromboembolism in women using oral contraceptives (OCs), we identified through computer search in the hospitals of the province of Parma, Italy, all women aged 15-44 who were resident in the province and had a documented thromboembolic event in the years 1989-93. The number of users and nonusers of OCs was estimated by the drug sale data for the province and by the demographic statistics. In cases with venous thromboembolism (VT) the prevalence of concomitant deficiency of antithrombin III, protein C, protein S, and of factor V gene mutation Arg506GIn was evaluated. The incidence rate of VT was 37/59,603 woman-years in users (0.62 per 1000) and 13/303,954 woman-years in nonusers (0.042 per 1000), for a relative risk (RR) of 14.5 (95% confidence interval: 7.8-27.1; P < 0.001); the rate of stroke per 1000 woman-years was 0.17 in users and 0.036 in nonusers (RR = 4.6; 2.9-10.7; P < 0.01). A congenital thrombophilia involving the protein C anticoagulant system was documented in about 25% of young women developing venous thromboembolism while on OCs.
- Published
- 1996
89. Natural history and risk factors for thrombosis in 360 patients with antiphospholipid antibodies: a four-year prospective study from the Italian Registry.
- Author
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Finazzi G, Brancaccio V, Moia M, Ciaverella N, Mazzucconi MG, Schinco PC, Ruggeri M, Pogliani EM, Gamba G, Rossi E, Baudo F, Manotti C, D'Angelo A, Palareti G, De Stefano V, Berrettini M, and Barbui T
- Subjects
- Adolescent, Adult, Aged, Antibodies, Anticardiolipin analysis, Anticoagulants therapeutic use, Cause of Death, Child, Child, Preschool, Cohort Studies, Female, Follow-Up Studies, Humans, Immunoglobulin G analysis, Incidence, Logistic Models, Male, Middle Aged, Pregnancy, Prospective Studies, Risk Factors, Thrombosis epidemiology, Thrombosis immunology, Time Factors, Warfarin therapeutic use, Antibodies, Antiphospholipid analysis, Thrombosis etiology
- Abstract
Purpose: To assess the natural history and risk factors for thrombosis in a large cohort of unselected patients with antiphospholipid antibodies., Patients and Methods: Three hundred sixty consecutive patients (118 males, 242 females, median age 39 years [range 2 to 78]) fulfilling the currently accepted criteria for diagnosis of lupus anticoagulant (LAC) (n = 326) and/or raised immunoglobulin G anticardiolipin antibodies (IgG ACA) (n = 185) were collected from 16 Italian institutions and prospectively observed for a median of 3.9 years (range 0.5 to 5). Main endpoints were the occurrence of arterial or venous thrombosis, the outcome of pregnancies, and any severe complications leading to hospitalization or death., Results: Thirty-four patients developed a thrombotic complication, with a total incidence of 2.5% patient-years. Multivariate logistic regression analysis identified two independent risk factors for thrombotic events: a previous thrombosis (RR 4.9; 95% CI, 1.76 to 13.7; P < 0.005) and IgG ACA titer above 40 units (RR 3.66; 95% CI, 1.24 to 10.8; P < 0.01). A total of 28 pregnancies were observed in 25 women and 11 (39%) were abortive. Adverse pregnancy outcomes were significantly more frequent in women with a history of miscarriage or vascular occlusion (9/16, 56%) than in asymptomatic women (2/12, 17%) (P = 0.035). Four patients developed non-Hodgkin's lymphoma during the follow-up. Eighteen patients died. Vascular events and hematological malignancies represented the most frequent causes of death (n = 5 for each)., Conclusions: The present study shows that: (a) previous thrombosis and ACA titer > 40 U are independent predictors of thrombosis; (b) history of miscarriage or vascular disease is significantly associated with adverse pregnancy outcome; (c) hematological malignancies can develop during follow-up in patients with antiphospholipid antibodies.
- Published
- 1996
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90. An acquired hemorrhagic disorder of fibrin crosslinking due to IgG antibodies to FXIII, successfully treated with FXIII replacement and cyclophosphamide.
