1. Hemolytic anemia results from the premature destruction of red blood cells, either intravascularly or extravascularly. It can be classified as acquired or hereditary.
2. Acquired hemolytic anemias are caused by extrinsic factors like antibodies, infections, toxins, or mechanical trauma. Hereditary hemolytic anemias result from intrinsic red blood cell defects.
3. Common causes of acquired hemolytic anemia include autoimmune hemolytic anemia, microangiopathic hemolysis, paroxysmal nocturnal hemoglobinuria, and isoimmune hemolytic anemia from blood transfusions. Hereditary forms often involve defects in the red blood cell membrane or interior
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
Hemolytic anemias share the following features:
A shortened red cell life span below the normal 120 days
Elevated erythropoietin levels and a compensatory increase in erythropoiesis
Accumulation of hemoglobin degradation products that are created as part of the process of red cell hemolysis
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
Hemolytic anemias share the following features:
A shortened red cell life span below the normal 120 days
Elevated erythropoietin levels and a compensatory increase in erythropoiesis
Accumulation of hemoglobin degradation products that are created as part of the process of red cell hemolysis
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.
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.
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.
causes of macrocytic anemia pathopysiology, sign and symptoms and the difference between macrocytic anemia megaloblastIc anemia. causes of hypersegmented neutrophils and its association between them. investigation and medical management plus pictures illustration.
Hemolytic anemia occurs when the bone marrow is unable to increase production to make up for the premature destruction of red blood cells and the abnormal breakdown of red blood cells either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired. Treatment depends on the cause and nature of the breakdown.Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications such as gallstones and pulmonary hypertension.
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.
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.
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.
causes of macrocytic anemia pathopysiology, sign and symptoms and the difference between macrocytic anemia megaloblastIc anemia. causes of hypersegmented neutrophils and its association between them. investigation and medical management plus pictures illustration.
Hemolytic anemia occurs when the bone marrow is unable to increase production to make up for the premature destruction of red blood cells and the abnormal breakdown of red blood cells either in the blood vessels (intravascular hemolysis) or elsewhere in the body (extravascular). It has numerous possible causes, ranging from relatively harmless to life-threatening. The general classification of hemolytic anemia is either inherited or acquired. Treatment depends on the cause and nature of the breakdown.Symptoms of hemolytic anemia are similar to other forms of anemia (fatigue and shortness of breath), but in addition the breakdown of red cells leads to jaundice and increases the risk of particular long-term complications such as gallstones and pulmonary hypertension.
Anemia And Its Classification By Dr Bashir Ahmed Dar Chinkipora Sopore KashmirProf Dr Bashir Ahmed Dar
Anaemia due to iron deficiency is the characteristic finding with a cancer of the colon (large bowel), stomach or gullet. Often the anaemia is the only clue to the presence of a bleeding source somewhere. Any person who develops iron deficiency anaemia with no obvious cause should be investigated for the presence of a bleeding point within the digestive system. Fortunately not all bleeding sources turn out to be cancers
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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.
MANAGEMENT OF ATRIOVENTRICULAR CONDUCTION BLOCK.pdfJim Jacob Roy
Cardiac conduction defects can occur due to various causes.
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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.
