most controversial topic in the field of transfusion medicine, most of the transfusions worldwide are associated with the deleterious effects of immunomodulation, simplified for PG students with latest article support
most controversial topic in the field of transfusion medicine, most of the transfusions worldwide are associated with the deleterious effects of immunomodulation, simplified for PG students with latest article support
Thrombocytopenia is generally defined as platelet count <150 × 109/L. It can occur due to several reasons, like decreased platelet production (e.g., inherited bone marrow failure syndromes, acquired aplastic anemia, leukemia), ineffective platelet production (myelodysplastic syndrome, megaloblastic anemia), increased destruction (ITP, HLH), increased consumption (DIC, TTP, HUS), sequestration (hypersplenism), or may be due to combination of multiple mechanisms described above.
During evaluating a case of thrombocytopenia, the first step is getting a detailed history and doing a proper clinical examination. Then the next step would be checking the other parameters of complete blood count (CBC), especially hemoglobin (Hb) and the total WBC count, complemented by a peripheral smear (PS) examination, which will clear many doubts and will help us pinpointing our diagnostic approach.
Many a times pseudo-thrombocytopenia is encountered in a PS due to platelet clumping by EDTA and can be rectified by collecting blood samples in a citrate or heparin vials or by doing a direct finger prick smear. Any accompanying cytopenia will expand the differential diagnosis and an isolated thrombocytopenia will further narrow it down. Presence of any additional abnormalities of red cells (megaloblasts) or white cells (presence of hyper-segmented neutrophils, atypical lymphoid/myeloid cells) could be present in megaloblastic anemia/MDS, leukemia respectively, while in the presence of fragmented red cells microangiopathic hemolytic anemia should always be ruled out by doing PT and aPTT (DIC, TTP, HUS). In case of isolated thrombocytopenia, the platelet morphology is also important. In many patients in India, especially in eastern region many people have large platelets with their normal platelet count around 100 × 109/L with normal platelet function (Harris platelet syndrome). However, presence of any abnormal platelet morphology along with a low platelet count may indicate a platelet function disorder (large platelets in Bernard Soulier syndrome/ Glanzmann thrombasthenia or small platelets in Wiskott-Aldrich syndrome), especially if encountered in early part of life during evaluation for bleeding symptoms. In case of isolated thrombocytopenia, presence of additional congenital anomalies may point out towards an inherited marrow failure syndrome, e.g. amegakayocytic thrombocytopenia. Exposure to certain drugs may result in isolated low platelet count, e.g., ceftriaxone, piperacillin, heparin. Presence of toxic changes in neutrophils may indicate sepsis related thrombocytopenia. By excluding all these, immune thrombocytopenia (ITP) to be thought as no specific tests or markers are available for this entity and its diagnosis is largely clinical. A further work up complemented by bone marrow examination and in few cases a platelet function test will definitely help in reaching the final diagnosis.
So, summarizing, in the evaluation of a case of thrombocytopenia, all the
leucodepletion is the removal of 99% leucocytes from the whole blood, pcv or platelets before transfusing into the donor.
this process many infections, transfusion reactions..
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.
Leucodepletion is a technical term for the removal of leucocytes (white blood cells) from blood components using special filters.
The leucocytes present in donated blood play no therapeutic role in transfusion and may be a cause of adverse transfusion reactions.
Removal of leucocytes may therefore have a number of potential benefits for transfusion recipients.
Thrombocytopenia is generally defined as platelet count <150 × 109/L. It can occur due to several reasons, like decreased platelet production (e.g., inherited bone marrow failure syndromes, acquired aplastic anemia, leukemia), ineffective platelet production (myelodysplastic syndrome, megaloblastic anemia), increased destruction (ITP, HLH), increased consumption (DIC, TTP, HUS), sequestration (hypersplenism), or may be due to combination of multiple mechanisms described above.
During evaluating a case of thrombocytopenia, the first step is getting a detailed history and doing a proper clinical examination. Then the next step would be checking the other parameters of complete blood count (CBC), especially hemoglobin (Hb) and the total WBC count, complemented by a peripheral smear (PS) examination, which will clear many doubts and will help us pinpointing our diagnostic approach.
