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Thrombosis Research Dec 2020The possibility of an acquired platelet function disorder should be considered in patients who present with recent onset muco-cutaneous bleeding. Despite the... (Review)
Review
The possibility of an acquired platelet function disorder should be considered in patients who present with recent onset muco-cutaneous bleeding. Despite the availability of newer and faster platelet function assays, light transmission aggregometry (LTA) remains the preferred diagnostic test. This review examines and discusses the causes of acquired platelet dysfunction; most commonly drugs, dietary factors, medical disorders and procedures. In addition to well-known antiplatelet therapies, clinicians should be alert for newer drugs which can affect platelets, such as ibrutinib. There is little clinical trial evidence to guide the management of acquired platelet function defects, but we summarise commonly employed strategies, which include addressing the underlying cause, antifibrinolytic agents, desmopressin infusions, and in selected patients, platelet transfusions.
Topics: Blood Platelet Disorders; Blood Platelets; Humans; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion
PubMed: 31229273
DOI: 10.1016/j.thromres.2019.06.009 -
Methods in Molecular Biology (Clifton,... 2023In the late 1990s, the antithrombotic antiplatelet agent, clopidogrel, a P2Y12 inhibitor, was introduced. Around the same time, there was an increase in a number of new...
In the late 1990s, the antithrombotic antiplatelet agent, clopidogrel, a P2Y12 inhibitor, was introduced. Around the same time, there was an increase in a number of new methods to measure platelet function (e.g., PFA-100 in 1995), and this has continued. It became evident that not all patients responded to clopidogrel in the same way and that some patients had a relative "resistance" to therapy, termed "high on-treatment platelet reactivity." This then led to some publications to advocate platelet function testing being used for patients on antiplatelet therapy. Platelet function testing was also suggested for use in patients awaiting cardiac surgery after stopping their antiplatelet therapy as a way of balancing thrombotic risk pre-surgery and bleeding risk perioperatively. This chapter will discuss some of the commonly used platelet function tests used in these settings, particularly those that are sometimes referred to as point-of-care tests or that require minimal laboratory sample manipulation. The latest guidance and recommendations for platelet function testing will be discussed following several clinical trials looking at the usefulness of platelet function testing in these clinical settings.
Topics: Humans; Platelet Aggregation Inhibitors; Clopidogrel; Ticlopidine; Blood Platelets; Platelet Function Tests
PubMed: 37204725
DOI: 10.1007/978-1-0716-3175-1_25 -
Journal of Cardiovascular Pharmacology... May 2020Antiplatelet therapy reduces atherothrombotic risk and has therefore become a cornerstone in the treatment of cardiovascular disease. Aspirin, adenosine diphosphate P2Y... (Review)
Review
Antiplatelet therapy reduces atherothrombotic risk and has therefore become a cornerstone in the treatment of cardiovascular disease. Aspirin, adenosine diphosphate P2Y receptor antagonists, glycoprotein IIb/IIIa inhibitors, and the thrombin receptor blocker vorapaxar are effective antiplatelet agents but significantly increase the risk of bleeding. Moreover, atherothrombotic events still impair the prognosis of many patients with cardiovascular disease despite established antiplatelet therapy. Over the last years, advances in the understanding of thrombus formation and hemostasis led to the discovery of various new receptors and signaling pathways of platelet activation. As a consequence, many new antiplatelet agents with high antithrombotic efficacy and supposedly only moderate effects on regular hemostasis have been developed and yielded promising results in preclinical and early clinical studies. Although their long journey from animal studies to randomized clinical trials and finally administration in daily clinical routine has just begun, some of the new agents may in the future become meaningful additions to the pharmacological armamentarium in cardiovascular disease.
Topics: Animals; Blood Platelets; Cardiovascular Diseases; Drug Development; Drug Discovery; Hemorrhage; Humans; Molecular Targeted Therapy; Platelet Activation; Platelet Aggregation Inhibitors; Signal Transduction; Treatment Outcome
PubMed: 31960728
DOI: 10.1177/1074248419899314 -
The Lancet. Haematology Aug 2020Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome.... (Review)
Review
Lifelong anticoagulation with warfarin or alternative vitamin K antagonist is the standard anticoagulant treatment for thrombotic antiphospholipid syndrome. Anticoagulant-refractory thrombotic antiphospholipid syndrome can be broadly defined as breakthrough thrombosis while on standard oral anticoagulation treatment and its management is a major challenge given the serious nature of the thrombotic disease observed, which has become refractory to oral anticoagulation. The factors (genetic and cellular) that cause anticoagulant-refractory thrombotic antiphospholipid syndrome are now better understood. However, efforts to use this greater understanding have not yet transformed the capacity to treat it successfully in many patients. In this Viewpoint, we review the factors that are likely to be contributing to the cause of this syndrome and consider how they might be modified or inhibited. We also discuss management, including general strategies to minimise thrombotic risk, intensification of anticoagulation, addition of an antiplatelet agent, adjunctive treatment for thrombosis, immunomodulatory therapy, complement inhibition, vascular options, and future potential therapeutic targets.
