This document discusses autoimmune hemolytic anemia (AIHA). It begins by defining hemolytic anemia and classifying it as either congenital/hereditary or acquired. It then discusses the classification of hemolytic anemias as either intracorpuscular or extracorpuscular. The mechanisms, clinical features, laboratory findings, and treatments of warm AIHA and cold AIHA are described in detail. Warm AIHA is mediated by IgG antibodies and most commonly involves the Rh blood group antigen. Cold AIHA involves IgM antibodies reactive below 37°C and usually targets the I antigen. Corticosteroids are first-line treatment for warm AIHA while cold AIHA may be associated with underlying infections or malignancies.
Autoimmune hemolytic anemia (or autoimmune haemolytic anaemia; AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to insufficient plasma concentration.
Autoimmune hemolytic anemia (AIHA) is a type of normochromic normocytic anemia that is caused by autoantibodies that are produced in the patient against his/her own blood cells, particularly against RBCs. As a result hemolysis occurs leading to anemia.
Autoantibodies are produced secondary to autoimmune diseases, lymphoproliferative disorder (LPDs), certain infections or immunodeficiency syndromes.
In this presentation AIHA is under consideration on a broader scale, with only basic information and concepts.
Autoimmune hemolytic anemia (or autoimmune haemolytic anaemia; AIHA) occurs when antibodies directed against the person's own red blood cells (RBCs) cause them to burst (lyse), leading to insufficient plasma concentration.
Autoimmune hemolytic anemia (AIHA) is a type of normochromic normocytic anemia that is caused by autoantibodies that are produced in the patient against his/her own blood cells, particularly against RBCs. As a result hemolysis occurs leading to anemia.
Autoantibodies are produced secondary to autoimmune diseases, lymphoproliferative disorder (LPDs), certain infections or immunodeficiency syndromes.
In this presentation AIHA is under consideration on a broader scale, with only basic information and concepts.
Haemolysis indicates that there is shortening of the normal red cell lifespan of 120 days. There are many causes.
To compensate, the bone marrow may increase its output of red cells six- to eightfold by increasing the proportion of red cells produced, expanding the volume of active marrow, and releasing reticulocytes prematurely. Anaemia occurs only if the rate of destruction exceeds this increased production rate.
This presentation is about anemia of chronic disease, nowadays also called as anemia of Inflammation. I have dealt with anemia in CKD and malignancy in detail.
This Presentation of Hemolytic Anemia try to cover important Hemato-pathological aspects of Red cell membrane disorders ( Hereditary Spherocytosis, others ) , Enzymopathies ( G6PD deficieny, others ) and Hemoglobinopathies ( Thallasemia, SCA) and their differentiation. References includes Robbins pathology, Wintrobes atlas and text, and others
Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University
Clinical case
Hemolytic Anemia
Intravascular vs extravascular hemolysis
Classification of hemolytic anemia
Approach to hemolysis
Patient history
Clinical features
Peripheral blood smear
Investigation
Treatment
Haemolysis indicates that there is shortening of the normal red cell lifespan of 120 days. There are many causes.
To compensate, the bone marrow may increase its output of red cells six- to eightfold by increasing the proportion of red cells produced, expanding the volume of active marrow, and releasing reticulocytes prematurely. Anaemia occurs only if the rate of destruction exceeds this increased production rate.
This presentation is about anemia of chronic disease, nowadays also called as anemia of Inflammation. I have dealt with anemia in CKD and malignancy in detail.
This Presentation of Hemolytic Anemia try to cover important Hemato-pathological aspects of Red cell membrane disorders ( Hereditary Spherocytosis, others ) , Enzymopathies ( G6PD deficieny, others ) and Hemoglobinopathies ( Thallasemia, SCA) and their differentiation. References includes Robbins pathology, Wintrobes atlas and text, and others
Dr Abdullah Ansari
MBBS, MD Medicine
Aligarh Muslim University
Clinical case
Hemolytic Anemia
Intravascular vs extravascular hemolysis
Classification of hemolytic anemia
Approach to hemolysis
Patient history
Clinical features
Peripheral blood smear
Investigation
Treatment
- 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
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
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
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
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.
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
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.
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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
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!
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
The prostate is an exocrine gland of the male mammalian reproductive system
It is a walnut-sized gland that forms part of the male reproductive system and is located in front of the rectum and just below the urinary bladder
Function is to store and secrete a clear, slightly alkaline fluid that constitutes 10-30% of the volume of the seminal fluid that along with the spermatozoa, constitutes semen
A healthy human prostate measures (4cm-vertical, by 3cm-horizontal, 2cm ant-post ).