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1.) Identify clinical and biological prognostic factors that can guide treatment decision making for older adults with MCL
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Lung Cancer: Artificial Intelligence, Synergetics, Complex System Analysis, S...Oleg Kshivets
RESULTS: Overall life span (LS) was 2252.1±1742.5 days and cumulative 5-year survival (5YS) reached 73.2%, 10 years – 64.8%, 20 years – 42.5%. 513 LCP lived more than 5 years (LS=3124.6±1525.6 days), 148 LCP – more than 10 years (LS=5054.4±1504.1 days).199 LCP died because of LC (LS=562.7±374.5 days). 5YS of LCP after bi/lobectomies was significantly superior in comparison with LCP after pneumonectomies (78.1% vs.63.7%, P=0.00001 by log-rank test). AT significantly improved 5YS (66.3% vs. 34.8%) (P=0.00000 by log-rank test) only for LCP with N1-2. Cox modeling displayed that 5YS of LCP significantly depended on: phase transition (PT) early-invasive LC in terms of synergetics, PT N0—N12, cell ratio factors (ratio between cancer cells- CC and blood cells subpopulations), G1-3, histology, glucose, AT, blood cell circuit, prothrombin index, heparin tolerance, recalcification time (P=0.000-0.038). Neural networks, genetic algorithm selection and bootstrap simulation revealed relationships between 5YS and PT early-invasive LC (rank=1), PT N0—N12 (rank=2), thrombocytes/CC (3), erythrocytes/CC (4), eosinophils/CC (5), healthy cells/CC (6), lymphocytes/CC (7), segmented neutrophils/CC (8), stick neutrophils/CC (9), monocytes/CC (10); leucocytes/CC (11). Correct prediction of 5YS was 100% by neural networks computing (area under ROC curve=1.0; error=0.0).
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2. DEFINITION AND CLASSIFICATION
Anaemias resulting from an increase in the rate of red
cell destruction.
Normally, red cells undergo lysis at the end of their
lifespan of 120±30 days within the cells of
reticuloendothelial (RE) system in
the spleen and elsewhere (extravascular haemolysis), and
haemoglobin is not liberated into the plasma in
appreciable amounts.
The red cell lifespan is shortened in haemolytic anaemia
i.e. there is accelerated haemolysis.
However, shortening of red cell lifespan does not
necessarily result in
anaemia.
In fact, compensatory bone marrow hyperplasia may
cause 6 to 8-fold increase in red cell production without
3. The premature destruction of red cells in
haemolytic
anaemia may occur by 2 mechanisms:
Firstly, the red cells undergo lysis in the circulation
and
release their contents into plasma (intravascular
haemolysis).
In these cases the plasma haemoglobin rises
substantially
and part of it may be excreted in the urine
(haemoglobinuria).
Secondly, the red cells are taken up by cells of the
RE
system where they are destroyed and digested
4. Extravascular haemolysis is more common than the
former.
Haemolytic anaemias are broadly classified into 2 main
categories:
I. Acquired haemolytic anaemias caused by a variety of
extrinsic environmental factors (extracorpuscular).
II. Hereditary haemolytic anaemias are usually the result
of
intrinsic red cell defects (intracorpuscular).
.
5.
6. CLASSIFICATION OF HAEMOLYTIC
ANAEMIAS
I. ACQUIRED (EXTRACORPUSCULAR)
A. Antibody: Immunohaemolytic anaemias
1. Autoimmune haemolytic anaemia (AIHA)
i) Warm antibody AIHA
ii) Cold antibody AIHA
2. Drug-induced immunohaemolytic anaemia
3. Isoimmune haemolytic anaemia
B. Mechanical trauma: Microangiopathic haemolytic anaemia
C. Direct toxic effects: Malaria, bacterial, infection and other
agents
D. Acquired red cell membrane abnormalities: paroxysmal
nocturnal haemoglobinuria (PNH)
E. Splenomegaly
7. II. HEREDITARY (INTRACORPUSCULAR)
A. Abnormalities of red cell membrane
1. Hereditary spherocytosis
2. Hereditary elliptocytosis (hereditary ovalocytosis)
3. Hereditary stomatocytosis
B. Disorders of red cell interior
1. Red cell enzyme defects (Enzymopathies)
i) Defects in the hexose monophosphate shunt: G6PD
deficiency
ii) Defects in the Embden-Meyerhof (or glycolytic) pathway:
pyruvate kinase deficiency
2. Disorders of haemoglobin (Haemoglobinopathies)
i) Structurally abnormal haemoglobins: sickle syndromes,
other haemoglobinopathies
ii) Reduced globin chain synthesis: thalassaemias
8. FEATURES OF HAEMOLYSIS
GENERAL CLINICAL FEATURES
1. Presence of pallor of mucous membranes.
2. Positive family history with life-long anaemia in
patients
with congenital haemolytic anaemia.
