This document discusses acquired hemolytic anemias, including their causes and classifications. It focuses on immune hemolytic anemias caused by autoantibodies, distinguishing between warm antibody type and cold antibody type. Warm antibody type is maximally active at body temperature and results in spherocytosis as antibodies coat and destroy red blood cells. Cold antibody type involves two mechanisms: cold agglutinins cause agglutination of red blood cells in peripheral vessels, while Donath-Landsteiner antibodies activate complement and cause intravascular hemolysis. Clinical features and laboratory findings are described for both types.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder characterized by hemolytic anemia. It arises due to a somatic mutation in the PIGA gene, causing deficiency of glycosylphosphatidylinositol-anchored proteins (GPI-APs) like CD55 and CD59 on the surface of blood cells. This renders the cells highly sensitive to complement-mediated lysis. Diagnosis involves flow cytometry to detect GPI-AP deficiency and tests like Ham and sucrose hemolysis to demonstrate complement sensitivity of the red blood cells. PNH is associated with hemoglobinuria, thrombosis, and bone marrow failure. It requires differentiation
Aplastic anemia is a condition where the bone marrow fails to produce sufficient new blood cells, leading to low blood cell counts and fatigue. It can be classified as idiopathic, secondary to drug reactions or infections, or constitutional/congenital forms like Fanconi anemia. Fanconi anemia is a genetic disorder characterized by bone marrow failure, physical abnormalities, and cancer predisposition. Diagnosis involves blood tests showing low cell counts and a bone marrow biopsy displaying a hypocellular marrow. Treatment options include blood transfusions, immunosuppressive drugs, and bone marrow transplantation.
This document summarizes different types of immune hemolytic anemia, including their mechanisms and diagnostic criteria. It discusses autoimmune hemolytic anemia, which can be warm or cold types. Alloimmune hemolytic anemia includes hemolytic transfusion reactions and hemolytic disease of the newborn. Drug-induced immune hemolytic anemia can occur through immune complex formation, drug adsorption, or true autoimmunity. Diagnosis involves tests like complete blood count, peripheral smear, direct antiglobulin test, and identifying the underlying antibody. Treatment depends on the specific type but may include corticosteroids, splenectomy, plasmapheresis, or discontinuing the causative drug.
This document provides information about multiple myeloma, including its definition, epidemiology, pathogenesis, clinical presentation, diagnostic criteria, staging system, imaging, laboratory findings, and treatment options. Key points include:
- Multiple myeloma is a neoplastic plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow.
- It accounts for 1% of cancers and 13% of hematological malignancies in Western countries. Median age at diagnosis is 70 years.
- Pathogenesis involves genetic alterations in plasma cells following activation in lymph nodes, resulting in monoclonal protein production and bone marrow homing.
- Clinical features include bone lesions, hypercalcemia, renal impairment, anemia, and infections.
Thalassemia refers to a group of inherited anemias caused by reduced or absent globin chain synthesis. There are two main types: alpha thalassemia results from alpha globin gene mutations and beta thalassemia from beta globin gene mutations. Symptoms range from none to severe anemia, bone abnormalities, organ enlargement, and other complications depending on severity. Treatment involves blood transfusions, iron chelation therapy, and in some cases bone marrow transplant or splenectomy.
The document discusses bone marrow failure syndromes, which occur when there is a decrease or damage to hematopoietic stem cells and their microenvironment resulting in hypoplastic or aplastic bone marrow. Some examples of bone marrow failure syndromes discussed include aplastic anemia, myelodysplastic syndromes, paroxysmal nocturnal hemoglobinuria, and various constitutional bone marrow failure syndromes such as Fanconi anemia, dyskeratosis congenita, and Diamond-Blackfan anemia. The causes, signs, diagnostic evaluation, and treatment approaches for different bone marrow failure syndromes are described.