It surrounds the urethra just below the urinary bladder. It has anterior, median, posterior and two lateral lobes
It’s work is regulated by androgens which are responsible for male sex characteristics
Generalised disease of the prostate due to hormonal derangement which leads to non malignant enlargement of the gland (increase in the number of epithelial cells and stromal tissue)to cause compression of the urethra leading to symptoms (LUTS
2. HEMOLYTIC ANEMIA
Definition:
Those anemias which result from an increase in RBC
destruction coupled with increased erythropoiesis
Classification:
Congenital / Hereditary
Acquired
7. HOW TO DIAGNOSE HEMOLYTIC ANEMIA
New onset pallor or anemia
Jaundice
Splenomegaly
Gall stones
Dark colored urine
Leg ulcers
8. GENERAL FEATURES
OF HEMOLYTIC DISORDERS
GENERAL EXAMINATION - JAUNDICE, PALLOR
BOSSING OF SKULL
PHYSICAL FINDINGS
HEMOGLOBIN
MCV
RETICULOCYTES
BILIRUBIN
LDH
HAPTOGLOBULIN
- ENLARGED SPLEEN
- FROM NORMAL TO SEVERELY REDUCED
- USUALLY INCREASED
- INCREASED
- INCREASED[MOSTLY UNCONJUGATED]
- INCREASED
- REDUCED TO ABSENT
12. CASE SCENARIO 1
A young male patient who is a soldier presented
with complaints of passage of dark urine
immediately following physical exertion in the
upright position, occasionally accompanied by
nausea, abdominal cramps, aching in the back or
legs, a “stitch in the side,” or a burning feeling in the
soles of the feet .
Physical examination is transient jaundice usually
unrevealing, hepatosplenomegaly and transient
jaundice have been rarely reported
13. Post exercise, his urine sample was
reddish brown in color with a specific
gravity of 1.030,
pH 5.5,
1+ protein,
3+ blood,
0 to 2 RBC/high powered field (HPF)
and
0 to 2 white blood cells/HPF.
His urine microscopy revealed 1 to 2
RBC/ HPF.
15. IMMUNE HEMOLYTIC ANEMIA:
When erythrocytes are destroyed prematurely by
an immune mediated process (antibody and/or
complement), the disorder is referred to as an
immune hemolytic anemia(IHA).
Autoimmune hemolytic anemia
Drug-induced hemolytic anemia
Alloimmune hemolytic anemia
16. AUTOIMMUNE DRUG INDUCED ALLOIMMUNE
Warm-reactive antibodies
Primary or idiopathic
Secondary
1. Autoimmune disorders (SLE,RA,
and others)
2. Chronic lymphocytic leukemia
and other immunoproliferative
diseases
3. Viral infections
4. Neoplastic disorders
5. Chronic inflammatory diseases
Cold-reactive antibodies
Primary or idiopathic (cold
hemagglutinin disease)
Secondary
1. Infectious diseases
(mycoplasma pneumoniae,
EBVand other organisms)
2. Lymphoproliferative disorders
3. Paroxysmal cold hemoglobinuria
Mixed - type
Drug adsorption
Immune complex
Autoantibody induction
Membrane modification
Hemolytic transfusion
reaction
Hemolytic disease of
the fetus and newborn
17. CLINCAL SCENARIO 2
Zohra begum,40yrs,female
Chief complaints: yellowing of skin,fatigue since 5
months,ulcer at back since 3 months
On examination:pallor+,icterus +
P/A examination splenomegaly +
Other systemic examination normal
I/V: Retic count :3.6%
LDH:1062U/L
DIRECT COOMB’S +
ANA +
19. AUTOIMMUNE HEMOLYTIC ANEMIA
AIHA is a complex and incompletely understood process
characterized by an immune reaction against self-antigens
and shortened erythrocyte survival .
Individuals produce antibodies against their own
erythrocyte antigens (autoantibodies).
The autoantibodies characteristically react not only with
the erythrocytes of the individual but also with the
erythrocytes of other individuals carrying the antigen.
20.
21. SITES AND FACTORS
THAT AFFECT HEMOLYSIS
Hemolysis can be intravascular or extravascular
Erythrocytes sensitized with antibody
or complement components attach to
macrophages in the spleen or liver
via macrophage receptors for the Fc
portion of immunoglobulin
or the C3b component of
complement. These
cells are then phagocytized .
