E. Zanon - Academia.edu (original) (raw)

Papers by E. Zanon

Research paper thumbnail of Emofilia acquisita: dalle criticità diagnostiche ad un corretto approccio terapeutico Acquired haemophilia: from critical diagnostic issues to correct therapeutic approach

Acquired haemophilia A is a rare disorder typically affecting older people and characterized by s... more Acquired haemophilia A is a rare disorder typically affecting older people and characterized by severe potentially life-threatening bleeding. Diagnostic delay and inadequate treatment are common. We describe two cases who were diagnosed and treated. We discuss critical steps in managing a patient with acquired hemophilia and provide orientation on best approach to diagnosis and treatment. INTRODUZIONE L'emofilia acquisita è una malattia caratterizza-ta da manifestazioni emorragiche improvvise in pazienti senza storia personale o familiare di di-sordini della coagulazione. È una condizione rara, con una incidenza di cir-ca 1,5 casi-per milione / anno; colpisce pazien-ti in età adulta o anziana (range 55-78 anni), senza distinzione di sesso, fatta eccezione per i casi di giovani donne nel post-partum 1. È dovuta alla presenza di auto-anticorpi specifi-camente diretti contro un fattore della coagula-zione che nel 95% dei casi è rappresentato dal FVIII. In circa il 50% dei casi non ...

Research paper thumbnail of Cerebrovascular diseases in hemophiliacs: A real, but underestimated risk

Haemophilia : the official journal of the World Federation of Hemophilia, Jan 21, 2017

Ischaemic heart disease and ischaemic stroke are the most important causes of death in the genera... more Ischaemic heart disease and ischaemic stroke are the most important causes of death in the general population, especially in developed countries. Usually, patients with haemophilia (PWH) are considered at low risk for these events because of their hypocoagulable state, but recent data revealed an unexpected risk of cardio-and cerebrovascular diseases in this population 1,2 as well. However, only a few cases of ischaemic strokes have been reported in PWH, though without detailed description. An occlusion of the sylvian artery in a patient with severe haemophilia B was cited by Luscher. 3 Six cases of cerebral thrombosis have been recorded by Girolami et al., 4 and four of them were ischaemic events. Wang et al. 2 collected data on 1054 PWH from 1997 to 2010 using a Taiwanese registry, finding 26 ischaemic strokes, a proportion comparable with those of normal subjects, whereas haemorrhagic stroke was seven times higher in the PWH. In this registry, it was also proved that the risk factors for atherosclerosis development, the first cause of thromboembolic injuries, had the same prevalence in both groups except for obesity, which was more frequent in PWH. Conversely, a very low estimated incidence was reported by Bezzina et al. 5 in their data collection on 2569 patients with haemophilia A, haemophilia B and von Willebrand disease from 52 centres in North and South America and in Europe. Over the 4.5

Research paper thumbnail of Controlled, cross-sectional MRI evaluation of joint status in severe haemophilia A patients treated with prophylaxis vs. on demand

Haemophilia : the official journal of the World Federation of Hemophilia, 2015

In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and jo... more In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and joint damage compared with on-demand therapy. To assess the effect of prophylaxis initiation age, magnetic resonance imaging (MRI) was used to evaluate bone and cartilage damage in patients with severe haemophilia A. In this cross-sectional, multinational investigation, patients aged 12-35 years were assigned to 1 of 5 groups: primary prophylaxis started at age <2 years (group 1); secondary prophylaxis started at age 2 to <6 years (group 2), 6 to <12 years (group 3), or 12-18 years (group 4); or on-demand treatment (group 5). Joint status at ankles and knees was assessed using Compatible Additive MRI scoring (maximum and mean ankle; maximum and mean of all 4 joints) and Gilbert scores in the per-protocol population (n = 118). All prophylaxis groups had better MRI joint scores than the on-demand group. MRI scores generally increased with current patient age and later start of proph...

Research paper thumbnail of Long-Term Use of Oral Contraceptive Therapy in Women With the Prothrombin 20210 G-A Polymorphism Without Thrombotic Complications: A Study of 13 Women (12 Heterozygotes and 1 Homozygote)

Thrombosis Research, 2001

Thirteen female patients with the prothrombin 20210 G-A abnormality (twelve heterozygotes and one... more Thirteen female patients with the prothrombin 20210 G-A abnormality (twelve heterozygotes and one homozygote) were selected out of 551 patients admitted to our Department of Medicine or to our Outpatient Hemostasis Units between January 1999 and October 2000. The selection was based on the fact that all patients had taken or were still taking oral contraceptives (OC) for a period of 3 years or longer than 3 years. None of these patents as gathered from history, physical examination, private physician records and our records has shown any DVT during or immediately after OC intake. Physical and compression ultrasonography examinations at the time of study were all negative. The average length of oral contraceptives therapy (OCT) was 10 years (range 3-23). The average age of patients at the time of oral contraception was 30 years. The 13 women had also 17 pregnancies without any venous thrombosis. The observations casts several doubt about the prothrombotic effect of this polymorphism. Since DVT has been shown to occur occasionally even in normal women, it is likely that the same may occur in women with this polymorphism regardless of the existence or not of any pathogenetic relationship between the two phenomena. Occasional reports suggesting a link between this polymorphism and oral contraception-related venous thrombosis should be carefully evaluated in order to avoid premature and incorrect conclusions.

Research paper thumbnail of Proposal of a standard approach to dental extraction in haemophilia patients. A case‐control study with good results

Haemophilia, 2000

We found no case–control studies on dental extraction in haemophilia patients in the literature e... more We found no case–control studies on dental extraction in haemophilia patients in the literature even though the use of antifibrinolytic agents following a single infusion of factor VIII or IX has been accompanied by a lower number of bleeding complications in dental extractions. In this study we verified the incidence of bleeding complications after dental extraction in a group of 77 haemophilia patients. One hundred and eighty‐four male patients requiring dental extraction represented the control group. All haemophilia patients received 20 mg kg–1 of tranexamic acid and a single infusion of factor VIII or IX to achieve a peak level about 30% of factor VIII or IX in vivo prior to dental extraction. Forty‐five of 98 (45.9%) dental extractions in haemophilia patients and 110 of 239 (46%) dental extractions in the control group were surgical ones. We registered two bleeding complications in the group of haemophilia patients (one late bleeding and one haematoma in the site of the anaest...

