Background The optimal duration of oral anticoagulation in patients with idiopathic venous thromb... more Background The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of d-dimer levels may play a role in the assessment of the need for prolonged anticoagulation. Methods
The choice to recommend antithrombotic therapy to patients with atrial fibrillation should rely o... more The choice to recommend antithrombotic therapy to patients with atrial fibrillation should rely on cardioembolic and bleeding risk stratification. Sharing some risk factors, schemes to predict thrombotic and bleeding risk are expected not to be independent, yet the degree of their association has never been clearly quantified. We described the cardioembolic (Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack [CHADS2]/Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack, Vascular disease, Age 65-75, Sex category i.e. females [CHA2DS2-VASc]) and bleeding risk (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly [HAS-BLED]) co-distribution among patients of the Euro Heart Survey on atrial fibrillation. We measured the within-patient...
Journal of thrombosis and haemostasis : JTH, Jan 7, 2015
In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to t... more In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. The ability of the VPM to distinguish patients' risk for recurrent VTE in the valida...
Haemophilia : the official journal of the World Federation of Hemophilia, 2014
People with haemophilia face many treatment decisions, which are largely informed by evidence fro... more People with haemophilia face many treatment decisions, which are largely informed by evidence from observational studies. Without evidence-based 'best' treatment options, patient preferences play a large role in decisions regarding therapy. The shared decision-making (SDM) process allows patients and health care providers to make decisions collaboratively based on available evidence, and patient preferences. Decision tools can help the SDM process. The objective of this project was to develop two-sided decision tools, decision boxes for physicians and patient decision aids for patients, to facilitate SDM for treatment decisions in haemophilia. Development of the decision tools comprised three phases: topic selection, prototype development and usability testing with targeted end-users. Topics were selected using a Delphi survey. Tool prototypes were based on a previously validated framework and were informed by systematic literature reviews. Patients, through focus groups, an...
Haemophilia : the official journal of the World Federation of Hemophilia, 2014
Although many aspects of inhibitor development have been elucidated, the role of switching FVIII ... more Although many aspects of inhibitor development have been elucidated, the role of switching FVIII product concentrate in the risk of inhibitors development in previously treated patients is still under discussion. To provide their contribution, Aznar et al [9] transparently showed the numerous different brands used over time and the number of patients treated with one or another class of concentrates in their center. This way of inclusively reporting data as generated in routine clinical practice would need to be adopted more broadly among hemophilia treater and scientists. Strength and limitations of the approach are discussed.
Haemophilia : the official journal of the World Federation of Hemophilia, 2014
A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effecti... more A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effectiveness of rAHF-PFM (ADVATE) use in haemophilia patients in routine clinical settings. The main aim of this project was to estimate the rate of inhibitors and other adverse events across ADVATE-PASS studies by meta-analysing individual patient data (IPD). Eligible Studies: PASS studies conducted in different countries, between 2003 and 2013, for which IPD were provided. Eligible patients: haemophilia A patients with baseline FVIII:C < 5%, with a known number of prior exposure days (EDs). de novo inhibitors in severe, previously treated patients (PTPs) with > 150 EDs. de novo inhibitors according to prior exposure and disease severity; other adverse events; annualized bleeding rate (ABR). random-effects logistic regression. Five of seven registered ADVATE-PASS (Australia, Europe, Japan, Italy and USA) and 1188 patients were included (median follow-up 384 days). Among severe PTPs with...
High-quality evidence is lacking in several areas of haemophilia treatment, in part because littl... more High-quality evidence is lacking in several areas of haemophilia treatment, in part because little time is allocated to the treatment and care of haemophilia in university education in Italy. Physicians caring for patients with haemophilia must, therefore, rely on their information on background pathophysiology and more experienced colleagues. This makes diagnostic and therapeutic choices difficult, especially when the patient has concomitant disorders or psychological issues. This article describes a course to educate young physicians who were already engaged in the management of haemophilia on the emerging and unmet issues of haemophilia care and to implement existing guidelines. Physicians (n=53) already caring for patients with haemophilia in their haematology, internal medicine, or paediatric practices in Italy attended the course. Problem-solving group activity and open discussion were the methods chosen to formulate consensus statements. During the specifically designed inter...
