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Biomedical subjects

Anna Falanga

Publications and source records attributed to Anna Falanga.

At least 19 recordsLinked to original sources
PubMed2006

Cancer and venous thromboembolism.

The evidence of the important two-way clinical correlation between cancer and venous thromboembolism (VTE) dates back to Trousseau's time. Over time it has been established that cancer patients not only exhibit a higher risk of developing VTE when compared with noncancer patients, but also that VTE, especially in its idiopathic presentation, sometimes acts as an epiphenomenon of a hidden cancer, offering possible chances for anticipated diagnosis of the pathology. Research has contributed greatly to the progression of this field through the identification of VTE risk factors in this setting, and through the assessment of the most adequate thromboprophylaxis and treatment modalities as well as secondary prophylaxis management. Anticoagulant drugs appear to be an attractive strategy in cancer treatment because there is growing evidence for their possible benefits in terms of cancer prognosis and patient survival.

Anticoagulants↗
PubMed2006

Anticoagulants and cancer survival.

The association between cancer and activation of blood coagulation has been described since Trousseau's time. The hypercoagulable state often encountered in cancer patients not only acts as an important risk factor for thrombosis, but also may play a role in tumor progression and metastasization. An antineoplastic effect of anticoagulants in this setting has often been hypothesized. The results of recently conducted clinical trials suggest that cancer patients could have a benefit from administration of low molecular weight heparin, particularly in those with nonadvanced disease. Additional clinical trials are needed to provide an important step forward in this challenging setting.

Anticoagulants↗
PubMed2006

Differential effect of the low-molecular-weight heparin, dalteparin, and unfractionated heparin on microvascular endothelial cell hemostatic properties.

BACKGROUND AND OBJECTIVES: Heparins, including unfractionated heparin (UFH) and low-molecular-weight heparins (LMWH), are glycosaminoglycans that are largely used as anti-thrombotic drugs. While the mechanisms of their anticoagulant actions in blood have been extensively studied, their effects on the hemostatic properties of the endothelium are still under investigation. The aim of this study was to compare the antithrombotic effects of a LMWH, i.e. dalteparin, with UFH on both microvascular (human microvascular endothelial cells [HMEC-1]) and macrovascular (human umbilical vein endothelial cells [HUVEC]) endothelial cells. DESIGN AND METHODS: Endothelial cells were incubated with dalteparin or UFH and exposed to an inflammatory stimulus (i.e. lipopolysaccharide [LPS]). The following parameters were evaluated: tissue factor (TF procoagulant activity, antigen and mRNA), tissue factor pathway inhibitor (TFPI), and thrombomodulin (TM). RESULTS: In HMEC-1 and HUVEC, both heparins inhibited LPS-induced endothelial cell TF expression. However, in HMEC-1, dalteparin was significantly more effective than UFH. Both heparins increased TFPI antigen release in HMEC-1 and HUVEC. Dalteparin also reversed LPS-induced reduction of TM in HMEC-1, while UFH did not. INTERPRETATION AND CONCLUSIONS: These data show that both dalteparin and UFH suppress inflammatory-mediated TF expression and increase the anticoagulant properties of macro- and micro-vascular endothelial cells. However, dalteparin has significantly greater effects than UFH in the microvascular endothelium, a site that plays a central role in many processes involved in inflammation and thrombosis.

Cells, Cultured↗
PubMed2005

Leukocyte-platelet interaction in patients with essential thrombocythemia and polycythemia vera.

OBJECTIVE: Circulating polymorphonuclear leukocyte (PMN) activation occurs in patients with essential thrombocythemia (ET) and polycythemia vera (PV). We want to define whether this phenomenon plays a role in the formation of circulating PMN-platelet aggregates in these conditions. METHODS: In 80 patients (46 ET and 34 PV) and 50 control subjects, we conducted a flow cytometric analysis to evaluate the levels of PMN-platelet aggregates (defined as the percentage of CD11b-positive PMN coexpressing a platelet-specific marker, i.e., CD42b or CD62P) and the levels of activated PMN and activated platelets. In addition, the in vitro PMN-platelet aggregate formation in response to N-formyl-methionyl-leucyl-phenylalanine (f-MLP)-induced activation of PMN was studied. RESULTS: Significantly high PMN-platelet aggregates in ET and PV patients were found and were associated with increased PMN surface CD11b and surface platelet CD62P expression. In vitro f-MLP stimulation upregulated PMN-CD11b expression and simultaneously increased CD11b/CD42b and CD11b/CD62P aggregates, without affecting platelet surface antigens. In ET patients receiving aspirin, the increments in f-MLP-induced PMN-CD11b and in PMN-platelet aggregates were significantly lower versus ET subjects not treated with aspirin. CONCLUSION: Our data show that in ET and PV patients PMN activation plays an important role in increasing circulating PMN-platelet aggregates and suggest that aspirin treatment may decrease their formation.

Adult↗
PubMed2005

Meeting report. Acute promyelocytic leukemia-associated coagulopathy, 21 January 2004, London, United Kingdom.

