This document summarizes various antiplatelet drugs used to treat thrombotic diseases. It discusses the pathophysiology of thrombosis and hemostasis, focusing on the interplay between the vessel wall, coagulation proteins, and platelets. Older antiplatelet drugs such as aspirin, clopidogrel, and GP IIb/IIIa inhibitors are described along with newer agents like ticagrelor, elinogrel, and cangrelor that inhibit the P2Y12 receptor on platelets. Other drug classes discussed include thromboxane receptor antagonists, thrombin receptor antagonists, and GPVI receptor antagonists. The challenges of preventing thrombosis without increased bleeding risks are also noted.
Ticagrelor in acute myocardial infarctionVasif Mayan
Potential benefits of dual antiplatelet therapy beyond 1 year after an MI has not been studied
Patients with MI are at increased risk of RECURRENT ISCHAEMIC EVENTS
Intensive secondary prevention is theoretically beneficial
Finding an ideal drug with best risk-benefit ratio is a challenge
TICAGRELOR
--- Direct acting
Not a pro-drug; does not require metabolic activation
Rapid onset of inhibitory effect on the P2Y12 receptor
Greater inhibition of platelet aggregation than clopidogrel
--- Reversibly bound
Degree of inhibition reflects plasma concentration
Faster offset of effect than clopidogrel
Functional recovery of circulating platelets within ~48 hours
PLATO trial
PEGASUS TIMI trial
Please find the power point on Pharmacology of Anticoagulants, antiplatelets . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
there are several limitation in VKA,to over come these problem NOACs came in picture but still limited indication for NOACs currently,required further study inter and intra comparison between anticoagulants.
Ticagrelor in acute myocardial infarctionVasif Mayan
Potential benefits of dual antiplatelet therapy beyond 1 year after an MI has not been studied
Patients with MI are at increased risk of RECURRENT ISCHAEMIC EVENTS
Intensive secondary prevention is theoretically beneficial
Finding an ideal drug with best risk-benefit ratio is a challenge
TICAGRELOR
--- Direct acting
Not a pro-drug; does not require metabolic activation
Rapid onset of inhibitory effect on the P2Y12 receptor
Greater inhibition of platelet aggregation than clopidogrel
--- Reversibly bound
Degree of inhibition reflects plasma concentration
Faster offset of effect than clopidogrel
Functional recovery of circulating platelets within ~48 hours
PLATO trial
PEGASUS TIMI trial
Please find the power point on Pharmacology of Anticoagulants, antiplatelets . I tried to present it on understandable way and all the contents are reviewed by experts and from very reliable references. Thank you
This presentation consists of various approaches to treat hypertension depending on severity. It also include treatment according to international guidelines. Classification and brief description of each antihypertensive agent has been mentioned.
there are several limitation in VKA,to over come these problem NOACs came in picture but still limited indication for NOACs currently,required further study inter and intra comparison between anticoagulants.
PLATO (Platelet Inhibition and Patient Outcomes)theheart.org
- Background:
Ticagrelor, a new antiplatet agent and not a thienopyridine, has a unique mechanism of action in that it is reversible
- Population and treatment:
18 624 ACS patient, with or without ST-segment elevation, randomized in a double-blind, double-dummy fashion to ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) or clopidogrel (300- to 600-mg loading dose, 75 mg thereafter) for one year
Patients also received aspirin 75 mg to 100 mg day, unless they could not tolerate the drug
- Primary outcome:
A composite of death from vascular causes, MI, or stroke
See the article at http://www.theheart.org/article/995621.do
My journey to AHA 2016 Shanghai.