Current treatment options in cardiovascular medicine, 2013
The management of patients with unprovoked venous thromboembolism is a common and challenging cli... more The management of patients with unprovoked venous thromboembolism is a common and challenging clinical problem. Although the initial antithrombotic management is well-established, there is uncertainty about the optimal long-term anticoagulant management, specifically whether patients should receive a short (i.e., 3- to 6-month) duration of anticoagulant therapy or indefinite anticoagulation. Factors that may be considered to estimate patients' risk for recurrent thromboembolism include the mode of initial clinical presentation, as deep vein thrombosis or pulmonary embolism, patient sex, antecedent hormonal therapy use, thrombophilia, D-dimer levels, and residual vein occlusion in patients with deep vein thrombosis. Many of these factors have been integrated into clinical prediction guides which stratify patients with unprovoked venous thromboembolism according to their risk for disease recurrence and, thereby, can assist clinicians in decisions about the duration of anticoagulat...
Only very few pharmacokinetic (PK) studies comparing plasma derived FVIII (pd-FVIII) against reco... more Only very few pharmacokinetic (PK) studies comparing plasma derived FVIII (pd-FVIII) against recombinant FVIII (rFVIII) concentrates are available. The studies have been generally conducted to demonstrate the bioequivalence of a new product with an old one. The switch from a plasma-derived FVIII (pd-FVIII) to a rFVIII concentrate is a good moment to enrol the patients in a comparative PK study. To achieve information on the PK characteristics of two different classes of FVIII concentrates, according to two different designs: a 10 FVIII concentration/time point design and a reduced 4-point design. A single dose PK comparing pd- and rFVIII concentrates has been performed in four Haemophilia Centres of Italy. Seventeen haemophilia A patients underwent two subsequent single dose PK studies at the moment of switching. Two-compartment- and Non-compartment-analysis did not show significant differences between the outcomes of PK of pd-FVIII and rFVIII, due to inter-patient variability. In vivo recovery (IVR) of rFVIII was slightly higher than that of pd-FVIII and rFVIII/pd-FVIII AUC ratio was 1.37 in 11/17 patients. The difference is only due to the initial distribution phase because after the first 10 h from the end of the infusion, the two decay curves are overlapping. The elimination half-life of the concentrates was very similar even though a complete bioequivalence was not demonstrated because of a higher AUC of rFVIII concentrates, limited to the distribution phase. The higher Cmax and IVR of rFVIII may be due to the presence of heterodimers activated forms of the recombinant molecules.
The in vivo recovery of recombinant factor IX (rFIX) is reported to be lower than that of plasma-... more The in vivo recovery of recombinant factor IX (rFIX) is reported to be lower than that of plasma-derived products, with potential clinical implications for dosing. In clinical practice, a conversion (augmentation) factor is suggested to calculate the necessary doses of rFIX. The aim of this study was to assess the range of values for the conversion factor in usual clinical practice in Italy. The study was questionnaire-based and proposed to all Italian Haemophilia centres treating patients with haemophilia B. Age, weight, dosage used in the last effective infusion, treatment regimen (prophylaxis versus on-demand), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) status, and years of previous therapy with rFIX were recorded for patients with severe haemophilia B treated with rFIX. Mean, standard deviation, median and range were calculated for demographic and treatment data for the overall population and for subgroups. The conversion factor for the theoretical dosage of ...