Despite successful treatment with all-trans retinoic acid and chemotherapy, life-threatening bleeding remains a challenging complication of acute promyelocytic leukemia (APL). Indeed, bleeding and thrombosis are major complications of APL that lead to early death in approximately 10% of patients despite the success of current treatment. This condition may be attributed, in part, to the diffuse activation of coagulation, hyperfibrinolysis, and non-specific proteolytic activity that is observed in patients with APL. Therapeutic agents that induce the differentiation of leukemia cells improve outcomes compared with those observed using chemotherapy alone. They also correct the hyperactivity of the coagulation and fibrinolytic systems, thereby reducing early death from bleeding. Prophylactic therapy with newer anticoagulants may prove beneficial in patients with APL, but this must be confirmed in well-designed, randomized, controlled trials. A workshop was convened 21 January 2004 in London, England, to discuss the clinical and biological aspects of the APL-associated coagulopathy and the application of recent findings to the management of patients with APL. Eight speakers participated in the workshop. This meeting report provides synopses of their presentations and a summary of highlights from the meeting.

Anticoagulants↗
PubMed2005

Cancer and venous thromboembolism.

Venous thromboembolism occurs commonly in patients with cancer. The pathogenetic mechanisms of thrombosis involve a complex interaction between tumour cells, the haemostatic system, and characteristics of the patient. Among risk factors for thromboembolism are long-term immobilisation, especially in hospital, surgery, and chemotherapy with or without adjuvant hormone therapy. Although prophylaxis and treatment of thromboembolism in patients with cancer draw on the agents that are commonly used in those without cancer, there are many special features of patients with cancer that make use of these drugs more challenging. Low-molecular-weight heparins are the cornerstone of prophylaxis and treatment of venous thromboembolism in patients with cancer. These drugs have the potential to increase survival, at least in patients with more favourable outlook. About 10% of patients with idiopathic venous thromboembolism have an underlying malignant disorder that can be detected by extensive diagnostic investigation. However, the issue of whether screening for occult malignant disease ultimately improves prognosis and survival remains to be resolved.

Anticoagulants↗
PubMed2005

Pathogenesis of thrombosis in essential thrombocythemia and polycythemia vera: the role of neutrophils.

Thrombotic complications are frequently observed in patients with polycythemia vera (PV) and essential thrombocythemia (ET). Abnormalities of red blood cells and platelets arising from the clonal rearrangement of hematopoietic cells have been considered, although causal relationships between any of these specific abnormalities and thrombosis have not been clearly established. The involvement of neutrophils and macrophages, which participate in thrombosis and hemostasis, has been insufficiently explored in PV and ET. Persistent activation of circulating neutrophils was recently demonstrated in ET and PV patients, in parallel with an increase in plasma concentrations of endothelial damage-derived and prothrombotic substances. Other studies have explored whether the augmentation of adhesion of neutrophils may affect neutrophil/platelet interaction since a significant increase in circulating neutrophil/platelet aggregates is found in ET and PV. This review summarizes the current knowledge of the pathogenesis of thrombosis in PV and ET, with emphasis on the role of neutrophils in hemostasis and their possible involvement in the mechanisms of the acquired thrombophilia of these patients. Available data suggest that these hemostatic markers deserve to be included in prospective clinical studies aimed at identifying their predictive role in the vascular complications of patients with ET and PV.

Cell Communication↗
PubMed2005

Thrombophilia in cancer.

Malignancy is an acquired thrombophilic condition associated with a significant risk of thrombosis. Venous and arterial thromboembolism is a common complication for patients with cancer, who also present with a hypercoagulable state, even in the absence of manifest thrombosis. Furthermore, clotting activation may play a role in tumor progression. The pathogenesis of thrombosis in cancer is multifactorial; however, a relevant role is attributed to the tumor cell capacity to interact with and activate the host hemostatic system. Among other factors, the prothrombotic action of antitumor therapies is also important. Thrombotic events can influence the morbidity and mortality of the underlying disease. Therefore, preventing these complications in cancer patients is a clinically relevant issue. Recently, new approaches to the prevention and cure of thrombosis in cancer have been investigated, and the hypothesis that strategies to inhibit clotting mechanism may favorably affect malignant disease is gaining increasing interest. In this article, the various aspects of the complex relationship between thrombosis and cancer, from pathophysiology to therapy, are reviewed.

Anticoagulants↗
PubMed2005

Effect of anticoagulant drugs in cancer.

