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Mannucci P.M.,anchi Bonomi Hemophilia And Thrombosis Center | Franchini M.,Carlo Poma Hospital
Thrombosis and Haemostasis | Year: 2015

Thrombophilia is defined as a condition predisposing to the development of venous thromboembolism (VTE) on the basis of a hypercoagulable state. Over the past decades, great advances in the pathogenesis of VTE have been made and nowadays it is well established that a thrombophilic state may be associated with acquired and/or inherited factors. The rare loss-of-function mutations of the genes encoding natural anticoagulant proteins (i. e. protein C, protein S and antithrombin) and the more common gain-of-function polymorphisms factor V Leiden and prothrombin G20210A are the main genetic determinants of thrombophilia. In addition, non-O blood group has been consistently demonstrated to be the most frequent inherited marker of an increased risk of VTE. The mechanism role of these inherited thrombophilia markers will be discussed in this narrative review. © Schattauer 2015. Source

Castelli R.,University of Milan | Bucciarelli P.,anchi Bonomi Hemophilia And Thrombosis Center | Porro F.,Emergency Medicine Unit | Depetri F.,University of Milan | Cugno M.,University of Milan
Thrombosis Research | Year: 2014

Background Pulmonary embolism (PE) is associated with high short-term mortality in elderly patients, even when hemodynamically stable. Methods One hundred and seventy hemodynamically stable patients with confirmed PE (41 < 65 years and 129 ≥ 65 years) were prospectively followed for one month in order to assess whether comorbidities can predict short-term mortality in elderly patients. Upon admission, patients' clinical characteristics (including instrumental and laboratory parameters) were evaluated, and two clinical scores were calculated: the Cumulative Illness Rating Scale (CIRS), commonly used to evaluate comorbidities in elderly patients, and the Pulmonary Embolism Severity Index (PESI). Results Fifteen patients (all elderly) died within one month from their PE diagnosis (mortality rate = 8.8%; 95%CI:4.6-13.1%). In these non survivors, arterial partial oxygen pressure (p < 0.0001) and saturation (p < 0.0001), pH (p = 0.001) and systolic blood pressure (p = 0.017) at admission were significantly lower than in survivors, whereas their respiratory rate (p < 0.0001), white blood cells (p < 0.0001), lactate dehydrogenase (p < 0.0001), troponin T (p = 0.001) and D-dimer (p = 0.023) were significantly higher. CIRS correlated with PESI (rho = 0.54, p < 0.0001), and was higher in non-survivors (p = 0.002). The age- and sex-adjusted odds ratio of 1-month mortality was 1.91 (95%CI:1.24-2.95) for every 1-point increase in CIRS. The AUC was 0.78 (95%CI:0.67-0.89) for the logistic model containing CIRS, and 0.88 (95%CI:0.79-0.96) for that containing PESI (p = 0.059). Conclusions In elderly patients with PE, CIRS demonstrated a fairly good performance in predicting short-term mortality. Its easiness and suitability for use in common clinical practice make CIRS a potentially useful prognostic score for short-term mortality in these patients. © 2014 Elsevier Ltd. Source

Somigliana E.,Infertility Unit | Peccatori F.A.,Italian National Cancer Institute | Filippi F.,Infertility Unit | Martinelli F.,Italian National Cancer Institute | And 2 more authors.
Human Reproduction Update | Year: 2014

