Having more than two year experiences, presently anticoagulant is an essential component of management of COVID 19
Its role is recommended in moderate to severe to critically ill patients with different opinion in the dosage
Giving anticoagulants in asymptomatic or mild cases is still need to be validated though there are suggestions in favor.
There is recommendation for post discharge patients who had clinically suspected/established thromboembolism events
Origin of virus??
Transmission of virus??
First case in Wuhan?
Aerosol transmission? Fomites? Re- infection/ reactivation
Vaccine/ safety & efficacy/ antibody test/ community transmission?
Case definition?
Pathophysiology/ pathology
Cardiovascular manifestations/ risk?
ACS
Role of aspirin
Low platelet in covid-19
Anti-coagulants
ACEI/ARB/ARNI
Diuretics
Clinical features
High risk groups
Antibiotics
HCQ& Lopinavir, Ritonavir
Anti viral drugs- remdisivir/ favipiravir
Biological therapy- tocilizumab
Convalescent plasma therapy
Systemic steroids
Ivermectin
NSAIDs
Respiratory failure
Other management in covid 19- fluid/ nebulization
Chemoprophylaxis
Bronchial asthma
Anti diabetics
Origin of virus??
Transmission of virus??
First case in Wuhan?
Aerosol transmission? Fomites? Re- infection/ reactivation
Vaccine/ safety & efficacy/ antibody test/ community transmission?
Case definition?
Pathophysiology/ pathology
Cardiovascular manifestations/ risk?
ACS
Role of aspirin
Low platelet in covid-19
Anti-coagulants
ACEI/ARB/ARNI
Diuretics
Clinical features
High risk groups
Antibiotics
HCQ& Lopinavir, Ritonavir
Anti viral drugs- remdisivir/ favipiravir
Biological therapy- tocilizumab
Convalescent plasma therapy
Systemic steroids
Ivermectin
NSAIDs
Respiratory failure
Other management in covid 19- fluid/ nebulization
Chemoprophylaxis
Bronchial asthma
Anti diabetics
A cardiologists perspective to current scenario in light of corona pandemic in india and world wide. cardiac procedures , heart disease , aceinhibitors , arni , heart failure , troponin, nt probnp
Webinar Series on COVID-19 vaccine: Jointly organized by Malaysian Society of Infection Control and Infectious Diseases (MyICID) & Institute for Clinical Research (ICR), NIH
Speaker: Dr. Low Lee Lee, Infectious Disease Physician at the Hospital Sultanah Bahiyah, Ministry of Health Malaysia.
This Presentation contains an international directory of guidelines collection from many international sources and best practice recommendations documents for the care and management of COVID-19 .
Contents
1-anticoagulation in COVID-19.
2-Antivirals in COVID-19.
3-immunomodulators in COVID-19.
4-antifibrotic therapy in COVID-19.
5-Antibiotic in COVID-19.
6-Nebulization in COVID-19.
7-Systemic steroids in COVID-19.
8- supplement in COVID-19.
9-radiation therapy in COVID-19.
10-Convalescent plasma in COVID-19.
11- COVID-19 in Pregnancy
12-Acute Kidney Injury in COVID-19.
13- Cardiology in COVID -19.
14-Critical Care in COVID-19.
15-Nutrition in ICU Patients in COVID-19.
16 Hypoxemia Management in COVID-19.
17-Mechanical Ventilation in COVID-19.
Endocarditis in adults with bacterial meningitisShadab Ahmad
Bacterial meningitis is a life-threatening disease that is associated with considerable mortality and morbidity.
Currently, Streptococcus pneumoniae is responsible for 70% of the cases in Europe and the United States.
Bacterial meningitis is often related to other foci of infection outside the central nervous system such as pneumonia, sinusitis, or otitis.
An uncommon focus of bacterial meningitis is infective endocarditis.
The power point is all about Blood culture negative Infective Endocarditis prepared by Dr Julieth Nachone Kabirigi, a Pediatric Cardiologist and a Lecturer at Catholic University.
These slides aiming to help other to understand the importance of history taking, multidisciplinary approach and various diversity on diagnosis and management of Infective Endocarditis especially in children
This presentation focuses on a recently published paper aiming to create an algorithm for the investigation of patients with new onset fever or instability
Updated Hypertension Management – ESH 2023.pdfDr. Nayan Ray
Hypertension is the most prevalent CV disorder in the world and according to the WHO, it affects 1.28 billion adults aged 30–79 years worldwide, two-thirds living in low-income and middle-income countries.
In 2019, the global age-standardized average prevalence of hypertension in adults aged 30–79 years was reported to be 34% in men and 32% in women.
At younger ages (<50 years), hypertension is more prevalent in men, whereas a steeper increase of SBP in women from their third decade (and more so following menopause) makes the prevalence of hypertension greater in women in older age categories (>65 years).