Fresh-frozen plasma (FFP) is unanimously recognised by international guidelines as the blood comp... more Fresh-frozen plasma (FFP) is unanimously recognised by international guidelines as the blood component of choice for the management of acute haemorrhage when accompanied by disorders of haemostasis, for disseminated intravascular coagulation in the presence of haemorrhage, for rare bleeding disorders when specific clotting factor concentrates are not available and for thrombotic thrombocytopenic purpura. The literature, however, reports a high percentage of inappropriate requests for FFP. This article presents the results of a pilot study of clinical auditing of the use of FFP in the Region of Umbria (Italy). This study was based on the examination of the requests for FFP made in April 2006 to four Immunotransfusion Services (ITS) in Umbria and of the clinical records of the patients receiving transfusions. The following indicators were identified and evaluated: completeness of the request, appropriateness of the indication and the dose, completeness of the records in the clinical c...
The clinical use of fresh-frozen plasma (FFP) is progressively increasing both nationally and int... more The clinical use of fresh-frozen plasma (FFP) is progressively increasing both nationally and internationally, despite the fact that many studies have shown the weaknesses of the indications for its use. Guidelines on the good use of plasma have, therefore, been adopted in various countries. The aim of the present study was to analyse some of the existing guidelines on the good use of plasma, applying a scientifically validated method, as a preliminary step in the implementation of Regional guidelines. Abibliographic search (1990-2006) was conducted in databases, websites, and the archives of scientific societies. Relevant articles were recovered in full. The selected guidelines were evaluated using theAGREE instrument, which assesses the completeness and structural quality of the guidelines and, in some aspects, the contents of the recommendations. The project, co-ordinated by the Regional Centre for Co-ordination and Compensation (CRCC) and carried out by four Services of Immunoha...
A high incidence of post-discharge venous thromboembolism in orthopaedic surgery patients has bee... more A high incidence of post-discharge venous thromboembolism in orthopaedic surgery patients has been recently reported drawing further attention to the unresolved issue of the optimal duration of the pharmacological prophylaxis. We performed an overview analysis in order to evaluate the incidence of late occurring clinically overt venous thromboembolism in major orthopaedic surgery patients discharged from the hospital with a negative venography and without further pharmacological prophylaxis. We selected the studies published from January 1974 to December 1995 on the prophylaxis of venous thromboembolism after major orthopaedic surgery fulfilling the following criteria: 1) adoption of pharmacological prophylaxis, 2) performing of a bilateral venography before discharge, 3) interruption of pharmacological prophylaxis at discharge in patients with negative venography, and 4) post-discharge follow-up of the patients for at least four weeks. Out of 31 identified studies, 13 fulfilled the...
The Journal of laboratory and clinical medicine, 1995
The natural history of acute myocardial infarction has been dramatically changed by the advent of... more The natural history of acute myocardial infarction has been dramatically changed by the advent of thrombolytic treatment, with a 30% mortality reduction, a better recovery of ventricular function, and a better quality of life. This treatment notwithstanding, failure or delay in achieving reperfusion, along with reocclusion and bleeding, still worry clinicians and challenge researchers to improve thrombolytic regimens and concomitant antithrombotic treatments. Platelet activation, at least in part because of thrombolytic treatment itself, plays a pivotal role in the pathogenesis of resistance to lysis and rethrombosis. The aim of this study was to compare in vitro the effects on platelets of therapeutic concentrations of streptokinase (SK) and recombinant type plasminogen activator (rt-PA). The effects of plasmin and thrombin were also studied as a reference. Fluorescence flow cytometry was used to evaluate (1) fibrinogen binding and (2) surface expression of GMP-140, a sensitive mar...
... assay. ▪ Moroctocog alfa Pharmacokinetics During the licensing process of moroctocog alfa in ... more ... assay. ▪ Moroctocog alfa Pharmacokinetics During the licensing process of moroctocog alfa in 1999, a set of studies demonstrated the efficacy, safety and pharmacokinetic characteristics of moroctocog alfa [2022]. The two ...
