Anticoagulant treatment and survival in cancer patients. The evidence from clinical studies

The association between cancer and an increased incidence of venous thromboembolism (Trousseau syndrome) is well characterized and recent studies have shown that the hemostatic system plays a key role at different stages in the process of tumorigenesis. Anticoagulant drugs therefore appear to be an attractive strategy in cancer therapy, with an effect that would surpass the benefit of preventing thrombosis. This hypothesis was initially supported by the post-hoc analysis of clinical trials not primarily designed to evaluate the effect of anticoagulants, mainly low molecular weight heparins (LMWH), on cancer survival. Other studies regarding the addition of unfractionated heparin or oral anticoagulants to standard cancer treatment offered controversial results. However, recent investigations among cancer patients without deep venous thrombosis, with cancer-related mortality as the primary end point, suggest that at least in some patients LMWH may exert an antineoplastic effect in vivo and alter the natural history of malignant disease by increasing the response rates and, therefore, improving survival. Additional research on this field is needed to clarify the biological mechanisms involved and to answer yet unsolved questions such as the types of tumor and stages of disease most suitable for this treatment as well as how to optimize treatment regimens

Diagnóstico y tratamiento de la trombosis venosa profunda

Deep-vein thrombosis (DVT) is a common condition that can lead to complications such as postphlebitic syndrome, pulmonary embolism and death. Currently, an algorithm strategy combining pretest probability, D-dimer testing and compression ultrasonography imaging allows for safe and convenient estimation of suspected lower-limb thrombosis. The mainstay of treatment is anticoagulation therapy. The use of low-molecular-weight heparin or pentasaccharide (fondaparinux) allows for outpatient management of most patients with DVT. The duration of anticoagulation depends on whether the primary event was idiopathic or secondary to a transient risk factor. Interventions such as thrombolysis and placement of inferior vena cava filter are reserved for special situations

Potential role of new anticoagulants for prevention and treatment of venous thromboembolism in cancer patients

Venous thromboembolism (VTE), encompassing deep vein thrombosis and pulmonary embolism, represents a major cause of morbidity and mortality in patients with cancer. Low molecular weight heparins are the preferred option for anticoagulation in cancer patients according to current clinical practice guidelines. Fondaparinux may also have a place in prevention of VTE in hospitalized cancer patients with additional risk factors and for initial treatment of VTE. Although low molecular weight heparins and fondaparinux are effective and safe, they require daily subcutaneous administration, which may be problematic for many patients, particularly if long-term treatment is needed. Studying anticoagulant therapy in oncology patients is challenging because this patient group has an increased risk of VTE and bleeding during anticoagulant therapy compared with the population without cancer. Risk factors for increased VTE and bleeding risk in these patients include concomitant treatments (surgery, chemotherapy, placement of central venous catheters, radiotherapy, hormonal therapy, angiogenesis inhibitors, antiplatelet drugs), supportive therapies (ie, steroids, blood transfusion, white blood cell growth factors, and erythropoiesis-stimulating agents), and tumor-related factors (local vessel damage and invasion, abnormalities in platelet function, and number). New anticoagulants in development for prophylaxis and treatment of VTE include parenteral compounds for once-daily administration (ie, semuloparin) or once-weekly dosing (ie, idraparinux and idrabiotaparinux), as well as orally active compounds (ie, dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban). In the present review, we discuss the pharmacology of the new anticoagulants, the results of clinical trials testing these new compounds in VTE, with special emphasis on studies that included cancer patients, and their potential advantages and drawbacks compared with existing therapies

Long-term outcome of critically III advanced cancer patients managed in an intermediate care unit

Background: To analyze the long-term outcomes for advanced cancer patients admitted to an intermediate care unit (ImCU), an analysis of a do not resuscitate orders (DNR) subgroup was made. Methods: A retrospective observational study was conducted from 2006 to January 2019 in a single academic medical center of cancer patients with stage IV disease who suffered acute severe complications. The Simplified Acute Physiology Score 3 (SAPS 3) was used as a prognostic and severity score. In-hospital mortality, 30-day mortality and survival after hospital discharge were calculated. Results: Two hundred and forty patients with stage IV cancer who attended at an ImCU were included. In total, 47.5% of the cohort had DNR orders. The two most frequent reasons for admission were sepsis (32.1%) and acute respiratory failure (excluding sepsis) (38.7%). Mortality in the ImCU was 10.8%. The mean predicted in-hospital mortality according to SAPS 3 was 51.9%. The observed in-hospital mortality was 37.5% (standard mortality ratio of 0.72). Patients discharged from hospital had a median survival of 81 (30.75-391.25) days (patients with DNR orders 46 days (19.5-92.25), patients without DNR orders 162 days (39.5-632)). The observed mortality was higher in patients with DNR orders: 52.6% vs. 23.8%, p 0 < 0.001. By multivariate logistic regression, a worse ECOG performance status (3-4 vs. 0-2), a higher SAPS 3 Score and DNR orders were associated with a higher in-hospital mortality. By multivariate analysis, non-invasive mechanical ventilation, higher bilirubin levels and DNR orders were significantly associated with 30-day mortality. Conclusion: For patients with advanced cancer disease, even those with DNR orders, who suffer from acute complications or require continuous monitoring, an ImCU-centered multidisciplinary management shows encouraging results in terms of observed-to-expected mortality ratios

Flow cytometry for fast screening and automated risk assessment in systemic light-chain amyloidosis