Rule of Halves
Half the people with high blood pressure are not known (“rule 1”),
Half of those known are not treated (“rule 2”) and
Half of those treated are not controlled (“rule 3”)'
Definition:
Hypertension is defined based on repeated office SBP values ≥ 140 mmHg and/or DBP ≥ 90 mmHg.
Renal function is greatly important in risk stratification, pharmacologic therapy, and the prognosis of patients with heart failure (HF).
The deterioration of heart function can result in the worsening renal function (WRF) and vice versa.
Besides the heart function itself, the Pharmacologic Treatment of HF is closely related to renal function as regards initiation, titration, and discontinuation, making the situation more complex.
A cardiologists perspective to current scenario in light of corona pandemic in india and world wide. cardiac procedures , heart disease , aceinhibitors , arni , heart failure , troponin, nt probnp
Webinar Series on COVID-19 vaccine: Jointly organized by Malaysian Society of Infection Control and Infectious Diseases (MyICID) & Institute for Clinical Research (ICR), NIH
Speaker: Dr. Low Lee Lee, Infectious Disease Physician at the Hospital Sultanah Bahiyah, Ministry of Health Malaysia.
This Presentation contains an international directory of guidelines collection from many international sources and best practice recommendations documents for the care and management of COVID-19 .
Contents
1-anticoagulation in COVID-19.
2-Antivirals in COVID-19.
3-immunomodulators in COVID-19.
4-antifibrotic therapy in COVID-19.
5-Antibiotic in COVID-19.
6-Nebulization in COVID-19.
7-Systemic steroids in COVID-19.
8- supplement in COVID-19.
9-radiation therapy in COVID-19.
10-Convalescent plasma in COVID-19.
11- COVID-19 in Pregnancy
12-Acute Kidney Injury in COVID-19.
13- Cardiology in COVID -19.
14-Critical Care in COVID-19.
15-Nutrition in ICU Patients in COVID-19.
16 Hypoxemia Management in COVID-19.
17-Mechanical Ventilation in COVID-19.
Endocarditis in adults with bacterial meningitisShadab Ahmad
Bacterial meningitis is a life-threatening disease that is associated with considerable mortality and morbidity.
Currently, Streptococcus pneumoniae is responsible for 70% of the cases in Europe and the United States.
Bacterial meningitis is often related to other foci of infection outside the central nervous system such as pneumonia, sinusitis, or otitis.
An uncommon focus of bacterial meningitis is infective endocarditis.
The power point is all about Blood culture negative Infective Endocarditis prepared by Dr Julieth Nachone Kabirigi, a Pediatric Cardiologist and a Lecturer at Catholic University.
These slides aiming to help other to understand the importance of history taking, multidisciplinary approach and various diversity on diagnosis and management of Infective Endocarditis especially in children
This presentation focuses on a recently published paper aiming to create an algorithm for the investigation of patients with new onset fever or instability
Updated Hypertension Management – ESH 2023.pdfDr. Nayan Ray
Hypertension is the most prevalent CV disorder in the world and according to the WHO, it affects 1.28 billion adults aged 30–79 years worldwide, two-thirds living in low-income and middle-income countries.
In 2019, the global age-standardized average prevalence of hypertension in adults aged 30–79 years was reported to be 34% in men and 32% in women.
At younger ages (<50 years), hypertension is more prevalent in men, whereas a steeper increase of SBP in women from their third decade (and more so following menopause) makes the prevalence of hypertension greater in women in older age categories (>65 years).
Rule of Halves
Half the people with high blood pressure are not known (“rule 1”),
Half of those known are not treated (“rule 2”) and
Half of those treated are not controlled (“rule 3”)'
Definition:
Hypertension is defined based on repeated office SBP values ≥ 140 mmHg and/or DBP ≥ 90 mmHg.
Renal function is greatly important in risk stratification, pharmacologic therapy, and the prognosis of patients with heart failure (HF).
The deterioration of heart function can result in the worsening renal function (WRF) and vice versa.
Besides the heart function itself, the Pharmacologic Treatment of HF is closely related to renal function as regards initiation, titration, and discontinuation, making the situation more complex.
Cardiac arrest is the cessation of functional cardiac contraction and is the final common pathway in death from any pathology.
In the clinical context, cardiac arrest refers to the sudden loss of cardiac output that prompts an emergency response.
Pathogenesis, prognosis and management of in-hospital and out-of-hospital cardiac arrest are subtly different; however, the basic principles of cardiopulmonary resuscitation (CPR) are to maintain forward flow of oxygenated blood, correct the causative factor and restore spontaneous circulation.
CVD Risk Managemnt- Focus on HTN & Dys.pdfDr. Nayan Ray
Cardiovascular disease is a major cause of disability and premature death throughout the world and contributes substantially to the escalating costs of health care.
The underlying pathology is atherosclerosis, which develops over many years and is usually advanced by the time symptoms occur, generally in middle age.