3. Mild fluctuating jaundice due to unconjugated
hyperbilirubinaemia.
4. Urine turns dark on standing due to excess of
urobilinogen in urine.
5. Splenomegaly is found in most chronic haemolytic
anaemias, both congenital and acquired.
6. Pigment gallstones are found in some cases.
9. LABORATORY EVALUATION
OF HAEMOLYSIS
1. Is there evidence of haemolysis?
2. What is the type of haemolytic mechanism?
3. What is the precise diagnosis?
findings are conveniently divided into the
following 4 groups:
10. I. TESTS OF INCREASED
RED CELL BREAKDOWN
1. Serum bilirubin—unconjugated (indirect) bilirubin is raised.
2. Urine urobilinogen is raised but there is no bilirubinuria.
3. Faecal stercobilinogen is raised.
4. Serum haptoglobin (α-globulin binding protein) is reduced
or absent.
5. Plasma lactic dehydrogenase (LDH) is raised.
6. Evidences of intravascular haemolysis in the form of
haemoglobinaemia, haemoglobinuria, methaemoglobinaemia
and haemosiderinuria.
11. II. TESTS OF INCREASED RED
CELL PRODUCTION
1. Reticulocyte count reveals reticulocytosis which is
generally early and is hence most useful initial test of
marrow
erythroid hyperplasia.
2. Routine blood film shows macrocytosis, polychromasia
and
presence of normoblasts.
3. Bone marrow shows erythroid hyperplasia with usually
raised iron stores.
4. X-ray of bones shows evidence of expansion of marrow
space, especially in tubular bones and skull.
12. III. TESTS OF DAMAGE TO
RED CELLS
1. Osmotic fragility is increased or decreased.
2. Autohaemolysis test with or without addition of
glucose.
3. Coombs’ antiglobulin test.
4. Electrophoresis for abnormal haemoglobins.
5. Estimation of HbA2.
6. Estimation of HbF.
7. Tests for sickling.
8. Screening test for G6PD deficiency and other
enzymes (e.g.
Heinz bodies test).
13. IV. TESTS FOR
SHORTENED RED
CELL LIFESPAN.
A shortened red cell survival is best tested by 51Cr
labelling method.
Normal RBC lifespan of 120 days .
shortened to 20-40 days in moderate haemolysis
and
5-20 days in severe haemolysis.
14. I. ACQUIRED
(EXTRACORPUSCULAR)
HAEMOLYTIC ANAEMIASA. IMMUNOHAEMOLYTIC ANAEMIAS
Immunohaemolytic anaemias are a group of anaemias
occurring due to antibody production by the body against its
own red cells.
Immune haemolysis in these cases may be induced by one of
the following three types of antibodies:
1. Autoimmune haemolytic anaemia (AIHA) characterised by
formation of autoantibodies against patient’s own red cells.
Depending upon the reactivity of autoantibody, AIHA is
further divided into 2 types:
i) ‘Warm’ antibody AIHA in which the autoantibodies are
reactive at body temperature (37°C).
ii) ‘Cold’ antibody AIHA in which the autoantibodies react
better with patient’s own red cells at 4°C.
15. 2. Drug-induced immunohaemolytic anaemia.
3. Isoimmune haemolytic anaemia in which the
antibodies are
acquired by blood transfusions, pregnancies and
haemolytic
disease of the newborn.
An important diagnostic tool in all cases of
immunohaemolytic
anaemias is Coombs’ antiglobulin test for
detection of incomplete Rh-antibodies in saline
directly (direct Coombs’) or after addition of
albumin (indirect Coombs’).
16. A. WARM ANTIBODY AIHA
1. Idiopathic (primary)
2. Lymphomas-leukaemias e.g. non-Hodgkin’s
lymphoma, CLL, Hodgkin's disease.