[Quote from AHA]
•AHA 大会是一个针对资深专业人士的武林小会,这个
武林小会有两个特点
•深- 在这里有各路门派的最顶尖高手,包括敏捷圈、测
试圈、技术圈、引导圈、专业教练圈、组织变革圈、视
觉圈里面的代表人物。
•跨-有机会一下子看到这么多门派的看家绝技,融合。
哪怕连小会的组委会都是一个跨界共创。
Jonas Ranstam MedicReS World Congress 2013MedicReS
Practical and statistical aspects of randomization
and blinding in clinical trials
Jonas Ranstam PhD
Department of Clinical Sciences
Lund University
Sweden
Antiplatelet therapy there is a gap between guidelines and implementationA.Salam Sharif
platelets play an important role in cardiovascular diseases, the final event leading to ACS is a spontaneous atherosclerotic plaques which initiates a platelet response with platelet adhesion to vascular wall with activation and agregation and finally clot formation with clinical sequences od CV deaths, MI and myocardial ischemia and arrhythmias, so atiplatelet therapy is crucial in treatment of ACS, in the topic I review the traditional agents and new agents , focusing on guidelines and real world of their cinical uses .
Learning Objectives:
After completing the topic, the student will be able to:
• Recognize the importance of hemostasis and thrombosis in health and disease.
• Describe the process that leads to platelet aggregation.
• Classify anti-platelets drugs and the mechanism by which they inhibit platelet
aggregation.
• Describe indications, contraindications, drug interactions & adverse effects of anti-
platelets drugs.
• Describe treatment recommendations for antiplatelet agents
Acetylsalicylic Acid (Aspirin)
• Irreversibly inhibits COX1 and, in higher doses, COX2.
• COX1 inhibition (main antithrombotic mechanism); the formation of prostaglandin H2 is blocked, thus
thromboxane A2 cannot be synthesized (TxA2 stimulates platelets aggregation).
Drug interactions
• Co-administration of non-selective COX1 inhibitors may impair its efficacy.
• About one-third of patients receiving aspirin manifest treatment failure (Thrombotic Complication or
Death).
Adverse Events
• Resulting from rebound thrombocyte activation after aspirin withdrawal.
• Single binding site and does not influence other thrombocyte receptors results in aspirin having less
antithrombotic effect than many other agents
DIC is one condition that always trouble patients and doctor, though its a nightmare for any clinician , its also a potent question in both UG and PG exams. I hope this will help you in answering those questions well.
New Directions in Targeted Therapeutic Approaches for Older Adults With Mantl...i3 Health
i3 Health is pleased to make the speaker slides from this activity available for use as a non-accredited self-study or teaching resource.
This slide deck presented by Dr. Kami Maddocks, Professor-Clinical in the Division of Hematology and
Associate Division Director for Ambulatory Operations
The Ohio State University Comprehensive Cancer Center, will provide insight into new directions in targeted therapeutic approaches for older adults with mantle cell lymphoma.
STATEMENT OF NEED
Mantle cell lymphoma (MCL) is a rare, aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for 5% to 7% of all lymphomas. Its prognosis ranges from indolent disease that does not require treatment for years to very aggressive disease, which is associated with poor survival (Silkenstedt et al, 2021). Typically, MCL is diagnosed at advanced stage and in older patients who cannot tolerate intensive therapy (NCCN, 2022). Although recent advances have slightly increased remission rates, recurrence and relapse remain very common, leading to a median overall survival between 3 and 6 years (LLS, 2021). Though there are several effective options, progress is still needed towards establishing an accepted frontline approach for MCL (Castellino et al, 2022). Treatment selection and management of MCL are complicated by the heterogeneity of prognosis, advanced age and comorbidities of patients, and lack of an established standard approach for treatment, making it vital that clinicians be familiar with the latest research and advances in this area. In this activity chaired by Michael Wang, MD, Professor in the Department of Lymphoma & Myeloma at MD Anderson Cancer Center, expert faculty will discuss prognostic factors informing treatment, the promising results of recent trials in new therapeutic approaches, and the implications of treatment resistance in therapeutic selection for MCL.
Target Audience
Hematology/oncology fellows, attending faculty, and other health care professionals involved in the treatment of patients with mantle cell lymphoma (MCL).
Learning Objectives
1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
2.) Evaluate emerging data on targeted therapeutic approaches for treatment-naive and relapsed/refractory MCL and their applicability to older adults
3.) Assess mechanisms of resistance to targeted therapies for MCL and their implications for treatment selection
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Anti ulcer drugs and their Advance pharmacology ||
Anti-ulcer drugs are medications used to prevent and treat ulcers in the stomach and upper part of the small intestine (duodenal ulcers). These ulcers are often caused by an imbalance between stomach acid and the mucosal lining, which protects the stomach lining.
||Scope: Overview of various classes of anti-ulcer drugs, their mechanisms of action, indications, side effects, and clinical considerations.