Acute coronary and cerebrovascular events frequently occur suddenly and are often fatal before medical care can be given.
Modification of risk factors has been shown to reduce mortality and morbidity in people with diagnosed or undiagnosed cardiovascular disease.
In patients with coronary artery disease (CAD), percutaneous coronary interventions (PCI) are the cornerstone of treatment for those presenting with an acute coronary syndrome (ACS); PCI has also been largely adopted in patients with chronic coronary syndromes (CCS).
Adjunctive pharmacotherapy, in particular antithrombotic therapy, has a pivotal role in optimising outcomes in patients undergoing PCI23. In fact, patients undergoing PCI may develop both acute and long-term ischaemic events.
Therefore, antithrombotic drugs, in particular antiplatelet agents, are key to the treatment and prevention of both local and systemic thrombotic complications.
Coronary Revascularization in Chronic Kidney Disease Patient.pptxDr. Nayan Ray
Chronic kidney disease (CKD) is an independent risk factor for the development of coronary artery disease, and for more severe coronary heart disease (CHD).
CKD is also associated with adverse outcomes in those with existing cardiovascular disease.
This includes increased mortality after an acute coronary syndrome, after percutaneous coronary intervention (PCI) with or without stenting, and after coronary artery bypass. In addition, patients with CKD are more likely to present with atypical symptoms, which may delay diagnosis and adversely affect outcomes.
Dyslipidemia in Chronic Kidney Diseases.pdfDr. Nayan Ray
Dyslipidaemia in Chronic Kidney Disease: An Approach to Pathogenesis and Treatment
Slides Include:
1. Stages of CKD
2. Developments of atherogenesis
3. Lipoprotein in CKD
4. Drug Therapies
5.Summary KDIGO Guideline
Management of HTN according to gender. This slides will answer some questions such as
1. Why there is BP variability difference between male and female?
2. What's the regulatory mechanism of HTN in gender?
These simplified slides by Dr. Sidra Arshad present an overview of the non-respiratory functions of the respiratory tract.
Learning objectives:
1. Enlist the non-respiratory functions of the respiratory tract
2. Briefly explain how these functions are carried out
3. Discuss the significance of dead space
4. Differentiate between minute ventilation and alveolar ventilation
5. Describe the cough and sneeze reflexes
Study Resources:
1. Chapter 39, Guyton and Hall Textbook of Medical Physiology, 14th edition
2. Chapter 34, Ganong’s Review of Medical Physiology, 26th edition
3. Chapter 17, Human Physiology by Lauralee Sherwood, 9th edition
4. Non-respiratory functions of the lungs https://academic.oup.com/bjaed/article/13/3/98/278874
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
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Couples presenting to the infertility clinic- Do they really have infertility...Sujoy Dasgupta
Dr Sujoy Dasgupta presented the study on "Couples presenting to the infertility clinic- Do they really have infertility? – The unexplored stories of non-consummation" in the 13th Congress of the Asia Pacific Initiative on Reproduction (ASPIRE 2024) at Manila on 24 May, 2024.
Tom Selleck Health: A Comprehensive Look at the Iconic Actor’s Wellness Journeygreendigital
Tom Selleck, an enduring figure in Hollywood. has captivated audiences for decades with his rugged charm, iconic moustache. and memorable roles in television and film. From his breakout role as Thomas Magnum in Magnum P.I. to his current portrayal of Frank Reagan in Blue Bloods. Selleck's career has spanned over 50 years. But beyond his professional achievements. fans have often been curious about Tom Selleck Health. especially as he has aged in the public eye.
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Introduction
Many have been interested in Tom Selleck health. not only because of his enduring presence on screen but also because of the challenges. and lifestyle choices he has faced and made over the years. This article delves into the various aspects of Tom Selleck health. exploring his fitness regimen, diet, mental health. and the challenges he has encountered as he ages. We'll look at how he maintains his well-being. the health issues he has faced, and his approach to ageing .
Early Life and Career
Childhood and Athletic Beginnings
Tom Selleck was born on January 29, 1945, in Detroit, Michigan, and grew up in Sherman Oaks, California. From an early age, he was involved in sports, particularly basketball. which played a significant role in his physical development. His athletic pursuits continued into college. where he attended the University of Southern California (USC) on a basketball scholarship. This early involvement in sports laid a strong foundation for his physical health and disciplined lifestyle.
Transition to Acting
Selleck's transition from an athlete to an actor came with its physical demands. His first significant role in "Magnum P.I." required him to perform various stunts and maintain a fit appearance. This role, which he played from 1980 to 1988. necessitated a rigorous fitness routine to meet the show's demands. setting the stage for his long-term commitment to health and wellness.
Fitness Regimen
Workout Routine
Tom Selleck health and fitness regimen has evolved. adapting to his changing roles and age. During his "Magnum, P.I." days. Selleck's workouts were intense and focused on building and maintaining muscle mass. His routine included weightlifting, cardiovascular exercises. and specific training for the stunts he performed on the show.
