Abstract Background Although patients with idiopathic VTE are at higher than normal risk of asymptomatic atherosclerosis and of cardiovascular events, the impact of cardiovascular risk factors on VTE ...is poorly understood. Objective To assess the prevalence of the metabolic syndrome and of its components in patients with early-onset idiopathic VTE. Methods As many as 323 patients referred to our Thrombosis Ward for a recent (< 6-months) early-onset idiopathic venous thromboembolism (VTE), were compared with 868 gender- and age-matched subjects, in whom a history of venous thrombosis had been excluded, referred during the same period time to our Ward. All had undergone a clinical assessment for smoking habits and for the presence of the components of the metabolic syndrome. Results The metabolic syndrome was detected in 76/323 cases (23.5%) and in 81/868 controls (9.3%) (p < 0.001; OR:2.990; 95%C.I.:2.119-4.217). Smoking was more common in patients with idiopathic VTE than in controls. In addition to the metabolic syndrome as a whole, its major individual determinants (arterial hypertension, impaired fasting glucose plasma levels, abdominal obesity, hypertriglyceridemia, low HDL-cholesterol) significantly correlated with idiopathic VTE (p always < 0.05). The prevalence of thrombotic events was lower in females than in males (p = 0.000; OR:2.217), the latter being most often hypertensives, smokers, hypertriglyceridemics, carriers of a metabolic syndrome and of impaired fasting glucose than females. In a multivariate analysis, arterial hypertension, impaired fasting glucose, abdominal obesity, and hypercholesterolemia independently predicted idiopathic venous events. Conclusions Both metabolic syndrome as a whole and its major components individually considered, independently predict early-onset idiopathic VTE.
Severe hyperhomocysteinemia due to cystathionine beta-synthase deficiency (CbetaSD) is associated with early atherothrombotic vascular disease. Homocysteine may exert its effects by promoting ...oxidative damage. In the present study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG) F(2alpha), a platelet-active product of arachidonic acid peroxidation, is enhanced in CbetaSD and whether it correlates with in vivo platelet activation, as reflected by thromboxane (TX) metabolite excretion.
Urine and blood samples were obtained from patients with homozygous CbetaSD (n=13) and age-matched healthy subjects. Urinary 8-iso-PGF(2alpha) excretion was significantly higher in CbetaSD patients than in control subjects (640+/-384 versus 213+/-43 pg/mg creatinine; P=0.0015) and correlated with plasma homocysteine (rho=0.398, P=0.0076). Similarly, urinary 11-dehydro-TXB(2) excretion was enhanced in CbetaSD (1166+/-415 versus 324+/-72 pg/mg creatinine; P=0.0015) and correlated with urinary 8-iso-PGF(2alpha) (rho=0.362, P=0.0153). Vitamin E supplementation (600 mg/d for 2 weeks) was associated with a statistically significant increase in its plasma levels (from 16.6+/-4.6 to 40.4+/-8.7 micromol/L, P=0.0002) and with reductions in 8-iso-PGF(2alpha) (from 790+/-159 to 559+/-111 pg/mg creatinine, P=0.018) and 11-dehydro-TXB(2) (from 1273+/-383 to 913+/-336 pg/mg creatinine, P=0.028). A statistically significant inverse correlation was found between urinary 8-iso-PGF(2alpha) and plasma vitamin E levels (rho=-0.745, P=0.0135).
The results of the present study suggest that enhanced peroxidation of arachidonic acid to form bioactive F(2)-isoprostanes may represent an important mechanism linking hyperhomocysteinemia and platelet activation in CbetaSD patients. Moreover, they provide a rationale for dose-finding studies of vitamin E supplementation in this setting.
Abstract Forty-five consecutive subjects (26M, 19F; mean age 54 ± 14 yrs) with a diagnosed retinal vein occlusion (RVO), were followed-up for 8 yrs. As many as 145 sex-age- and blood pressure-matched ...individuals (78M, 67F; mean age 54.4 ± 13.5 yrs), that did not experience any vascular event, served as controls. At the time of the RVO, controls and subjects did not differ as to hypercholesterolemia, hypertrigliceridemia, diabetes mellitus, smoking habits, inherited/acquired thrombophilia. At the follow-up completion, they differed as to statin consumption ( p = 0.016). During the 8-yrs follow-up, in the control population, 11 out of 145 (7.6%) subjects had experienced a major vascular event (8 coronary artery disease; 3 cerebral non-fatal ischemic stroke). In contrast, of the 45 subjects with a history of RVO, as many as 10 (22.2%) had experienced a major vascular event: 4 coronary artery disease; 4 cerebral non-fatal ischemic stroke; 2 cardiovascular + cerebrovascular event ( p = 0.012). A prolonged antiplatelet treatment, prior to the major vascular event, was found in 5/45 cases (11.1%) vs 23/145 (15.9%) controls ( p = 0.63). In contrast, a long-lasting administration of anti-hypertensive drugs, to achieve a control of blood pressure, was found in 83.4% of controls and only in 46.7% of cases ( p < 0.0001). In conclusion, in a 8-yr follow-up, coronary artery disease and/or non-fatal ischemic stroke were more common in subjects with a history of RVO than in a large setting of subjects comparable for cardiovascular risk factors. These data also argue for RVO as a vascular disease in which aggressive anti-hypertensive therapy to prevent stroke and/or myocardial infarction is needed.
