- Email: [email protected]
Plenary session
Thursday, November 6th, 2014 / Thrombosis Research 134S2 (2014) S1–S103 1 Department of Clinical Medicine and Surgery, “Federico II” University Hospital, Napoli, Italy; 2 European Institute of Oncology, Milano, Italy; 3 Department of Public Health, “Federico II” University Hospital, Napoli, Italy; 4 Department of Cardiac Surgery, IRCCS Policlinico San Donato, Milano, Italy
Background: The risk of venous thromboembolism (VTE) is increased by a factor of approximately 6 in patients with cancer compared with noncancer patients, and cancer patients account for approximately 20% of all newly diagnosed cases of VTE. Venous thromboembolic risk assessment models has been developed, that include clinical and laboratory markers. An improvement in risk stratification would allow better identification of patients for primary VTE prevention. Materials and methods: The study population includes 843 patients enrolled between October 2012 and April 2014 in the ONCOTEV, a prospective, bi-centric, observational study performed at “Federico II” University of Napoli and University Cancer Center of Leipzig. We collected clinical, laboratory and imaging data from cancer patients undergoing anti tumoral treatments. We determined the prevalence of VTE (symptomatic and asymptomatic) and tested the Khorana score in this population. Different VTE risk factors were investigated in order to create a risk assessment model. Results: We found a VTE prevalence of 7.5% (n=63), over a median follow up of 7.5 months (interquartile range 3.9–10.8). Four out of these 63 events (6%) were asymptomatic. Median time from primary diagnosis to VTE onset is 21 months (interquartile range 11.1–44.4). According to Khorana score, VTE rates were 7.9% (30/378), 6.5% (22/338) in and 21.7% (10/46) in low, intermediate and high risk categories, respectively. Odds Ratio (OR) for high risk was 2.74 compared to intermediate risk. In the univariate analysis we found that gastric and pancreatic primary sites (OR=2.89, p=0.003), previous VTE (OR=3.26, p<0.01), metastatic disease (OR=3.75, p<0.01), vascular/lymphatic compression by tumor (OR 4.47, p<0.01), leg edema (OR=3.51, p<0.01) and positive tumor markers (OR=2.31, p=0.014) were predictors of VTE, while surgery within 6 months (OR=0.39, p<0.001) was associated to a reduced risk. In the multivariate analysis Khorana score >2 (OR 3.44, p=0.008), previous VTE (OR 3.39, p=0.002), metastatic disease (OR 4.6, p=0.001) and vascular/lymphatic compression (OR 3.43, p=0.002) were independently associated with the outcome. Conclusions: The study confirms the prediction value of Khorana score in our cancer patient population. However, this study shows that other easy-to-measure variables predict the risk of VTE. If confirmed in the future, these findings may represent the first step to the validation of a new risk score that can accurately detect patients to switch to primary VTE prevention.
Plenary session SY-13 Pneumonia and thrombosis: an emergent new clinical model F. Violi I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Roma, Italy An enhanced risk of cardiovascular mortality has been observed after pneumonia. Epidemiological studies have shown that respiratory tract infections are associated with an increased risk of thrombotic-related vascular disease such as myocardial infarction, ischemic stroke and venous thrombosis. Myocardial infarction and stroke have been detected essentially in the early phase of the disease, i.e. within 48 hours from hospital admission, with an incidence ranging from as low as 1% to as high as 11%. Age, previous cardiovascular events and high pneumonia severity index were independent predictors of myocardial infarction; clinical predictors of stroke were not identified. Deep venous thrombosis and pulmonary embolism may also occur after pneumonia but incidence and clinical predictors must be defined. Biological plausibility of such association may be deduced by experimental and clinical studies, showing that lung infection is complicated by platelet aggregation and clotting system activation, as documented by up-regulation of Tissue Factor and down-regulation of activated Protein C. The effect of antithrombotic drugs have been examined in experimental and clinical studies but results are still inconclusive. Thrombotic-related vascular disease such as myocardial infarction, stroke
S17
and venous thromboembolism may complicate the clinical course of pneumonia and worsen its prognosis. Further definition of predictors may help to identify patients at higher risk of artery and venous thrombosis. Patients with pneumonia could benefit from antithrombotic strategy including anticoagulants and/or antiplatelet drugs but this should be tested in randomized clinical studies.