PURPOSE OF REVIEW: The aim of this review is to perform a critical analysis of all completed studies evaluating the role of anticoagulant agents in improving survival in patients with cancer. Furthermore, the rationale for testing anticoagulant drugs in this setting, and the recent basic research studies providing new evidence for a link between tissue malignant transformation of tissues and hemostatic proteins, are also briefly reviewed. RECENT FINDINGS: Four prospective randomized clinical studies to test the impact of low-molecular-weight heparin on mortality in cancer patients have been published. The results suggest a benefit from treatment, particularly in patients with nonadvanced disease. Inhibition of specific clotting pathways by anticoagulants may be hypothesized, particularly those involved in the malignant behavior of tissues. In the same vein, a direct action of anticoagulants on mechanisms of tumor growth and progression can be considered. SUMMARY: An antineoplastic effect of anticoagulant agents has often been suggested. Heparin and vitamin K antagonists have both been tested in this context. Heparin has been more extensively studied. Data from clinical trials of thromboprophylaxis in cancer patients have suggested that heparin may have beneficial effects on survival in these patients, with a major role for low-molecular-weight heparin compared with unfractionated heparin. Recently, the results of new prospective randomized clinical trials to evaluate the effect of low-molecular-weight heparin on cancer survival have become available. The published data look promising and provide an important step forward in the research knowledge in this field.

Anticoagulants↗
PubMed2005

Incidence of thrombotic complications in patients with haematological malignancies with central venous catheters: a prospective multicentre study.

This prospective, observational and multicentre study assessed the incidence of, and risk factors for, symptomatic venous thrombotic complications after central venous catheter (CVC) positioning in patients with haematological malignancies. A total of 458 consecutive CVC insertions were registered in 416 patients (81.2% of whom had severe thrombocytopenia). Over the observation period (3 months or up to catheter removal), the incidence of events was: CVC-related deep vein thrombosis (DVT), 1.5%; lower limb DVT, 0.4%; pulmonary embolism (PE), 1.3%; fatal PE, 0.6%; CVC-related superficial thrombophlebitis, 3.9%; CVC-occlusion/malfunction of thrombotic origin, 6.1%; major arterial events, 1.1%. Severe bleeding and CVC-related infections were observed in 3.5% and 4.6% of cases respectively. A composite end point (any venous thromboembolism or superficial thrombophlebitis or CVC occlusion/malfunction) was defined in order to consider venous thrombotic events with a significant impact on clinical practice. With this criterion, the overall incidence was 12.0% (2.54 cases/1000 catheter days). No factor helped to predict venous thrombotic complications: only thrombocytopenia was associated with a weak trend for a reduced risk (odds ratio 0.52; 95% confidence interval 0.26-1.07). No severe bleeding was observed in those patients who received antithrombotic prophylaxis. This study shows that the impact on clinical practice of symptomatic CVC-related thrombotic complications is not negligible in patients with haematological malignancies.

Adolescent↗
PubMed2004

Catheter-related thrombosis in hematologic patients.

For many years central venous catheters (CVC) have been utilized to monitor hemodynamics and to deliver parenteral nutrition, blood products, pharmacological therapies or infusion fluids. Recently, CVC use has greatly increased with significant impact on the administration of chemotherapy, stem cell transplantation and other treatments to cancer patients. However, CVC use may be accompanied by a variety of side-effects, which increase with the duration of implantation. The most common catheter-related complications are thrombotic events and blood-stream infections. The true incidence of these complications is still uncertain and has changed over time due to CVC device improvement. More data are available in solid tumor than in oncohematologic patients. Recently, much attention has been paid to the issues of prevention and treatment of these complications. Some strategies have been proposed: fixed dose warfarin or low molecular weight heparins have been evaluated in some clinical trials of thromboprophylaxis in this condition. However, more studies are still needed to address this issue. This review will focus on CVC use and complications in oncohematologic patients.

Catheterization, Central Venous↗
PubMed2004

Venous thromboembolism in oncology.

Thromboembolic events represent well-recognised complications of neoplastic disease contributing, in a significant manner, to the morbidity and mortality from cancer. The close relationship between the activation of blood coagulation and tumor growth is known since 1865, when Armand Trousseau first described the clinical association between primary or idiopathic venous thromboembolism and an underlying occult malignancy. However, only in the last decades significant advances in this field have been achieved, both on the comprehension of the complex interactions between the tumor and the hemostatic system, and on the prophylaxis and therapy of the thromboembolic manifestations in cancer patients.

Anticoagulants↗
PubMed2003

Pathogenesis and management of the bleeding diathesis in acute promyelocytic leukaemia.

Life-threatening bleeding, which remains a challenging complication of acute leukaemia, is particularly characteristic of the subtype, acute promyelocytic leukaemia (APL). The clinical picture and laboratory abnormalities are most compatible with the diagnosis of disseminated intravascular coagulation (DIC). Evidence for diffuse activation of the coagulation system, hyperfibrinolysis and systemic elaboration of non-specific protease activity can usually be demonstrated and occurs most commonly during induction chemotherapy. While both host- and tumour-associated mechanisms can be implicated in the pathogenesis of the coagulopathy, leukaemic cell properties appear to be the proximate cause of activation of the haemostatic mechanisms. In this chapter we summarize the current state of knowledge of the pathogenesis of the coagulopathy of APL and the therapeutic approaches that have proved most useful for the management of this complication. Special attention is devoted to the use of all-trans-retinoic acid (ATRA), which has revolutionized the treatment of APL and markedly ameliorated the APL-related coagulopathy.

Disseminated Intravascular Coagulation↗