We sequenced the SERPINC1 gene in 26 patients (11 males) with antithrombin (AT) deficiency (22 type I, 4 type II), belonging to 18 unrelated families from Southern Italy. Heterozygous mutations were ...identified in 15/18 (83.3%) families. Of them, eight were novel mutations, each being identified in one family. Seven clearly cause impaired protein synthesis (four frameshift, one non-stop, one splicing and one 21bp deletion). One, present in a single patient, is a missense mutation thought to be causative because: a) it is absent in 100 chromosomes from controls; b) it involves a highly conserved amino acid, whose change is predicted to impair AT activity; c) no other mutation is present in the propositus. Severe mutations (i.e. nonsense, frameshift, deletions) were invariably identified in type I patients. In type II patients, 3/4 were missense mutations; the fourth leads to a 19 nucleotides shift in the stop codon. In addition to the type of mutation, the co-existence of other predisposing factors in most patients helps explain the severity of the present type I cases (age at first event, recurrence during prophylaxis). In the five families in which there was more than one member affected, the same genotype and a concordant clinical expression of the disease were found. We conclude that the molecular bases of AT deficiency in Southern Italy are different as compared to other geographic areas, and that molecular analysis and the study of the effect of the mutation may help predict the clinical expression of the disease.
Introduction
Persons with haemophilia (PWH) experience recurrent joint bleeding which leads from early synovitis to irreversible joint damage. Pain strongly affects patients’ quality of life, as PWH ...suffer from acute pain associated with haemarthroses and chronic pain due to arthritic and degenerative complications.
Aim
To investigate pain issues among PWH and their treaters in Italy.
Methods
Persons with haemophilia and specialist physicians responded to a survey focused on pain characteristics, assessment, and management by phone call and online, respectively.
Results
One hundred and nineteen patients (76% severe haemophilia, 61% ≥18 years) and 44 physicians were involved. Pain was reported by 61% of PWH; among those who did not experience pain, 70% were children on prophylaxis. Patients described pain as chronic (71%), acute (69%) or postoperative (8%), and rated it as severe in 65% of cases. Clinicians reported lower percentages of patients with pain (46%), classified as chronic (58%), acute (33%) or postoperative (21%), half using specific scales. Pain was systematically investigated by treaters according to 36% of patients. Paracetamol was largely the most prescribed first‐line pain therapy (89%), as well the most employed analgesic by PWH (51%), who also used non‐steroidal anti‐inflammatory drugs (24%), cyclo‐oxygenase‐2 inhibitors (21%) or opioids (26%). To manage pain, 61% of clinicians stated to collaborate with other specialists. Physiotherapy was often suggested but less frequently used by PWH.
Conclusions
Pain is under‐recognized and unsatisfactorily addressed by haemophilia treatment centre (HTC) clinicians, with discrepant management compared to PWH responses. Education in systematic pain assessment and multidisciplinary treatment and development of management guidelines are highly needed.
Confronting the psychological burden of haemophilia COPPOLA, A.; CERBONE, A. M.; MANCUSO, G. ...
Haemophilia : the official journal of the World Federation of Hemophilia,
01/2011, Letnik:
17, Številka:
1
Journal Article
Recenzirano
Providing comprehensive care, counselling and support to haemophilic patients, and their parents have always been quite complex for haemophilia treatment centres. Nowadays, starting with recent ...developments in genetic counselling, prenatal diagnosis and carrier testing, the psychological burden on patients and parents might possibly have increased, compared with even the recent past. The emotional strains and worries associated with a possibly affected newborn and his care through childhood and adolescence may also have a grievous impact on couple dynamics and marital relationship. The impact may be even higher in families in which haemophilia is newly diagnosed. The main psychological problems faced by parents and then by affected individuals are herein chronologically reviewed, starting from genetic counselling before conception through childhood, adolescence and adulthood. Aware of the psychosocial burden on patients and their families associated with haemophilia, from prenatal diagnosis and carrier testing until later stages of life of the affected individual, a board of Italian haemophilia specialists and psychologists is designing and organizing an innovative network of psychological support services in some Italian haemophilia centres and promoting specific educational programmes in this setting.