SY-14 Thrombosis and cancer: a token to the memory of Roberto Lorenzet M.B. Donati Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy Our group has been working since the seventies to explore the possible interactions between the hemostatic system and the growth and dissemination of tumors, using both cellular and experimental models. Since those years the topic has been widely extended and moved from the interest of few pioneers to an issue of wide clinical concern. This change has been operated mainly thanks to the extension of the reports on thrombosis complicating both solid and hematological malignancies and to the observation that a thrombotic episode could occur even many months before the clinical manifestation of a hidden cancer. The pathogenesis of the involvement of the hemostatic system in cancer is multifaceted and multifactorial, but finds a pivotal mechanism in the expression of tumor cell-associated procoagulant activities, which play an important role in tumor development and progression. It appears increasingly clear that activation of several prototypic oncogenic pathways alters the expression, activity and vesicular release of coagulation effectors as exemplified by Tissue Factor (TF). The latter was proven to impact on tumor/metastasis growth both when expressed by host cells (such as tumor-infiltrating macrophages and endothelial cells in the angiogenetic process) and when up-regulated as a constitutive mediator in most types of cancer cells, as shown by work of Roberto Lorenzet and his group since the early eighties and subsequently, during the following two decades, till his last studies on the TF/Vascular Endothelial Growth Factor loop, to explore the mechanisms of the pro-thrombotic effects of antiangiogenic drugs. In this context, Roberto’s work explored as well the modulation of TF , this crucial middleman of so many physiopathological pathways, by pharmacological and nutraceutical approaches, thus providing a rational basis for the development of novel prevention strategies.
SY-15 The platelet P2Y12 receptor for ADP: structure and function M. Cattaneo Medicina III, Ospedale San Paolo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Italy P2Y12 , one of the two platelet receptors for adenosine diphosphate (ADP), plays a central role in platelet function. It maps to chromosome 3q21-q25, contains 342 amino acid residues, and displays two potential N-linked glycosylation sites at its extra-cellular amino-terminus which may modulate its activity. P2Y12 is coupled to inhibition of adenylyl-cyclase (AC) activity through Gαi2 , which bears no causal relationship to platelet aggregation, although it may contribute to platelet thrombus formation in vivo by counteracting the antiplatelet effect of AC stimulators. Different isoforms of phosphoinositide 3-kinase (PI3-K) play a crucial role in ADP-dependent P2Y12 receptor-mediated amplification of platelet activation. ADP induces slow and sustained P2Y12 /PI3-K-dependent platelet aggregation not preceded by platelet shape change, when the other ADP receptor, P2Y1 , is inhibited. The interaction of ADP with P2Y12 amplifies platelet secretion induced by strong agonists, stabilizes platelet aggregates and mediates shear-induced platelet aggregation. P2Y12 shares with P2Y1 the ability to contribute to collagen-induced platelet microparticle formation in whole blood and to the formation of platelet-leukocyte aggregates, which results in tissue factor exposure at the surface of leukocytes. P2Y12 is also involved in the exposure of phosphatidylserine by platelet agonists. In addition to its role in hemostasis, the platelet P2Y12 receptor plays also a role in inflammatory reactions. Patients with congenital P2Y12 defects display a mild-to-moderate bleeding diathesis. Defects of P2Y12 should be suspected when ADP, even at high concentrations, is unable to induce full, irreversible platelet aggregation. Tests that evaluate the degree of inhibition of AC by ADP should be used to confirm the diagnosis. Inherited point mutations
S18
Thursday, November 6th, 2014 / Thrombosis Research 134S2 (2014) S1–S103
in the P2Y12 gene, associated with the synthesis of normal amounts of dysfunctional receptor helped in the characterization of structure/function relationships of the receptor. Drugs that inhibit P2Y12 are potent antithrombotic drugs, attesting the central role played by P2Y12 in platelet thrombus formation.