- Author
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Tosetto A, Rodeghiero F, Gatto E, Manotti C, and Poli T
- Subjects
- Aged, Aged, 80 and over, Drug Therapy, Combination, Factor XIII immunology, Factor XIII physiology, Factor XIII Deficiency complications, Factor XIII Deficiency immunology, Female, Fibrin physiology, Humans, Immunoglobulin G immunology, Cyclophosphamide therapeutic use, Factor XIII therapeutic use, Factor XIII Deficiency drug therapy, Fibrin antagonists & inhibitors, Hematoma drug therapy, Hematoma etiology
- Abstract
We report a new case of severe bleeding diathesis due to an acquired inhibitor of fibrin crosslinking. The patient, an 80-year-old woman, was admitted to the hospital for a massive subcutaneous hematoma, with severe anemia requiring red cell transfusion; a subsequent retroperitoneal hematoma developed 2 weeks later. Coagulation studies were normal except for a thromboelastographic pattern suggestive of FXIII deficiency. Clot solubility test was abnormal even after 1:1 mix with normal plasma. Immunochemical studies confirmed the presence of a monoclonal IgG lambda inhibitor directed against FXIII activity (type II FXIII inhibitor). The patient IgG fraction selectively inhibited FXIII transamidating activity but did not inhibit the thrombin-mediated activation of FXIII. The patient was treated with high doses of FXIII concentrate to overcome the inhibitor and immunosuppressive therapy with cyclophosphamide and discharged in good conditions. High doses of commercially available FXIII appear to be a safe and effective method of controlling acute episodes of bleeding in patients with acquired FXIII deficiency.
- Published
- 1995
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91. Seasonal variation of oral anticoagulant effect.
- Author
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Manotti C, Quintavalla R, Pattacini C, and Pini M
- Subjects
- Administration, Oral, Diet, Humans, Retrospective Studies, Acenocoumarol pharmacology, Seasons
- Published
- 1994
92. A comparative study on the quality of oral anticoagulant therapy (warfarin versus acenocoumarol).
- Author
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Pattacini C, Manotti C, Pini M, Quintavalla R, and Dettori AG
- Subjects
- Acenocoumarol adverse effects, Acenocoumarol standards, Administration, Oral, Aged, Case-Control Studies, Female, Humans, Male, Middle Aged, Quality Control, Retrospective Studies, Safety, Time Factors, Warfarin adverse effects, Warfarin standards, Acenocoumarol administration & dosage, Warfarin administration & dosage
- Abstract
In our Center for the Surveillance of Anticoagulant Treatment, most of the 1700 patients followed-up are traditionally treated with acenocoumarol, while warfarin is administered nowadays to an increasing proportion of patients. To assess if the difference in the pharmacokinetics of these two drugs may determine a different laboratory quality of treatment, a retrospective study was performed on the computerized files of all 142 patients on treatment with warfarin for more than 100 days and on a control group of 142 patients treated with acenocoumarol, matched for age, sex, disease state and duration of oral anticoagulant therapy (OAT). The study considered 7071 assays for a total of 432 patient-years of treatment. The overall quality of treatment was significantly better in patients treated with warfarin (72% of controls within the therapeutic range versus 67% on acenocoumarol, p < 0.001). Also the individual quality of therapy, which was assessed as the percentage of patients with 75% or more assays in range, was in favour of warfarin (50.7% vs 34.5%, p < 0.05). Warfarin therapy was more stable and fewer assays were required for treatment monitoring. Confounding factors possibly influencing the treatment stability, such as interfering drugs, diagnostic or therapeutical procedures requiring withdrawal of anticoagulation, were evaluated and no significant difference between the two groups was found. The difference in the laboratory quality of OAT was marked in patients treated for prevention of arterial thromboembolism, while it was negligible in patients with venous thromboembolic disease, whose mean duration of OAT was considerably shorter. Since there is no evidence that acenocoumarol is more efficacious or safer than warfarin, the latter seems to be preferable for patients who are candidate to very prolonged OAT.
