Platelets and circulating (tumor) cells: partners in promoting metastatic cancer.

Purpose Of Review: Despite being discovered decades ago, metastasis remains a formidable challenge in cancer treatment. During the intermediate phase of metastasis, tumor cells detach from primary tumor or metastatic sites and travel through the bloodstream and lymphatic system to distant tissues. These tumor cells in the circulation are known as circulating tumor cells (CTCs), and a higher number of CTCs has been linked to poor prognoses in various cancers.

Platelet Angiopoietin-1 Protects Against Murine Models of Tumor Metastasis.

Background: In addition to their fundamental roles in preserving vascular integrity, platelets also contribute to tumor angiogenesis and metastasis. However, despite being a reservoir for angiogenic and metastatic cytokines, platelets also harbor negative regulators of tumor progression. Angpt1 (angiopoietin-1) is a cytokine essential for developmental angiogenesis that also protects against tumor cell metastasis through an undefined mechanism.

Platelet Factor 4 Antibodies and Severe AKI.

Key Points: Patients testing positive for platelet factor 4 antibodies have a >50% higher odds of developing severe AKI compared with those who test negative. The relationship between platelet factor 4 antibodies and severe AKI was independent of demographics, comorbidities, laboratory values, and severity-of-illness characteristics.

Background: Heparin-induced thrombocytopenia, which results from production of antibodies that bind to heparin-platelet factor 4 (PF4) complexes, is a hypercoagulable state associated with considerable morbidity and mortality due to thrombotic complications.

One-year retrospective analysis of anti-FXa apixaban and rivaroxaban levels demonstrates utility for management decisions in various urgent and nonurgent clinical situations.

Objectives: Quantification of direct oral anticoagulant (DOAC) plasma levels can guide clinical management, but insight into clinical scenarios surrounding DOAC-calibrated anti-FXa assays is limited.

Methods: Apixaban- and rivaroxaban-calibrated chromogenic anti-Xa assays performed over a 1-year period were retrospectively analyzed. Patient demographics, DOAC history, concomitant medications, and renal/liver comorbidities were obtained.

Rapid Onset Severe Immune Thrombocytopenia following mRNA COVID-19 Vaccine in a Young Patient.

The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people around the world. Vaccination against COVID-19 has been approved for the following three vaccines in the United States: Pfizer-BioNTech, Moderna, and Janssen. Hematological complications of vaccination have been reported in the literature but remain as a rare phenomenon.

Pro-inflammatory megakaryocyte gene expression in murine models of breast cancer.

Despite abundant research demonstrating that platelets can promote tumor cell metastasis, whether primary tumors affect platelet-producing megakaryocytes remains understudied. In this study, we used a spontaneous murine model of breast cancer to show that tumor burden reduced megakaryocyte number and size and disrupted polyploidization. Single-cell RNA sequencing demonstrated that megakaryocytes from tumor-bearing mice exhibit a pro-inflammatory phenotype, epitomized by increased , , , and transcripts.

Cardiac megakaryocytes in SARS-CoV-2-positive autopsies.

Thromboembolic phenomena are an important complication of infection by severe acute respiratory coronavirus 2 (SARS-CoV-2). Increasing focus on the management of the thrombotic complications of Coronavirus Disease 2019 (COVID-19) has led to further investigation into the role of platelets, and their precursor cell, the megakaryocyte, during the disease course. Previously published postmortem evaluations of patients who succumbed to COVID-19 have reported the presence of megakaryocytes in the cardiac microvasculature.

Platelets and (Lymph)angiogenesis.

The formation of new blood and lymphatic vessels is essential for both the development of multicellular organisms and (patho)physiological processes like wound repair and tumor growth. In the 1990s, circulating blood platelets were first postulated to regulate tumor angiogenesis by interacting with the endothelium and releasing angiogenic regulators from specialized α granules. Since then, many studies have validated the contributions of platelets to tumor angiogenesis, while uncovering novel roles for platelets in other angiogenic processes like wound resolution and retinal vascular disease.

Platelets upregulate tumor cell programmed death ligand 1 in an epidermal growth factor receptor-dependent manner in vitro.

Programmed death ligand 1 (PD-L1) is an immune checkpoint protein that suppresses cytotoxic T lymphocytes and is often overexpressed in cancers. Due to favorable clinical trial results, immune checkpoint inhibition (ICI) is part of Food and Drug Administration approved immuno-oncology therapies; however, not all patients benefit from ICI therapy. High blood platelet-to-lymphocyte ratio has been associated with failure of ICI treatment, but whether platelets have a role in hindering ICI response is unclear.

Rivaroxaban-calibrated chromogenic anti-Xa assay in cirrhosis: Use to rule out disseminated intravascular coagulation.