IgG4-related disease is a chronic fibroinflammatory condition characterized by tumefactive lesions rich in IgG4-positive plasma cells and storiform fibrosis. It commonly involves the pancreas, salivary glands, lacrimal glands, and retroperitoneum. Diagnosis involves elevated serum IgG4 levels, histopathological examination showing lymphoplasmacytic infiltrate and fibrosis, and often fulfilling clinical diagnostic criteria. Differential diagnosis includes cancers, infections and other diseases. Treatment involves glucocorticoids as first line with potential use of immunosuppressants. Relapse is common requiring glucocorticoid tapers or maintenance therapy.
Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, acquired hematopoietic stem cell disorder characterized by hemolytic anemia. It arises due to a somatic mutation in the PIGA gene, causing deficiency of glycosylphosphatidylinositol-anchored proteins (GPI-APs) like CD55 and CD59 on the surface of blood cells. This renders the cells highly sensitive to complement-mediated lysis. Diagnosis involves flow cytometry to detect GPI-AP deficiency and tests like Ham and sucrose hemolysis to demonstrate complement sensitivity of the red blood cells. PNH is associated with hemoglobinuria, thrombosis, and bone marrow failure. It requires differentiation
Aplastic anemia is a condition where the bone marrow fails to produce sufficient new blood cells, leading to low blood cell counts and fatigue. It can be classified as idiopathic, secondary to drug reactions or infections, or constitutional/congenital forms like Fanconi anemia. Fanconi anemia is a genetic disorder characterized by bone marrow failure, physical abnormalities, and cancer predisposition. Diagnosis involves blood tests showing low cell counts and a bone marrow biopsy displaying a hypocellular marrow. Treatment options include blood transfusions, immunosuppressive drugs, and bone marrow transplantation.
This document summarizes different types of immune hemolytic anemia, including their mechanisms and diagnostic criteria. It discusses autoimmune hemolytic anemia, which can be warm or cold types. Alloimmune hemolytic anemia includes hemolytic transfusion reactions and hemolytic disease of the newborn. Drug-induced immune hemolytic anemia can occur through immune complex formation, drug adsorption, or true autoimmunity. Diagnosis involves tests like complete blood count, peripheral smear, direct antiglobulin test, and identifying the underlying antibody. Treatment depends on the specific type but may include corticosteroids, splenectomy, plasmapheresis, or discontinuing the causative drug.
This document provides information about multiple myeloma, including its definition, epidemiology, pathogenesis, clinical presentation, diagnostic criteria, staging system, imaging, laboratory findings, and treatment options. Key points include:
- Multiple myeloma is a neoplastic plasma cell disorder characterized by clonal proliferation of malignant plasma cells in the bone marrow.
- It accounts for 1% of cancers and 13% of hematological malignancies in Western countries. Median age at diagnosis is 70 years.
- Pathogenesis involves genetic alterations in plasma cells following activation in lymph nodes, resulting in monoclonal protein production and bone marrow homing.
- Clinical features include bone lesions, hypercalcemia, renal impairment, anemia, and infections.
Thalassemia refers to a group of inherited anemias caused by reduced or absent globin chain synthesis. There are two main types: alpha thalassemia results from alpha globin gene mutations and beta thalassemia from beta globin gene mutations. Symptoms range from none to severe anemia, bone abnormalities, organ enlargement, and other complications depending on severity. Treatment involves blood transfusions, iron chelation therapy, and in some cases bone marrow transplant or splenectomy.
The document discusses bone marrow failure syndromes, which occur when there is a decrease or damage to hematopoietic stem cells and their microenvironment resulting in hypoplastic or aplastic bone marrow. Some examples of bone marrow failure syndromes discussed include aplastic anemia, myelodysplastic syndromes, paroxysmal nocturnal hemoglobinuria, and various constitutional bone marrow failure syndromes such as Fanconi anemia, dyskeratosis congenita, and Diamond-Blackfan anemia. The causes, signs, diagnostic evaluation, and treatment approaches for different bone marrow failure syndromes are described.