Selleck adjusted his fitness routine as he aged to suit his body's needs. Today, his workouts focus on maintaining flexibility, strength, and cardiovascular health. He incorporates low-impact exercises such as swimming, walking, and light weightlifting. This balanced approach helps him stay fit without putting undue strain on his joints and muscles.
Importance of Flexibility and Mobility
In recent years, Selleck has emphasized the importance of flexibility and mobility in his fitness regimen. Understanding the natural decline in muscle mass and joint flexibility with age. he includes stretching and yoga in his routine. These practices help prevent injuries, improve posture, and maintain mobilit
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Ve...kevinkariuki227
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
TEST BANK for Operations Management, 14th Edition by William J. Stevenson, Verified Chapters 1 - 19, Complete Newest Version.pdf
Report Back from SGO 2024: What’s the Latest in Cervical Cancer?bkling
Are you curious about what’s new in cervical cancer research or unsure what the findings mean? Join Dr. Emily Ko, a gynecologic oncologist at Penn Medicine, to learn about the latest updates from the Society of Gynecologic Oncology (SGO) 2024 Annual Meeting on Women’s Cancer. Dr. Ko will discuss what the research presented at the conference means for you and answer your questions about the new developments.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
Atrioventricular conduction blocks ( AV blocks ) are classified into 3 types.
This document describes the acute management of AV block.
micro teaching on communication m.sc nursing.pdfAnurag Sharma
Microteaching is a unique model of practice teaching. It is a viable instrument for the. desired change in the teaching behavior or the behavior potential which, in specified types of real. classroom situations, tends to facilitate the achievement of specified types of objectives.
Title: Sense of Smell
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 primary categories of smells and the concept of odor blindness.
Explain the structure and location of the olfactory membrane and mucosa, including the types and roles of cells involved in olfaction.
Describe the pathway and mechanisms of olfactory signal transmission from the olfactory receptors to the brain.
Illustrate the biochemical cascade triggered by odorant binding to olfactory receptors, including the role of G-proteins and second messengers in generating an action potential.
Identify different types of olfactory disorders such as anosmia, hyposmia, hyperosmia, and dysosmia, including their potential causes.
Key Topics:
Olfactory Genes:
3% of the human genome accounts for olfactory genes.
400 genes for odorant receptors.
Olfactory Membrane:
Located in the superior part of the nasal cavity.
Medially: Folds downward along the superior septum.
Laterally: Folds over the superior turbinate and upper surface of the middle turbinate.
Total surface area: 5-10 square centimeters.
Olfactory Mucosa:
Olfactory Cells: Bipolar nerve cells derived from the CNS (100 million), with 4-25 olfactory cilia per cell.
Sustentacular Cells: Produce mucus and maintain ionic and molecular environment.
Basal Cells: Replace worn-out olfactory cells with an average lifespan of 1-2 months.
Bowman’s Gland: Secretes mucus.
Stimulation of Olfactory Cells:
Odorant dissolves in mucus and attaches to receptors on olfactory cilia.
Involves a cascade effect through G-proteins and second messengers, leading to depolarization and action potential generation in the olfactory nerve.
Quality of a Good Odorant:
Small (3-20 Carbon atoms), volatile, water-soluble, and lipid-soluble.
Facilitated by odorant-binding proteins in mucus.
Membrane Potential and Action Potential:
Resting membrane potential: -55mV.
Action potential frequency in the olfactory nerve increases with odorant strength.
Adaptation Towards the Sense of Smell:
Rapid adaptation within the first second, with further slow adaptation.
Psychological adaptation greater than receptor adaptation, involving feedback inhibition from the central nervous system.
Primary Sensations of Smell:
Camphoraceous, Musky, Floral, Pepperminty, Ethereal, Pungent, Putrid.
Odor Detection Threshold:
Examples: Hydrogen sulfide (0.0005 ppm), Methyl-mercaptan (0.002 ppm).
Some toxic substances are odorless at lethal concentrations.
Characteristics of Smell:
Odor blindness for single substances due to lack of appropriate receptor protein.
Behavioral and emotional influences of smell.
Transmission of Olfactory Signals:
From olfactory cells to glomeruli in the olfactory bulb, involving lateral inhibition.
Primitive, less old, and new olfactory systems with different path
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
Pulmonary Thromboembolism - etilogy, types, medical- Surgical and nursing man...VarunMahajani
Disruption of blood supply to lung alveoli due to blockage of one or more pulmonary blood vessels is called as Pulmonary thromboembolism. In this presentation we will discuss its causes, types and its management in depth.
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.
2. Introduction
• Having more than a year experiences, presently
anticoagulant is an essential component of management
of COVID 19
• Its role is recommended in moderate to severe to critically
ill patients with different opinion in the dosage
• Giving anticoagulants in asymptomatic or mild cases is still
need to be validated though there are suggestions in favor.