Research paper thumbnail of Efficacy and safety during formulation switch of a pasteurized VWF/FVIII concentrate: results from an Italian prospective observational study in patients with von Willebrand disease

Haemophilia, 2012

Von Willebrand disease (VWD) is an inherited bleeding disorder caused by the quantitative or qual... more Von Willebrand disease (VWD) is an inherited bleeding disorder caused by the quantitative or qualitative deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived VWF/factor VIII (FVIII) concentrates is required in patients unresponsive to desmopressin. To assess the efficacy, safety and ease of use of a new, volume-reduced (VR) formulation of VWF/FVIII concentrate Haemate ® P in patients requiring treatment for bleeding or prophylaxis for recurrent bleeding or for invasive procedures. Pharmacoeconomic variables were also recorded. Data were analysed using descriptive statistics. This was a multicentre, prospective, observational study. Consecutively enrolled patients received Haemate ® P VR according to their needs, and were followed for 24 months. Of the 121 patients enrolled, 25.6% had type 3 VWD and more than 40% had severe disease. All patients were followed for 2 years, for a total of 521 visits. Ondemand treatment was given to 61.9% of patients, secondary long-term prophylaxis to 25.6% and prophylaxis for surgery, dental or invasive procedures to 45.5%. The response to treatment was rated as good to excellent in >93-99% of interventions. The new formulation was well tolerated by all patients with no report of drug-related adverse events. The switch to volume-reduced Haemate ® P was easy to perform and infusion duration was decreased twofold compared with the previous formulation. Volume-reduced Haemate ® P was at least as effective and well-tolerated as the previous formulation.

Research paper thumbnail of Whole blood rotation thromboelastometry (ROTEM®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V

Haemophilia, 2011

The coagulation pattern and the determinants of portal vein thrombosis (PVT), both in patients wi... more The coagulation pattern and the determinants of portal vein thrombosis (PVT), both in patients with and without cirrhosis, are still largely unknown. The aim of this study was to evaluate whole blood thromboelastometry profile, performed by ROTEM®, of both cirrhotic and non-cirrhotic subjects with PVT. Two different groups were considered: i) 14 non-cirrhotic PVT patients, ii) 35 cirrhotic patients with PVT. Controls were sex-and age-matched healthy volunteers and cirrhotic subjects without PVT, respectively. ROTEM® assays (i.e. INTEM, EXTEM, NATEM, and FIBTEM) and traditional coagulative parameters (i.e. platelet count, PT/INR, aPTT, and fibrinogen) were performed on blood samples from each subject. There were no significant differences in ROTEM® profile, as for INTEM, EXTEM, and NATEM assays, and in traditional coagulative parameters, between PVT patients, both with and without cirrhosis, and control groups. Interestingly, Maximum Clot Firmness (MCF) in FIBTEM was significantly higher in non-cirrhotic PVT patients (19 mm) than in healthy volunteers (11 mm, p b 0.05). The amplitude of MCF in FIBTEM revealed to be a useful tool to discriminate non-cirrhotic subjects with PVT from those without thrombotic events. Larger prospective studies are needed to evaluate the relevance of the association between the alterations of ROTEM® profiles and PVT in cirrhotic patients.

Research paper thumbnail of Prevalence of Antiphospholipid Antibodies and Lupus Anticoagulant in Juvenile Patients with Objectively Documented Deep-vein Thrombosis

Clinical and Applied Thrombosis/Hemostasis, 1996

The reported prevalence of antiphospholipid antibodies in women with a chief complaint of pregnan... more The reported prevalence of antiphospholipid antibodies in women with a chief complaint of pregnancy loss varies, as does the risk of adverse outcomes in subsequent pregnancies. Our objectives were to assess the prevalence of antiphospholipid antibodies meeting revised Sapporo thresholds among women presenting with a chief complaint of pregnancy loss and risks in subsequent pregnancies for these women. We examined a retrospective cohort of patients presenting with a chief complaint of pregnancy loss between 2003 and 2012. Antiphospholipid antibodies were assessed at the providers' discretion, and patients were considered positive if they met the revised Sapporo criteria. Patient data were obtained by review of the medical records. 338/390 women (86.7%) presented with a chief complaint of pregnancy loss and had testing for antiphospholipid antibodies. 19/338 women (5.6%) persistently tested positive for at least one antiphospholipid antibody. Seven women who tested positive had isolated recurrent early pregnancy loss ≤10 weeks, and 12 women who tested positive had venous thromboembolism (VTE), systemic lupus erythematosus (SLE), delivery <34 weeks for pre-eclampsia, and/or placental insufficiency, or fetal demise >10 weeks. Subsequent pregnancy outcomes were available for 13 patients. Compared with women with recurrent early pregnancy loss alone, subsequent obstetric morbidity was significantly more likely in those patients with a history of SLE and/or VTE (p = 0.048). We conclude that the prevalence of positive antiphospholipid antibodies in women with a chief complaint of pregnancy loss and without autoimmune disease or prior thrombosis is low and that among these women, subsequent pregnancy outcomes are largely favorable.