Flu Vaccine Alert in Bangalore Karnatakaaddon Scans
As flu season approaches, health officials in Bangalore, Karnataka, are urging residents to get their flu vaccinations. The seasonal flu, while common, can lead to severe health complications, particularly for vulnerable populations such as young children, the elderly, and those with underlying health conditions.
Dr. Vidisha Kumari, a leading epidemiologist in Bangalore, emphasizes the importance of getting vaccinated. "The flu vaccine is our best defense against the influenza virus. It not only protects individuals but also helps prevent the spread of the virus in our communities," he says.
This year, the flu season is expected to coincide with a potential increase in other respiratory illnesses. The Karnataka Health Department has launched an awareness campaign highlighting the significance of flu vaccinations. They have set up multiple vaccination centers across Bangalore, making it convenient for residents to receive their shots.
To encourage widespread vaccination, the government is also collaborating with local schools, workplaces, and community centers to facilitate vaccination drives. Special attention is being given to ensuring that the vaccine is accessible to all, including marginalized communities who may have limited access to healthcare.
Residents are reminded that the flu vaccine is safe and effective. Common side effects are mild and may include soreness at the injection site, mild fever, or muscle aches. These side effects are generally short-lived and far less severe than the flu itself.
Healthcare providers are also stressing the importance of continuing COVID-19 precautions. Wearing masks, practicing good hand hygiene, and maintaining social distancing are still crucial, especially in crowded places.
Protect yourself and your loved ones by getting vaccinated. Together, we can help keep Bangalore healthy and safe this flu season. For more information on vaccination centers and schedules, residents can visit the Karnataka Health Department’s official website or follow their social media pages.
Stay informed, stay safe, and get your flu shot today!
- Video recording of this lecture in English language: https://youtu.be/lK81BzxMqdo
- Video recording of this lecture in Arabic language: https://youtu.be/Ve4P0COk9OI
- Link to download the book free: https://nephrotube.blogspot.com/p/nephrotube-nephrology-books.html
- Link to NephroTube website: www.NephroTube.com
- Link to NephroTube social media accounts: https://nephrotube.blogspot.com/p/join-nephrotube-on-social-media.html
Title: Sense of Taste
Presenter: Dr. Faiza, Assistant Professor of Physiology
Qualifications:
MBBS (Best Graduate, AIMC Lahore)
FCPS Physiology
ICMT, CHPE, DHPE (STMU)
MPH (GC University, Faisalabad)
MBA (Virtual University of Pakistan)
Learning Objectives:
Describe the structure and function of taste buds.
Describe the relationship between the taste threshold and taste index of common substances.
Explain the chemical basis and signal transduction of taste perception for each type of primary taste sensation.
Recognize different abnormalities of taste perception and their causes.