SY-16 Behçet syndrome as a model of inflammatory thrombosis D. Prisco, E. Silvestri, G. Emmi, L. Emmi SOD Patologia Medica, Center for Autoimmune Systemic Diseases – Behçet Center and Lupus Clinic – AOU Careggi and Dept. of Experimental and Clinical Medicine, University of Firenze, Italy Behçet syndrome (BS) is a systemic vasculitis of unknown origin characterized by bipolar aphthosis and ocular lesions, as well as articular, neurological and gastrointestinal involvement. Cardiovascular manifestations affect up to 45% of BS patients involving vessels of all sizes. Deep vein thrombosis (DVT) and superficial vein thrombophlebitis of lower extremities are the typical manifestations. DVT is an important cause of morbidity and mortality, occurs more frequently in male patients with active disease and usually tends to recur. The pathophysiology of thrombosis in BS is not well known but systemic inflammation seems to be the main trigger. Inflammation and haemostasis are closely linked and the immune system plays a role in prothrombotic process leading to an alteration of endothelial cells, coagulation cascade and fibrinolytic system. On the other hand, coagulation system promotes inflammation and thrombosis. T cells, monocytes, neutrophils and pro-inflammatory cytokines such as TNF-α, IL-1 and IL-6 along with endothelial cell dysfunction (ECD) are the main mechanisms involved. ECD, resulting from immunological and inflammatory stimulations, seems to be a characteristic feature of BS and to play a key role in thrombogenesis in BS patients. Of note, traditional immunosuppressive treatment is the first line therapy of vascular thrombosis in BS. Anti-inflammatory treatment seems to be able to reduce inflammation of vessels and thrombus formation and to prevent its recurrence. More recently, the use of anti-tumor necrosis factor alpha (TNFα) agents has shown a good efficacy in refractory venous thrombosis or in patients intolerant to conventional immunosuppressive therapy, whereas cyclophosphamide is always the cornerstone of arterial damage. Also in our own experience the use of anti-TNFα, and particularly adalimumab (a fully human anti-TNFα monoclonal antibody), has proven effective not only in refractory forms, but also as first line treatment in active angio-Behçet.
probably even less intense) in many IDDVTs. We believe that the now oral anticoagulants may play an important role for the treatment of IDDVTs.
SY-18 Back to the phenotype in the post-genomic era? F. Rodeghiero Department of Cell Therapy and Hematology, Hemostasis and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy Recently, genomic technologies have become a routine part of human genetic analysis. The increasing possibilities of DNA sequencing have brought to an unprecedented understanding of human genetic variation and to the identification of a myriad of variants that may theoretically impact on the individual phenotype. The aim of this presentation is to offer some critical considerations on the real utility of these technological possibilities in the specific setting of hemostatic disorders. I will base my analysis on personal experience in the context of a hospital referral center during almost 40 years of epidemiological, clinical and biological research, enriched by a continuous discussion within my group and by extensive international collaborations. Two main overlapping periods will ideally be considered. The first period is characterized by the effort to improve the identification of the different phenotypes of patients with distinct disorders by means of personal and family history, clinical features and laboratory measurements of biological or antigenic specific activities, and with the aid of classical genetics, where appropriate. The second period, still in full expansion, starts with the application of molecular biology techniques in our laboratories and is now extending into the post-genomic era. The promises of this period are represented by an increasing application of personalized medicine and by a better identification of molecular prognostic markers. Taking some diseases, such as FXIII deficiency, VWD, thrombophilia and immune thrombocytopenia as epitomes, I will propose the need to critically reconsider our global approach in the investigation and management of patients with hemorrhagic and thrombotic disorders by posing again the phenotype of the individual patient as one of the main objects of our research. At variance with what the expectations in oncology are, the phenotype still offers – at least in our field – the most accurate representation of environment/gene interactions interplay in the individual patient and new efforts should be taken to improve its characterization.