Research paper thumbnail of Cancers in Patients with von Willebrand Disease: A Survey from the Italian Association of Haemophilia Centres

Seminars in Thrombosis and Hemostasis, 2015

Besides its essential role in hemostasis, there is growing evidence that von Willebrand factor (V... more Besides its essential role in hemostasis, there is growing evidence that von Willebrand factor (VWF) has an additional antitumor effect. To elucidate the clinical significance of this biological activity we conducted a retrospective study on cancers among Italian patients with von Willebrand disease (VWD) on behalf of the Italian Association of Haemophilia Centres (AICE). A questionnaire to collect demographic, clinical, and treatment data of VWD patients with cancer was sent to all the 54 Italian Haemophilia Treatment Centres (HTCs) members of AICE. Overall, 18 HTCs (33%) provided information on 92 VWD patients (61 alive and 31 deceased) with 106 cancers collected during the period 1981 to 2014. Of them, 19 (18%) were hematological cancers and 87 (82%) were solid cancers. A total of 61% of patients had type 1, 36% type 2 (12% type 2A, 14% type 2B, 9% type 2M, and 1% type 2N), and 3% type 3 VWD: this distribution was significantly different from that observed in the whole VWD population (79% type 1, 16% type 2 [8% type 2A, 4% type 2B, 2% type 2M, 2% type 2N], and 5% type 3; type 2 vs. non-type 2: p < 0.001). Overall, VWD patients with cancer underwent 52 invasive and 72 surgical procedures, were treated with VWF/factor VIII (FVIII) concentrates in 77 cases, with desmopressin (DDAVP) alone in 24 cases and with DDAVP and VWF/FVIII Ã The complete list of coauthors for the study (Italian Association of Haemophilia Centres, with the site of the Haemophilia Centre given in parentheses, is as follows.

Research paper thumbnail of Principles of treatment and update of recommendations for the management of haemophilia and congenital bleeding disorders in Italy

Blood transfusion = Trasfusione del sangue, 2014

Research paper thumbnail of Thromboembolic disease developing during oral contraceptive therapy in young females with antiphospholipid antibodies

Blood Coagulation & Fibrinolysis, 1996

The role of oral contraceptives as a triggering factor for thrombosis in patients with lupus anti... more The role of oral contraceptives as a triggering factor for thrombosis in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA) has not yet been established. We describe the cases of three women aged 19, 29 and 48 years who developed venous thrombosis after 16 +/- 3.4 (mean +/- SD) cycles of oral contraceptives. They were all asymptomatic before taking the pill. Two patients subsequently developed venous and/or arterial recurrence of thrombosis. Laboratory studies performed after the diagnosis of thrombosis, showed the presence of LA and elevated levels of ACA (IgG and IgM) in all three patients. None of these patients had autoimmune diseases and therefore appeared to have a primary antiphospholipid antibody syndrome. The three patients belonged to a group of 45 young females who experienced their first thrombotic event while taking the pill. This group had a similar prevalence (8%) for antithrombin deficiency and antiphospholipid antibodies. We surmise that some of the women who developed venous thrombosis while taking the pill might have an undetected primary antiphospholipid syndrome.

Research paper thumbnail of Serological markers of autoimmunity in patients with hemophilia A: the role of hepatitis C virus infection, alpha-interferon and factor VIII treatment in skewing the immune system toward autoreactivity

Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 1999

The aim of this study was to investigate whether the immune system of patients with hemophilia A ... more The aim of this study was to investigate whether the immune system of patients with hemophilia A is skewed toward an aspecific activation and to identify the causative factors. It is well known that an immune derangement does exist in patients with hemophilia A. At least three factors potentially play a role: hepatitis C virus (HCV) infection, alpha-interferon therapy and the administration of factor VIII (FVIII). Sixty human immunodeficiency virus (HIV)-negative patients with severe or moderate hemophilia A were studied retrospectively. The serological markers of autoimmunity were evaluated and the results correlated with anti-HCV antibodies, FVIII treatment and alpha-interferon therapy. The role of these factors in the development of the anti-FVIII antibody was estimated concomitantly. The prevalence of autoantibodies and anti-FVIII antibodies was higher in HCV-positive than in HCV-negative patients before any treatment, although the difference was not statistically significant. T...

Research paper thumbnail of The effect of a single course of alpha-2B-interferon in patients with HIV-related and chronic idiopathic immune thrombocytopenia

Autoimmunity, 1993

13 patients with HIV-related immune thrombocytopenia (HIV-ITP) and 10 patients with chronic idiop... more 13 patients with HIV-related immune thrombocytopenia (HIV-ITP) and 10 patients with chronic idiopathic thrombocytopenic purpura (C-ITP) were treated with a single course of alpha-2b-Interferon (IFN 3 x 10(6) IU subcutaneously for 12 d). The patients had platelet counts lower than 40 x 10(9)/L and thrombocytopenia persisting for over 1 year (range 1-22 years); 7 patients were refractory to previous conventional therapy, 5 were responsive, and 11 had not been previously treated. The response to IFN was complete in 8 patients (platelets > 100 x 10(9)/L), partial in 7 (platelets 50-100 x 10(9)/L); 8 patients showed no response. The treatment with IFN was stopped after 4 d in one patient due to a fall in platelet count. The maximal platelet count (median peak 116 +/- 55 SD x 10(9)/L platelets) was obtained after 13.7 +/- 2.98 d and the improvement in platelet count was maintained for 22.8 +/- 8.6 d. No difference in platelets response was observed between HIV-ITP and C-ITP. The respon...

Research paper thumbnail of Pharmacokinetics of plasma-derived vs. recombinant FVIII concentrates: a comparative study

Haemophilia, 2014

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.

Research paper thumbnail of Thrombosis of abdominal aorta in congenital afibrinogenemia: case report and review of literature

Haemophilia, 2014

Thrombotic events in congenital hypo-afibrinogenemia have been rarely reported, either in associa... more Thrombotic events in congenital hypo-afibrinogenemia have been rarely reported, either in association or not with replacement therapy or thrombotic risk factors. We describe clinical findings and management of thrombosis of abdominal aorta with peripheral embolism in a patient with congenital afibrinogenemia. A review of arterial thrombosis in inherited hypo-afibrinogenemia was also performed. The patient with a severe bleeding history requiring prophylaxis with fibrinogen concentrates (FC) was admitted for ischaemia of the 4th right toe. An angio-CT of abdominal aorta showed a thrombosis from the origin of renal arteries to the carrefour with a distal floating part. No thrombotic risk factors were found; a previous traumatic lesion of aortic wall might have triggered the thrombus formation, whereas the role of FC prophylaxis remains uncertain. The patient was successfully treated with FC, enoxaparin followed by fondaparinux, and low-dose aspirin without bleeding or thrombosis recurrence. After 2 years, aortic thrombus was almost completely recovered. Sixteen hypo/afibrinogenemia patients with arterial thrombosis were found in Literature, showing that thrombosis often occurs at a young age, involves large vessels, its recurrence is not unusual, and therapeutic strategy is not defined yet. Our therapeutic approach was effective and also safe, but further studies are needed to improve the knowledge of pathogenesis and the anti-thrombotic management in this peculiar setting.