Cost of care of haemophilia with inhibitors MINNO, M. N. D. DI; MINNO, G. DI; CAPUA, M. DI ...
Haemophilia : the official journal of the World Federation of Hemophilia,
01/2010, Letnik:
16, Številka:
1
Journal Article
Recenzirano
In Western countries, the treatment of patients with inhibitors is presently the most challenging and serious issue in haemophilia management, direct costs of clotting factor concentrates accounting ...for >98% of the highest economic burden absorbed for the healthcare of patients in this setting. Being designed to address questions of resource allocation and effectiveness, decision models are the golden standard to reliably assess the overall economic implications of haemophilia with inhibitors in terms of mortality, bleeding‐related morbidity, and severity of arthropathy. However, presently, most data analyses stem from retrospective short‐term evaluations, that only allow for the analysis of direct health costs. In the setting of chronic diseases, the cost‐utility analysis, that takes into account the beneficial effects of a given treatment/healthcare intervention in terms of health‐related quality of life, is likely to be the most appropriate approach. To calculate net benefits, the quality adjusted life year, that significantly reflects such health gain, has to be compared with specific economic impacts. Differences in data sources, in medical practice and/or in healthcare systems and costs, imply that most current pharmacoeconomic analyses are confined to a narrow healthcare payer perspective. Long‐term/lifetime prospective or observational studies, devoted to a careful definition of when to start a treatment; of regimens (dose and type of product) to employ, and of inhibitor population (children/adults, low‐responding/high responding inhibitors) to study, are thus urgently needed to allow for newer insights, based on reliable data sources into resource allocation, effectiveness and cost‐utility analysis in the treatment of haemophiliacs with inhibitors.
Background: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies against coagulation factor VIII and characterized by spontaneous hemorrhage in patients with no previous ...family or personal history of bleeding. Although data on several AHA cohorts have been collected, limited information is available on the optimal management of AHA.
Objectives: The European Acquired Hemophilia Registry (EACH2) was established to generate a prospective, large‐scale, pan‐European database on demographics, diagnosis, underlying disorders, bleeding characteristics, treatment and outcome of AHA patients.
Results: Five hundred and one (266 male, 235 female) patients from 117 centers and 13 European countries were included in the registry between 2003 and 2008. In 467 cases, hemostasis investigations and AHA diagnosis were triggered by a bleeding event. At diagnosis, patients were a median of 73.9 years. AHA was idiopathic in 51.9%; malignancy or autoimmune diseases were associated with 11.8% and 11.6% of cases. Fifty‐seven per cent of the non‐pregnancy‐related cases were male. Four hundred and seventy‐four bleeding episodes were reported at presentation, and hemostatic therapy initiated in 70.5% of patients. Delayed diagnosis significantly impacted treatment initiation in 33.5%. Four hundred and seventy‐seven patients underwent immunosuppression, and 72.6% achieved complete remission.
Conclusions: Representing the largest collection of consecutive AHA cases to date, EACH2 facilitates the analysis of a variety of open questions in AHA.
Acquired hemophilia A is a rare bleeding disorder caused by autoantibodies to coagulation FVIII. Bleeding episodes at presentation are spontaneous and severe in most cases. Optimal hemostatic therapy ...is controversial, and available data are from observational and retrospective studies only. The EACH2 registry, a multicenter, pan-European, Web-based database, reports current patient management. The aim was to assess the control of first bleeding episodes treated with a bypassing agent (rFVIIa or aPCC), FVIII, or DDAVP among 501 registered patients. Of 482 patients with one or more bleeding episodes, 144 (30%) received no treatment for bleeding; 31 were treated with symptomatic therapy only. Among 307 patients treated with a first-line hemostatic agent, 174 (56.7%) received rFVIIa, 63 (20.5%) aPCC, 56 (18.2%) FVIII, and 14 (4.6%) DDAVP. Bleeding was controlled in 269 of 338 (79.6%) patients treated with a first-line hemostatic agent or ancillary therapy alone. Propensity score matching was applied to allow unbiased comparison between treatment groups. Bleeding control was significantly higher in patients treated with bypassing agents versus FVIII/DDAVP (93.3% vs 68.3%; P = .003). Bleeding control was similar between rFVIIa and aPCC (93.0%; P = 1). Thrombotic events were reported in 3.6% of treated patients with a similar incidence between rFVIIa (2.9%) and aPCC (4.8%).
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