Inhibitor development represents the most serious side effect of haemophilia treatment. Any diffe... more Inhibitor development represents the most serious side effect of haemophilia treatment. Any difference in risk of inhibitor formation depending on the product used might be of clinical relevance. It was this study's objective to assess inhibitor development according to clotting factor concentrate in severe haemophilia A and B. The European Haemophilia Safety Surveillance (EUHASS) was set up as a study monitoring adverse events overall and according to concentrate. Since October 2008, inhibitors were reported at least quarterly. Number of treated patients was reported annually, specifying the number of patients completing 50 exposure days (Previously Untreated Patients, PUPs) without inhibitor development. Cumulative incidence, incidence rates and 95 % confidence intervals (CI) were calculated. Data from October 1, 2008 to December 31, 2012 were analysed for 68 centres that validated their data. Inhibitors developed in 108/417 (26 %; CI 22-30 %) PUPs with severe haemophilia A an...
The development of alloantibodies or inhibitors is the most serious complication a patient with s... more The development of alloantibodies or inhibitors is the most serious complication a patient with severe hemophilia can experience from treatment with clotting factor concentrates. Although common in previously untreated patients, inhibitor development is rare in multiply exposed, well-tolerized patients. There has been a nonevidence-based reluctance to change concentrate because of a perceived greater inhibitor risk after the switch, even though most patients are now likely to be using a concentrate on which they did not begin. Inhibitors in previously treated patients are observed in approximately 2 per 1000 patient/years, which makes it difficult to study and compare rates among different products. Because the baseline inhibitor risk in previously treated patients may vary over time, it is important to compare the risk in patients switching to a new product with that in a parallel control group of nonswitching patients or within a case-controlled study. The study designs imposed by...
The prevalence of cardiovascular disease (CVD) risk and events in patients with haemophilia (PWH)... more The prevalence of cardiovascular disease (CVD) risk and events in patients with haemophilia (PWH) is expected to increase as the longevity of this cohort increases due to treatment advances since the 1950s. The aims of this study were to assess publications of CVD and haemophilia for robustness, determine if the increasing longevity of PWH and associated age-related CVD risk factors result in CVD events; assess the need for an extension of the circle of care for ageing PWH due to the shift in comorbidities. A scoping review was conducted, resulting in a final pool of 30 articles which were organized based on publication dates. A matrix was created to illustrate which articles cited articles published prior to its own publication. This led to the identification of the primary articles, receiving the highest number of citations by other publications, which drive the research pertaining to the study of age-related risk factors of CVD in PWH. The scoping review revealed 14 original articles, four of which indicated a protective effect of haemophilia toward CVD. Twelve articles demonstrated a similar prevalence of CVD in PWH compared to the general population while seven articles concluded a difference in the prevalence of CVD in the ageing haemophilia population. The existing literature presented conflicting evidence regarding the possibility of a protective effect of haemophilia against CVD. The scoping review was not able to finalize whether the longevity of PWH and their associated age-related CVD risk factors result in CVD events because the articles assessed reported conflicting results.
... Pharmacoeconomics 1998; 13:667ą76. 6 Richardson PH, Vincent CA. ... 9 Patel MS, Gutzwiller F,... more ... Pharmacoeconomics 1998; 13:667ą76. 6 Richardson PH, Vincent CA. ... 9 Patel MS, Gutzwiller F, Paccaud F, Marazzi A. A meta-analysis of acupuncture for chronic pain. Int J Epidemiol 1989; 18:900ą 6. 10 Ter Riet G, Kleijnen J, Knipschild P. Acupuntuur en chronische pijn. ...
Background The optimal duration of oral anticoagulation in patients with idiopathic venous thromb... more Background The optimal duration of oral anticoagulation in patients with idiopathic venous thromboembolism is uncertain. Testing of d-dimer levels may play a role in the assessment of the need for prolonged anticoagulation. Methods
The choice to recommend antithrombotic therapy to patients with atrial fibrillation should rely o... more The choice to recommend antithrombotic therapy to patients with atrial fibrillation should rely on cardioembolic and bleeding risk stratification. Sharing some risk factors, schemes to predict thrombotic and bleeding risk are expected not to be independent, yet the degree of their association has never been clearly quantified. We described the cardioembolic (Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack [CHADS2]/Congestive heart failure, Hypertension, Age >75, Diabetes mellitus, and prior Stroke or transient ischemic attack, Vascular disease, Age 65-75, Sex category i.e. females [CHA2DS2-VASc]) and bleeding risk (Hypertension, Abnormal renal/liver function, Stroke, Bleeding history or predisposition, Labile international normalized ratio, Elderly (>65 years), Drugs/alcohol concomitantly [HAS-BLED]) co-distribution among patients of the Euro Heart Survey on atrial fibrillation. We measured the within-patient...