Intravascular hemolysis
occurs if the complement cascade is
activated through C9 (the membrane
attack complex).
INTRAVASCULAREXTRAVASCULAR
27. IgG mediates erythrocyte destruction by first attaching to
the erythrocyte membrane antigens through the Fab portion
of the Ig molecule.
Fc receptors on macrophages in the red pulp of the
spleen bind to the Fc portion of the attached IgG
After binding, the macrophage pits the antigen antibody
(Ag/Ab) complex, fragmenting the cell membrane
spherocyte
RIGID
LESS DEFORMABALE
Phagocytosed by splenic macrophages
31. IGM MEDIATED HEMOLYSIS
Macrophages doesn’t have receptors for
Fc portion IgM
IgM is efficient activator of complement
EXTRAVASCULAR:
- complement activation incomlete
- C3b coats RBCs and sensitised cells
destroyed extravascularly via CR1 and
CR3 receptors on macrophages
IgM can agglutinate cells in addition to activating
complement.
32. LABORATORY IDENTIFICATION
OF SENSITIZED RED CELLS
When immune hemolytic anemia is suspected,
tests to detect and identify the causative antibody
are indicated. In general, two distinct techniques
are used:
• Agglutination in saline, which will detect antibodies
of the IgM class
• Antihuman globulin (AHG) test, which will
detect antibodies of the IgG class and/or
complement
33. ANTIHUMAN GLOBULIN TEST:
IgM antibodies can be detected by agglutination
reactions between test sera and appropriate
erythrocytes suspended in saline.
Erythrocytes Zeta potiential(25nm)
Direct: detects erythrocytes coated with antibody
in vivo
Indirect: detects antibodies in the plasma or serum
34.
35.
36.
37.
38. WARM AUTOIMMUNE
HEMOLYTIC ANEMIA
Most common form of AIHA (70% of cases)
Incidence-1/50,000 -75,000
Mediated by IgG antibodies whose maximal reactivity is
at 37°C.
• Primary or idiopathic: no underlying disease
• Secondary: underlying disease present
• Lymphoproliferative disease
• Neoplastic diseases
• Autoimmune disoders
• Viral and bacterial infections
• Vaccinations
40. Other neoplastic disorders
Thymoma
Ovarian dermoid cyst
Teratoma
Kaposi sarcoma
Carcinoma
Viral infections
Epstein-Barr virus
Hepatitis C virus
HIV/AIDS
Other
Diphtheria-pertussis-tetanus vaccinations
Pregnancy
Bone marrow transplantation
Congenital immune deficiency states
Hypogammaglobulinemia
Dysglobulinemia
41. ANTIBODY CHARACTERISTICS
Immunochemistry and Origin
Most antibodies are IgG (IgG1>IgG3)
Blood Group Specificity
Warm autoantibodies are panagglutinins
Rh is the most common (70%),
Other blood group include Wright (Wrb), Ena,
Duffy (Fyb), Gerbich (Ge), Kidd (Jka), Kell (K),
Lutheran (Lu), LW, M, N, S, Pr, A, B, IT, Sc3, U, Vel,
and Xga .
42. PATHOPHYSIOLOGY
The warm autoantibody in AIHA is reactive with
antigens on the patient’s erythrocytes.
Specificity of the antibody is directed against
antigens of the Rh system.
Most hemolysis in WAIHA is extravascular via
splenic macrophages.
If both antibody and complement are on the cell
membrane, phagocytosis is enhanced.
Direct complement- mediated intravascular
hemolysis associated with IgM antibodies in warm
AIHA is rare.
43.
44. CLINICAL FEATURES:
Idiopathic AIHA:
Progressive weakness,
Dizziness,
Dyspnea on exertion,
Back or abdominal pain,
Jaundice.
Secondary AIHA:
patient can present with signs and
symptoms of both the underlying disease and
hemolysis or just the disease.
45.
46.
47. Laboratory Findings Associated with
WAIHA
Common findings
Other laboratory findings
that can be associated
with hemolysis in WAIHA
Positive DAT
Normocytic, normochromic anemia
Increased reticulocytes
Spherocytes and other erythrocyte
abnormalities
Presence of autoantibody in the serum
Increased serum bilirubin (total and
unconjugated)
Decreased serum haptoglobin
Positive antibody screen with all cells
including autocontrol
Incompatible crossmatches with all donors
Increased osmotic fragility
Increased urine and fecal urobilinogen
Hemoglobinemia,* hemoglobinuria,
methemoglobinemia,
hemosiderinurea
48.