Topics: Anticoagulants; Antiphospholipid Syndrome; Drug Resistance; Fibrinolytic Agents; Humans; Platelet Aggregation Inhibitors; Thrombolytic Therapy; Thrombosis
PubMed: 32735839
DOI: 10.1016/S2352-3026(20)30116-2 -
Interventional Neuroradiology : Journal... Feb 2022Antiplatelet therapies are commonly used in neurointerventional procedures. However, specific guidelines for their use in these settings is lacking and it can often be... (Review)
Review
Antiplatelet therapies are commonly used in neurointerventional procedures. However, specific guidelines for their use in these settings is lacking and it can often be difficult to balance the potential risks and benefits of these medications. Considering the continued growth and adoption of neurointerventional procedures, it is crucial to understand the properties of these agents in order to use them safely. Large-scale clinical trials are still needed to clarify many of these aspects for this emerging field. However, the existing literature already provides insight into which antiplatelet drugs are of benefit to the neurointerventionalist as well as their associated risks of ischemic and hemorrhagic complications. Hence, this review focuses on the applications of GPIIb/IIIA inhibitors to neurointerventional procedures.
Topics: Humans; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex
PubMed: 33947250
DOI: 10.1177/15910199211015038 -
Ugeskrift For Laeger Apr 2024Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended... (Review)
Review
Pre-eclampsia affects 3-4% of pregnancies and is associated with maternal and infant mortality and morbidity. High-risk pregnancies in Denmark are recommended prophylactic low-dose acetylsalicylic acid (LDA). If new screening algorithms are implemented, LDA will be recommended to around 10% of pregnant women. The use of LDA may slightly increase the risk of minor bleeding disturbances. Otherwise, there is a lot of promising data regarding the safety of LDA use during pregnancy, as argued in this review.
Topics: Humans; Pre-Eclampsia; Pregnancy; Aspirin; Female; Platelet Aggregation Inhibitors
PubMed: 38704715
DOI: 10.61409/V10230682 -
Molecules (Basel, Switzerland) Dec 2022Acetylsalicylic acid (ASA) is one of the first drugs to be obtained by synthesis while being the most used. It has experienced the longest lasting commercial success and... (Review)
Review
Acetylsalicylic acid (ASA) is one of the first drugs to be obtained by synthesis while being the most used. It has experienced the longest lasting commercial success and is considered the most popular drug of the modern era. ASA, originally used as an anti-inflammatory medication, nowadays is predominantly used as an antiplatelet agent for prophylaxis in cardiac patients. Many studies show that the benefits of using ASA far outweigh the potential risk of side effects. With particular emphasis on the possibility of ASA repositioning for new therapies, extending the indications for use beyond the diseases from the spectrum of atherosclerotic diseases, such as cancer, requires shifting the benefit-risk ratio, although very good, even more towards safety. Interesting activities consisting not only of changing the formulation but also modifying the drug molecule seem to be an important goal of the 21st century. ASA has become a milestone in two important fields: pharmacy and medicine. For a pharmacist, ASA is a long-used drug for which individual indications are practically maintained. For a doctor, acetylsalicylic acid is primarily an antiplatelet drug that saves millions of lives of patients with coronary heart disease or after a stroke. These facts do not exempt us from improving therapeutic methods based on ASA, the main goal of which is to reduce the risk of side effects, as well as to extend effectiveness. Modified acetylsalicylic acid molecules already seem to be a promising therapeutic option.