SY-17 Venous thrombosis confined to the calf: what we know and what to do
Poster sessions
G. Palareti Professor in Cardiovascular Diseases, University of Bologna, Italy
Poster session I Hemophilia, rare bleeding disorders, VWD and platelets
Thromboses limited to the calf veins (IDDVTs) are frequently diagnosed in subjects with suspected pulmonary embolism or DVT, and account for 30% of all diagnosed DVTs of the leg. Their natural history and the real risk of thromboembolic complications are, however, still uncertain and it is debated whether they warrant diagnosis and treatment. Diagnosis is based on compression ultrasonography of veins, which is more operator-dependent and less sensitive for distal compared to proximal veins. From what we know, it is reasonable to affirm that most IDDVTs are self-limiting and inconsequential for patients; in some cases, however, they can be associated with complications and warrant diagnosis and treatment. The available guidelines for treatment of IDDVTs give different indications ranging from serial imaging of the deep veins for 2 weeks, in order to detect and treat only in case of proximal extension, to giving oral anticoagulation in all IDDVT patients for three months. We are convinced that once diagnosed in symptomatic outpatients all IDDVTs should receive anticoagulant treatment. However, the type, dose, and duration of treatment may be regulated differently depending on a series of factors: history of VTE, nature of the event (idiopathic or secondary), extension of thrombosis, presence of important predisposing diseases. All these conditions are similar to those mentioned by the authors of the last ACCP guidelines, the only difference being that they suggest using the presence or absence of these factors as criterion for deciding whether to give anticoagulation or to proceed with serial imaging alone. In contrast, our approach is based on the use of these conditions as criteria for regulating the type and duration of anticoagulation, since we believe there is evidence for shorter anticoagulation (and
P-1 Efficacy of bevacizumab in hereditary haemorrhagic telangiectasia (Rendu Osler syndrome): a case report M. Marzolo 1 , E. Buscarini 3 , S. Aggio 2 , C. Rossetti 1 , S.C.a.E. Ramazzina 1 1 Internal Medicine-Angiology Unit; 2 Cardiology Unit, General Hospital of Rovigo; 3 Gastroenterology Unit, Maggiore Hospital of Crema, Italy Hereditary Haemorrhagic Teleangiectasia (HHT) is a genetic vascular disorder. It is characterized by recurrent haemorrhages, cutaneous and visceral arteriovenous malformations (AVMs); liver AVMs can overload systemic circulation with progressive heart failure and secondary pulmonary hypertension. At present the only curative option for liver AVMs is liver transplant. Since 2008 anti-vascular endothelial growth factor treatment bevacizumab, has been reported as effective treatment for liver AVMs complications We describe the use of bevacizumab in a 71 yo female with HHT, high output cardiac failure and pulmonary hypertension secondary to severe liver AVMs. The patient failed to respond to intensive cardiological treatment over 12 months, she was also excluded from liver transplant because of age. In the 12 month period of medical treatment the patient had seven hospital admissions for cardiac decompensation, severe recurrent nosebleeds with high transfusional requirement. The pulmonary systolic pressure (PAPS) had progressively risen to very high levels (100 mmHg cardiac cath/echo). On July 2013 bevacizumab infusion was started (5 mg/kg every 3 weeks for
Background: The risk of venous thromboembolism (VTE) is increased by a factor of approximately 6 in patients with cancer compared with noncancer patients, and cancer patients account for approximately 20% of all newly diagnosed cases of VTE. Venous thromboembolic risk assessment models has been developed, that include clinical and laboratory markers. An improvement in risk stratification would allow better identification of patients for primary VTE prevention. Materials and methods: The study population includes 843 patients enrolled between October 2012 and April 2014 in the ONCOTEV, a prospective, bi-centric, observational study performed at “Federico II” University of Napoli and University Cancer Center of Leipzig. We collected clinical, laboratory and imaging data from cancer patients undergoing anti tumoral treatments. We determined the prevalence of VTE (symptomatic and asymptomatic) and tested the Khorana score in this population. Different VTE risk factors were investigated in order to create a risk assessment model. Results: We found a VTE prevalence of 7.5% (n=63), over a median follow up of 7.5 months (interquartile range 3.9–10.8). Four out of these 63 events (6%) were asymptomatic. Median time from primary diagnosis to VTE onset is 21 months (interquartile range 11.1–44.4). According to Khorana score, VTE rates were 7.9% (30/378), 6.5% (22/338) in and 21.7% (10/46) in low, intermediate and high risk categories, respectively. Odds Ratio (OR) for high risk was 2.74 compared to intermediate risk. In the univariate analysis we found that gastric and pancreatic primary sites (OR=2.89, p=0.003), previous VTE (OR=3.26, p<0.01), metastatic disease (OR=3.75, p<0.01), vascular/lymphatic compression by tumor (OR 4.47, p<0.01), leg edema (OR=3.51, p<0.01) and positive tumor markers (OR=2.31, p=0.014) were predictors of VTE, while surgery within 6 months (OR=0.39, p<0.001) was associated to a reduced risk. In the multivariate analysis Khorana score >2 (OR 3.44, p=0.008), previous VTE (OR 3.39, p=0.002), metastatic disease (OR 4.6, p=0.001) and vascular/lymphatic compression (OR 3.43, p=0.002) were independently associated with the outcome. Conclusions: The study confirms the prediction value of Khorana score in our cancer patient population. However, this study shows that other easy-to-measure variables predict the risk of VTE. If confirmed in the future, these findings may represent the first step to the validation of a new risk score that can accurately detect patients to switch to primary VTE prevention.