Key Topics:
Significance of Taste Sensation:
Differentiation between pleasant and harmful food
Influence on behavior
Selection of food based on metabolic needs
Receptors of Taste:
Taste buds on the tongue
Influence of sense of smell, texture of food, and pain stimulation (e.g., by pepper)
Primary and Secondary Taste Sensations:
Primary taste sensations: Sweet, Sour, Salty, Bitter, Umami
Chemical basis and signal transduction mechanisms for each taste
Taste Threshold and Index:
Taste threshold values for Sweet (sucrose), Salty (NaCl), Sour (HCl), and Bitter (Quinine)
Taste index relationship: Inversely proportional to taste threshold
Taste Blindness:
Inability to taste certain substances, particularly thiourea compounds
Example: Phenylthiocarbamide
Structure and Function of Taste Buds:
Composition: Epithelial cells, Sustentacular/Supporting cells, Taste cells, Basal cells
Features: Taste pores, Taste hairs/microvilli, and Taste nerve fibers
Location of Taste Buds:
Found in papillae of the tongue (Fungiform, Circumvallate, Foliate)
Also present on the palate, tonsillar pillars, epiglottis, and proximal esophagus
Mechanism of Taste Stimulation:
Interaction of taste substances with receptors on microvilli
Signal transduction pathways for Umami, Sweet, Bitter, Sour, and Salty tastes
Taste Sensitivity and Adaptation:
Decrease in sensitivity with age
Rapid adaptation of taste sensation
Role of Saliva in Taste:
Dissolution of tastants to reach receptors
Washing away the stimulus
Taste Preferences and Aversions:
Mechanisms behind taste preference and aversion
Influence of receptors and neural pathways
Impact of Sensory Nerve Damage:
Degeneration of taste buds if the sensory nerve fiber is cut
Abnormalities of Taste Detection:
Conditions: Ageusia, Hypogeusia, Dysgeusia (parageusia)
Causes: Nerve damage, neurological disorders, infections, poor oral hygiene, adverse drug effects, deficiencies, aging, tobacco use, altered neurotransmitter levels
Neurotransmitters and Taste Threshold:
Effects of serotonin (5-HT) and norepinephrine (NE) on taste sensitivity
Supertasters:
25% of the population with heightened sensitivity to taste, especially bitterness
Increased number of fungiform papillae
Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
CONCLUSIONS: 5YS of LCP after radical procedures significantly depended on: 1) PT early-invasive cancer; 2) PT N0--N12; 3) cell ratio factors; 4) blood cell circuit; 5) biochemical factors; 6) hemostasis system; 7) AT; 8) LC characteristics; 9) LC cell dynamics; 10) surgery type: lobectomy/pneumonectomy; 11) anthropometric data. Optimal diagnosis and treatment strategies for LC are: 1) screening and early detection of LC; 2) availability of experienced thoracic surgeons because of complexity of radical procedures; 3) aggressive en block surgery and adequate lymph node dissection for completeness; 4) precise prediction; 5) adjuvant chemoimmunoradiotherapy for LCP with unfavorable prognosis.
ARTIFICIAL INTELLIGENCE IN HEALTHCARE.pdfAnujkumaranit
Artificial intelligence (AI) refers to the simulation of human intelligence processes by machines, especially computer systems. It encompasses tasks such as learning, reasoning, problem-solving, perception, and language understanding. AI technologies are revolutionizing various fields, from healthcare to finance, by enabling machines to perform tasks that typically require human intelligence.
These lecture slides, by Dr Sidra Arshad, offer a quick overview of physiological basis of a normal electrocardiogram.
Learning objectives:
1. Define an electrocardiogram (ECG) and electrocardiography
2. Describe how dipoles generated by the heart produce the waveforms of the ECG
3. Describe the components of a normal electrocardiogram of a typical bipolar leads (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
Study Resources:
1. Chapter 11, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 9, Human Physiology - From Cells to Systems, Lauralee Sherwood, 9th edition
3. Chapter 29, Ganong’s Review of Medical Physiology, 26th edition
4. Electrocardiogram, StatPearls - https://www.ncbi.nlm.nih.gov/books/NBK549803/
5. ECG in Medical Practice by ABM Abdullah, 4th edition
6. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
Prix Galien International 2024 Forum ProgramLevi Shapiro
June 20, 2024, Prix Galien International and Jerusalem Ethics Forum in ROME. Detailed agenda including panels:
- ADVANCES IN CARDIOLOGY: A NEW PARADIGM IS COMING
- WOMEN’S HEALTH: FERTILITY PRESERVATION
- WHAT’S NEW IN THE TREATMENT OF INFECTIOUS,
ONCOLOGICAL AND INFLAMMATORY SKIN DISEASES?
- ARTIFICIAL INTELLIGENCE AND ETHICS
- GENE THERAPY
- BEYOND BORDERS: GLOBAL INITIATIVES FOR DEMOCRATIZING LIFE SCIENCE TECHNOLOGIES AND PROMOTING ACCESS TO HEALTHCARE
- ETHICAL CHALLENGES IN LIFE SCIENCES
- Prix Galien International Awards Ceremony
Explore natural remedies for syphilis treatment in Singapore. Discover alternative therapies, herbal remedies, and lifestyle changes that may complement conventional treatments. Learn about holistic approaches to managing syphilis symptoms and supporting overall health.