Topics: Humans; Aspirin; Platelet Aggregation Inhibitors; Stroke
PubMed: 36500502
DOI: 10.3390/molecules27238412 -
Seminars in Thrombosis and Hemostasis Feb 2020Platelet transfusions aim to improve primary hemostasis and to prevent or treat bleeding in patients with reduced platelet numbers and/or platelet function. In this... (Review)
Review
Platelet transfusions aim to improve primary hemostasis and to prevent or treat bleeding in patients with reduced platelet numbers and/or platelet function. In this review, the authors address the role of platelet transfusions with a focus on perioperative medicine. They summarize different causes of thrombocytopenia in perioperative patients, describe general characteristics and potential adverse effects of different platelet concentrates, describe principles of perioperative platelet transfusion strategies, and highlight specific perioperative scenarios, for example, in patients undergoing antiplatelet therapy. The evidence for any transfusion threshold in perioperative patients based on platelet numbers is low. The evidence supporting prophylactic platelet transfusions in the perioperative setting is very low, and all recommended thresholds for preintervention platelet transfusions are based on weak evidence or expert opinion. Besides the platelet count, platelet function, additional risk factors for bleeding, and the pharmacokinetic properties of concomitant antiplatelet drugs are important criteria for the decision to transfuse or not to transfuse platelets. The few available prospective trials give at least a signal that a liberal platelet transfusion strategy might be associated with poorer outcomes compared with a restrictive platelet transfusion strategy in critically ill patients. Given the unknown risks for adverse outcomes, a therapeutic transfusion strategy during surgery (eventually guided by point of care testing in cardiac surgery, major liver surgery, and major trauma) may be most appropriate for interventions, in which intraoperative bleeding can be controlled until platelets are available, and during the postsurgery period.
Topics: Blood Loss, Surgical; Clinical Decision-Making; Humans; Perioperative Care; Platelet Aggregation Inhibitors; Platelet Count; Platelet Transfusion; Surgical Procedures, Operative
PubMed: 31830766
DOI: 10.1055/s-0039-1697951 -
Current Cardiology Reports Nov 2019Peripheral artery disease (PAD) affects close to 200 million people worldwide. Claudication is the most common presenting symptom for patients with PAD. This review... (Review)
Review
PURPOSE OF THE REVIEW
Peripheral artery disease (PAD) affects close to 200 million people worldwide. Claudication is the most common presenting symptom for patients with PAD. This review summarizes the current diagnostic and treatment options for patients with claudication. Comprehensive history and physical examination in order to differentiate between claudication secondary to vascular disease vs. neurogenic causes is paramount for initial diagnosis. Ankle-brachial index is the most commonly used test for screening and diagnostic purposes. Treatment consists of four different approaches, which are best utilized in combination: non-pharmacological treatment for claudication improvement, pharmacological treatment for claudication improvement, pharmacological treatment for secondary risk reduction, and interventional treatment for claudication improvement.
RECENT FINDINGS
Cilostazol is the only Food and Drug Administration (FDA)-approved agent for symptomatic treatment of claudication. Supervised exercise programs provide the maximum benefit for claudication improvement, but home-based exercise programs are an alternative. High-intensity statins and an antiplatelet agent should be prescribed to all patients with PAD. Angiotensin-converting-enzyme inhibitors can provide additional risk reduction, especially in patients with diabetes or hypertension. Rivaroxaban of low dosage (2.5 mg twice daily) in combination with aspirin further decreases cardiovascular risk, but this reduction comes at the cost of higher bleeding risk. Peripheral artery disease (PAD) is a form of atherosclerotic disease that affects hundreds of millions of people worldwide-one of its most common manifestations is intermittent claudication (IC), which results from insufficient blood flow to meet the metabolic demands of an affected extremity. This paper reviews the current literature regarding the workup, diagnosis, diagnostic modalities, treatment options, and management of intermittent claudication.
Topics: Angiotensin-Converting Enzyme Inhibitors; Ankle Brachial Index; Cilostazol; Humans; Intermittent Claudication; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Treatment Outcome; Vasodilator Agents
PubMed: 31728766
DOI: 10.1007/s11886-019-1227-4 -
Seminars in Thrombosis and Hemostasis Apr 2023Cardiovascular disease, particularly coronary artery disease (CAD), remains the leading cause of mortality and morbidity in industrialized countries. Platelet activation... (Review)
Review
Cardiovascular disease, particularly coronary artery disease (CAD), remains the leading cause of mortality and morbidity in industrialized countries. Platelet activation and aggregation at the site of endothelial injury play a key role in the processes ultimately resulting in thrombus formation with vessel occlusion and subsequent end-organ damage. Consequently, antiplatelet therapy has become a mainstay in the pharmacological treatment of CAD. Several drug classes have been developed over the last decades and a broad armamentarium of antiplatelet agents is currently available. This review portrays the evolution of antiplatelet therapy, and provides an overview on previous and current antiplatelet drugs and strategies.
Topics: Humans; Platelet Aggregation Inhibitors; Coronary Artery Disease; Cardiovascular Diseases; Thrombosis
PubMed: 36455618
DOI: 10.1055/s-0042-1758821