Many a times pseudo-thrombocytopenia is encountered in a PS due to platelet clumping by EDTA and can be rectified by collecting blood samples in a citrate or heparin vials or by doing a direct finger prick smear. Any accompanying cytopenia will expand the differential diagnosis and an isolated thrombocytopenia will further narrow it down. Presence of any additional abnormalities of red cells (megaloblasts) or white cells (presence of hyper-segmented neutrophils, atypical lymphoid/myeloid cells) could be present in megaloblastic anemia/MDS, leukemia respectively, while in the presence of fragmented red cells microangiopathic hemolytic anemia should always be ruled out by doing PT and aPTT (DIC, TTP, HUS). In case of isolated thrombocytopenia, the platelet morphology is also important. In many patients in India, especially in eastern region many people have large platelets with their normal platelet count around 100 × 109/L with normal platelet function (Harris platelet syndrome). However, presence of any abnormal platelet morphology along with a low platelet count may indicate a platelet function disorder (large platelets in Bernard Soulier syndrome/ Glanzmann thrombasthenia or small platelets in Wiskott-Aldrich syndrome), especially if encountered in early part of life during evaluation for bleeding symptoms. In case of isolated thrombocytopenia, presence of additional congenital anomalies may point out towards an inherited marrow failure syndrome, e.g. amegakayocytic thrombocytopenia. Exposure to certain drugs may result in isolated low platelet count, e.g., ceftriaxone, piperacillin, heparin. Presence of toxic changes in neutrophils may indicate sepsis related thrombocytopenia. By excluding all these, immune thrombocytopenia (ITP) to be thought as no specific tests or markers are available for this entity and its diagnosis is largely clinical. A further work up complemented by bone marrow examination and in few cases a platelet function test will definitely help in reaching the final diagnosis.
So, summarizing, in the evaluation of a case of thrombocytopenia, all the
leucodepletion is the removal of 99% leucocytes from the whole blood, pcv or platelets before transfusing into the donor.
this process many infections, transfusion reactions..
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.
Leucodepletion is a technical term for the removal of leucocytes (white blood cells) from blood components using special filters.
The leucocytes present in donated blood play no therapeutic role in transfusion and may be a cause of adverse transfusion reactions.
Removal of leucocytes may therefore have a number of potential benefits for transfusion recipients.
Jorge A. Marrero, MD, MS, Anthony El-Khoueiry, MD, Richard S. Finn, MD, and Laura M. Kulik, MD, prepared useful practice aids pertaining to HCC management for this CME activity titled "Surveying the View From the Driver’s Seat in Hepatocellular Carcinoma: Bringing Into Focus Hepatology’s Key Role in Guiding HCC Care Down the Path to Improved Outcomes." For the full presentation, monograph, complete CME information, and to apply for credit, please visit us at http://bit.ly/2Pj9wM8. CME credit will be available until December 20, 2019.
Sipuleucel_T Immunotherapy for Metastatic Prostate Cancer after Failing Hormo...mjavan2001
This PowerPoint presentation demonstrates findings on a clinical trial of sipuleucel-T in HRPC patients to evaluate overall survival in this group. The FDA approval of Provenge was based on the results of IMPACT study.
Molecular mechanisms of action and potential biomarkers of growth inhibition ...Enrique Moreno Gonzalez
Molecular targeted therapy has emerged as a promising treatment of Hepatocellular carcinoma (HCC). One potential target is the Src family Kinase (SFK). C-Src, a non-receptor tyrosine kinase is a critical link of multiple signal pathways that regulate proliferation, invasion, survival, metastasis, and angiogenesis. In this study, we evaluated the effects of a novel SFK inhibitor, dasatinib (BMS-354825), on SFK/FAK/p130CAS, PI3K/PTEN/Akt/mTOR, Ras/Raf/MAPK and Stats pathways in 9 HCC cell lines.