- Published
- 1994
93. Pharmacological activity of a low molecular weight dermatan sulfate (desmin) in healthy volunteers.
- Author
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Dettori AG, Galli G, Manotti C, and Palazzini E
- Subjects
- Adolescent, Adult, Blood Coagulation drug effects, Desmin administration & dosage, Desmin pharmacokinetics, Dose-Response Relationship, Drug, Drug Administration Schedule, Drug Evaluation, Female, Fibrinolysis drug effects, Humans, Injections, Intramuscular, Injections, Intravenous, Injections, Subcutaneous, Male, Middle Aged, Molecular Weight, Reference Values, Desmin pharmacology
- Published
- 1994
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94. Variation in hemostatic parameters after intra-arterial and intravenous administration of iodinated contrast media.
- Author
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Manotti C, Quintavalla R, Ugolotti U, Del Favero C, and Dettori AG
- Subjects
- Angiography, Digital Subtraction, Antithrombin III analysis, Blood Coagulation Tests, Brain diagnostic imaging, Fibrinogen analysis, Fibrinopeptide A analysis, Humans, Injections, Intra-Arterial, Injections, Intravenous, Iopamidol pharmacology, Ioxaglic Acid pharmacology, Leg blood supply, Peptide Hydrolases analysis, Plasminogen Activator Inhibitor 1 blood, Tissue Plasminogen Activator blood, Tomography, X-Ray Computed, Hemostasis drug effects, Iopamidol administration & dosage, Ioxaglic Acid administration & dosage
- Abstract
Rationale and Objectives: A few case reports have suggested a possible thrombogenic effect of nonionic contrast media. In vitro investigations have lead to conflicting results. The authors performed three ex vivo studies to evaluate the influence of an ionic, ioxaglate, and a nonionic, iopamidol, low-osmolality contrast medium on a series of clotting and fibrinolytic parameters, after intravenous or intra-arterial administration, during routine diagnostic procedures., Methods: In the first study, iopamidol was given to 20 consecutive patients through an arterial catheter for digital subtraction arteriography (DSA). In the second study, iopamidol was compared with ioxaglate. The media were randomly and blindly administered intravenously to 21 consecutive patients undergoing brain computed tomography (CT). Finally, ioxaglate was administered intra-arterially to 20 consecutive patients, in a situation comparable with that of the first study., Results: In the first study, a weak anticoagulant effect and an activation of fibrinolysis were found, associated with indirect markers of thrombin generation, such as increased plasma levels of fibrinopeptide A (FpA) and thrombin-antithrombin III complexes (TAT). In the second study, no significant changes were seen with either contrast medium, for thrombin or fibrinolysis activation parameters. In the third study, the intra-arterially administered contrast medium elicited a marked increase of FpA and TAT, together with an anticoagulant effect., Conclusion: Both ionic and nonionic contrast media are able to interfere with the clotting/fibrinolytic system in the general circulation when they are administered to patients at the usual dosages. Ioxaglate shows more marked anticoagulant and thrombin-generating effects than iopamidol. The procedure (ie, arterial catheter versus intravenous infusion) seems to be more important than the category of contrast medium in conditioning the magnitude of these effects.
- Published
- 1992
- Full Text
- View/download PDF
95. Warfarin induced dermatitis and venous thrombosis in a patient with Protein S deficiency.
- Author
-
Quintavalla R, Pini M, Manotti C, and Pattacini C
- Subjects
- Aged, Creatine Kinase blood, Humans, Male, Phlebography, Protein S, Thrombophlebitis diagnostic imaging, Blood Proteins deficiency, Drug Eruptions etiology, Glycoproteins deficiency, Thrombophlebitis chemically induced, Warfarin adverse effects
- Abstract
A case of warfarin-induced dermatitis in a 79 year-old patient with Protein S deficiency is described. Both total Protein S antigen and free Protein S were moderately reduced (about 50%). The skin lesion did not progress to frank necrosis and it was associated with elevated creatin phosphokinase (CPK) levels in plasma and with thrombosis of the anterior tibial vein localized to the area of dermatitis (probably warfarin-induced deep venous thrombosis). After warfarin withdrawal and beginning of heparin therapy, serum CPK rapidly normalized and the skin lesion improved.
- Published
- 1991
96. [Oral anticoagulants and antiaggregants in heart valve prostheses].