IgG4-related disease is a chronic fibroinflammatory condition characterized by tumefactive lesions rich in IgG4-positive plasma cells and storiform fibrosis. It commonly involves the pancreas, salivary glands, lacrimal glands, and retroperitoneum. Diagnosis involves elevated serum IgG4 levels, histopathological examination showing lymphoplasmacytic infiltrate and fibrosis, and often fulfilling clinical diagnostic criteria. Differential diagnosis includes cancers, infections and other diseases. Treatment involves glucocorticoids as first line with potential use of immunosuppressants. Relapse is common requiring glucocorticoid tapers or maintenance therapy.
Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis characterized by thickening of the glomerular basement membrane, proliferation of mesangial cells and capillary loops, and activation of the complement system. There are two main types - type I is caused by immune complex deposition and type II (dense deposit disease) results from abnormal alternative complement pathway regulation leading to dense material deposition in the glomerular basement membrane. MPGN follows a progressive clinical course and can lead to end stage renal disease within 10 years if left untreated. Treatment aims to slow disease progression and control symptoms.
Bernard-Soulier syndrome is a rare inherited bleeding disorder characterized by large platelets and prolonged bleeding times. It results from mutations that cause a dysfunctional platelet glycoprotein receptor complex, leading to defective platelet adhesion. Patients present with mucocutaneous bleeding from an early age. Diagnosis involves identifying thrombocytopenia, large platelets on smear, and abnormal platelet aggregation tests. Treatment focuses on transfusions and minimizing trauma; stem cell transplantation may be considered for severe cases.
1. The document discusses the differentiation between myeloid leukemoid reaction, chronic myeloid leukemia (CML), and chronic neutrophilic leukemia (CNL).
2. Key differences include peripheral smear findings, bone marrow aspirate/biopsy pictures, LAP scores, cytogenetics, and immunophenotyping results.
3. A leukemoid reaction is secondary to an underlying cause and shows features of that cause, while CML and CNL are myeloproliferative neoplasms with distinct clinical features, lab findings, and disease progression.
The document discusses myeloproliferative disorders (MPDs), which are clonal stem cell disorders characterized by increased blood cell counts and enlarged spleen and bone marrow. It focuses on chronic myeloid leukemia (CML), describing it as a MPD caused by a genetic mutation that results in uncontrolled white blood cell growth. CML progresses through chronic, accelerated, and blast phases, with symptoms ranging from fatigue to organ enlargement. Diagnosis involves blood and bone marrow tests detecting elevated white and platelet counts and the Philadelphia chromosome genetic abnormality associated with CML.
Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell production which leads to thickened blood and risk of blood clots. Diagnosis is based on criteria including elevated red blood cell count and spleen enlargement. Treatment aims to reduce blood thickness and prevent clots through regular blood removal and medications to suppress bone marrow activity.
Monoclonal Gammopathy and Renal DiseaseMostafa Aly
1) MGRS refers to monoclonal gammopathy of renal significance, where a monoclonal immunoglobulin secreted by a nonmalignant or premalignant B cell or plasma cell clone leads to renal damage without meeting criteria for multiple myeloma or lymphoma.
2) MGRS can be categorized as those with organized monoclonal immunoglobulin deposits, those with non-organized deposits, or those without immunoglobulin deposits affecting the kidneys.
3) Examples of organized monoclonal immunoglobulin deposits affecting the kidneys include amyloidosis, monoclonal fibrillary glomerulonephritis, and immunotactoid glomerulonephritis.
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
The document summarizes key topics related to plasma cell dyscrasias and multiple myeloma, including definitions, investigations, classifications, and treatment approaches. It describes the typical features of plasma cells, abnormalities like Russell bodies and Mott cells. It outlines criteria for monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, solitary plasmacytoma, extramedullary plasmacytoma, and multiple myeloma. It discusses workup, staging, cytogenetics, and management options for multiple myeloma including stem cell transplantation and novel agents.
Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis characterized by thickening of the glomerular capillary walls. It accounts for 7-10% of biopsy-confirmed glomerulonephritis cases. MPGN is classified into three main types based on electron microscopy findings of immune complex deposition. Type I has subendothelial deposits, Type II has dense deposits in the glomerular basement membrane, and Type III has both subendothelial and subepithelial deposits. Treatment involves addressing any underlying causes and may include immunosuppressive agents like corticosteroids and cytotoxic drugs. A randomized control trial found alternate-day pred
This document discusses thalassemias, which are hereditary disorders involving reduced synthesis of one or more globin polypeptide chains. It is classified into alpha and beta thalassemias. Alpha thalassemia involves defective synthesis of alpha globin chains, while beta thalassemia involves reduced beta chain synthesis. The classification ranges from severe homozygous forms like hydrops fetalis to mild heterozygous forms like thalassemia minor. The clinical features, laboratory findings, and treatment approaches are described for different forms of alpha and beta thalassemias. Prevention can be achieved through antenatal screening and diagnosis.
1. Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an overproduction of red blood cells without an identifiable stimulus. It commonly presents with erythrocytosis, splenomegaly, thrombosis, and pruritus.
2. The main cause of PV is a mutation in the JAK2 gene, but some patients have mutations in exon 12. Diagnosis requires tests to distinguish absolute from relative erythrocytosis. Treatment focuses on phlebotomy and medications to control symptoms and prevent complications.
3. Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm involving clonal proliferation and
This document provides guidance on sampling, allocating, and fixing renal biopsy tissue for light microscopy, immunofluorescence, and electron microscopy evaluation. It discusses obtaining adequate sample sizes from different renal regions and dividing tissue between fixatives. Common stains used for light microscopy like H&E, PAS, trichrome, and silver stains are also described. Normal renal histology of the glomerulus, interstitium, tubules, and vessels is outlined.
The document discusses the thalassemias, a group of inherited blood disorders caused by defects in hemoglobin synthesis. There are two main types: alpha thalassemia results from reduced alpha globin chain production, while beta thalassemia is caused by reduced beta globin chains. Symptoms range from none to severe anemia requiring blood transfusions, depending on the number of defective genes. Thalassemias are most common in people from Mediterranean, African, and Southeast Asian descent and are diagnosed based on blood tests showing microcytic anemia and abnormalities in hemoglobin electrophoresis and red blood cell indices.
Autoimmune hemolytic anemia is caused by antibodies that bind to and prematurely destroy red blood cells. It is classified into warm and cold types based on antibody characteristics and mechanisms of hemolysis. Workup involves a Coombs test to detect antibodies coating red blood cells via direct or indirect agglutination. Treatment depends on type but may include steroids, splenectomy, cold protection, or rituximab.
This document discusses hemolytic anemias caused by extracorpuscular defects. It describes immune and non-immune mechanisms that can destroy red blood cells, including autoimmune disorders, drug reactions, alloimmune responses to blood transfusions or pregnancy, infections, and membrane defects. The main types of immune hemolytic anemias are autoimmune (warm or cold antibody types), alloimmune (due to blood transfusions or pregnancy), and drug-induced. Workup may include blood tests to detect anemia, spherocytes, a positive direct Coombs test, and the thermal amplitude of any detected antibodies. Management depends on the underlying cause.
This document discusses antineutrophil cytoplasmic antibodies (ANCA). It notes that ANCA are autoantibodies related to inflammatory disorders and were first associated with Wegener's granulomatosis in 1985. The two main ANCA antigens are proteinase 3 and myeloperoxidase. ANCA testing can aid in diagnosing and monitoring ANCA-associated vasculitis conditions. However, increasing ANCA titers do not reliably predict disease relapses.
Multiple myeloma is a cancer of plasma cells that are found in the bone marrow. It is characterized by an overproduction of abnormal plasma cells which produce a monoclonal protein known as M protein. Symptoms include bone pain or fractures, anemia, kidney problems, and infections. Diagnosis involves blood and urine tests to detect the M protein as well as imaging tests and a bone marrow biopsy. Treatment depends on disease severity and transplant eligibility and may include chemotherapy, steroids, and stem cell transplantation.
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.