Plenary session SY-13 Pneumonia and thrombosis: an emergent new clinical model F. Violi I Clinica Medica, Atherothrombosis Center, Department of Internal Medicine and Medical Specialties, Sapienza University of Roma, Italy An enhanced risk of cardiovascular mortality has been observed after pneumonia. Epidemiological studies have shown that respiratory tract infections are associated with an increased risk of thrombotic-related vascular disease such as myocardial infarction, ischemic stroke and venous thrombosis. Myocardial infarction and stroke have been detected essentially in the early phase of the disease, i.e. within 48 hours from hospital admission, with an incidence ranging from as low as 1% to as high as 11%. Age, previous cardiovascular events and high pneumonia severity index were independent predictors of myocardial infarction; clinical predictors of stroke were not identified. Deep venous thrombosis and pulmonary embolism may also occur after pneumonia but incidence and clinical predictors must be defined. Biological plausibility of such association may be deduced by experimental and clinical studies, showing that lung infection is complicated by platelet aggregation and clotting system activation, as documented by up-regulation of Tissue Factor and down-regulation of activated Protein C. The effect of antithrombotic drugs have been examined in experimental and clinical studies but results are still inconclusive. Thrombotic-related vascular disease such as myocardial infarction, stroke
S17
and venous thromboembolism may complicate the clinical course of pneumonia and worsen its prognosis. Further definition of predictors may help to identify patients at higher risk of artery and venous thrombosis. Patients with pneumonia could benefit from antithrombotic strategy including anticoagulants and/or antiplatelet drugs but this should be tested in randomized clinical studies.
SY-14 Thrombosis and cancer: a token to the memory of Roberto Lorenzet M.B. Donati Department of Epidemiology and Prevention, IRCCS Istituto Neurologico Mediterraneo Neuromed, Pozzilli, Italy Our group has been working since the seventies to explore the possible interactions between the hemostatic system and the growth and dissemination of tumors, using both cellular and experimental models. Since those years the topic has been widely extended and moved from the interest of few pioneers to an issue of wide clinical concern. This change has been operated mainly thanks to the extension of the reports on thrombosis complicating both solid and hematological malignancies and to the observation that a thrombotic episode could occur even many months before the clinical manifestation of a hidden cancer. The pathogenesis of the involvement of the hemostatic system in cancer is multifaceted and multifactorial, but finds a pivotal mechanism in the expression of tumor cell-associated procoagulant activities, which play an important role in tumor development and progression. It appears increasingly clear that activation of several prototypic oncogenic pathways alters the expression, activity and vesicular release of coagulation effectors as exemplified by Tissue Factor (TF). The latter was proven to impact on tumor/metastasis growth both when expressed by host cells (such as tumor-infiltrating macrophages and endothelial cells in the angiogenetic process) and when up-regulated as a constitutive mediator in most types of cancer cells, as shown by work of Roberto Lorenzet and his group since the early eighties and subsequently, during the following two decades, till his last studies on the TF/Vascular Endothelial Growth Factor loop, to explore the mechanisms of the pro-thrombotic effects of antiangiogenic drugs. In this context, Roberto’s work explored as well the modulation of TF , this crucial middleman of so many physiopathological pathways, by pharmacological and nutraceutical approaches, thus providing a rational basis for the development of novel prevention strategies.