DRUG INFORMATIONOF GILTERITINIB AND ITS EFFICACY IN REFRACTORY FLT3- MUTATED AMLPARUL UNIVERSITY
Acute myeloid leukemia is a malignancy of proliferative, abnormally, or poorly differentiated cells of the hematopoietic system,
characterized by genetic heterogeneity. FMS-like tyrosine kinase 3- internal tandem duplication remains one of the most frequently mutated
genes in acute myeloid leukemia, especially in those with normal cytogenetics. The FMS-like tyrosine kinase 3- internal tandem duplication
and FLT3 tyrosine kinase domain mutations are biomarkers for high-risk acute myeloid leukemia and are associated with drug resistance
and high risk of relapse. Various FLT3 inhibitors are in clinical development, including lestaurtinib, tandutinib, quizartinib, midostaurin,
gilteritinib, and crenolanib. Gilteritinib is a small molecule that inhibits multiple receptor tyrosine kinases that also act as FMS-like tyrosine
kinase 3. Gilteritinib, a next-generation tyrosine kinase inhibitor, is approved in several countries worldwide for the treatment of relapsed or
refractory acute myeloid leukemia in adults with FMS-like tyrosine kinase 3 mutations. Gilteritinib demonstrated the ability to inhibit FLT3
receptor signaling and production in cells exogenously expressing FLT3 including FLT3 internal tandem duplication and tyrosine kinase
domain mutations FLT3-D835Y and FLT3-ITD-D835Y, and it induced apoptosis in leukemic cells possessing FLT3 internal tandem
duplication. In conclusion, gilteritinib therapy led to higher percentages of patients with the response and longer survival than salvage
chemotherapy among patients with relapsed or refractory FLT3-mutated acute myeloid leukemia
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
Ozempic: Preoperative Management of Patients on GLP-1 Receptor Agonists Saeid Safari
Preoperative Management of Patients on GLP-1 Receptor Agonists like Ozempic and Semiglutide
ASA GUIDELINE
NYSORA Guideline
2 Case Reports of Gastric Ultrasound
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
Ethanol (CH3CH2OH), or beverage alcohol, is a two-carbon alcohol
that is rapidly distributed in the body and brain. Ethanol alters many
neurochemical systems and has rewarding and addictive properties. It
is the oldest recreational drug and likely contributes to more morbidity,
mortality, and public health costs than all illicit drugs combined. The
5th edition of the Diagnostic and Statistical Manual of Mental Disorders
(DSM-5) integrates alcohol abuse and alcohol dependence into a single
disorder called alcohol use disorder (AUD), with mild, moderate,
and severe subclassifications (American Psychiatric Association, 2013).
In the DSM-5, all types of substance abuse and dependence have been
combined into a single substance use disorder (SUD) on a continuum
from mild to severe. A diagnosis of AUD requires that at least two of
the 11 DSM-5 behaviors be present within a 12-month period (mild
AUD: 2–3 criteria; moderate AUD: 4–5 criteria; severe AUD: 6–11 criteria).
The four main behavioral effects of AUD are impaired control over
drinking, negative social consequences, risky use, and altered physiological
effects (tolerance, withdrawal). This chapter presents an overview
of the prevalence and harmful consequences of AUD in the U.S.,
the systemic nature of the disease, neurocircuitry and stages of AUD,
comorbidities, fetal alcohol spectrum disorders, genetic risk factors, and
pharmacotherapies for AUD.
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
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!
Knee anatomy and clinical tests 2024.pdfvimalpl1234
This includes all relevant anatomy and clinical tests compiled from standard textbooks, Campbell,netter etc..It is comprehensive and best suited for orthopaedicians and orthopaedic residents.
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.
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
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.
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.
1. Anti-Thymocyte globulin [Equine] associated hypersensitivity
reaction
8/5/2021 Department of Clinical Pharmacology 1
Dr. Miteshkumar Maurya
Assistant Professor
Department of Clinical Pharmacology
Seth GSMC & KEMH
2. Polyclonal IgG component prepared & collected from serum
of rabbit/horse/ goat/pig that have been immunized against
human thymocytes or other lymphocytes.