Research paper thumbnail of Bioequivalence of B-domain deleted and plasma derived FVIII concentrates

Research paper thumbnail of Cognitive dysfunctions and cerebral microbleeds in adult patients with haemophilia A: A clinical and MRI pilot-study

Thrombosis Research, 2014

Studies providing information about the cognitive profile of adult haemophiliacs are lacking. To ... more Studies providing information about the cognitive profile of adult haemophiliacs are lacking. To assess the neuropsychological profile in a group of Haemophiliac patients; to detect asymptomatic cerebral microbleeds (CMBs) and any correlation between CMBs and cognitive dysfunctions; to verify how several contributing factors may determine cognitive dysfunctions and/or Magnetic Resonance Imaging (MRI) findings. Adult haemophiliacs without history of brain bleeding were prospectively enrolled on Padua Haemophilia Centre. Patients underwent: i) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Short Neuropsychological Test&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; assessing cognitive functions (Short Neuropsychological Examination) to obtain an overall cognitive performance (OCP) profile standardised on a cohort matched for age, sex, cultural profile; ii) MRI of the brain to evaluate areas of brain atrophy or haemorrhagic lesions. We collected information on anti-haemorrhagic treatment, cardiovascular risk profile, viral infections, birth trauma. 49 adults with haemophilia (31 severe-moderate, 18 mild) were enrolled. 73% of patients presented a reduction in OCP. According to OCP, no significant difference between severe and mild haemophilia was observed though scores tended to be worse in severe haemophilia (mean Z score 0.20 ± 0.10 vs s0.15 ± 0.11). Considering risk factors, OCP correlated significantly with coronary artery disease (p=0.02). MRI findings in 44 patients, indicated CMBs were inversely related to OCP (R=-0.32 p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). CMBs were associated with cardiovascular risk factors (p=0.018). Adult haemophiliacs seem to present high prevalence of mild cognitive dysfunctions that doesn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;t correlate with the severity of haemophilia probably for the few number of patients evaluated. OCP impairment seems to be related to the presence of CMBs and of risk factors for cardiovascular disease.

Research paper thumbnail of Management of dental extraction in patients undergoing anticoagulant treatment. Results from a large, multicentre, prospective, case-control study

Thrombosis and Haemostasis, 2010

Following favourable results from a previous study, a large, multicentre, prospective, case-contr... more Following favourable results from a previous study, a large, multicentre, prospective, case-control study was performed to further assess the incidence of bleeding complications after dental extraction in patients taking oral anticoagulant therapy (OAT). Four hundred fifty-one patients being treated with warfarin who required dental extraction were compared with a control group of 449 non-anticoagulated subjects undergoing the same procedure. In the warfarin-treated group, the oral anticoagulant regimen was maintained unchanged, such that the patients had an International Normalised Ratio ranging between 1.8 and 4, and local haemostatic measures (i.e. fibrin sponges, silk sutures and gauzes saturated with tranexamic acid) were adopted. All the procedures were performed in an outpatient setting. Seven bleeding complications occurred in the OAT group and four in the control group; the dif

Research paper thumbnail of Anti-β2-Glycoprotein I Antibodies in Patients with Acute Venous Thromboembolism

Thrombosis Research, 1999

served in patients without these antibodies (15 of 51, 29.4%; ORϭ3.3; 95% CI, 1.1-9.83; pϭ0.28). ... more served in patients without these antibodies (15 of 51, 29.4%; ORϭ3.3; 95% CI, 1.1-9.83; pϭ0.28). To establish the prevalence of antibodies against We conclude that in patients with acute venous ␤ 2-glycoprotein I (␤ 2 GPI) in unselected patients thromboembolism the prevalence of antibodies with venous thromboembolism, as well as the assoagainst ␤ 2 GPI is unexpectedly high. The presence ciation with antiphospholipid antibodies (aPL) and of these antibodies seems to identify a subgroup a history of previous thromboembolism, we investiof patients with antiphospholipid antibodies who gated the presence of these antibodies in 227 conhave a peculiarly high risk of thrombotic recursecutive patients with acute deep vein thrombosis rences. Further prospective studies are indicated or pulmonary embolism, of whom 63 were carriers to better define the role of anti-␤ 2 GPI antibodies in of aPL with or without lupus anticoagulant (LA), the development of recurrent thromboembolism.

Research paper thumbnail of Myocardial Infarction, Other Arterial Thrombosis and Invasive Coronary Procedures, in Hemaophilia B: A Critical Evaluation of Reported Cases

Journal of Thrombosis and Thrombolysis, 2005

Myocardial infarction and other arterial thrombosis are commonly maintained to be rare in hemophi... more Myocardial infarction and other arterial thrombosis are commonly maintained to be rare in hemophilia patients. This, in general, seems true but the occurrence of a thrombotic event in hemophilia B is not exceptional. A thorough search of the literature has yielded 13 patients with myocardial infarction and 1 patient with a cerebrovascular accident. There were three fatalities. In five cases MI occurred after infusion of Prothrombin Complex Concentrates. In three additional patients the event occurred after infusion of plasma, Feiba or cryoprecipitate supernatant. Four patients had an antero-lateral infarction. Two had a non-Q infarction and one each showed a multiple or a posterior-inferior form. Several therapeutic coronary procedures (GABG and PTCA) were carried out in hemophilia B patients without undue complication providing adequate level of FIX were maintained. Heparin prophilaxis was used in all patients but one. The analysis of the literature indicates that (1) MI may occur in hemophilia B patients and (2) that invasive coronary artery therapeutic procedures may be carried out without complications.