• There is recommendation for post discharge patients who
had clinically suspected/established thromboembolism
events
3. Intro….
• Both arterial and venous thromboembolism are prevalent in
COVID 19 patients
• Both macro and microvascular thrombosis are evident
• Overall incidence of VTE among inpatients with COVID-19 was
estimated at 17%
• Post mortem studies show the presence of thrombosis
• Thrombotic events occur in hospitalized patients - more in
ICU admitted than in ward patients (28% vs 7%)
JACC Vol 77, No 15, April 20,2021
4. • SARS-CoV-2 enters endothelial cells through ACE2 receptors and
may impair their intrinsic antithrombotic properties
• Endothelial activation takes place due to viremia, hypoxia and
inflammatory response and increased tissue factor
• There is activation of coagulation cascade and inhibition of
plasminogen activators
• Increased reactivity of platelets
• Excessive inflammatory response plays an important role in the
pathogenesis of thrombosis (thrombo-inflammation), including
pulmonary - and pulmonary intravascular coagulopathy
JACC Vol 77, No 15, April 20,2021
Intro….
5. Why Anticoagulants???
1. Therapeutic - signs of thromboembolism - DVT, PE
2. Primary prophylaxis - in anticipation of
thromboembolism
3. Ongoing anticoagulant - atrial fibrillation or patients
with mechanical valves
4. Secondary prophylaxis - post-discharge patients
7. • Pathophysiology of the diseases process
• Epidemiological data
• Observational studies
• Autopsy studies
Primary Prophylaxis: Rationale
8. Clinical and Pathophysiological Staging in COVID
• Stage 1 Patients who are ambulant or admitted to hospital because of
other reasons
Symptoms
Mild, do not need respiratory support
Inflammatory reaction
Mild
Coagulation markers
D-dimer 2-3 times the ULN
Fibrinogen normal
Prothrombin time normal
Platelet count normal
Thrombotic events
Limited local pulmonary (inflammatory)
microthrombi
Lancet Hoematol | Published online April 27, 2021
9. Clinical and Pathophysiological Staging in COVID
• Stage 2 Patients who are admitted to hospital and need increased oxygen
supply
Symptoms
More severe, need respiratory support
Inflammatory reaction
Pronounced
Coagulation markers
D-dimer 3-6 times the UUN
Fibrinogen mildly increased
Prothrombin time mildly increased
Platelet count 100-500x109 platelets per L
Thrombotic events
Increased incidence of (inflammatory)
microthrombi and macrothrombi
Lancet Hoematol | Published online April 27, 2021
10. Symptoms
Critically ill patients who need organ support-eg, high flow
oxygen therapy or mechanical ventilatory support, or both
Inflammatory reaction
Cytokine storm
Coagulation markers
D-dimer more than 6 times the ULNFibrinogen markedly
increasedProthrombin time markedly increasedPlatelet
countless than 100 x 109 platelets per L
Thrombotic events
High incidence of microthrombi andmacrothrombi
Lancet Haematol Published online April 27, 2021
• Stage 3 Critically ill patients in need of organ support
Clinical and Pathophysiological Staging in COVID
11. • Post-discharge Patients who are discharged from hospital
Symptoms
Recovering. Functional limitations are often still
present 3 months after discharge
Inflammatory reaction
Restored
Coagulation markers
Restored
Thrombotic events
Unknown
Lancet Haematol / Published online April 27, 2021
Clinical and Pathophysiological Staging in COVID
12. Pathophysiology Supporting Anticoagulant
• In COVID 19, all the three components of Virchow's triad
come into play: endothelitis activation of coagulation
cascade as well as platelet activation-stasis (less
movement in general; prolonged bed confinement of ICU
patients).
• There are abundant ACE2 receptors on the vascular
endothelium, so the virus enters the endothelium
resulting in the endothelitis impairing intrinsic
antithrombotic properties.
• Hypoxemia takes part in the genesis of endothelial injury
13. Hypercoagulable State
• Inflammatory cytokines and endothelial activation results
in decreased anti-thrombin and plasminogen activators and
increased platelet activity.
• Increased level of plasminogen inhibitors, von Willabrand
factor, fibrinogen, factors V, VII, VIII and X-all lead to hyper-
coagulable state.
• COVID 19 is associated with excessive inflammatory
response in comparison with other viral/inflammatory
conditions resulting in more intense hyper-coagulable
state.
• Inflammation associated with SARS-CoV-2 infection leads
to a "COVID-19 related coagulopathy" resulting in
increased thrombosis
JACC Vol 76 No 16, October 2020; Vol 77, No 15 April 2021
14. Stasis
• Fatigue
• Hypoxemia
• Hospitalization
• Pneumonia
• Cardiac involvement - myocarditis, heart failure
• Connection with medical appliances
• ICU admitted
JACC Vol 76 No 16,October,2020; Vol 77, No 15 April 2021
15.