Journal of thrombosis and haemostasis : JTH, Jan 7, 2015
In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to t... more In order to stratify patients with a first unprovoked venous thromboembolism (VTE) according to their recurrence risk and to identify those who would actually benefit from indefinite anticoagulation, three prediction models have been developed so far; none of them has been yet externally validated. To externally validate the Vienna Prediction Model (VPM), a prediction guide for estimating the recurrence risk after a first unprovoked VTE developed through Cox modeling and including sex, D-dimer and index VTE site as predictors. Nine hundred and four patients pooled from five prospective studies evaluating the prognostic value of D-dimer for VTE recurrence served as the validation cohort. The validity of the VPM in stratifying patients according to their relative recurrence risk (discrimination) and in predicting the absolute recurrence risk (calibration) was tested with survival analysis methods. The ability of the VPM to distinguish patients' risk for recurrent VTE in the valida...
Haemophilia : the official journal of the World Federation of Hemophilia, 2014
People with haemophilia face many treatment decisions, which are largely informed by evidence fro... more People with haemophilia face many treatment decisions, which are largely informed by evidence from observational studies. Without evidence-based 'best' treatment options, patient preferences play a large role in decisions regarding therapy. The shared decision-making (SDM) process allows patients and health care providers to make decisions collaboratively based on available evidence, and patient preferences. Decision tools can help the SDM process. The objective of this project was to develop two-sided decision tools, decision boxes for physicians and patient decision aids for patients, to facilitate SDM for treatment decisions in haemophilia. Development of the decision tools comprised three phases: topic selection, prototype development and usability testing with targeted end-users. Topics were selected using a Delphi survey. Tool prototypes were based on a previously validated framework and were informed by systematic literature reviews. Patients, through focus groups, an...
Haemophilia : the official journal of the World Federation of Hemophilia, 2014
Although many aspects of inhibitor development have been elucidated, the role of switching FVIII ... more Although many aspects of inhibitor development have been elucidated, the role of switching FVIII product concentrate in the risk of inhibitors development in previously treated patients is still under discussion. To provide their contribution, Aznar et al [9] transparently showed the numerous different brands used over time and the number of patients treated with one or another class of concentrates in their center. This way of inclusively reporting data as generated in routine clinical practice would need to be adopted more broadly among hemophilia treater and scientists. Strength and limitations of the approach are discussed.
Haemophilia : the official journal of the World Federation of Hemophilia, 2014
A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effecti... more A Post-Authorization Safety Study (PASS) global program was designed to assess safety and effectiveness of rAHF-PFM (ADVATE) use in haemophilia patients in routine clinical settings. The main aim of this project was to estimate the rate of inhibitors and other adverse events across ADVATE-PASS studies by meta-analysing individual patient data (IPD). Eligible Studies: PASS studies conducted in different countries, between 2003 and 2013, for which IPD were provided. Eligible patients: haemophilia A patients with baseline FVIII:C < 5%, with a known number of prior exposure days (EDs). de novo inhibitors in severe, previously treated patients (PTPs) with > 150 EDs. de novo inhibitors according to prior exposure and disease severity; other adverse events; annualized bleeding rate (ABR). random-effects logistic regression. Five of seven registered ADVATE-PASS (Australia, Europe, Japan, Italy and USA) and 1188 patients were included (median follow-up 384 days). Among severe PTPs with...