Background: Compared with the general population, cancer patients have a higher risk of venous thromboembolism as well as arterial thrombotic events such as stroke, myocardial infarction and peripheral arterial embolism. Therefore a possible concern for women with malignancies undergoing ovarian stimulation for fertility preservation is the increased risk of venous or arterial thrombosis. Methods: In this article, we revised current available literature on the risk of thrombosis in patients with cancer and in women undergoing ovarian stimulation, with the ultimate aim of drawing some indications for preventive measures. Results: Unfortunately, there are no specific data on the risk of thrombosis in women with cancer undergoing ovarian stimulation for fertility preservation. However, the literature suggests that the cancer type and stage, surgery, and chemotherapy all influence the risk of venous and, possibly, arterial thrombosis. Reports of cases of ovarian stimulation in women without malignancies have shown that venous thrombosis rarely occurs unless a pregnancy is achieved, while arterial thrombosis can occur in the absence of pregnancy but is usually only associated with ovarian hyperstimulation syndrome (OHSS). OHSS increases the risk of thrombotic events, but only the early form of the syndrome is relevant for women undergoing fertility preservation. Conclusions: The available evidence on the risks of thrombosis for women undergoing ovarian stimulation for fertility preservation due to a malignancy is reassuring. However the avoidance of the early form of OHSS in women preserving oocytes/embryos due to malignancy is crucial. For these cycles, we advocate the use of a regimen of ovarian stimulation with gonadotrophin releasing hormone (GnRH) antagonists using GnRH agonists to trigger ovulation, an approach that has been shown tomarkedly reduce the risk ofOHSS. Antithrombotic prophylaxis should be administered only to selected subgroups of women such as thosewith other risk factors or thosewho do develop early OHSS. © The Author 2014. Source

Coppola A.,University of Naples Federico II | Franchini M.,Carlo Poma Hospital | Makris M.,University of Sheffield | Santagostino E.,anchi Bonomi Hemophilia And Thrombosis Center | And 2 more authors.
Haemophilia | Year: 2012

Thrombotic adverse events (AEs) after clotting factor concentrate administration are rare but the actual rate is unknown. A systematic review of prospective studies (1990-2011) reporting safety data of factor concentrates in patients with haemophilia A (HA), haemophilia B (HB) and von Willebrand disease (VWD) was conducted to identify the incidence and type of thrombotic AEs. In 71 studies (45 in HA, 15 HB, 11 VWD) enrolling 5528 patients treated with 27 different concentrates (20 plasma-derived, 7 recombinant), 20 thrombotic AEs (2 HA, 11 HB, 7 VWD) were reported, including two major venous thromboembolic episodes (both in VWD patients on prolonged replacement for surgery). The remaining thrombotic AEs were superficial thrombophlebitis, mostly occurring at infusion sites in surgical patients and/or during concentrate continuous infusion. The overall prevalence was 3.6 per 10 3 patients (3.6 per 10 4 for severe AEs) and 1.13 per 10 5 infusions, with higher figures in VWD than in haemophilia. Thrombotic AEs accounted for 1.9% of non-inhibitor-related AEs. Thrombosis-related complications occurred in 10.8% of patients with central venous access devices (CVADs) reported in six studies, the risk increasing with time of CVAD use. Data from prospective studies over the last 20years suggest that the risk of thrombotic AEs from factor concentrate administration is small and mainly represented by superficial thrombophlebitis. These findings support the high degree of safety of products currently used for replacement treatment. © 2012 Blackwell Publishing Ltd. Source

Peyvandi F.,anchi Bonomi Hemophilia And Thrombosis Center | Peyvandi F.,University of Milan | Menegatti M.,University of Milan | Palla R.,University of Milan
Seminars in Thrombosis and Hemostasis | Year: 2013

Rare bleeding disorders (RBDs) comprise the inherited deficiencies of coagulation factors such as fibrinogen, factor (F)II, FV, FV + FVIII, FVII, FX, FXI, and FXIII, and are usually transmitted as autosomal recessive disorders. RBDs are characterized by a wide variety of symptoms from mild to severe; however, due to their rarity, only little information is available on the adequate management of patients affected with these deficiencies. Moreover, the limitations of laboratory assays and the lack of a definitive consensus concerning their classification have prevented adoption of optimal approaches to their individual management. To overcome these limitations, new strategies are therefore necessary, such as the establishment of global collaborations and networks among treatment centers, as well as increasing support provided by public health organizations. © 2013 by Thieme MedicalPublishers, Inc. Source

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