Acquired hemolytic anemias can be caused by extracorpuscular factors or environmental changes and include immune-mediated hemolytic anemias. Immune causes include warm-reacting antibodies, cold-reacting antibodies, drug-dependent antibodies, and autoimmune causes. Hypersplenism results in cytopenias due to increased destruction of red blood cells, white blood cells, and platelets in an enlarged spleen. Immune hemolytic anemias are caused by antibodies against a person's own red blood cells and are classified as warm or cold antibody types depending on antibody reactivity at body temperature versus cold temperature.
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
Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis characterized by thickening of the glomerular basement membrane, proliferation of mesangial cells and capillary loops, and activation of the complement system. There are two main types - type I is caused by immune complex deposition and type II (dense deposit disease) results from abnormal alternative complement pathway regulation leading to dense material deposition in the glomerular basement membrane. MPGN follows a progressive clinical course and can lead to end stage renal disease within 10 years if left untreated. Treatment aims to slow disease progression and control symptoms.
Bernard-Soulier syndrome is a rare inherited bleeding disorder characterized by large platelets and prolonged bleeding times. It results from mutations that cause a dysfunctional platelet glycoprotein receptor complex, leading to defective platelet adhesion. Patients present with mucocutaneous bleeding from an early age. Diagnosis involves identifying thrombocytopenia, large platelets on smear, and abnormal platelet aggregation tests. Treatment focuses on transfusions and minimizing trauma; stem cell transplantation may be considered for severe cases.
1. The document discusses the differentiation between myeloid leukemoid reaction, chronic myeloid leukemia (CML), and chronic neutrophilic leukemia (CNL).
2. Key differences include peripheral smear findings, bone marrow aspirate/biopsy pictures, LAP scores, cytogenetics, and immunophenotyping results.
3. A leukemoid reaction is secondary to an underlying cause and shows features of that cause, while CML and CNL are myeloproliferative neoplasms with distinct clinical features, lab findings, and disease progression.
The document discusses myeloproliferative disorders (MPDs), which are clonal stem cell disorders characterized by increased blood cell counts and enlarged spleen and bone marrow. It focuses on chronic myeloid leukemia (CML), describing it as a MPD caused by a genetic mutation that results in uncontrolled white blood cell growth. CML progresses through chronic, accelerated, and blast phases, with symptoms ranging from fatigue to organ enlargement. Diagnosis involves blood and bone marrow tests detecting elevated white and platelet counts and the Philadelphia chromosome genetic abnormality associated with CML.
Polycythemia vera is a chronic myeloproliferative disorder characterized by increased red blood cell production which leads to thickened blood and risk of blood clots. Diagnosis is based on criteria including elevated red blood cell count and spleen enlargement. Treatment aims to reduce blood thickness and prevent clots through regular blood removal and medications to suppress bone marrow activity.
Monoclonal Gammopathy and Renal DiseaseMostafa Aly
1) MGRS refers to monoclonal gammopathy of renal significance, where a monoclonal immunoglobulin secreted by a nonmalignant or premalignant B cell or plasma cell clone leads to renal damage without meeting criteria for multiple myeloma or lymphoma.
2) MGRS can be categorized as those with organized monoclonal immunoglobulin deposits, those with non-organized deposits, or those without immunoglobulin deposits affecting the kidneys.
3) Examples of organized monoclonal immunoglobulin deposits affecting the kidneys include amyloidosis, monoclonal fibrillary glomerulonephritis, and immunotactoid glomerulonephritis.
UAEU - CMHS - Hematology-Oncology Course - MMH 302 - HONC 320. Education material for medical students - It cover basic principles of hematology and oncology, including CAR-T and gene editing. It can be used for study and review. It illustrates main principles of hematology and oncology.
The document summarizes key topics related to plasma cell dyscrasias and multiple myeloma, including definitions, investigations, classifications, and treatment approaches. It describes the typical features of plasma cells, abnormalities like Russell bodies and Mott cells. It outlines criteria for monoclonal gammopathy of undetermined significance (MGUS), smoldering myeloma, solitary plasmacytoma, extramedullary plasmacytoma, and multiple myeloma. It discusses workup, staging, cytogenetics, and management options for multiple myeloma including stem cell transplantation and novel agents.