In past, produced as anti-lymphocyte serum [ALS] that was a
cytotoxic heterologous antibody directed against lymphoid
cells.
Russian immunologist Élie Metchnikoff first produced it by
injecting rabbit lymph node cells into guinea pigs in 1899.
Levey and Medawar showed ALS produced in rabbit against
mouse thymus cells had immunosuppressive effects.
Anti-thymocyte globulin (ATG)- History
Russian immunologist
Élie Metchnikoff [1845-1916]
Nobel Prize in Physiology or
Medicine[1908] in recognition of
work on immunity with Paul
Ehlrich
8/5/2021 Department of Clinical Pharmacology 2
3. 8/5/2021 Department of Clinical Pharmacology 3
Mechanisms of T-cell depletion by anti-thymocyte globulin [ATG]
Complement-dependent lysis
Selective elimination of in vivo activated T-cells in organ transplantation
Opsonization & phagocytosis by lymphocytes in liver, spleen & lung
macrophages
Apoptotic cell death with subsequent phagocytosis by macrophages
[lymphoid tissues of spleen & in lymph nodes] - main mechanism of
depletion
Peripheral T-cell counts restores graduallyafter cessation of Rabbit anti-thymocyte globulin,
with a partial increase at 3 months.
4. 8/5/2021 Department of Clinical Pharmacology 4
Types
of
Anti-thymocyte
globulin
–
rabbit
&
equine
5. 8/5/2021 Department of Clinical Pharmacology 5
US FDA approved Dosage & administration for anti-thymocyte globulin [IgG]
Indication -acute rejection in patients receiving a
kidney transplant/ in conjunction with concomitant
immunosuppression
Dose Regimen [i.v infusion]
Prophylaxis 1.5 mg/kg of body weight administered
daily for 4 to 7 days
Treatment 1.5 mg/kg of body weight administered
daily for 7 to 14 days
Indication –renal transplant recipients and aplastic
anemia
Dose Regimen [i.v infusion]
Renal allograft recipients to prevent first graft
rejection episode [concomitant with Azathioprine &
corticosteroids]
10-30 mg/kg body weight in adults daily while 5-25
mg/kg body weight daily in pediatric population.
[Rx- 10-15 mg/kg daily / delay-15mg/kg daily-for 14 days
Aplastic Anemia [concomitant with cyclosporine &
corticosteroids]
10-20 mg/kg daily for 8 to 14 days. Additional alternate
day therapy up to total 21 doses can be administered.
Rabbit ATG, r-ATG, Thymoglobulin
Equine ATG, h-ATG, Thymogam, Atgam
6. 8/5/2021 Department of Clinical Pharmacology 6
Diagnostic criteria for aplastic anemia [Camitta criteria]
Incidence of aplastic anemia varied from 10- 52.7% among patients with pancytopenia.
7. 8/5/2021 Department of Clinical Pharmacology 7
Treatment modalities for aplastic anemia
Allogenic
Hemopoietic
Stem cell
transplantation
[HSCT]- Young
patients with HLA
matched donor
Bone marrow
transplantation
[superior over
PBPC]
Peripheral blood
progenitor cells
[PBPC] with
granulocyte-
colony
stimulating factor
(G-CSF)
Anti-thymocyte
globulin with
cyclosporin –
decrease
cGVHD[chronic
graft versus host
disease]
Severe acquired aplastic anemia, hematopoietic failure is the result of immune-mediated
destruction of bone marrow stem and progenitor cells.