3. Collagen vascular diseases e.g SLE
4. Drugs e.g. methyldopa, penicillin, quinidine group
5. Post-viral
B. COLD ANTIBODY AIHA
1. Cold agglutinin disease
a) Acute: Mycoplasma infection, infectious
mononucleosis
b) Chronic: Idiopathic, lymphomas
2. PCH (Mycoplasma infection, viral flu, measles,
17. ‘WARM’ ANTIBODY AIHA
PATHOGENESIS.
Warm antibodies reactive at body temperature and
coating the red cells are generally IgG class antibodies
and occasionally they are IgA.
Human red cells coated with IgG antibodies are bound to
the surface of RE cells, especially splenic macrophages.
A part of the coated cell membrane is lost resulting in
spherical transformation of the red cells (acquired
spherocytosis).
Red cells coated with IgG along with C3 on the surface
further promote this red cell-leucocyte interaction,
accounting for more severe haemolysis.
The spleen is particularly efficient in trapping red cells
coated
with IgG antibodies. It is, thus, the major site of red cell
destruction in warm antibody AIHA.
18. CLINICAL FEATURES
Warm antibody AIHA may occur at any age and in
either sex.
The disease may occur without any apparent cause
(idiopathic) but about a quarter of patients develop
this disorder as a complication of an underlying
disease affecting the immune system such as
SLE, chronic lymphocytic leukaemia, lymphomas
and certain
drugs such as methyl DOPA, penicillin
The disease tends to have remissions and relapses.
1. Chronic anaemia of varying severity with
remissions and
relapses.
2. Splenomegaly.
19. LABORATORY FINDINGS.
1. Mild to moderate chronic anaemia.
2. Reticulocytosis.
3. Prominent spherocytosis in the peripheral blood film.
4. Positive direct Coombs’ (antiglobulin) test for
presence of warm antibodies on the red cell, best
detected at 37°C.
5. A positive indirect Coombs’ (antiglobulin) test at 37°C
may indicate presence of large quantities of warm
antibodies in the serum.
6. Unconjugated (indirect) hyperbilirubinaemia.
7. Co-existent immune thrombocytopenia along with
occasional venous thrombosis may be present (termed
Evans’ syndrome).
8. In more severe cases, haemoglobinaemia and
haemoglobinuria may be present.
20. ‘COLD’ ANTIBODY AIHA
PATHOGENESIS.
Antibodies which are reactive in the cold (4°C) may
induce haemolysis under 2 conditions:
1. Cold agglutinin disease. In cold agglutinin disease, the
antibodies are IgM type which bind to the red cells best
at
4°C.
These cold antibodies are usually directed against the I
antigen on the red cell surface. Agglutination of red
blood cells by IgM cold agglutinins is most profound at
very low temperature but upon warming to 37°C or
above, disagglutination occurs quickly.
Haemolytic effect is mediated through fixation of C3 to
the red blood cell surface and not by agglutination alone.
Most cold agglutinins affect juvenile red blood cells.
21. 2. Paroxysmal cold haemoglobinuria (PCH).
In PCH, cold antibody is an IgG antibody (Donath-
Landsteiner antibody)
which is directed against P blood group antigen and
brings
about complement-mediated haemolysis.
Attacks of PCH are precipitated by exposure to cold.
PCH is uncommon and may be seen in association with
tertiary syphilis or as a complication of certain
infections such
as Mycoplasma pneumonia, flu, measles and mumps.
22. CLINICAL FEATURES
1. Chronic anaemia which is worsened by exposure to
cold.
2. Raynaud’s phenomenon.
3. Cyanosis affecting the cold exposed regions such as
tips
of nose, ears, fingers and toes.
4. Haemoglobinaemia and haemoglobinuria occur on
exposure to cold.
Treatment consists of keeping the patient warm and
treating the underlying cause.
23. LABORATORY FINDINGS.
1. Chronic anaemia.
2. Low reticulocyte count since young red cells are
affected
more.