Research paper thumbnail of Emofilia acquisita: dalle criticità diagnostiche ad un corretto approccio terapeutico Acquired haemophilia: from critical diagnostic issues to correct therapeutic approach

Acquired haemophilia A is a rare disorder typically affecting older people and characterized by s... more Acquired haemophilia A is a rare disorder typically affecting older people and characterized by severe potentially life-threatening bleeding. Diagnostic delay and inadequate treatment are common. We describe two cases who were diagnosed and treated. We discuss critical steps in managing a patient with acquired hemophilia and provide orientation on best approach to diagnosis and treatment. INTRODUZIONE L'emofilia acquisita è una malattia caratterizza-ta da manifestazioni emorragiche improvvise in pazienti senza storia personale o familiare di di-sordini della coagulazione. È una condizione rara, con una incidenza di cir-ca 1,5 casi-per milione / anno; colpisce pazien-ti in età adulta o anziana (range 55-78 anni), senza distinzione di sesso, fatta eccezione per i casi di giovani donne nel post-partum 1. È dovuta alla presenza di auto-anticorpi specifi-camente diretti contro un fattore della coagula-zione che nel 95% dei casi è rappresentato dal FVIII. In circa il 50% dei casi non ...

Research paper thumbnail of Cerebrovascular diseases in hemophiliacs: A real, but underestimated risk

Haemophilia : the official journal of the World Federation of Hemophilia, Jan 21, 2017

Ischaemic heart disease and ischaemic stroke are the most important causes of death in the genera... more Ischaemic heart disease and ischaemic stroke are the most important causes of death in the general population, especially in developed countries. Usually, patients with haemophilia (PWH) are considered at low risk for these events because of their hypocoagulable state, but recent data revealed an unexpected risk of cardio-and cerebrovascular diseases in this population 1,2 as well. However, only a few cases of ischaemic strokes have been reported in PWH, though without detailed description. An occlusion of the sylvian artery in a patient with severe haemophilia B was cited by Luscher. 3 Six cases of cerebral thrombosis have been recorded by Girolami et al., 4 and four of them were ischaemic events. Wang et al. 2 collected data on 1054 PWH from 1997 to 2010 using a Taiwanese registry, finding 26 ischaemic strokes, a proportion comparable with those of normal subjects, whereas haemorrhagic stroke was seven times higher in the PWH. In this registry, it was also proved that the risk factors for atherosclerosis development, the first cause of thromboembolic injuries, had the same prevalence in both groups except for obesity, which was more frequent in PWH. Conversely, a very low estimated incidence was reported by Bezzina et al. 5 in their data collection on 2569 patients with haemophilia A, haemophilia B and von Willebrand disease from 52 centres in North and South America and in Europe. Over the 4.5

Research paper thumbnail of Controlled, cross-sectional MRI evaluation of joint status in severe haemophilia A patients treated with prophylaxis vs. on demand

Haemophilia : the official journal of the World Federation of Hemophilia, 2015

In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and jo... more In patients with haemophilia A, factor VIII (FVIII) prophylaxis reduces bleeding frequency and joint damage compared with on-demand therapy. To assess the effect of prophylaxis initiation age, magnetic resonance imaging (MRI) was used to evaluate bone and cartilage damage in patients with severe haemophilia A. In this cross-sectional, multinational investigation, patients aged 12-35 years were assigned to 1 of 5 groups: primary prophylaxis started at age <2 years (group 1); secondary prophylaxis started at age 2 to <6 years (group 2), 6 to <12 years (group 3), or 12-18 years (group 4); or on-demand treatment (group 5). Joint status at ankles and knees was assessed using Compatible Additive MRI scoring (maximum and mean ankle; maximum and mean of all 4 joints) and Gilbert scores in the per-protocol population (n = 118). All prophylaxis groups had better MRI joint scores than the on-demand group. MRI scores generally increased with current patient age and later start of proph...

Research paper thumbnail of Long-Term Use of Oral Contraceptive Therapy in Women With the Prothrombin 20210 G-A Polymorphism Without Thrombotic Complications: A Study of 13 Women (12 Heterozygotes and 1 Homozygote)

Thrombosis Research, 2001

Thirteen female patients with the prothrombin 20210 G-A abnormality (twelve heterozygotes and one... more Thirteen female patients with the prothrombin 20210 G-A abnormality (twelve heterozygotes and one homozygote) were selected out of 551 patients admitted to our Department of Medicine or to our Outpatient Hemostasis Units between January 1999 and October 2000. The selection was based on the fact that all patients had taken or were still taking oral contraceptives (OC) for a period of 3 years or longer than 3 years. None of these patents as gathered from history, physical examination, private physician records and our records has shown any DVT during or immediately after OC intake. Physical and compression ultrasonography examinations at the time of study were all negative. The average length of oral contraceptives therapy (OCT) was 10 years (range 3-23). The average age of patients at the time of oral contraception was 30 years. The 13 women had also 17 pregnancies without any venous thrombosis. The observations casts several doubt about the prothrombotic effect of this polymorphism. Since DVT has been shown to occur occasionally even in normal women, it is likely that the same may occur in women with this polymorphism regardless of the existence or not of any pathogenetic relationship between the two phenomena. Occasional reports suggesting a link between this polymorphism and oral contraception-related venous thrombosis should be carefully evaluated in order to avoid premature and incorrect conclusions.

Research paper thumbnail of Proposal of a standard approach to dental extraction in haemophilia patients. A case‐control study with good results

Haemophilia, 2000

We found no case–control studies on dental extraction in haemophilia patients in the literature e... more We found no case–control studies on dental extraction in haemophilia patients in the literature even though the use of antifibrinolytic agents following a single infusion of factor VIII or IX has been accompanied by a lower number of bleeding complications in dental extractions. In this study we verified the incidence of bleeding complications after dental extraction in a group of 77 haemophilia patients. One hundred and eighty‐four male patients requiring dental extraction represented the control group. All haemophilia patients received 20 mg kg–1 of tranexamic acid and a single infusion of factor VIII or IX to achieve a peak level about 30% of factor VIII or IX in vivo prior to dental extraction. Forty‐five of 98 (45.9%) dental extractions in haemophilia patients and 110 of 239 (46%) dental extractions in the control group were surgical ones. We registered two bleeding complications in the group of haemophilia patients (one late bleeding and one haematoma in the site of the anaest...