9. 8/5/2021 Department of Clinical Pharmacology 9
Inclusion Criteria
Exclusion Criteria
1. Severe aplastic anemia characterized by bone marrow cellularity less than 30% (excluding lymphocytes) and
at least two of the following:
• Absolute neutrophil count less than 500/microliter
• Platelet count less than 20,000/microliter
• Absolute reticulocyte count less than 60,000/microliter
2. Age greater than or equal to 2 years old & weight greater than 12 kg
1. Diagnosis of Fanconi's anemia or evidence of a clonal disorder on cytogenetics.
2. Prior immunosuppressive therapy with ATG, ALG, alemtuzumab, or high dose cyclophosphamide.
3. Infection not responding to Rx or Serologic evidence of HIV infection.
4. Moribund status or concurrent hepatic, renal, cardiac, neurologic, pulmonary, infectious, or metabolic disease
[death within 7-10 days is likely]
5. Potential subjects with cancer who are on active chemotherapeutic treatment / take drugs with
hematological effects
6. Current pregnancy or unwillingness to take OCP or refrain from pregnancy if of childbearing potential.
7. Not able to understand the investigational nature of the study or give informed consent
10. 8/5/2021 Department of Clinical Pharmacology 10
• Absolute neutrophil count > 500/ μL
• Platelet count > 20,000/ μL
• Reticulocyte count > 60,000/ μL
• Improvement in counts that are dependent upon exogenously administered growth
factors or transfusion will not be considered as fulfilling response criteria.
Primary outcome measures
Hematologic response at 3 month, 6 month and 12 month time duration
Hematologic response is defined as subjects having blood counts in Severe Aplastic Anemia,
equivalent to two of following values obtained on two serial blood count measurements at
least one week apart at landmark time points (3, 6 and 12 months)
11. 8/5/2021 Department of Clinical Pharmacology 11
RCTs on Severe Aplastic anemia patients at single facility
Study duration: Dec 2005-july 2010
60 patients Rx with
rabbit ATG
60 patients Rx with
horse ATG
Outcome- Hematologic
response[HR] at 6 months
[blood counts]
Outcome- Hematologic response
[HR] at 6 months [blood counts]
HR6- 37% [95% CI-24 to 49]
OS3-76% (95% CI, 61 to 95)
HR6- 68% [95% CI-56 to 80]
OS3- 96% (95% CI, 90 to 100)
HR, P<0.001
OS3, P<0.04
12. 8/5/2021 Department of Clinical Pharmacology 12
ATG + Cyclosporin protocol for severe aplastic anemia
After giving test dose, start ATG [equine] 40 mg/kg/day for 4 days OD [d1-d4]
Tab. Prednisolone 1 mg/kg/day [d5-d13], taper dose [d14-d18], stop by d19
Tab. Cyclosporine 5mg/kg/day on d18 onwards [TDM from d32]
To monitor Blood Pressue, Complete Blood Counts, Serum Creatinine daily during
ATG therapy
Prophylaxis -Tab. Valciclovir 500 mg OD, Tab. Septran DS OD [Mon./Wed./Fri.],Tab.
Fluconazole 4mg/kg OD for 3 months.
Absolute Lymphocyte Count monitoring at regular intervals
13. 8/5/2021 Department of Clinical Pharmacology 13
Parameters Horse [equine] Anti-thymocyte globulin
[standard therapy]
Rabbit Anti-thymocyte globulin [RATG]-
preferred
Potent with respect to
depleting peripheral blood
lymphocytes [CD3 T-cell
lympopenia]
less potent more potent
Reversing acute rejection
episodes & preventing
recurrent rejection
episodes in renal transplant
recipients.
76% 88%
Hematological response &
overall survival [RCTs]
Better [68%] Poor [37%]
KIM J.M et al study-
delayed graft function &
graft survival
lower higher
Choice between equine [h-ATG] & rabbit [r-ATG]anti-thymocyte globulin
14. 8/5/2021 Department of Clinical Pharmacology 14
Summary
Anti-Thymocyte globulin is commonly used immunosuppressing agent from equine or
rabbit origin.
Equine Anti-thymocyte globulin has shown superiorty over the rabbit ATG in hematology
clinical trials for aplastic anemia [hematologic response] while rabbit ATG proved
superior over equine ATG in renal Tx recipients [renal graft outcomes].
Adverse drug reactions such as chronic Graft versus host disease [cGVHD] are result of
therapeutic [ATG] failure while other infusion/hematologic related complications could
be either due to ATG or apalstic disease that need adequate evaluation.