3. Spherocytosis is less marked.
4. Positive direct Coombs’ test for detection of C3 on the
red cell surface but IgM responsible for C3 coating on
red
cells is not found.
5. The cold antibody titre is very high at 4°C and very low
at 37°C (Donath-Landsteiner test).
24. ISOIMMUNE HAEMOLYTIC
ANAEMIA
Isoimmune haemolytic anaemias are caused by
acquiring
isoantibodies or alloantibodies by blood
transfusions,
pregnancies and in haemolytic disease of the
newborn.
These antibodies produced by one individual are
directed against red blood cells of the other.
25. B. MICROANGIOPATHIC HAEMOLYTIC
ANAEMIA
Microangiopathic haemolytic anaemia is caused by
abnormalities in the microvasculature.
It is generally due to mechanical trauma to the red
cells in circulation and is
characterised by red cell fragmentation
(schistocytosis).
There are 3 different ways by which
microangiopathic haemolytic anaemia results:
26. 1. EXTERNAL IMPACT. Direct external trauma to red
blood cells when they pass through microcirculation,
especially
over the bony prominences, may cause haemolysis
during various activities e.g. in prolonged marchers,
joggers,
karate players etc. These patients develop
haemoglobinaemia,
haemoglobinuria (march haemoglobinuria), and
sometimes myoglobinuria as a result of damage to
muscles.
2. CARDIAC HAEMOLYSIS. A small proportion of
patients who received prosthetic cardiac valves or
artificial
grafts develop haemolysis. This has been attributed to
27. 3. FIBRIN DEPOSIT IN MICROVASCULATURE.
Deposition of fibrin in the microvasculature exposes the
red cells to physical obstruction and eventual
fragmentation of red cells and trapping of the platelets.
Fibrin deposits in the small vessels may occur in the
following conditions:
i) Abnormalities of the vessel wall e.g. in hypertension,
eclampsia, disseminated cancers, transplant rejection,
haemangioma etc.
ii) Thrombotic thrombocytopenic purpura.
iii) Haemolytic-uraemic syndrome.
iv) Disseminated intravascular coagulation (DIC)
v) Vasculitis in collagen diseases.
28. D. PAROXYSMAL NOCTURNAL
HAEMOGLOBINURIA (PNH)
PNH is a rare acquired disorder of red cell
membrane in
which there is chronic intravascular haemolysis due
to undue
sensitivity of red blood cells to complement due to
defective
synthesis of a red cell membrane protein.
The defect affects all the cells of myeloid
progenitor lineage (RBCs, WBCs, platelets)
suggesting a deficient haematopoiesis.
The disorder generally presents in adult life.
29. PATHOGENESIS
PNH is considered as an acquired clonal disease of the
cell membrane while normal clone also continues to
proliferate.
The defect is a mutation in the stem cells affecting
myeloid progenitor cells that is normally required for
the biosynthesis of glycosyl phosphatidyl inositol (GPI)
essential for anchoring of the cell; the mutant form of
the gene is an X-linked gene called PIG-A
(phosphatidyl inositol glycan).
Thus, as a result of mutation, there is partial or
complete deficiency of anchor protein.
Out of about 20 such proteins described so far, the
lack of two of
the proteins—decay accelerating factor (DAF, CD55)
and a
membrane inhibitor of reactive lysis (MIRL, CD59),
30. CLINICAL AND LABORATORY
FINDINGS
ii) Pancytopenia (mild granulocytopenia and
thrombocytopenia frequent).
iii) Intermittent clinical haemoglobinuria; acute
haemolytic episodes occur at night identified by passage
of brown urine in the morning.
iv) Haemosiderinuria.
v) Venous thrombosis as a common complication.
The presence of inordinate sensitivity of red blood cells,
leucocytes and platelets to complement in PNH can be
demonstrated in vitro by Ham’s test using red cell lysis
at acidic pH or by sucrose haemolysis test.