Research paper thumbnail of Efficacy and safety during formulation switch of a pasteurized VWF/FVIII concentrate: results from an Italian prospective observational study in patients with von Willebrand disease

Haemophilia, 2012

Von Willebrand disease (VWD) is an inherited bleeding disorder caused by the quantitative or qual... more Von Willebrand disease (VWD) is an inherited bleeding disorder caused by the quantitative or qualitative deficiency of von Willebrand factor (VWF). Replacement therapy with plasma-derived VWF/factor VIII (FVIII) concentrates is required in patients unresponsive to desmopressin. To assess the efficacy, safety and ease of use of a new, volume-reduced (VR) formulation of VWF/FVIII concentrate Haemate ® P in patients requiring treatment for bleeding or prophylaxis for recurrent bleeding or for invasive procedures. Pharmacoeconomic variables were also recorded. Data were analysed using descriptive statistics. This was a multicentre, prospective, observational study. Consecutively enrolled patients received Haemate ® P VR according to their needs, and were followed for 24 months. Of the 121 patients enrolled, 25.6% had type 3 VWD and more than 40% had severe disease. All patients were followed for 2 years, for a total of 521 visits. Ondemand treatment was given to 61.9% of patients, secondary long-term prophylaxis to 25.6% and prophylaxis for surgery, dental or invasive procedures to 45.5%. The response to treatment was rated as good to excellent in >93-99% of interventions. The new formulation was well tolerated by all patients with no report of drug-related adverse events. The switch to volume-reduced Haemate ® P was easy to perform and infusion duration was decreased twofold compared with the previous formulation. Volume-reduced Haemate ® P was at least as effective and well-tolerated as the previous formulation.

Research paper thumbnail of Whole blood rotation thromboelastometry (ROTEM®) in nine severe factor V deficient patients and evaluation of the role of intraplatelets factor V

Haemophilia, 2011

The coagulation pattern and the determinants of portal vein thrombosis (PVT), both in patients wi... more The coagulation pattern and the determinants of portal vein thrombosis (PVT), both in patients with and without cirrhosis, are still largely unknown. The aim of this study was to evaluate whole blood thromboelastometry profile, performed by ROTEM®, of both cirrhotic and non-cirrhotic subjects with PVT. Two different groups were considered: i) 14 non-cirrhotic PVT patients, ii) 35 cirrhotic patients with PVT. Controls were sex-and age-matched healthy volunteers and cirrhotic subjects without PVT, respectively. ROTEM® assays (i.e. INTEM, EXTEM, NATEM, and FIBTEM) and traditional coagulative parameters (i.e. platelet count, PT/INR, aPTT, and fibrinogen) were performed on blood samples from each subject. There were no significant differences in ROTEM® profile, as for INTEM, EXTEM, and NATEM assays, and in traditional coagulative parameters, between PVT patients, both with and without cirrhosis, and control groups. Interestingly, Maximum Clot Firmness (MCF) in FIBTEM was significantly higher in non-cirrhotic PVT patients (19 mm) than in healthy volunteers (11 mm, p b 0.05). The amplitude of MCF in FIBTEM revealed to be a useful tool to discriminate non-cirrhotic subjects with PVT from those without thrombotic events. Larger prospective studies are needed to evaluate the relevance of the association between the alterations of ROTEM® profiles and PVT in cirrhotic patients.

Research paper thumbnail of Prevalence of Antiphospholipid Antibodies and Lupus Anticoagulant in Juvenile Patients with Objectively Documented Deep-vein Thrombosis

Clinical and Applied Thrombosis/Hemostasis, 1996

The reported prevalence of antiphospholipid antibodies in women with a chief complaint of pregnan... more The reported prevalence of antiphospholipid antibodies in women with a chief complaint of pregnancy loss varies, as does the risk of adverse outcomes in subsequent pregnancies. Our objectives were to assess the prevalence of antiphospholipid antibodies meeting revised Sapporo thresholds among women presenting with a chief complaint of pregnancy loss and risks in subsequent pregnancies for these women. We examined a retrospective cohort of patients presenting with a chief complaint of pregnancy loss between 2003 and 2012. Antiphospholipid antibodies were assessed at the providers' discretion, and patients were considered positive if they met the revised Sapporo criteria. Patient data were obtained by review of the medical records. 338/390 women (86.7%) presented with a chief complaint of pregnancy loss and had testing for antiphospholipid antibodies. 19/338 women (5.6%) persistently tested positive for at least one antiphospholipid antibody. Seven women who tested positive had isolated recurrent early pregnancy loss ≤10 weeks, and 12 women who tested positive had venous thromboembolism (VTE), systemic lupus erythematosus (SLE), delivery <34 weeks for pre-eclampsia, and/or placental insufficiency, or fetal demise >10 weeks. Subsequent pregnancy outcomes were available for 13 patients. Compared with women with recurrent early pregnancy loss alone, subsequent obstetric morbidity was significantly more likely in those patients with a history of SLE and/or VTE (p = 0.048). We conclude that the prevalence of positive antiphospholipid antibodies in women with a chief complaint of pregnancy loss and without autoimmune disease or prior thrombosis is low and that among these women, subsequent pregnancy outcomes are largely favorable.