High-quality evidence is lacking in several areas of haemophilia treatment, in part because littl... more High-quality evidence is lacking in several areas of haemophilia treatment, in part because little time is allocated to the treatment and care of haemophilia in university education in Italy. Physicians caring for patients with haemophilia must, therefore, rely on their information on background pathophysiology and more experienced colleagues. This makes diagnostic and therapeutic choices difficult, especially when the patient has concomitant disorders or psychological issues. This article describes a course to educate young physicians who were already engaged in the management of haemophilia on the emerging and unmet issues of haemophilia care and to implement existing guidelines. Physicians (n=53) already caring for patients with haemophilia in their haematology, internal medicine, or paediatric practices in Italy attended the course. Problem-solving group activity and open discussion were the methods chosen to formulate consensus statements. During the specifically designed inter...
Current treatment options in cardiovascular medicine, 2013
The management of patients with unprovoked venous thromboembolism is a common and challenging cli... more The management of patients with unprovoked venous thromboembolism is a common and challenging clinical problem. Although the initial antithrombotic management is well-established, there is uncertainty about the optimal long-term anticoagulant management, specifically whether patients should receive a short (i.e., 3- to 6-month) duration of anticoagulant therapy or indefinite anticoagulation. Factors that may be considered to estimate patients' risk for recurrent thromboembolism include the mode of initial clinical presentation, as deep vein thrombosis or pulmonary embolism, patient sex, antecedent hormonal therapy use, thrombophilia, D-dimer levels, and residual vein occlusion in patients with deep vein thrombosis. Many of these factors have been integrated into clinical prediction guides which stratify patients with unprovoked venous thromboembolism according to their risk for disease recurrence and, thereby, can assist clinicians in decisions about the duration of anticoagulat...
Only very few pharmacokinetic (PK) studies comparing plasma derived FVIII (pd-FVIII) against reco... more Only very few pharmacokinetic (PK) studies comparing plasma derived FVIII (pd-FVIII) against recombinant FVIII (rFVIII) concentrates are available. The studies have been generally conducted to demonstrate the bioequivalence of a new product with an old one. The switch from a plasma-derived FVIII (pd-FVIII) to a rFVIII concentrate is a good moment to enrol the patients in a comparative PK study. To achieve information on the PK characteristics of two different classes of FVIII concentrates, according to two different designs: a 10 FVIII concentration/time point design and a reduced 4-point design. A single dose PK comparing pd- and rFVIII concentrates has been performed in four Haemophilia Centres of Italy. Seventeen haemophilia A patients underwent two subsequent single dose PK studies at the moment of switching. Two-compartment- and Non-compartment-analysis did not show significant differences between the outcomes of PK of pd-FVIII and rFVIII, due to inter-patient variability. In vivo recovery (IVR) of rFVIII was slightly higher than that of pd-FVIII and rFVIII/pd-FVIII AUC ratio was 1.37 in 11/17 patients. The difference is only due to the initial distribution phase because after the first 10 h from the end of the infusion, the two decay curves are overlapping. The elimination half-life of the concentrates was very similar even though a complete bioequivalence was not demonstrated because of a higher AUC of rFVIII concentrates, limited to the distribution phase. The higher Cmax and IVR of rFVIII may be due to the presence of heterodimers activated forms of the recombinant molecules.
The in vivo recovery of recombinant factor IX (rFIX) is reported to be lower than that of plasma-... more The in vivo recovery of recombinant factor IX (rFIX) is reported to be lower than that of plasma-derived products, with potential clinical implications for dosing. In clinical practice, a conversion (augmentation) factor is suggested to calculate the necessary doses of rFIX. The aim of this study was to assess the range of values for the conversion factor in usual clinical practice in Italy. The study was questionnaire-based and proposed to all Italian Haemophilia centres treating patients with haemophilia B. Age, weight, dosage used in the last effective infusion, treatment regimen (prophylaxis versus on-demand), human immunodeficiency virus (HIV) and hepatitis C virus (HCV) status, and years of previous therapy with rFIX were recorded for patients with severe haemophilia B treated with rFIX. Mean, standard deviation, median and range were calculated for demographic and treatment data for the overall population and for subgroups. The conversion factor for the theoretical dosage of ...