SY-15 The platelet P2Y12 receptor for ADP: structure and function M. Cattaneo Medicina III, Ospedale San Paolo, Dipartimento di Scienze della Salute, Università degli Studi di Milano, Italy P2Y12 , one of the two platelet receptors for adenosine diphosphate (ADP), plays a central role in platelet function. It maps to chromosome 3q21-q25, contains 342 amino acid residues, and displays two potential N-linked glycosylation sites at its extra-cellular amino-terminus which may modulate its activity. P2Y12 is coupled to inhibition of adenylyl-cyclase (AC) activity through Gαi2 , which bears no causal relationship to platelet aggregation, although it may contribute to platelet thrombus formation in vivo by counteracting the antiplatelet effect of AC stimulators. Different isoforms of phosphoinositide 3-kinase (PI3-K) play a crucial role in ADP-dependent P2Y12 receptor-mediated amplification of platelet activation. ADP induces slow and sustained P2Y12 /PI3-K-dependent platelet aggregation not preceded by platelet shape change, when the other ADP receptor, P2Y1 , is inhibited. The interaction of ADP with P2Y12 amplifies platelet secretion induced by strong agonists, stabilizes platelet aggregates and mediates shear-induced platelet aggregation. P2Y12 shares with P2Y1 the ability to contribute to collagen-induced platelet microparticle formation in whole blood and to the formation of platelet-leukocyte aggregates, which results in tissue factor exposure at the surface of leukocytes. P2Y12 is also involved in the exposure of phosphatidylserine by platelet agonists. In addition to its role in hemostasis, the platelet P2Y12 receptor plays also a role in inflammatory reactions. Patients with congenital P2Y12 defects display a mild-to-moderate bleeding diathesis. Defects of P2Y12 should be suspected when ADP, even at high concentrations, is unable to induce full, irreversible platelet aggregation. Tests that evaluate the degree of inhibition of AC by ADP should be used to confirm the diagnosis. Inherited point mutations
S18
Thursday, November 6th, 2014 / Thrombosis Research 134S2 (2014) S1–S103
in the P2Y12 gene, associated with the synthesis of normal amounts of dysfunctional receptor helped in the characterization of structure/function relationships of the receptor. Drugs that inhibit P2Y12 are potent antithrombotic drugs, attesting the central role played by P2Y12 in platelet thrombus formation.
SY-16 Behçet syndrome as a model of inflammatory thrombosis D. Prisco, E. Silvestri, G. Emmi, L. Emmi SOD Patologia Medica, Center for Autoimmune Systemic Diseases – Behçet Center and Lupus Clinic – AOU Careggi and Dept. of Experimental and Clinical Medicine, University of Firenze, Italy Behçet syndrome (BS) is a systemic vasculitis of unknown origin characterized by bipolar aphthosis and ocular lesions, as well as articular, neurological and gastrointestinal involvement. Cardiovascular manifestations affect up to 45% of BS patients involving vessels of all sizes. Deep vein thrombosis (DVT) and superficial vein thrombophlebitis of lower extremities are the typical manifestations. DVT is an important cause of morbidity and mortality, occurs more frequently in male patients with active disease and usually tends to recur. The pathophysiology of thrombosis in BS is not well known but systemic inflammation seems to be the main trigger. Inflammation and haemostasis are closely linked and the immune system plays a role in prothrombotic process leading to an alteration of endothelial cells, coagulation cascade and fibrinolytic system. On the other hand, coagulation system promotes inflammation and thrombosis. T cells, monocytes, neutrophils and pro-inflammatory cytokines such as TNF-α, IL-1 and IL-6 along with endothelial cell dysfunction (ECD) are the main mechanisms involved. ECD, resulting from immunological and inflammatory stimulations, seems to be a characteristic feature of BS and to play a key role in thrombogenesis in BS patients. Of note, traditional immunosuppressive treatment is the first line therapy of vascular thrombosis in BS. Anti-inflammatory treatment seems to be able to reduce inflammation of vessels and thrombus formation and to prevent its recurrence. More recently, the use of anti-tumor necrosis factor alpha (TNFα) agents has shown a good efficacy in refractory venous thrombosis or in patients intolerant to conventional immunosuppressive therapy, whereas cyclophosphamide is always the cornerstone of arterial damage. Also in our own experience the use of anti-TNFα, and particularly adalimumab (a fully human anti-TNFα monoclonal antibody), has proven effective not only in refractory forms, but also as first line treatment in active angio-Behçet.
probably even less intense) in many IDDVTs. We believe that the now oral anticoagulants may play an important role for the treatment of IDDVTs.