- Author
-
Dettori AG and Manotti C
- Subjects
- Anticoagulants adverse effects, Endocarditis etiology, Humans, Platelet Aggregation Inhibitors adverse effects, Thromboembolism etiology, Thromboembolism prevention & control, Anticoagulants therapeutic use, Heart Valve Prosthesis adverse effects, Platelet Aggregation Inhibitors therapeutic use
- Published
- 1990
97. A computerized regulation of dosage in oral anticoagulant therapy.
- Author
-
Mariani G, Manotti C, and Dettori AG
- Subjects
- Administration, Oral, Follow-Up Studies, Humans, Prothrombin Time, Software, Anticoagulants administration & dosage, Drug Therapy, Computer-Assisted, Therapy, Computer-Assisted
- Abstract
The results of a cooperative study on the quality of treatment of patients with prosthetic heart valves (PHV) on long-term oral anticoagulants (OA) are reported. The study was carried out on 695 patients bearing PHV (with an overall 8,340 checks carried out in 1988) through a computer-assisted system for monitoring the laboratory and treatment follow-up. The specifications of the software are described in detail in the text. The mean INR slightly differed in the two participating centers (Rome and Parma) (3.25 vs 3.19) as did the weekly mean dosage (18.2 vs 20.7 mg) of oral anticoagulant, which was always Acenocoumarol. More than 70% of the checks were within the range in both centers as evaluated by a check randomly chosen once a month for each single patient. Considering the whole bunch of data, about 80% of the patients had greater than 50% of their checks within the therapeutic range and more than 30% had greater than 75% of the checks within the range. This study demonstrates that the availability of a computerized program for monitoring oral anticoagulant therapy allows to perform multicenter studies and to obtain data which can improve the quality of treatment of patients on OA.
- Published
- 1990
98. Pregnancy, antithrombin III deficiency and venous thrombosis: report of another case.
- Author
-
Megha A, Finzi G, Poli T, Manotti C, and Dettori AG
- Subjects
- Acenocoumarol administration & dosage, Antithrombin III administration & dosage, Drug Therapy, Combination, Female, Heparin administration & dosage, Humans, Pregnancy, Recurrence, Antithrombin III Deficiency, Pregnancy Complications, Hematologic drug therapy, Thrombophlebitis drug therapy
- Published
- 1990
- Full Text
- View/download PDF
99. Human platelet aggregation tests in vitro. Effects of dilazep.
- Author
-
Ponari O and Manotti C
- Subjects
- Adenosine Diphosphate antagonists & inhibitors, Blood Coagulation, Clot Retraction, Collagen antagonists & inhibitors, Epinephrine antagonists & inhibitors, Fibrinolysis drug effects, Hemostasis drug effects, Humans, In Vitro Techniques, Azepines pharmacology, Dilazep pharmacology, Platelet Aggregation drug effects
- Abstract
The effect of 1,4-bis-[3(3,4,,5-trimethoxybenzoyl-oxy)-propyl]-perhydro-1,4-diazepine (dilazep, Cormelian), a coronaroactive drug, was studied by various tests of hemostasis in vitro on human plasma. The antiplatelet action of the drug was clearly demonstrated: it inhibited, in appropriate concentrations, ADP, adrenaline and collagen induced aggregation platelet factor 3 (PF3) availability and clot retraction induced by ADP-reptilase. Conversely, coagulation tests as well as the lysis time of diluted whole blood were unaffected by the drug.
- Published
- 1981
100. [Increased blood level of factor VIII. A critical review (author's transl)].
- Author
-
Ponari O and Manotti C
- Subjects
- Blood Coagulation drug effects, Catecholamines adverse effects, Contraceptives, Oral adverse effects, Delivery, Obstetric, Female, Humans, Immune System Diseases complications, Insulin adverse effects, Kidney Diseases complications, Liver Diseases complications, Nicotinic Acids adverse effects, Physical Exertion, Pregnancy, Pregnancy Complications, Surgical Procedures, Operative adverse effects, Vasopressins adverse effects, Blood Coagulation Disorders etiology, Factor VIII
- Published
- 1981
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