16. Platelet and Endothelial Activation as
Potential Mechanisms Behind the Thrombotic
Complications of COVID-19 Patients
• JACC 2020;75(23):2950-73.June 16
• Several mechanisms can promote platelet activation in COVID-19:
• Endothelial dysfunction and lack of NO activity
• No direct effect of the virus
• Aspirin and P2Y12 inhibitors prevent platelet activation induced
by COVID-19 plasma.
• Severe COVID-19 patients may develop pulmonary
embolism/small local thrombi despite prophylactic and even
empiric treatment-dose anticoagulation suggesting that an other
antithrombotic therapy may be necessary for this therapeutic
goal
17. • In COVID-19 patients there is sustained platelet activation
with formation of PLA that may be involved in the
microthrombi found in autoptic specimens.
• COVID-19 plasma, added to the blood of healthy subjects,
induces platelet activation which is blunted by
pretreatment with tocilizumab.
• IL-6-mediated platelet activation that triggers the
hypercoagulable state in COVID-19, suggesting the
potential effectiveness of anti-IL 6 antibodies and
antiplatelet drugs
JACC Basic Trans Science 2021,6203-18
Platelet and Endothelial Activation as
Potential Mechanisms Behind the Thrombotic
Complications of COVID-19 Patients
18. • Quantitative analysis of 28,173 hospitalized patients of 66
studies
• VTE occurs in 22.7% of ICU and 7.9% of non-ICU
hospitalized patients.
• Thromboprophylaxis is a key element in the medical care
of patients with COVID-19, especially in those with severe
illness
• High incidence of VTE despite prophylactic or even
therapeutic anticoagulation.
• Ideal anticoagulation approach needs to be studied
further
• D-dimer guided anticoagulation
October, 2020, Vol 4, Issue 7
20. Arterial Thromboembolism
• Patients with SARS-CoV-2 are at risk risk for acute arterial
thromboembolic complications (Journal Vascular Surgery.
Volume 73, Issue 2, February 2021, Pages 381-389.e1) In 40
diagnosed arterial thromboembolism, 37.5 % were COVID
positive.
• In another series of 20 patients with arterial
thromboembolic events have been reported in 209
admitted patients (9.6%) (International Journal of
Cardiology. Volume 323, 15 January 2021, Pages 281-284)
21. Anticoagulation. Bledding, Mortality
and Pathology in Hospitalized Patients
in Covid 19
• Retrospective analysis 4,389 patients including 72 autopsy
studies.
• Bleeding rates were low overall, but as expected, were
slightly higher in the therapeutic AC group (3%) compared
with the prophylactic (1.7%) and no AC groups (1.9%)
• Bleeding rates were higher in patients on LMWH versus
DOACs (2.6% vs 1.3%)
• Autopsy findings revealed high prevalence of
thromboembolism (42%) including those receiving AC. In
most cases there was no clinical suspicion of
thromboembolism. JACC Vol 76, No 16, October, 2020
23. Therapeutic versus prophylactic
anticoagulation for severe COVID-19: A
randomized phase II clinical trial
(HESACOVID)
• Patients on mechanical ventilation – 10 received
therapeutic anticoagulation and 10 prophylactic
anticoagulation.
• Therapeutic enoxaparin improves gas exchange and
decreases the need for mechanical ventilation in severe
COVID-19.
Thrombosis Research , Volume 196, December 2020, Pages 359-366T
24. • Incidence of VTE ( met analysis of 66 studies) – 14.1%
• ICU patients – 45.6% ( 3 times higher than other viral
infection)
• Post-discharge within 90 days - 2.6%
• Pre-hospital ( mild cases) incidence is not recorded
• Increased prevalence of arterial thrombotic events such
as myocardial and cerebral infarction (up to 3%) in the
ICU setting
Lancet Haematol, April 27, 2021
26. • Fondaparinux - 2.5 mg sc once daily in patients with HIT
having acceptable renal function (Crcl 230 mL/min)
• 8.3% incidence of VTE for patients on hospital wards
• It is noteworthy that reports of excessive bleeding in
COVID-19– infected patients residing in the hospital have
not been published. Two groups with patients receiving
anticoagulants reported bleeding rates of 0% to 3%.
Myo Clinic Recommendation
Mayo Clin Proc. 2020 Nov; 95(11): 2467–2486
27.
28. NIH Recommendations
• In non hospitalized patients with COVID-19, there are
currently no data to support the measurement of
coagulation markers (e.g., D-dimers, prothrombin time,
platelet count, fibrinogen) (AIII).
• For non hospitalized patients with COVID-19,
anticoagulants and antiplatelet therapy should not be
initiated for the prevention of venous thromboembolism
(VTE) or arterial thrombosis unless the patient has other
indications for the therapy or is participating in a clinical
trial (AIII).
• Patients who are receiving anticoagulant or antiplatelet
therapies for underlying conditions should continue these
medications if they receive a diagnosis of COVID-19 (AIII).