SY-18 Back to the phenotype in the post-genomic era? F. Rodeghiero Department of Cell Therapy and Hematology, Hemostasis and Thrombosis Center, San Bortolo Hospital, Vicenza, Italy Recently, genomic technologies have become a routine part of human genetic analysis. The increasing possibilities of DNA sequencing have brought to an unprecedented understanding of human genetic variation and to the identification of a myriad of variants that may theoretically impact on the individual phenotype. The aim of this presentation is to offer some critical considerations on the real utility of these technological possibilities in the specific setting of hemostatic disorders. I will base my analysis on personal experience in the context of a hospital referral center during almost 40 years of epidemiological, clinical and biological research, enriched by a continuous discussion within my group and by extensive international collaborations. Two main overlapping periods will ideally be considered. The first period is characterized by the effort to improve the identification of the different phenotypes of patients with distinct disorders by means of personal and family history, clinical features and laboratory measurements of biological or antigenic specific activities, and with the aid of classical genetics, where appropriate. The second period, still in full expansion, starts with the application of molecular biology techniques in our laboratories and is now extending into the post-genomic era. The promises of this period are represented by an increasing application of personalized medicine and by a better identification of molecular prognostic markers. Taking some diseases, such as FXIII deficiency, VWD, thrombophilia and immune thrombocytopenia as epitomes, I will propose the need to critically reconsider our global approach in the investigation and management of patients with hemorrhagic and thrombotic disorders by posing again the phenotype of the individual patient as one of the main objects of our research. At variance with what the expectations in oncology are, the phenotype still offers – at least in our field – the most accurate representation of environment/gene interactions interplay in the individual patient and new efforts should be taken to improve its characterization.
SY-17 Venous thrombosis confined to the calf: what we know and what to do
Poster sessions
G. Palareti Professor in Cardiovascular Diseases, University of Bologna, Italy
Poster session I Hemophilia, rare bleeding disorders, VWD and platelets
Thromboses limited to the calf veins (IDDVTs) are frequently diagnosed in subjects with suspected pulmonary embolism or DVT, and account for 30% of all diagnosed DVTs of the leg. Their natural history and the real risk of thromboembolic complications are, however, still uncertain and it is debated whether they warrant diagnosis and treatment. Diagnosis is based on compression ultrasonography of veins, which is more operator-dependent and less sensitive for distal compared to proximal veins. From what we know, it is reasonable to affirm that most IDDVTs are self-limiting and inconsequential for patients; in some cases, however, they can be associated with complications and warrant diagnosis and treatment. The available guidelines for treatment of IDDVTs give different indications ranging from serial imaging of the deep veins for 2 weeks, in order to detect and treat only in case of proximal extension, to giving oral anticoagulation in all IDDVT patients for three months. We are convinced that once diagnosed in symptomatic outpatients all IDDVTs should receive anticoagulant treatment. However, the type, dose, and duration of treatment may be regulated differently depending on a series of factors: history of VTE, nature of the event (idiopathic or secondary), extension of thrombosis, presence of important predisposing diseases. All these conditions are similar to those mentioned by the authors of the last ACCP guidelines, the only difference being that they suggest using the presence or absence of these factors as criterion for deciding whether to give anticoagulation or to proceed with serial imaging alone. In contrast, our approach is based on the use of these conditions as criteria for regulating the type and duration of anticoagulation, since we believe there is evidence for shorter anticoagulation (and
P-1 Efficacy of bevacizumab in hereditary haemorrhagic telangiectasia (Rendu Osler syndrome): a case report M. Marzolo 1 , E. Buscarini 3 , S. Aggio 2 , C. Rossetti 1 , S.C.a.E. Ramazzina 1 1 Internal Medicine-Angiology Unit; 2 Cardiology Unit, General Hospital of Rovigo; 3 Gastroenterology Unit, Maggiore Hospital of Crema, Italy Hereditary Haemorrhagic Teleangiectasia (HHT) is a genetic vascular disorder. It is characterized by recurrent haemorrhages, cutaneous and visceral arteriovenous malformations (AVMs); liver AVMs can overload systemic circulation with progressive heart failure and secondary pulmonary hypertension. At present the only curative option for liver AVMs is liver transplant. Since 2008 anti-vascular endothelial growth factor treatment bevacizumab, has been reported as effective treatment for liver AVMs complications We describe the use of bevacizumab in a 71 yo female with HHT, high output cardiac failure and pulmonary hypertension secondary to severe liver AVMs. The patient failed to respond to intensive cardiological treatment over 12 months, she was also excluded from liver transplant because of age. In the 12 month period of medical treatment the patient had seven hospital admissions for cardiac decompensation, severe recurrent nosebleeds with high transfusional requirement. The pulmonary systolic pressure (PAPS) had progressively risen to very high levels (100 mmHg cardiac cath/echo). On July 2013 bevacizumab infusion was started (5 mg/kg every 3 weeks for