Membranoproliferative glomerulonephritis (MPGN) is a type of glomerulonephritis characterized by thickening of the glomerular capillary walls. It accounts for 7-10% of biopsy-confirmed glomerulonephritis cases. MPGN is classified into three main types based on electron microscopy findings of immune complex deposition. Type I has subendothelial deposits, Type II has dense deposits in the glomerular basement membrane, and Type III has both subendothelial and subepithelial deposits. Treatment involves addressing any underlying causes and may include immunosuppressive agents like corticosteroids and cytotoxic drugs. A randomized control trial found alternate-day pred
This document discusses thalassemias, which are hereditary disorders involving reduced synthesis of one or more globin polypeptide chains. It is classified into alpha and beta thalassemias. Alpha thalassemia involves defective synthesis of alpha globin chains, while beta thalassemia involves reduced beta chain synthesis. The classification ranges from severe homozygous forms like hydrops fetalis to mild heterozygous forms like thalassemia minor. The clinical features, laboratory findings, and treatment approaches are described for different forms of alpha and beta thalassemias. Prevention can be achieved through antenatal screening and diagnosis.
1. Polycythemia vera (PV) is a chronic myeloproliferative neoplasm characterized by an overproduction of red blood cells without an identifiable stimulus. It commonly presents with erythrocytosis, splenomegaly, thrombosis, and pruritus.
2. The main cause of PV is a mutation in the JAK2 gene, but some patients have mutations in exon 12. Diagnosis requires tests to distinguish absolute from relative erythrocytosis. Treatment focuses on phlebotomy and medications to control symptoms and prevent complications.
3. Primary myelofibrosis (PMF) is a chronic myeloproliferative neoplasm involving clonal proliferation and
This document provides guidance on sampling, allocating, and fixing renal biopsy tissue for light microscopy, immunofluorescence, and electron microscopy evaluation. It discusses obtaining adequate sample sizes from different renal regions and dividing tissue between fixatives. Common stains used for light microscopy like H&E, PAS, trichrome, and silver stains are also described. Normal renal histology of the glomerulus, interstitium, tubules, and vessels is outlined.
The document discusses the thalassemias, a group of inherited blood disorders caused by defects in hemoglobin synthesis. There are two main types: alpha thalassemia results from reduced alpha globin chain production, while beta thalassemia is caused by reduced beta globin chains. Symptoms range from none to severe anemia requiring blood transfusions, depending on the number of defective genes. Thalassemias are most common in people from Mediterranean, African, and Southeast Asian descent and are diagnosed based on blood tests showing microcytic anemia and abnormalities in hemoglobin electrophoresis and red blood cell indices.
Autoimmune hemolytic anemia is caused by antibodies that bind to and prematurely destroy red blood cells. It is classified into warm and cold types based on antibody characteristics and mechanisms of hemolysis. Workup involves a Coombs test to detect antibodies coating red blood cells via direct or indirect agglutination. Treatment depends on type but may include steroids, splenectomy, cold protection, or rituximab.
This document discusses hemolytic anemias caused by extracorpuscular defects. It describes immune and non-immune mechanisms that can destroy red blood cells, including autoimmune disorders, drug reactions, alloimmune responses to blood transfusions or pregnancy, infections, and membrane defects. The main types of immune hemolytic anemias are autoimmune (warm or cold antibody types), alloimmune (due to blood transfusions or pregnancy), and drug-induced. Workup may include blood tests to detect anemia, spherocytes, a positive direct Coombs test, and the thermal amplitude of any detected antibodies. Management depends on the underlying cause.
This document discusses antineutrophil cytoplasmic antibodies (ANCA). It notes that ANCA are autoantibodies related to inflammatory disorders and were first associated with Wegener's granulomatosis in 1985. The two main ANCA antigens are proteinase 3 and myeloperoxidase. ANCA testing can aid in diagnosing and monitoring ANCA-associated vasculitis conditions. However, increasing ANCA titers do not reliably predict disease relapses.
