Impacts of Commonly Used Edible Plants on the Modulation of Platelet Function

Cardiovascular diseases (CVDs) are a primary cause of deaths worldwide. Thrombotic diseases, specifically stroke and coronary heart diseases, account for around 85% of CVDs-induced deaths. Platelets (small circulating blood cells) are responsible for the prevention of excessive bleeding upon vascular injury, through blood clotting (haemostasis). However, unnecessary activation of platelets under pathological conditions, such as upon the rupture of atherosclerotic plaques, results in thrombus formation (thrombosis), which can cause life threatening conditions such as stroke or heart attack. Therefore, antiplatelet medications are usually prescribed for people who are at a high risk of thrombotic diseases. The currently used antiplatelet drugs are associated with major side effects such as excessive bleeding, and some patients are resistant to these drugs. Therefore, numerous studies have been conducted to develop new antiplatelet agents and notably, to establish the relationship between edible plants, specifically fruits, vegetables and spices, and cardiovascular health. Indeed, healthy and balanced diets have proven to be effective for the prevention of CVDs in diverse settings. A high intake of fruits and vegetables in regular diet is associated with lower risks for stroke and coronary heart diseases because of their plethora of phytochemical constituents. In this review, we discuss the impacts of commonly used selected edible plants (specifically vegetables, fruits and spices) and/or their isolated compounds on the modulation of platelet function, haemostasis and thrombosis.

D-dimer kit with a High FDP/D-Dimer Ratio is Useful for Diagnosing Thrombotic Diseases

Introduction Although D-dimer is a useful biomarker of thrombosis, there are many D-dimer kits, with high and low fibrinogen and fibrin degradation products (FDP)/ D-dimer ratios. Methods Plasma D-dimer levels were measured using three different kits in critically ill patients to examine the usefulness of such measurements for detecting the thrombotic diseases and determining the correlation with the FDP and FDP/D-dimer ratio. Results Although three D-dimer kits showed marked utility for diagnosing disseminated intravascular coagulation (DIC) and peripheral arterial and venous thromboembolism (PAVTE), the D-dimer levels determined using the three kits varied among diseases. Indeed, one D-dimer kit showed a high FDP/D-dimer ratio, and another kit showed a low FDP/D-dimer ratio. D-dimer kit with low FDP/D-dimer ratio tended to have high cut-off values and low specificity for diagnosing DIC and PAVTE. In D-dimer kit with high FDP/D-dimer ratio, FDP/D-dimer ratios in patients with thrombosis was significantly higher than that in patients without thrombosis. Conclusion All three D-dimer kits show utility for detecting thrombotic diseases. However, the D-dimer levels determined using the kits varied due to differences in the FDP/D-dimer ratio. In combination with the FDP level, a D-dimer kit with a high FDP/D-dimer ratio may be useful.

COVID-19 and Venous Thromboembolism: From Pathological Mechanisms to Clinical Management

Coronavirus disease 2019 (COVID-19), which is becoming a global pandemic, is caused by SARS-CoV-2 infection. In COVID-19, thrombotic events occur frequently, mainly venous thromboembolism (VTE), which is closely related to disease severity and clinical prognosis. Compared with historical controls, the occurrence of VTE in hospitalized and critical COVID-19 patients is incredibly high. However, the pathophysiology of thrombosis and the best strategies for thrombosis prevention in COVID-19 remain unclear, thus needing further exploration. Virchow’s triad elements have been proposed as important risk factors for thrombotic diseases. Therefore, the three factors outlined by Virchow can also be applied to the formation of venous thrombosis in the COVID-19 setting. A thorough understanding of the complex interactions in these processes is important in the search for effective treatments for COVID-19. In this work, we focus on the pathological mechanisms of VTE in COVID-19 from the aspects of endothelial dysfunction, hypercoagulability, abnormal blood flow. We also discuss the treatment of VTE as well as the ongoing clinical trials of heparin anticoagulant therapy. In addition, according to the pathophysiological mechanism of COVID-19-associated thrombosis, we extended the range of antithrombotic drugs including antiplatelet drugs, antifibrinolytic drugs, and anti-inflammatory drugs, hoping to find effective drug therapy and improve the prognosis of VTE in COVID-19 patients.

Fibrinogen and Antifibrinolytic Proteins: Interactions and Future Therapeutics

Thrombus formation remains a major cause of morbidity and mortality worldwide. Current antiplatelet and anticoagulant therapies have been effective at reducing vascular events, but at the expense of increased bleeding risk. Targeting proteins that interact with fibrinogen and which are involved in hypofibrinolysis represents a more specific approach for the development of effective and safe therapeutic agents. The antifibrinolytic proteins alpha-2 antiplasmin (α2AP), thrombin activatable fibrinolysis inhibitor (TAFI), complement C3 and plasminogen activator inhibitor-2 (PAI-2), can be incorporated into the fibrin clot by FXIIIa and affect fibrinolysis by different mechanisms. Therefore, these antifibrinolytic proteins are attractive targets for the development of novel therapeutics, both for the modulation of thrombosis risk, but also for potentially improving clot instability in bleeding disorders. This review summarises the main properties of fibrinogen-bound antifibrinolytic proteins, their effect on clot lysis and association with thrombotic or bleeding conditions. The role of these proteins in therapeutic strategies targeting the fibrinolytic system for thrombotic diseases or bleeding disorders is also discussed.