Alll: for Strong recommendation - expert opinion
29. • In hospitalized patients with COVID-19, hematologic and
coagulation parameters are commonly measured, although
there are currently insufficient data to recommend either for or
against using this data to guide management decisions.
• Hospitalized adults with COVID-19 should receive prophylactic
dose anticoagulation (AIII).
• Anticoagulant or antiplatelet therapy should not be used to
prevent arterial thrombosis outside of the usual standard of care
for patients without COVID-19 (AIII).
• For hospitalized COVID-19 patients who experience rapid
deterioration of pulmonary, cardiac, or neurological function, or
of sudden, localized loss of peripheral perfusion, the possibility
of thromboembolic disease should be evaluated (AIII).
NIH Recommendations
30. • Incident thromboembolic event or who are highly suspected to
have thromboembolic disease should be managed with
therapeutic doses of anticoagulant therapy (AIII).
• Extracorporeal membrane oxygenation or continuous renal
replacement therapy or who have thrombosis of catheters or
extracorporeal filters should be treated with antithrombotic
therapy as per the standard institutional protocols for those
without COVID-19 (AIII).
• DOAC is contraindicated in lactating mothers – UFH, LMWH and
warfarin not secreted in breast milk.
• Hospitalized patients with COVID-19 should not routinely be
discharged from the hospital while on VTE prophylaxis (AIII).
• Extended VTE prophylaxis after hospital discharge can be
considered for patients who are at low risk for bleeding and high
risk for VTE (BI). FDA approval of the use of Rivaroxaban 10 mg
daily for 31 to 39 days in these patients.
NIH Recommendations
31. • In hospitalized, critically ill patients, LMWH or UFU is preferred
over oral anticoagulants due to shorter half-lives, can be
administered iv or sc, and have fewer drug-drug interactions
(AIII).
• Whenever anticoagulant or antiplatelet therapy is used, potential
drug-drug interactions with other concomitant drugs must be
considered (AIII).
• COVID-19 outpatients receiving warfarin may be candidates for
switching to DOAC therapy to avoid INR measurement.
NIH Recommendations
32. • In pregnancy, LMWH is recommended, rather than
unfractionated heparin, for the prevention and
treatment of VTE
• Warfarin to be avoided
• No safety data of DOACS
NIH Recommendations
38. Covid 19 associated coagulopathy and
Anti thrombotic Agents – Lessons After 1 year
• High risk of bleeding despite high risk of thrombosis in
critically ill patients due to pronounced thrombocytopenia,
platelet dysfunction or coagulation factor deficiencies, or
both comparing to moderately ill patients.
• Overwhelming inflammatory reaction and accompanying
thrombotic complications in critically ill patients are too
pronounced to be restored; whereas in non-ICU patients,
therapeutic anticoagulation might still help to maintain an
adequate balance
• Routine dose thromboprophylaxis over intermediate dose
for all patients admitted to hospital (ICU and non-ICU
patients) is recommended.
Lancet Hematol, April, 27,2021
41. ACTIV Trials
ACTIV 1:
• Role of immune modulators in hospitalized adults with moderate to severe COVID-19
disease as add-on therapy to remdesivir and dexamethasone
ACTIV 2:
• Potential utility of monoclonal antibodies and other novel therapeutics in outpatients with
COVID-19
ACTIV 3:
• Similar questions of efficacy and risk in inpatients with COVID-19
ACTIV 4:
• COVID 19 antithrombotics
• 4a: Inpatient - prophylactic versus therapeutic dose heparin
• 46: Outpatient - Placebo vs Aspirin vs prophylactic apixaban vs therapeutic apixaban
• 4c: Convalescent - Placebo vs prophylactic apixaban
42. ATTACC, ACTIV-4a & REMAP-CAP
Multiplatform RCT
• Hospitalised non ICU patients: Therapeutic dose superior to
usual care venous thromboprophylaxis. Major bleeding rate <2%
• ICU admitted patients: Therapeutic heparin is inferior (harmful)
compared to thromboprophylaxis. Major bleeding rate 3.7%
Pre-publication Interim results. January 28,2021
43. • To evaluate the effects of intermediate-dose (1 mg/kg daily) vs standard- dose
prophylactic (40mg daily) enoxparin among patients with COVID-19 admitted to
the intensive care unit (ICU).
• 562 patients.
• Intermediate-dose prophylactic anticoagulation, compared with standard- dose
prophylactic anticoagulation, did not result in a significant difference in the
primary outcome of a composite venous or arterial thrombosis and 30 day
mortality.
JAMA, March 21,2021
44. Dose in Critically Ill patients
• In the INSPIRATION trial, there is no statistically significant
differences in the thrombotic events between intermediate
dose of LMWH (0.5 mg/kg twice daily or 1 mg/kg daily) vs
standard dose (40mg twice daily ) in critically ill patients with
COVID-19. Major bleeding occurred more in intermediate dose
(2.5% vs 1.4%).