Research paper thumbnail of Cancers in Patients with von Willebrand Disease: A Survey from the Italian Association of Haemophilia Centres

Seminars in Thrombosis and Hemostasis, 2015

Besides its essential role in hemostasis, there is growing evidence that von Willebrand factor (V... more Besides its essential role in hemostasis, there is growing evidence that von Willebrand factor (VWF) has an additional antitumor effect. To elucidate the clinical significance of this biological activity we conducted a retrospective study on cancers among Italian patients with von Willebrand disease (VWD) on behalf of the Italian Association of Haemophilia Centres (AICE). A questionnaire to collect demographic, clinical, and treatment data of VWD patients with cancer was sent to all the 54 Italian Haemophilia Treatment Centres (HTCs) members of AICE. Overall, 18 HTCs (33%) provided information on 92 VWD patients (61 alive and 31 deceased) with 106 cancers collected during the period 1981 to 2014. Of them, 19 (18%) were hematological cancers and 87 (82%) were solid cancers. A total of 61% of patients had type 1, 36% type 2 (12% type 2A, 14% type 2B, 9% type 2M, and 1% type 2N), and 3% type 3 VWD: this distribution was significantly different from that observed in the whole VWD population (79% type 1, 16% type 2 [8% type 2A, 4% type 2B, 2% type 2M, 2% type 2N], and 5% type 3; type 2 vs. non-type 2: p < 0.001). Overall, VWD patients with cancer underwent 52 invasive and 72 surgical procedures, were treated with VWF/factor VIII (FVIII) concentrates in 77 cases, with desmopressin (DDAVP) alone in 24 cases and with DDAVP and VWF/FVIII Ã The complete list of coauthors for the study (Italian Association of Haemophilia Centres, with the site of the Haemophilia Centre given in parentheses, is as follows.

Research paper thumbnail of Principles of treatment and update of recommendations for the management of haemophilia and congenital bleeding disorders in Italy

Blood transfusion = Trasfusione del sangue, 2014

Research paper thumbnail of Thromboembolic disease developing during oral contraceptive therapy in young females with antiphospholipid antibodies

Blood Coagulation & Fibrinolysis, 1996

The role of oral contraceptives as a triggering factor for thrombosis in patients with lupus anti... more The role of oral contraceptives as a triggering factor for thrombosis in patients with lupus anticoagulant (LA) and/or anticardiolipin antibodies (ACA) has not yet been established. We describe the cases of three women aged 19, 29 and 48 years who developed venous thrombosis after 16 +/- 3.4 (mean +/- SD) cycles of oral contraceptives. They were all asymptomatic before taking the pill. Two patients subsequently developed venous and/or arterial recurrence of thrombosis. Laboratory studies performed after the diagnosis of thrombosis, showed the presence of LA and elevated levels of ACA (IgG and IgM) in all three patients. None of these patients had autoimmune diseases and therefore appeared to have a primary antiphospholipid antibody syndrome. The three patients belonged to a group of 45 young females who experienced their first thrombotic event while taking the pill. This group had a similar prevalence (8%) for antithrombin deficiency and antiphospholipid antibodies. We surmise that some of the women who developed venous thrombosis while taking the pill might have an undetected primary antiphospholipid syndrome.

Research paper thumbnail of Serological markers of autoimmunity in patients with hemophilia A: the role of hepatitis C virus infection, alpha-interferon and factor VIII treatment in skewing the immune system toward autoreactivity

Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis, 1999

The aim of this study was to investigate whether the immune system of patients with hemophilia A ... more The aim of this study was to investigate whether the immune system of patients with hemophilia A is skewed toward an aspecific activation and to identify the causative factors. It is well known that an immune derangement does exist in patients with hemophilia A. At least three factors potentially play a role: hepatitis C virus (HCV) infection, alpha-interferon therapy and the administration of factor VIII (FVIII). Sixty human immunodeficiency virus (HIV)-negative patients with severe or moderate hemophilia A were studied retrospectively. The serological markers of autoimmunity were evaluated and the results correlated with anti-HCV antibodies, FVIII treatment and alpha-interferon therapy. The role of these factors in the development of the anti-FVIII antibody was estimated concomitantly. The prevalence of autoantibodies and anti-FVIII antibodies was higher in HCV-positive than in HCV-negative patients before any treatment, although the difference was not statistically significant. T...

Research paper thumbnail of The effect of a single course of alpha-2B-interferon in patients with HIV-related and chronic idiopathic immune thrombocytopenia

Autoimmunity, 1993

13 patients with HIV-related immune thrombocytopenia (HIV-ITP) and 10 patients with chronic idiop... more 13 patients with HIV-related immune thrombocytopenia (HIV-ITP) and 10 patients with chronic idiopathic thrombocytopenic purpura (C-ITP) were treated with a single course of alpha-2b-Interferon (IFN 3 x 10(6) IU subcutaneously for 12 d). The patients had platelet counts lower than 40 x 10(9)/L and thrombocytopenia persisting for over 1 year (range 1-22 years); 7 patients were refractory to previous conventional therapy, 5 were responsive, and 11 had not been previously treated. The response to IFN was complete in 8 patients (platelets > 100 x 10(9)/L), partial in 7 (platelets 50-100 x 10(9)/L); 8 patients showed no response. The treatment with IFN was stopped after 4 d in one patient due to a fall in platelet count. The maximal platelet count (median peak 116 +/- 55 SD x 10(9)/L platelets) was obtained after 13.7 +/- 2.98 d and the improvement in platelet count was maintained for 22.8 +/- 8.6 d. No difference in platelets response was observed between HIV-ITP and C-ITP. The respon...

Research paper thumbnail of Pharmacokinetics of plasma-derived vs. recombinant FVIII concentrates: a comparative study

Haemophilia, 2014

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.

Research paper thumbnail of Thrombosis of abdominal aorta in congenital afibrinogenemia: case report and review of literature

Haemophilia, 2014

Thrombotic events in congenital hypo-afibrinogenemia have been rarely reported, either in associa... more Thrombotic events in congenital hypo-afibrinogenemia have been rarely reported, either in association or not with replacement therapy or thrombotic risk factors. We describe clinical findings and management of thrombosis of abdominal aorta with peripheral embolism in a patient with congenital afibrinogenemia. A review of arterial thrombosis in inherited hypo-afibrinogenemia was also performed. The patient with a severe bleeding history requiring prophylaxis with fibrinogen concentrates (FC) was admitted for ischaemia of the 4th right toe. An angio-CT of abdominal aorta showed a thrombosis from the origin of renal arteries to the carrefour with a distal floating part. No thrombotic risk factors were found; a previous traumatic lesion of aortic wall might have triggered the thrombus formation, whereas the role of FC prophylaxis remains uncertain. The patient was successfully treated with FC, enoxaparin followed by fondaparinux, and low-dose aspirin without bleeding or thrombosis recurrence. After 2 years, aortic thrombus was almost completely recovered. Sixteen hypo/afibrinogenemia patients with arterial thrombosis were found in Literature, showing that thrombosis often occurs at a young age, involves large vessels, its recurrence is not unusual, and therapeutic strategy is not defined yet. Our therapeutic approach was effective and also safe, but further studies are needed to improve the knowledge of pathogenesis and the anti-thrombotic management in this peculiar setting.