Multiple myeloma is a cancer of plasma cells that are found in the bone marrow. It is characterized by an overproduction of abnormal plasma cells which produce a monoclonal protein known as M protein. Symptoms include bone pain or fractures, anemia, kidney problems, and infections. Diagnosis involves blood and urine tests to detect the M protein as well as imaging tests and a bone marrow biopsy. Treatment depends on disease severity and transplant eligibility and may include chemotherapy, steroids, and stem cell transplantation.
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.
Acquired hemolytic anemias can be caused by extracorpuscular factors or environmental changes and include immune-mediated hemolytic anemias. Immune causes include warm-reacting antibodies, cold-reacting antibodies, drug-dependent antibodies, and autoimmune causes. Hypersplenism results in cytopenias due to increased destruction of red blood cells, white blood cells, and platelets in an enlarged spleen. Immune hemolytic anemias are caused by antibodies against a person's own red blood cells and are classified as warm or cold antibody types depending on antibody reactivity at body temperature versus cold temperature.
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
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.
This document defines and classifies haemolytic anaemia. It describes acquired haemolytic anaemia, which can be immune or non-immune. Immune haemolytic anaemia is further divided into autoimmune, alloimmune, and drug-induced types. Warm and cold autoimmune haemolytic anaemias are explained in detail, including their causes, clinical features, laboratory findings, and treatments. Other types of non-immune haemolytic anaemias such as paroxysmal nocturnal haemoglobinuria, red cell fragmentation syndromes, and traumatic cardiac haemolytic anaemia are also summarized.
This document discusses approaches to extracorpuscular hemolytic anemia. It begins by defining extracorpuscular anemias as defects in which red blood cells are normal but destroyed due to mechanical, immunologic, infectious, or metabolic/oxidant damage. It then covers the etiology of non-immune and immune hemolytic anemias, including infections, mechanical factors like prosthetic valves, chemicals/drugs, and autoimmune disorders. Warm and cold agglutinin diseases are described as types of autoimmune hemolytic anemia. The document concludes by covering non-immune causes such as mechanical heart valves, burns, and microangiopathic anemias.
1. Autoimmune hemolytic anemia (AIHA) is characterized by the abnormal production of antibodies that destroy red blood cells, leading to anemia.
2. There are three main types of AIHA - warm, cold, and mixed - defined by the temperature at which antibodies cause hemolysis.
3. Warm AIHA is the most common type and causes hemolysis at normal body temperatures, while cold AIHA antibodies are only active at low temperatures below 37°C.
4. The symptoms of AIHA include paleness, fatigue, fever, and signs of anemia. Diagnosis involves blood tests showing low hemoglobin and a positive direct Coombs test indicating antibodies on red blood
Autoimmune hemolytic anemia (AIHA) is caused by autoantibodies that bind to and destroy a person's own red blood cells. There are several subtypes depending on the temperature sensitivity of the autoantibodies. Warm AIHA is the most common type and involves IgG autoantibodies that bind to red blood cells at 37°C, leading to their destruction. Cold AIHA involves IgM autoantibodies that agglutinate red blood cells at 4°C and activate the complement system. Symptoms are typically slow in onset and include anemia, jaundice, and splenomegaly. Diagnosis involves detection of antibody-coated red blood cells via the direct antiglobulin
This document summarizes immune hemolytic anemia, including the three main types: autoimmune hemolytic anemia, alloimmune hemolytic anemia, and drug-induced immune hemolytic anemia. It focuses on autoimmune hemolytic anemia, describing the warm antibody type and cold antibody type in detail. For warm antibody type, it covers pathophysiology, clinical features, laboratory features, treatment options, and related conditions like Evan syndrome. For cold antibody type, it discusses cold hemagglutinin disease and paroxysmal cold hemoglobinuria, including characteristics, pathophysiology, clinical and laboratory features.