• In a cohort of 2089 critically ill patients from 67 centres in USA
no benefit of therapeutic dose anticoagulation initiated within
2 days of ICU admission compared with standard-dose
thromboprophylaxis.
• Interim results of multiplatform randomized clinical trial, (a
collaboration between 3 trials - ATTACC, REMAP-CAP, and
ACTIV-4), not better with therapeutic with added bleeding risk.
Lancet Haematol, April 27, 2021
45. Thromboprophylaxis
• Hospitalized non ICU patients may benefit from the
escalation of anticoagulant dose. escalated
thromboprophylaxis could be appropriate in moderately ill
hospitalized patients with COVID-19. Major bleeding <2%.
• Therapeutic anticoagulation decreased the need for organ
support from approximately 25% to 18% in patients with a
high D-dimer at baseline and from 19% to 13% in those with
a low D-dimer at baseline (Multiplatform RCTs).
• Effect of outpatient thromboprophylaxis for patients with
mild COVID-19 not requiring hospital admission is still
unknown.
• Utility of post discharge thromboprophylaxis is yet to be
decided.
Lancet Haematol, April 27, 2021
46. • Cases of immune thrombocytopenia and bleeding without thrombosis
that were induced or revealed after exposure to the messenger RNA
(mRNA)-based vaccines produced by Moderna (mRNA-1273) and Pfizer-
BioNTech (BNT162b2) and ChAdox1 nCOV-19 (AstraZeneca).
• High degree of suspicion when patients present with central nervous
system or abdominal symptoms after receiving any SARS-CoV-2 vaccine.
• High levels of d-dimers and low levels of fibrinogen were common and
suggest systemic activation of coagulation.
• The incidence of VITT, is perhaps 1 case per 100,000 exposures.
• IV immunoglobulins and high dose glucocorticoids along with LMWH/
Fondaparinux improve the condition.
• “The very low prevalence of this complication of vaccination, however
severe, relative to the benefits of preventing Covid-19 (a condition with 1
to 2% mortality and potential long-term sequelae) must be emphasized."
NEJM editorial, April 16, 2021
47. • Analysis of 28 patients (by the time > 82 million doses are
administered)
• All are tested positive for antibodies against PF4
• 9 had cerebral venous thrombosis,
• 3 had splanchnic-vein thrombosis,
• 3 had pulmonary embolism, and
• 4 had other thromboses; of these patients,
• 6 died.
• Five patients -DIC.
• Feature mimic HIT - VITT
• Treatment suggestions : Immunoglobulins + Non-heparin
anticoagulant
NEJM ,April 9, 2021
48. • 12 cases are reported
• The initial 12 US cases of cerebral venous sinus
thrombosis with thrombocytopenia 6-15 days after
vaccination.
• The condition mimics HIT
• Mortality 3
JAMA, 30 April, 2021
49. • Post COVID-19 thrombosis is mainly due to endothelial
dysfunction following overactive immune response leading
to prolonged vasculitis. Breach of endothelium causes
exposure of tissue factors and procoagulant cytokines
triggering tissue factor driven secondary hemostasis.
• Virus poses significant chronic immuno-thrombogenicity
which may cumulate eventually in a major thrombotic event
that occurs unexpectedly many weeks later in fit patients
with mild or asymptomatic COVID-19 infection.
Presentation:
1 Stroke
2. Myocardial infarction
3. Acute limb ischaemia
Semin Thromb Hemost, online 15.4.21
50. Issues Need to be Addressed
• Can we use DOAC in prehospital stage instead of LMWH
(ACTIV 4b trial is undergoing with apixaban; RIVACOD (
Bangladesh) – results pending )
• Whether we can use DOAC in moderate to severe cases
instead of LMWH?
• Role of Aspirin / P2Y12 inhibitors (ACTIV 4b, ACT- COVID
trial results are pending)
• Understanding thrombotic events in "Long COVID" patients
51. Take Home Message
• In COVID 19, thromboembolism is prevalent as evident
by clinical, biochemical, imaging and autopsy studies.
• Venous events are more common than arterial.
• There is interplay of virus entry into the endothelium
resulting in endothelitis, activation of coagulation
system, inhibition of plasminogen activators, increase in
platelet reactivity along with decreased mobility.
• Cytokines augments the process of thrombosis
• In mild form, there is no solid evidence of usefulness of
anticoagulants though there is weak suggestion.
52. • In moderate to severe form, thromboprophylaxis is
universally recommended. Recent evidence is in favour of
therapeutic anticoagulation.
• In ICU admitted cases, prophylactic dose is advocated.
• When DVT or PE is suspected/diagnosed – treatment is as
per protocol.
• Role of anti-platelets are logical but yet to be
substantiated
• Anti-IL6 is effective in "cytokine storm” in preventing
immunothrombosis
Take Home Message