2. • Thrombosis is defined as
“Hemostasis in the wrong place”
• Thrombosis is the formation of an unwanted clot
within a blood vessel - the most common abnormality
of hemostasis
• It is a major cause of morbidity and mortality
morbidity and mortality in a wide range of arterial
and venous diseases and patient population
3. Hemostasis and thrombosis primarily involve the
interplay among three factors
• Vessel wall
• Coagulation proteins
• Platelets
5. PLATELET PATHOPHYSIOLOGY
• 1011
platelets produced per day
• Anucleate cells
• Source of chemokines, cytokines that are
preformed and stored as granules
• Activated platelets synthesize TXA2
21. P2Y12 INHIBITORS
• ADP receptors
• P2Y1 and P2Y12 subtypes
• GPCR
• Both needed for aggregation – P2Y12 pathway
plays a principal role
ADP
RECEPTOR
ANTAGONIST
27. TICAGRELOR
• Oral drug
• Non-thienopyridine - reversible inhibitor
• Binding site different from ADP -allosteric antagonist
• Does not require metabolic activation
• Maximum levels of both the drug and platelet
inhibition occur about two hours after
• Loading dose -180 mg - Maintenance dose of 90 mg
twice a day
28. • Advantage of not requiring metabolism by the CYP450 - minimizes the potential for
drug- drug interactions
• (e.g., proton pump inhibitors and clopidogrel)
• ELINOGREL
• Reversible antagonist
• Oral or parenteral
• This unique dual formulation provides the potential benefit for smooth transition from short term
intravenous to long term oral antiplatelet therapy
• More effective at inhibiting platelet activation by lower, rather than higher, concentrations of ADP
• Maximum platelet inhibition occurs at 20 minutes
• Under PHASE III trial
29. CANGRELOR
• Rapid onset and offset of action – iv route
• Ultra-short half life 3-6 minutes
• Infusion of 4μg/kg per minute peak inhibition in 15
minutes - Rapid offset, with in 60 minutes
• >90% platelet inhibition
• More desirable for elective treatment of stenotic coronary
arteries, high risk acute coronary syndromes treated with
immediate coronary stenting, and for bridging those
surgery patients who require P2Y12 inhibition
• Under PHASE III trial
30. • Limitations of current therapies include
• Weak inhibition of platelet function (Eg. aspirin),
• Blockade of only one pathway of ADP-mediated
signaling (Eg. clopidogrel),
• Slow onset of action
• Interpatient response variability with poor inhibition of
platelet function in some patients
31. GPIIa/IIIb INHIBITORS
• It’s a platelet surface integrin
• Designated as αIIbβ3
• Main use:
• Percutaneous Intervention (PCI)
• Limited efficacy after Myocardial Infarction
32.
33. ABCIXIMAB
EPTIFIBATIDE
TIROFIBAN
Molecule Fab fragment -
chimeric
Cyclic peptide Non peptide
For GPIIa/IIIb Non specific Specific Specific
Half-life Short -10 – 30mts 2.5 hrs 2 hrs
Adverse effects Hge
Thrombocytopenia
Expensive
Hge
Thrombocytopenia
Hge
Thrombocytopenia
34. • ABCIXIMAB
• It also binds to the vitronectin receptor on
platelets, vascular endothelial cells, and smooth
muscle cells.
(Vitronectin is a GP present in serum and in
matrix. It promotes Adhesion)
35. ORAL GPIIa/IIIb INHIBITORS
XEMILOFIBAN
Prodrug
Non-peptide
Phase III study tested the hypothesis that
chronic (up to 6 month) oral blockade of the
GP IIb/IIIa receptor would provide both acute
and ongoing protection from death, myocardial
infarction, and the need for urgent
revascularization
36. • OTHER ORAL GPIIa/IIIb INHIBITORS
• Orbofiban – PHASE III
• Lotrafiban – PHASE III
• Sibrafiban
37. TRIPLE ANTI-PLATELET THERAPY
• Based on IV GPIIb/IIIa inhibitors is more effective than
aspirin-based dual therapy in reducing vascular events, MI and
death in patients with acute coronary syndromes (STEMI and
NSTEMI).