49. THERAPY:
CORTICOSTEROIDS:
Glucocorticoids are the initial therapy of choice for
warm AIHA
Dose:1.0 to 1.5 mg/kg or 40 mg/m2/day of
prednisone or its equivalent.
Response: noticeable by 7 days.
Tapering: Rapid responders can reduce their dose
by 50% over 4 to 6 weeks, tapering should proceed
more slowly over 3 to 4 months
50. SPLENECTOMY
Splenectomy is indicated in those surgical
candidates who have not responded to prednisone,
And who requires prednisone doses >10-20 mg/day
to maintain remission, or
Intolerable side effects.
52. Rituximab: is a chimeric human/murine
monoclonal anti-CD20 antibody
Mycophenolate mofetil: Doses begin at 1
g/day and are then increased to 2 g/day.
Cyclosporine A:
Doses of 3 mg/kg/day with target serum levels of
200–400 ng/ml
• 375 mg/m2/week
× 4 weeksRituximab
53. Other Therapies
Intravenous immunoglobulin (IVIG) has not enjoyed
the success in AIHA that it has in immune
thrombocytopenia.
Escalating the dose from the standard 0.4 g/kg/day
(× 5 days) to 1.0 g/kg/day may be helpful.
Plasmapheresis
54. COLD AUTOIMMUNE HEMOLYTIC
ANEMIA (AIHA)
Cold AIHA, also termed cold agglutinin disease
(CAD), is associated with an IgM antibody that fixes
complement and is reactive below 37°C.
This disorder, which comprises 16–30% of the
AIHAs
IgA and IgG antibodies rarely have been implicated
in hemolysis in CAD
55. ANTIBODY CHARACTERISTICS
Immunochemistry and Origin:
Cold agglutinins are IgM.
Specificity for the I antigen:
I antigen-90%
i antigen-10%
Adult RBCs are used to detect anti-I agglutinins and
cord RBCs are needed to detect anti-i agglutinins.
M. pneumoniae induces anti-I antibodies in the majority
of patients is potentially related to the finding that
sialylated I/i antigens serve as specific Mycoplasma
receptors
59. PATHOPHYSIOLOGY:
The severity of CAD is related to the thermal range
of the antibody(up to 32%)
I antigen specificity
Cold-reacting antibody is usually directed against
the I antigen.
The second most common specificity for cold
autogglutinins is anti-Pr.1.
60.
61.
62. CLINICAL FEATURES
Mild, chronic hemolytic anemia with exacerbations in the
winter.
and jaundice may occur if the rate of hemolysis is
greater than the endogenous capability to metabolize
bilirubin .
Intermittent bursts of hemolysis associated with
hemoglobinemia and hemoglobinuria on exposure to
cold.
Acrocyanosis can occur from agglutination of RBCs in
the cooler vessels of the hands, ears, nose, and feet.
Digits may become cold, stiff, painful, or numb and may
turn purplish
Chronic CAD patients have mild splenomegaly or
hepatomegaly
63.
64.
65.
66.
67. THERAPY
The most effective therapy is usually achieved by
keeping the individual’s extremities warm.
Chemotherapy using cyclophosphamide or
chlorambucil can be instituted(Underlying
lymphoproliferative disease)
Plasma exchange.
Rituximab has been used as treatment in both
primary and secondary disease.
Chlorambucil, beginning with 2 to 4 mg/day and increasing by
2 mg every 2 months
Pulse therapy with cyclophosphamide (250 mg/day) and
prednisone (100 mg/day × 4 days) every 2 to 3 weeks
68. CASE SCENARIO 3
A four-year-old male presents to the emergency department
with a history of six days of fever and acute onset of red
colored urine. There has been no recent travel. He was seen
by his Doctor approximately five days ago for evaluation of
cough and rhinorrhea and was prescribed Antibiotics for an
ear infection.No h/o dysuria, bloody stools, hemoptysis, or
epistaxis. He has no increased bruising, no petechiae, and no
extremity pain. He has been having intermittent fevers for
three days.
Physical Exam: (+) scleral icterus, (+) jaundice, (+) soft flow
murmur on cardiac exam. Physical exam is otherwise normal.
