Neutrophils are well known for their role in infection and inflammatory disease and are first responders at sites of infection or injury. Platelets have an established role in hemostasis and ...thrombosis and are first responders at sites of vascular damage. However, neutrophils are increasingly recognized for their role in thrombosis, while the immunemodulatory properties of platelets are being increasingly studied. Platelets and neutrophils interact during infection, inflammation and thrombosis and modulate each other’s functions. This review will discuss the consequences of platelet–neutrophil interactions in infection, thrombosis, atherosclerosis and tissue injury and repair.
It has been well established that inherited or acquired hypercoagulability is a risk factor for venous thrombosis. In addition, hypercoagulability may contribute to the risk of arterial events. Much ...less is known regarding the role of the fibrinolytic system in the risk of thrombotic disease, which partly relates to the lack of validated assays. A plasma-based global fibrinolysis assay, which is sensitive to plasma levels of plasminogen, regulators of fibrinolysis, and proteins involved in coagulation, has been used in large epidemiological studies to assess the role of fibrinolysis in thrombosis. It has been demonstrated that a hypofibrinolytic state increases the risk of a first venous thrombosis, but not of a recurrence. This increased risk of venous thrombosis associated with plasma hypofibrinolysis appears primarily driven by elevated plasma levels of thrombin-activatable fibrinolysis inhibitor and plasminogen activator inhibitor type 1. The combination of hypercoagulability and hypofibrinolysis synergistically enhances the risk of a first venous event. Plasma hypofibrinolysis may constitute a risk factor for the postthrombotic syndrome. Decreased fibrinolytic potential is also associated with an increased risk of arterial thrombosis, but only in individuals younger than 55 years. The association between hypofibrinolysis and myocardial infarction appears primarily driven by elevated levels of α
-antiplasmin. Although recent studies have clearly demonstrated a role of the fibrinolytic system in thrombotic disease, the clinical utility of plasma-based clot lysis assays is probably limited.
Platelets are key players in thrombosis and hemostasis. Alterations in platelet count and function are common in liver disease, and may contribute to bleeding or thrombotic complications in liver ...diseases and during liver surgery. In addition to their hemostatic function, platelets may modulate liver diseases by mechanisms that are incompletely understood. Here, we present clinical evidence for a role of platelets in the progression of chronic and acute liver diseases, including cirrhosis, acute liver failure, and hepatocellular carcinoma. We also present clinical evidence that platelets promote liver regeneration following partial liver resection. Subsequently, we summarize studies in experimental animal models that support these clinical observations, and also highlight studies that are in contrast with clinical observations. The combined results of clinical and experimental studies suggest that platelets may be a therapeutic target in the treatment of liver injury and repair, but the gaps in our understanding of mechanisms involved in platelet-mediated modulation of liver diseases call for caution in clinical application of these findings.
Platelets have multiple functions beyond their roles in thrombosis and hemostasis. Platelets support liver regeneration, which is required after partial hepatectomy and acute or chronic liver injury. ...Although it is widely assumed that platelets stimulate liver regeneration by local excretion of mitogens stored within platelet granules, definitive evidence for this is lacking, and alternative mechanisms deserve consideration. In-depth knowledge of mechanisms of platelet-mediated liver regeneration may lead to new therapeutic strategies to treat patients with failing regenerative responses.
Background
COVID‐19 is associated with a substantial risk of venous thrombotic events, even in the presence of adequate thromboprophylactic therapy.
Objectives
We aimed to better characterize the ...hypercoagulable state of COVID‐19 patients in patients receiving anticoagulant therapy.
Methods
We took plasma samples of 23 patients with COVID‐19 who were on prophylactic or intensified anticoagulant therapy. Twenty healthy volunteers were included to establish reference ranges.
Results
COVID‐19 patients had a mildly prolonged prothrombin time, high von Willebrand factor levels and low ADAMTS13 activity. Most rotational thromboelastometry parameters were normal, with a hypercoagulable maximum clot firmness in part of the patients. Despite detectable anti‐activated factor X activity in the majority of patients, ex vivo thrombin generation was normal, and in vivo thrombin generation elevated as evidenced by elevated levels of thrombin‐antithrombin complexes and D‐dimers. Plasma levels of activated factor VII were lower in patients, and levels of the platelet activation marker soluble CD40 ligand were similar in patients and controls. Plasmin‐antiplasmin complex levels were also increased in patients despite an in vitro hypofibrinolytic profile.
Conclusions
COVID‐19 patients are characterized by normal in vitro thrombin generation and enhanced clot formation and decreased fibrinolytic potential despite the presence of heparin in the sample. Anticoagulated COVID‐19 patients have persistent in vivo activation of coagulation and fibrinolysis, but no evidence of excessive platelet activation. Ongoing activation of coagulation despite normal to intensified anticoagulant therapy indicates studies on alternative antithrombotic strategies are urgently required.
Portal vein thrombosis (PVT) is a relatively frequent event in patients with cirrhosis. While different risk factors for PVT have been reported, such as decreased portal blood flow velocity (PBFV) ...and parameters related with severity of portal hypertension, these are based on retrospective studies assessing only a discrete number of parameters. The aim of the current study was to evaluate the incidence and risks factors for non-tumoral PVT development in a large prospective cohort of patients with cirrhosis.
We performed an exhaustive evaluation of clinical, biochemical, inflammatory and acquired/hereditary hemostatic profiles in 369 patients with cirrhosis without PVT who were prospectively followed-up. Doppler ultrasound was performed at baseline and every 6 months or whenever clinically indicated. PVT development was always confirmed by computed tomography.
Twenty-nine patients developed non-tumoral PVT, with an incidence of 1.6%, 6% and 8.4% at 1, 3 and 5 years, respectively. Low platelet count, PBFV <15 cm/sec and history of variceal bleeding were factors independently associated with a high PVT risk. No relationship between PVT development and any other clinical biochemical, inflammatory and acquired or hereditary hemostatic parameter was found.
In patients with cirrhosis, the factors predictive of PVT development were mainly those related to the severity of portal hypertension. Our results do not support the role of hemostatic alterations (inherited or acquired) and inflammatory markers in the prediction of PVT in patients with cirrhosis.
Patients with cirrhosis and more severe portal hypertension are at higher risk of non-tumoral portal vein thrombosis development. Acquired or inherited hemostatic disorders, as well as inflammatory status, do not seem to predict the development of portal vein thrombosis in patients with cirrhosis.
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•Factors related to more severe portal hypertension are associated with higher risk of PVT in cirrhosis.•Acquired and inherited alterations of coagulation do not predict PVT development during follow-up.•Cirrhosis-associated inflammation or generation of NETs are not relevant factors predicting PVT development.
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