Research paper thumbnail of Bioequivalence of B-domain deleted and plasma derived FVIII concentrates

Research paper thumbnail of Cognitive dysfunctions and cerebral microbleeds in adult patients with haemophilia A: A clinical and MRI pilot-study

Thrombosis Research, 2014

Studies providing information about the cognitive profile of adult haemophiliacs are lacking. To ... more Studies providing information about the cognitive profile of adult haemophiliacs are lacking. To assess the neuropsychological profile in a group of Haemophiliac patients; to detect asymptomatic cerebral microbleeds (CMBs) and any correlation between CMBs and cognitive dysfunctions; to verify how several contributing factors may determine cognitive dysfunctions and/or Magnetic Resonance Imaging (MRI) findings. Adult haemophiliacs without history of brain bleeding were prospectively enrolled on Padua Haemophilia Centre. Patients underwent: i) &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot;Short Neuropsychological Test&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;quot; assessing cognitive functions (Short Neuropsychological Examination) to obtain an overall cognitive performance (OCP) profile standardised on a cohort matched for age, sex, cultural profile; ii) MRI of the brain to evaluate areas of brain atrophy or haemorrhagic lesions. We collected information on anti-haemorrhagic treatment, cardiovascular risk profile, viral infections, birth trauma. 49 adults with haemophilia (31 severe-moderate, 18 mild) were enrolled. 73% of patients presented a reduction in OCP. According to OCP, no significant difference between severe and mild haemophilia was observed though scores tended to be worse in severe haemophilia (mean Z score 0.20 ± 0.10 vs s0.15 ± 0.11). Considering risk factors, OCP correlated significantly with coronary artery disease (p=0.02). MRI findings in 44 patients, indicated CMBs were inversely related to OCP (R=-0.32 p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05). CMBs were associated with cardiovascular risk factors (p=0.018). Adult haemophiliacs seem to present high prevalence of mild cognitive dysfunctions that doesn&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;t correlate with the severity of haemophilia probably for the few number of patients evaluated. OCP impairment seems to be related to the presence of CMBs and of risk factors for cardiovascular disease.

Research paper thumbnail of Management of dental extraction in patients undergoing anticoagulant treatment. Results from a large, multicentre, prospective, case-control study

Thrombosis and Haemostasis, 2010

Following favourable results from a previous study, a large, multicentre, prospective, case-contr... more Following favourable results from a previous study, a large, multicentre, prospective, case-control study was performed to further assess the incidence of bleeding complications after dental extraction in patients taking oral anticoagulant therapy (OAT). Four hundred fifty-one patients being treated with warfarin who required dental extraction were compared with a control group of 449 non-anticoagulated subjects undergoing the same procedure. In the warfarin-treated group, the oral anticoagulant regimen was maintained unchanged, such that the patients had an International Normalised Ratio ranging between 1.8 and 4, and local haemostatic measures (i.e. fibrin sponges, silk sutures and gauzes saturated with tranexamic acid) were adopted. All the procedures were performed in an outpatient setting. Seven bleeding complications occurred in the OAT group and four in the control group; the dif

Research paper thumbnail of Anti-β2-Glycoprotein I Antibodies in Patients with Acute Venous Thromboembolism

Thrombosis Research, 1999

served in patients without these antibodies (15 of 51, 29.4%; ORϭ3.3; 95% CI, 1.1-9.83; pϭ0.28). ... more served in patients without these antibodies (15 of 51, 29.4%; ORϭ3.3; 95% CI, 1.1-9.83; pϭ0.28). To establish the prevalence of antibodies against We conclude that in patients with acute venous ␤ 2-glycoprotein I (␤ 2 GPI) in unselected patients thromboembolism the prevalence of antibodies with venous thromboembolism, as well as the assoagainst ␤ 2 GPI is unexpectedly high. The presence ciation with antiphospholipid antibodies (aPL) and of these antibodies seems to identify a subgroup a history of previous thromboembolism, we investiof patients with antiphospholipid antibodies who gated the presence of these antibodies in 227 conhave a peculiarly high risk of thrombotic recursecutive patients with acute deep vein thrombosis rences. Further prospective studies are indicated or pulmonary embolism, of whom 63 were carriers to better define the role of anti-␤ 2 GPI antibodies in of aPL with or without lupus anticoagulant (LA), the development of recurrent thromboembolism.

Research paper thumbnail of Myocardial Infarction, Other Arterial Thrombosis and Invasive Coronary Procedures, in Hemaophilia B: A Critical Evaluation of Reported Cases

Journal of Thrombosis and Thrombolysis, 2005

Myocardial infarction and other arterial thrombosis are commonly maintained to be rare in hemophi... more Myocardial infarction and other arterial thrombosis are commonly maintained to be rare in hemophilia patients. This, in general, seems true but the occurrence of a thrombotic event in hemophilia B is not exceptional. A thorough search of the literature has yielded 13 patients with myocardial infarction and 1 patient with a cerebrovascular accident. There were three fatalities. In five cases MI occurred after infusion of Prothrombin Complex Concentrates. In three additional patients the event occurred after infusion of plasma, Feiba or cryoprecipitate supernatant. Four patients had an antero-lateral infarction. Two had a non-Q infarction and one each showed a multiple or a posterior-inferior form. Several therapeutic coronary procedures (GABG and PTCA) were carried out in hemophilia B patients without undue complication providing adequate level of FIX were maintained. Heparin prophilaxis was used in all patients but one. The analysis of the literature indicates that (1) MI may occur in hemophilia B patients and (2) that invasive coronary artery therapeutic procedures may be carried out without complications.