The role of coagulation and platelets in colon cancer-associated thrombosis.

Cancer-associated thrombosis is a common first presenting sign of malignancy and is currently the second leading cause of death in cancer patients after their malignancy. However, the molecular mechanisms underlying cancer-associated thrombosis remain undefined. In this study, we aimed to develop a better understanding of how cancer cells affect the coagulation cascade and platelet activation to induce a prothrombotic phenotype.

A Temporal Examination of Platelet Counts as a Predictor of Prognosis in Lung, Prostate, and Colon Cancer Patients.

Platelets, components of hemostasis, when present in excess (>400 K/μL, thrombocytosis) have also been associated with worse outcomes in lung, ovarian, breast, renal, and colorectal cancer patients. Associations between thrombocytosis and cancer outcomes have been made mostly from single-time-point studies, often at the time of diagnosis. Using laboratory data from the Department of Veterans Affairs (VA), we examined the potential benefits of using longitudinal platelet counts in improving patient prognosis predictions.

The Predictive Value of Inflammation-Related Peripheral Blood Measurements in Cancer Staging and Prognosis.

In this review, we discuss the interaction between cancer and markers of inflammation (such as levels of inflammatory cells and proteins) in the circulation, and the potential benefits of routinely monitoring these markers in peripheral blood measurement assays. Next, we discuss the prognostic value and limitations of using inflammatory markers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and C-reactive protein measurements. Furthermore, the review discusses the benefits of combining multiple types of measurements and longitudinal tracking to improve staging and prognosis prediction of patients with cancer, and the ability of novel frameworks to leverage this high-dimensional data.

Carpe low-dose aspirin: the new anti-cancer face of an old anti-platelet drug.

Cancer metastasis is a dynamic process during which cancer cells separate from a primary tumor, migrate through the vessel wall into the bloodstream, and extravasate at distant sites to form secondary colonies. During this process, circulating tumor cells are subjected to shear stress forces from blood flow, and in contact with plasma proteins and blood cells of the immune and hemostatic system, including platelets. Many studies have shown an association between high platelet count and cancer metastasis, suggesting that platelets may play an occult role in tumorigenesis.

Platelet count as a predictor of metastasis and venous thromboembolism in patients with cancer.

Platelets are anucleate cells in the blood at concentrations of 150,000 to 400,000 cells/µL and play a key role in hemostasis. Several studies have suggested that platelets contribute to cancer progression and cancer-associated thrombosis. In this review, we provide an overview of the biochemical and biophysical mechanisms by which platelets interact with cancer cells and review the evidence supporting a role for platelet-enhanced metastasis of cancer, and venous thromboembolism (VTE) in patients with cancer.

Dynamics of blood flow and thrombus formation in a multi-bypass microfluidic ladder network.

The reaction dynamics of a complex mixture of cells and proteins, such as blood, in branched circulatory networks within the human microvasculature or extravascular therapeutic devices such as extracorporeal oxygenation machine (ECMO) remains ill-defined. In this report we utilize a multi-bypass microfluidics ladder network design with dimensions mimicking venules to study patterns of blood platelet aggregation and fibrin formation under complex shear. Complex blood fluid dynamics within multi-bypass networks under flow were modeled using COMSOL.

Utility of microfluidic devices to study the platelet-endothelium interface.

The integration of biomaterials and understanding of vascular biology has led to the development of perfusable endothelialized flow models, which have been used as valuable tools to study the platelet-endothelium interface under shear. In these models, the parameters of geometry, compliance, biorheology, and cellular complexity are varied to recapitulate the physical biology of platelet recruitment and activation under physiologically relevant conditions of blood flow. In this review, we summarize the mechanistic insights learned from perfusable microvessel models and discuss the potential utility as well as challenges of endothelialized microfluidic devices to study platelet function in the bloodstream in vitro.

Differential Roles for the Coagulation Factors XI and XII in Regulating the Physical Biology of Fibrin.

In the contact activation pathway of the coagulation, zymogen factor XII (FXII) is converted to FXIIa, which triggers activation of FXI leading to the activation of FIX and subsequent thrombin generation and fibrin formation. Feedback activation of FXI by thrombin has been shown to promote thrombin generation in a FXII-independent manner and FXIIa can bypass FXI to directly activate FX and prothrombin in the presence of highly negatively charged molecules, such as long-chain polyphosphates (LC polyP). We sought to determine whether activation of FXII or FXI differentially regulate the physical biology of fibrin formation.

Aspirin therapy reduces the ability of platelets to promote colon and pancreatic cancer cell proliferation: Implications for the oncoprotein c-MYC.

Aspirin, an anti-inflammatory and antithrombotic drug, has become the focus of intense research as a potential anticancer agent owing to its ability to reduce tumor proliferation in vitro and to prevent tumorigenesis in patients. Studies have found an anticancer effect of aspirin when used in low, antiplatelet doses. However, the mechanisms through which low-dose aspirin works are poorly understood.

Platelet bioreactor-on-a-chip.

Platelet transfusions total >2.17 million apheresis-equivalent units per year in the United States and are derived entirely from human donors, despite clinically significant immunogenicity, associated risk of sepsis, and inventory shortages due to high demand and 5-day shelf life. To take advantage of known physiological drivers of thrombopoiesis, we have developed a microfluidic human platelet bioreactor that recapitulates bone marrow stiffness, extracellular matrix composition,micro-channel size, hemodynamic vascular shear stress, and endothelial cell contacts, and it supports high-resolution live-cell microscopy and quantification of platelet production.

Sustained hypoxia leads to the emergence of cells with enhanced growth, migratory, and promitogenic potentials within the distal pulmonary artery wall.

All forms of chronic pulmonary hypertension (PH) are characterized by structural remodeling of the pulmonary artery (PA) media, a process previously attributed solely to changes in the phenotype of resident smooth muscle cells (SMC). However, recent experimental evidence in both systemic and pulmonary circulations suggests that other cell types, including circulating and local progenitors, contribute significantly to this process. The goal of this study was to determine if hypoxia-induced remodeling of distal PA (dPA) media involves the emergence of cells with phenotypic and functional characteristics distinct from those of resident dPA SMC and fibroblasts.