Fresh-frozen plasma (FFP) is unanimously recognised by international guidelines as the blood comp... more Fresh-frozen plasma (FFP) is unanimously recognised by international guidelines as the blood component of choice for the management of acute haemorrhage when accompanied by disorders of haemostasis, for disseminated intravascular coagulation in the presence of haemorrhage, for rare bleeding disorders when specific clotting factor concentrates are not available and for thrombotic thrombocytopenic purpura. The literature, however, reports a high percentage of inappropriate requests for FFP. This article presents the results of a pilot study of clinical auditing of the use of FFP in the Region of Umbria (Italy). This study was based on the examination of the requests for FFP made in April 2006 to four Immunotransfusion Services (ITS) in Umbria and of the clinical records of the patients receiving transfusions. The following indicators were identified and evaluated: completeness of the request, appropriateness of the indication and the dose, completeness of the records in the clinical c...
The clinical use of fresh-frozen plasma (FFP) is progressively increasing both nationally and int... more The clinical use of fresh-frozen plasma (FFP) is progressively increasing both nationally and internationally, despite the fact that many studies have shown the weaknesses of the indications for its use. Guidelines on the good use of plasma have, therefore, been adopted in various countries. The aim of the present study was to analyse some of the existing guidelines on the good use of plasma, applying a scientifically validated method, as a preliminary step in the implementation of Regional guidelines. Abibliographic search (1990-2006) was conducted in databases, websites, and the archives of scientific societies. Relevant articles were recovered in full. The selected guidelines were evaluated using theAGREE instrument, which assesses the completeness and structural quality of the guidelines and, in some aspects, the contents of the recommendations. The project, co-ordinated by the Regional Centre for Co-ordination and Compensation (CRCC) and carried out by four Services of Immunoha...
A high incidence of post-discharge venous thromboembolism in orthopaedic surgery patients has bee... more A high incidence of post-discharge venous thromboembolism in orthopaedic surgery patients has been recently reported drawing further attention to the unresolved issue of the optimal duration of the pharmacological prophylaxis. We performed an overview analysis in order to evaluate the incidence of late occurring clinically overt venous thromboembolism in major orthopaedic surgery patients discharged from the hospital with a negative venography and without further pharmacological prophylaxis. We selected the studies published from January 1974 to December 1995 on the prophylaxis of venous thromboembolism after major orthopaedic surgery fulfilling the following criteria: 1) adoption of pharmacological prophylaxis, 2) performing of a bilateral venography before discharge, 3) interruption of pharmacological prophylaxis at discharge in patients with negative venography, and 4) post-discharge follow-up of the patients for at least four weeks. Out of 31 identified studies, 13 fulfilled the...
The Journal of laboratory and clinical medicine, 1995
The natural history of acute myocardial infarction has been dramatically changed by the advent of... more The natural history of acute myocardial infarction has been dramatically changed by the advent of thrombolytic treatment, with a 30% mortality reduction, a better recovery of ventricular function, and a better quality of life. This treatment notwithstanding, failure or delay in achieving reperfusion, along with reocclusion and bleeding, still worry clinicians and challenge researchers to improve thrombolytic regimens and concomitant antithrombotic treatments. Platelet activation, at least in part because of thrombolytic treatment itself, plays a pivotal role in the pathogenesis of resistance to lysis and rethrombosis. The aim of this study was to compare in vitro the effects on platelets of therapeutic concentrations of streptokinase (SK) and recombinant type plasminogen activator (rt-PA). The effects of plasmin and thrombin were also studied as a reference. Fluorescence flow cytometry was used to evaluate (1) fibrinogen binding and (2) surface expression of GMP-140, a sensitive mar...