Peritoneovenous shunts (PVSs) are used to relieve ascites in cirrhosis. Disseminated intervascular coagulation (DIC) is a complication of PVSs requiring immediate PVS removal. We report a patient who developed new elevations of prothrombin time (PT) and activated partial thromboplastin time (aPTT) 6 hours after PVS placement, concerning for new-onset DIC.

Inherited Platelet Disorders.

Bleeding disorders due to platelet dysfunction are a common hematologic complication affecting patients, and typically present with mucocutaneous bleeding or hemorrhage. An inherited platelet disorder should be suspected in individuals with a suggestive family history and no identified secondary causes of bleeding. Genetic defects have been described at all levels of platelet activation, including receptor binding, signaling, granule release, cytoskeletal remodeling, and platelet hematopoiesis.

Lessons to learn from tumor-educated platelets.

Platelets have long been known to play important roles beyond hemostasis and thrombosis. Now recognized as a bona fide mediator of malignant disease, platelets influence various aspects of cancer progression, most notably tumor cell metastasis. Interestingly, platelets isolated from cancer patients often display distinct RNA and protein profiles, with no clear alterations in hemostatic activity.

Network medicine framework shows that proximity of polyphenol targets and disease proteins predicts therapeutic effects of polyphenols.

Polyphenols, natural products present in plant-based foods, play a protective role against several complex diseases through their antioxidant activity and by diverse molecular mechanisms. Here we develop a network medicine framework to uncover mechanisms for the effects of polyphenols on health by considering the molecular interactions between polyphenol protein targets and proteins associated with diseases. We find that the protein targets of polyphenols cluster in specific neighbourhoods of the human interactome, whose network proximity to disease proteins is predictive of the molecule's known therapeutic effects.

NEDD9 Is a Novel and Modifiable Mediator of Platelet-Endothelial Adhesion in the Pulmonary Circulation.

Data on the molecular mechanisms that regulate platelet-pulmonary endothelial adhesion under conditions of hypoxia are lacking, but may have important therapeutic implications. To identify a hypoxia-sensitive, modifiable mediator of platelet-pulmonary artery endothelial cell adhesion and thrombotic remodeling. Network medicine was used to profile protein-protein interactions in hypoxia-treated human pulmonary artery endothelial cells.

Clinical Significance of CBC and WBC Morphology in the Diagnosis and Clinical Course of COVID-19 Infection.

Objectives: To investigate the clinical significance of numeric and morphologic peripheral blood (PB) changes in coronavirus disease 2019 (COVID-19)-positive patients in predicting the outcome, as well as to compare these changes between critically ill COVID-19-positive and COVID-19-negative patients.

Methods: The study included 90 COVID-19-positive (51 intensive care unit [ICU] and 39 non-ICU) patients and 30 COVID-19-negative ICU patients. We collected CBC parameters (both standard and research) and PB morphologic findings, which were independently scored by two hematopathologists.

COVID-19 concerns aggregate around platelets.

In this issue of , articles by Manne et al and Hottz et al highlight platelet hyperactivity in COVID-19–associated pathophysiology. Although the hallmarks of COVID-19 include a brisk inflammatory response and respiratory symptoms, the hematologic manifestations of this infection have also garnered attention, with thrombotic complications taking center stage. COVID-19–associated coagulopathy has been characterized by an elevated D-dimer, mild thrombocytopenia, and a prolongation of the activated partial thromboplastin time.

Approach to the Patient with COVID-19-Associated Thrombosis: A Case-Based Review.

Coronavirus disease 2019 (COVID-19) is a current global pandemic caused by the novel coronavirus SARS-CoV-2. Alongside its potential to cause severe respiratory illness, studies have reported a distinct COVID-19-associated coagulopathy that is characterized by elevated D-dimer levels, hyperfibrinogenemia, mild thrombocytopenia, and slight prolongation of the prothrombin time. Studies have also reported increased rates of thromboembolism in patients with COVID-19, but variations in study methodologies, patient populations, and anticoagulation strategies make it challenging to distill implications for clinical practice.

Catechol-O-Methyltransferase and Cardiovascular Disease: MESA.

Background Genetic variation in catechol-O-methyltransferase (), a key enzyme in estrogen and catecholamine metabolism, has plausible physiological links to cardiovascular disease (CVD) and its risk factors. In WHS (Women's Health Study), variants rs4818 and rs4680 were associated with a lower risk of CVD among women receiving placebo but not aspirin, suggesting a possible role of in thrombosis. Methods and Results To evaluate potential pathways linking with CVD, and effect modification of aspirin in prevention, we examined association with CVD risk and subclinical measures, coronary artery calcium, and carotid intima-media thickness in MESA (Multi-Ethnic Study of Atherosclerosis).