Early diagnosis and risk stratification are key to improve outcomes in light-chain (AL) amyloidosis. Here we used multidimensional-flow-cytometry (MFC) to characterize bone marrow (BM) plasma cells (PCs) from a series of 166 patients including newly-diagnosed AL amyloidosis (N = 94), MGUS (N = 20) and multiple myeloma (MM, N = 52) vs. healthy adults (N = 30). MFC detected clonality in virtually all AL amyloidosis (99%) patients. Furthermore, we developed an automated risk-stratification system based on BMPCs features, with independent prognostic impact on progression-free and overall survival of AL amyloidosis patients (hazard ratio: ≥ 2.9;P ≤ .03). Simultaneous assessment of the clonal PCs immunophenotypic protein expression profile and the BM cellular composition, mapped AL amyloidosis in the crossroad between MGUS and MM; however, lack of homogenously-positive CD56 expression, reduction of B-cell precursors and a predominantly-clonal PC compartment in the absence of an MM-like tumor PC expansion, emerged as hallmarks of AL amyloidosis (ROC-AUC = 0.74;P < .001), and might potentially be used as biomarkers for the identification of MGUS and MM patients, who are candidates for monitoring pre-symptomatic organ damage related to AL amyloidosis. Altogether, this study addressed the need for consensus on how to use flow cytometry in AL amyloidosis, and proposes a standardized MFC-based automated risk classification ready for implementation in clinical practice

Trombosis arterial y polimorfismos genéticos: demasiados actores, escenario complejo

La trombosis arterial es una enfermedad compleja y multifactorial, resultado de interacciones entre factores genéticos y ambientales. La tríada de Virchow, clásicamente empleada para definir la trombosis venosa, también se aplica a la trombosis arterial: alteraciones reológicas, disfunción endotelial y alteraciones hemostáticas que producen hipercoagulabilidad sanguínea. Algunos estudios llevados a cabo en la última década han identificado numerosos polimorfismos en genes involucrados en diversos componentes de esta tríada, entre los que destacan polimorfismos en factores de coagulación, fibrinólisis y receptors plaquetarios, en el metabolismo de la homocisteína, en la enzima óxido nítrico sintetasa, polimorfismos asociados con alteraciones reológicas y, finalmente, los relacionados con el estrés oxidativo.En conjunto, la contribución individual de estos polimorfismos a la trombosis arterial es modesta, mientras que interacciones gen-gen y gen-factores de riesgo parecen ser más relevantes en el desarrollo de la trombosis arterial

Anticoagulant treatment and survival in cancer patients. The evidence from clinical studies

The association between cancer and an increased incidence of venous thromboembolism (Trousseau syndrome) is well characterized and recent studies have shown that the hemostatic system plays a key role at different stages in the process of tumorigenesis. Anticoagulant drugs therefore appear to be an attractive strategy in cancer therapy, with an effect that would surpass the benefit of preventing thrombosis. This hypothesis was initially supported by the post-hoc analysis of clinical trials not primarily designed to evaluate the effect of anticoagulants, mainly low molecular weight heparins (LMWH), on cancer survival. Other studies regarding the addition of unfractionated heparin or oral anticoagulants to standard cancer treatment offered controversial results. However, recent investigations among cancer patients without deep venous thrombosis, with cancer-related mortality as the primary end point, suggest that at least in some patients LMWH may exert an antineoplastic effect in vivo and alter the natural history of malignant disease by increasing the response rates and, therefore, improving survival. Additional research on this field is needed to clarify the biological mechanisms involved and to answer yet unsolved questions such as the types of tumor and stages of disease most suitable for this treatment as well as how to optimize treatment regimens

Trombosis arterial y polimorfismos genéticos: demasiados actores, escenario complejo

La trombosis arterial es una enfermedad compleja y multifactorial, resultado de interacciones entre factores genéticos y ambientales. La tríada de Virchow, clásicamente empleada para definir la trombosis venosa, también se aplica a la trombosis arterial: alteraciones reológicas, disfunción endotelial y alteraciones hemostáticas que producen hipercoagulabilidad sanguínea. Algunos estudios llevados a cabo en la última década han identificado numerosos polimorfismos en genes involucrados en diversos componentes de esta tríada, entre los que destacan polimorfismos en factores de coagulación, fibrinólisis y receptors plaquetarios, en el metabolismo de la homocisteína, en la enzima óxido nítrico sintetasa, polimorfismos asociados con alteraciones reológicas y, finalmente, los relacionados con el estrés oxidativo.En conjunto, la contribución individual de estos polimorfismos a la trombosis arterial es modesta, mientras que interacciones gen-gen y gen-factores de riesgo parecen ser más relevantes en el desarrollo de la trombosis arterial

Alternativas farmacológicas a la transfusión sanguínea: ¿Qué hay de nuevo?

Pharmacological approaches to reduce blood transfusion include the protease inhibitor aprotinin, lysine-analogue antifibrinolytics synthetic arginine-vasopressin derivatives (DDAVP) and recombinant factor VII (rfVIIa). These agents are known to prevent the need for blood after major surgery (cardiac, hepatic, and orthopaedic). Among the nonhemostatic agents erythropoietin (EPO) may be effective to reduce blood requirements in medical and surgical patients. Aprotinin is consistently effective in reducing blood transfusion in cardiac and hepatic surgical procedures, but there is little data to support its use in elective orthopaedic surgery. Antifibrinolytics show no evidence of efficacy in cardiac and hepatic surgery and its use is not warranted in orthopaedic surgery. Limited data suggest that DDAVP may be effective when a defect in platelet function is demonstrated. rFVIIa emerges as a promising haemostatic agent with proven benefit to reduce bleeding in haemophiliacs with inhibitors but might also be effective in patients with thrombocytopenia and thrombopathy, as well as in life-threatening hemorrhage in postsurgical patients. Ongoing studies will established its role a possible "universal haemostatic agent". Hematopoietic cytokines, such as EPO, may have a place to avoid blood transfusion in a variety of clinical conditions, including cancer and critically ill patients