... assay. ▪ Moroctocog alfa Pharmacokinetics During the licensing process of moroctocog alfa in ... more ... assay. ▪ Moroctocog alfa Pharmacokinetics During the licensing process of moroctocog alfa in 1999, a set of studies demonstrated the efficacy, safety and pharmacokinetic characteristics of moroctocog alfa [2022]. The two ...
Inhibitor development represents the most serious side effect of haemophilia treatment. Any diffe... more Inhibitor development represents the most serious side effect of haemophilia treatment. Any difference in risk of inhibitor formation depending on the product used might be of clinical relevance. It was this study's objective to assess inhibitor development according to clotting factor concentrate in severe haemophilia A and B. The European Haemophilia Safety Surveillance (EUHASS) was set up as a study monitoring adverse events overall and according to concentrate. Since October 2008, inhibitors were reported at least quarterly. Number of treated patients was reported annually, specifying the number of patients completing 50 exposure days (Previously Untreated Patients, PUPs) without inhibitor development. Cumulative incidence, incidence rates and 95 % confidence intervals (CI) were calculated. Data from October 1, 2008 to December 31, 2012 were analysed for 68 centres that validated their data. Inhibitors developed in 108/417 (26 %; CI 22-30 %) PUPs with severe haemophilia A an...
The development of alloantibodies or inhibitors is the most serious complication a patient with s... more The development of alloantibodies or inhibitors is the most serious complication a patient with severe hemophilia can experience from treatment with clotting factor concentrates. Although common in previously untreated patients, inhibitor development is rare in multiply exposed, well-tolerized patients. There has been a nonevidence-based reluctance to change concentrate because of a perceived greater inhibitor risk after the switch, even though most patients are now likely to be using a concentrate on which they did not begin. Inhibitors in previously treated patients are observed in approximately 2 per 1000 patient/years, which makes it difficult to study and compare rates among different products. Because the baseline inhibitor risk in previously treated patients may vary over time, it is important to compare the risk in patients switching to a new product with that in a parallel control group of nonswitching patients or within a case-controlled study. The study designs imposed by...
The prevalence of cardiovascular disease (CVD) risk and events in patients with haemophilia (PWH)... more The prevalence of cardiovascular disease (CVD) risk and events in patients with haemophilia (PWH) is expected to increase as the longevity of this cohort increases due to treatment advances since the 1950s. The aims of this study were to assess publications of CVD and haemophilia for robustness, determine if the increasing longevity of PWH and associated age-related CVD risk factors result in CVD events; assess the need for an extension of the circle of care for ageing PWH due to the shift in comorbidities. A scoping review was conducted, resulting in a final pool of 30 articles which were organized based on publication dates. A matrix was created to illustrate which articles cited articles published prior to its own publication. This led to the identification of the primary articles, receiving the highest number of citations by other publications, which drive the research pertaining to the study of age-related risk factors of CVD in PWH. The scoping review revealed 14 original articles, four of which indicated a protective effect of haemophilia toward CVD. Twelve articles demonstrated a similar prevalence of CVD in PWH compared to the general population while seven articles concluded a difference in the prevalence of CVD in the ageing haemophilia population. The existing literature presented conflicting evidence regarding the possibility of a protective effect of haemophilia against CVD. The scoping review was not able to finalize whether the longevity of PWH and their associated age-related CVD risk factors result in CVD events because the articles assessed reported conflicting results.
... Pharmacoeconomics 1998; 13:667ą76. 6 Richardson PH, Vincent CA. ... 9 Patel MS, Gutzwiller F,... more ... Pharmacoeconomics 1998; 13:667ą76. 6 Richardson PH, Vincent CA. ... 9 Patel MS, Gutzwiller F, Paccaud F, Marazzi A. A meta-analysis of acupuncture for chronic pain. Int J Epidemiol 1989; 18:900ą 6. 10 Ter Riet G, Kleijnen J, Knipschild P. Acupuntuur en chronische pijn. ...
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Papers by Alfonso Iorio