38. • A significant increase in minor bleeding complications
was observed among STEMI and elective PCI patients.
• In patients undergoing elective PCI, triple therapy had no
beneficial effect - associated with an 80% increase in
transfusions and an eightfold increase in
thrombocytopenia.
39. THROMBOXANE A2 RECEPTOR ANTAGONISTS
• Thromboxane receptorα (TPα)
• GPCR that is coupled to Gq and G12/13
• Blocks TP activation through other ligands such as
Endoperoxides
• Some have additional TXA2 synthase inhibition
• GPCRs – IP3/DAG – Ca++
40. • TERUTROBAN
• Oral reversible inhibitor of TP receptor
• Dose dependently prolonged occlusive thrombus formation in animal models
• Dose dependent inhibition of platelet aggregation in patients with peripheral artery disease
• RIDOGREL
• The drug is a combined
• TXA2 synthase inhibitor
• TXA2 receptor blocker
• Prostaglandin endoperoxide receptor antagonist
• While aspirin inhibits COX, ridogrel inhibitsTXA2 synthesis directly
FAILED TO MEET
PRIMARY
ENDPOINT
41. PICOTAMIDE
• Combined inhibitor
• At variance with aspirin, does not interfere
with endothelial PGI2 production
• Moreover long-term picotamide treatment in
diabetes promotes the reduction of
microalbuminuria and the inhibition of
growth of carotid plaques
RAMATROBAN
43. VORAPAXOR – approved on May 8, 2014
• Oral Reversible antagonist PAR-1 – first agent
• High affinity and low molecular weight
• PAR-1 is a GPCR found in platelets and vascular endothelium – 40mg loading – 2.5mg maintenance
• Blocks the cellular activation of thrombin without inhibiting thrombin mediated cleavage of
fibrinogen
• Does not influence hemostasis as well as bleeding time
In theory this agent should result in less bleeding
ATOPAXAR
• QT prolongation
44. AJW200
• An IgG4 humanized monoclonal antibody to vWF
which has been shown to specifically inhibit high-
shear-stress-induced platelet aggregation.
ARC1779
• Continuous infusion increased platelet counts in
critically ill TTP - preventing platelet aggregation
and loss of platelets.
45. GPVI RECEPTOR ANTAGONISTS
REVACEPT
• Dimeric Glycoprotein VI-Fc fusion protein
• Specifically and efficiently inhibited
collagen-induced platelet aggregation
• Under PHASE II trial
47. Aggregating the evidence on antiplatelet
drugs:
A review of recent clinical trials
Author: Niteesh K. Choudhry, M.D., Ph.D., Nihar R.
Desai, M.D., M.P.H.
Consultants: Jerry Avorn, M.D., Michael Fischer, M.D.,
M.S.
Platelets play a central role in the development of thrombi and subsequent ischemic events. The process of platelet-mediated thrombus formation involves adhesion, activation, and aggregation.
Within seconds of injury, platelets adhere to collagen fibrils through glycoprotein (GP) Ia/IIa receptors. An adhesive glycoprotein, von Willebrand factor (vWF) allows platelets to stay attached to the subendothelial vessel wall (via GP Ib) despite high shear forces. Following adhesion, platelets are activated to secrete a variety of agonists including thrombin, serotonin, adenosine diphosphate (ADP), and thromboxane A2 (TXA2). These agonists, which further augment the platelet activation process, bind to specific receptor sites on the platelets to activate the GP IIb/IIIa receptor complex, the final common pathway to platelet aggregation. Once activated, the GP IIb/IIIa receptor undergoes a conformational change that enables it to bind with fibrinogen.[1,2]
Handin RI. Bleeding and thrombosis. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s Principles of Internal Medicine. Vol 1. 14th ed. New York, NY: McGraw-Hill; 1998:339-345.
Schafer AI. Antiplatelet therapy. Am J Med. 1996;101:199-209.