A Clot Waveform Analysis Showing a Hypercoagulable State in Patients with Malignant Neoplasms

(1) Objective: hypercoagulability in patients with malignant neoplasm were evaluated to examine the relationship with thrombosis. (2) Methods: clot waveform analysis (CWA)—activated partial thromboplastin time (APTT) and CWA—small amount of tissue factor induced FIX activation (sTF/FIXa) assays were performed in 92 patients with malignant neoplasm and the relationship between hypercoagulability and thrombosis was retrospectively examined. (3) Results: The study population included 92 patients with malignant neoplasms. Twenty-six (28.3%) had thrombotic diseases and 9 (9.8%) patients died within 28 days after the CWA. The peak time of the CWA-APTT could not show hypercoagulability in patients with malignant neoplasms. There were almost no significant differences in the peak times of the sTF/FIXa among patients with malignant neoplasms and healthy volunteers. In contrast, the peak heights of the CWA-sTF/FIXa in patients with various malignant neoplasms were significantly higher than those in healthy volunteers. Furthermore, among patients with malignant neoplasms, the peak heights of the sTF/FIXa in patients with thrombosis were significantly higher than those in patients without thrombosis. (4) Conclusions: although the routine APTT cannot evaluate the hypercoagulability, the peak heights of CWA-sTF/FIXa were significantly high in patients with malignant neoplasms, especially in those with thrombosis, suggesting that an elevated peak height of the CWA-sTF/FIXa may be a risk factor for thrombosis.

The evaluation of urinary vanillylmandelic acid level in patients with generalized anxiety disorder

Background and objectives: The prevalence of anxiety disorders is increasing in the world. Studies revealed that generalized anxiety disorder may lead to change in circulating catecholamine levels. Thus, the changes of catecholamine metabolite like urinary vanillylmandelic acid may increase the future risk of thrombotic diseases in patients with generalized anxiety disorder (GAD). The aim of this present study is to evaluate urinary vanillylmandelic acid (VMA) levels in patients with generalized anxiety disorder. Materials and methods: A cross-sectional study was performed in the Department of Physiology, Dhaka Medical College, Dhaka from July 2019 to June 2020.After obtaining ethical clearance, a total 144 individuals were selected based on inclusion and exclusion criteria with age ranging from 18-50 years. Group A was study group selected from Out Patient Department of Psychiatry of Dhaka Medical College Hospital, Dhaka diagnosed by the experienced psychiatrist. Group B was control group who were apparently healthy adults selected from different area of Dhaka city. The subjects were interviewed and detailed history regarding personal, family, medical and drug history were taken. Prior to sample collection, informed written consent was taken from the participants. Urinary vanillylmandelic acid levels were measured in the Department of Endocrinology, BIRDEM General Hospital, Dhaka. Statistical analysis: For statistical analysis, Unpaired Student’s ‘t’ test was considered using SPSS 25.0 version. Results: Urinary vanillylmandelic acid of generalized anxiety disorder patients was significantly higher (p< 0.001) than control group. Conclusion: It can be concluded that generalized anxiety disorder patients may have more chance of thrombotic diseases due to significantly higher urinary vanillylmandelic acid (VMA) levels than healthy adults.

Bioactive Natural Compounds with Antiplatelet and Anticoagulant Activity and Their Potential Role in the Treatment of Thrombotic Disorders

Natural anticoagulant drugs can be obtained from plants, rich in secondary bioactive metabolites which, in addition to being effective antioxidants, also possess anticoagulant and antiplatelet properties and, for this reason, can be excellent candidates for the treatment of thrombotic diseases. This review reports an overview of the hemostatic process and thrombotic disorders together with data on plants, more and less common from around the world, containing bioactive compounds characterized by antiplatelet and anticoagulant activity. The reported literature was obtained from Medline, PubMed, Elsevier, Web of Science, Google Scholar considering only articles in the English language, published in peer-reviewed journals. The number of citations of the articles and the impact factor of the journals were other parameters used to select the scientific papers to be included in the review. The analysis of the literature data selected demonstrates that many plants’ bioactive compounds show antiplatelet and anticoagulant activity that make them potential candidates to be used as new natural compounds able to interfere with both primary and secondary hemostasis. Moreover, they could be used together with anticoagulants currently administered in clinical practice to increase their efficacy and to reduce complications in the treatment of thrombotic disorders.

An update of the efficacy and comparative characteristics of direct (new) oral anticoagulants (DOACs)

: Direct (New-generation) Oral Anticoagulants (DOACs) have emerged as effective agents which are used in place of vitamin-K antagonists in treatment and prophylaxis of Venous Thromboembolism (VTE), atrial fibrillation and other thrombotic diseases. Among them, the FIIa-direct thrombin inhibitor dabigatran and FXa inhibitors (rivaroxaban, apixaban, edoxaban) are the most broadly used. Anticoagulant dosing may differ under special considerations. The patients’ physiological reserves, organ functional status and failures should be taken into account in clinical decision-making processes. The advantages and drawbacks of each specific agent should be weighed with special regard to metabolism, pharmacokinetics and pharmacodynamics, along with the efficiency of the agents in different indications. This article aims to review the most recent literature to highlight the usage and efficacy of the agents in different clinical conditions.