69. LABS:
Initial hemoglobin 10.4 g/dL--> decreased to 6.3 g/dL 12
hours later,
Platelets 153,000 cells/UL,
Reticulocyte count 0.4%,
White blood cells 11.1 x103cells
Coagulation studies normal.
Liver function test are normal.
LDH is 5056 Units/ml,
Haptoglobin 12 mg/dL (low).
Unconjugated bilirubin is 3.7 mg/dL,
Conjugated bilirubin is 1.2 mg/dL.
Electrolytes are all within normal limits. Viral panel is pending.
DAT: IgG, C3 (+).
Urinalysis: dark, red-brown urine, 3+ blood, 3+ protein, 0-4
RBCs/hpf, 0-4 WBCs/hpf, urobilinogen >8mg/dL.
70. PAROXYSMAL COLD
HEMOGLOBINURIA
Characterized by massive intermittent acute hemolysis
and hemoglobinuria.
Can occur at any age ,frequently seen in children less
than 5 years.
The infections linked to PCH include
Epstein-Barr virus,
Cytomegalovirus,
Measles, mumps,
Heamophilus influenzae,
Klebsiella pneumoniae.
Parvovirus 19,
Onset : 5 days to 3 weeks after onset of the infection
71. PATHOPHYSIOLOGY
Donath-Landsteiner (D-L) antibody.
Biphasic refers to the two temperatures necessary
for optimal lysis of the erythrocytes.
The antibody reacts with
erythrocytes in the
capillaries at temperatures
less than 20°C and avidly
binds the early acting
complement components.
The antibody molecule
disperses from the cell, but
the membrane attack
complement components
are activated on the cell
membrane causing cell
lysis.
TEMP <20°C TEMP @37°C
73. LAB INVESTIGATIONS
Neutropenia.
Reticulocytopenia.
Serum bilirubin, BUN, and LD are elevated
Serum complement and haptoglobin are
decreased.
DAT with anticomplement antisera :Weakly
positive.
IAT can be positive if performed in the cold
D-L antibodies :low titres(1:32)
74.
75.
76. THERAPY
PCH associated with acute infections terminates
upon recovery from the infection.
Steroids are not usually helpful.
Transfusion can be required if the hemolysis is
severe.
In rare cases when the hemolysis persists,
plasmapheresis can be used.
Rituximab (anti-CD20) has also been used as
therapy
77. MIXED-TYPE AIHA
Mixed-type AIHA is characterized by the presence
of a warmreacting IgG autoantibody and a cold-
reacting IgM autoantibody that has both high titer
and increased thermal amplitude.
About 50% of the cases are idiopathic.
Associated with diseases such as systemic lupus
erythematosus, lymphoma, and HIV.
Patients usually respond well to treatment with
corticosteroids and do not require transfusion.
Rituiximab has been used in cases with underlying
lymphoproliferative disease
78. DRUG-INDUCED HEMOLYTIC ANEMIAS
It is recognized that certain drugs can cause
immune cytopenias that involve one or several cell
lines including neutrophils, platelets, and
erythrocytes.
Three classic hypotheses
• Drug absorption
• Immune complex formation
• Autoantibody induction
79.
80.
81.
82.
83.
84.
85. CASE SCENARIO
32 yr old presented 4 days history of distention
of
abdomen and rt hypochondrial pain and has
h/o passage of dark colored urine at night for
weeks
On USG- hepatomegaly,gross
ascites,hepatic vein thrombosis
Lab : Hb – 7gm%. WBC- 2200, PLC- 80,000
LDH- 600, S.BR- 4 mg%
urine bile pigment +,heme dip stick++
What is the diagnosis
86. CASE SCENARIO
14 YR old female present with anemia, jaundice
Rt hypochondrial pain
o/e-vitals stable.pallor+,icterus+,splenomegaly +
Usg- cholilithiasis
Lab; elevated ,LDH, S.Bilirubin
Peripheral smear shows
87. CASE SCENARIO
25 yr old male with RHD – severe MR done
MVR,after 10
days presented with pallor, palpitation,jaundice
CBC shows Hb – 7.5 gm %, Hct -22 %
Lab : S.bilirubin -4.5mg%
LDH -600
Retic count 10%
Peripheral smear –
88. REFERENCES:
Wintrobe’s Clinical Hematology
12th Edition
Williams Hematology 9E
Harrison’s principles of Internal Medicine
Pearson New International Edition
Clinical Laboratory Hematology
Shirlyn B. McKenzie Second Edition