This document discusses various types of acquired hemolytic anemias, including immune and non-immune causes. It covers autoimmune hemolytic anemia, distinguishing between warm and cold types. It also discusses alloimmune hemolytic anemias like hemolytic disease of the newborn. Non-immune causes discussed include red cell fragmentation syndromes, infections, chemicals/physical agents, and acquired membrane disorders. Aplastic anemia is also summarized, covering etiology, pathogenesis, clinical features, and differential diagnosis.
This document summarizes autoimmune hemolytic anemia (AIHA). It discusses the classification of AIHA into types based on antibody temperature reactivity (warm, cold, mixed). The laboratory evaluation involves serology to detect autoantibodies via direct antiglobulin test and identification of antibodies in eluates. AIHA can be idiopathic or secondary to underlying conditions like lymphoproliferative disorders, infections, or autoimmune diseases. Treatment depends on the AIHA type and severity of symptoms.
Autoimmune haemolytic anaemia is caused by abnormalities of the immune system where antibodies attack a person's own red blood cells. There are two main types: warm antibody haemolytic anaemia, which is the most common type, and cold agglutinin disease. Warm antibody haemolytic anaemia can be primary or secondary to other conditions and causes haemolysis mainly in the spleen. Cold agglutinin disease is caused by antibodies that react at low temperatures and causes haemolysis in the liver and spleen. Symptoms are due to anaemia and may include fatigue, jaundice, and dark urine. Diagnosis involves blood tests showing anaemia and antibodies on the direct antiglobulin test. Treatment depends on the severity but may include
This document discusses hemolytic disorders and provides details on various types. It begins with definitions of hemolytic disorder and hemolytic anemia. It then covers topics like hemopoiesis, regulation of hemopoiesis, the red blood cell, pathophysiology of hemolysis, classification of hemolytic anemias, clinical presentation, laboratory evaluation, red blood cell morphology, immune hemolytic anemia, drug and toxin induced hemolytic anemia, hereditary hemolytic disorders like G6PD deficiency and sickle cell disease, and traumatic hemolysis. In summary, it provides a comprehensive overview of the causes, pathophysiology, clinical features and laboratory findings of different hemolytic disorders.
Approach to Autoimmune Hemolytic AnemiaGayathri Nair
This document discusses different types of autoimmune hemolytic anemias (AIHA). It begins by defining autoimmunity and describing the main types of AIHA - warm, cold agglutinin disease, and paroxysmal cold hemoglobinuria. For each type, it covers characteristics, pathophysiology, clinical findings, laboratory evaluation, therapy and key differences. Warm AIHA is the most common and can be primary or associated with other diseases. Cold agglutinin disease usually affects the elderly and involves cold agglutinins while paroxysmal cold hemoglobinuria is typically post-viral and involves Donath-Landsteiner antibodies. Therapy depends on severity and underlying cause but may include corticosteroids
1) Autoimmune hemolytic anemia (AIHA) is caused by antibodies that target a person's own red blood cells. There are warm and cold types classified by the temperature at which the autoantibodies react.
2) Warm AIHA is caused by IgG antibodies that react at 37°C and cause intravascular hemolysis. Cold agglutinin disease (CAD) and paroxysmal cold hemoglobinuria (PCH) are caused by IgM or IgG antibodies that react at cold temperatures and cause extravascular or intravascular hemolysis.
3) Treatment depends on the type and severity of AIHA. Supportive care includes transfusion and keeping patients warm. Corticosteroids
Cold agglutinin disease (CAD) is a rare autoimmune hemolytic anemia caused by cold-reactive antibodies that agglutinate and lyse red blood cells at cold temperatures. It most often affects elderly women and can be associated with infections or malignancies. Clinical manifestations include anemia and acrocyanosis of the extremities in cold temperatures. Diagnosis involves detection of high-titer cold agglutinins and a positive direct Coombs test. Management focuses on avoiding cold, transfusions using a blood warmer, immunosuppressants in severe cases, and addressing any underlying condition.
Type II hypersensitivity reactions involve antibody-mediated destruction of cells through three main mechanisms: complement-mediated cell lysis, antibody-dependent cell-mediated cytotoxicity (ADCC), and target cell dysfunction. Complement-mediated lysis results from membrane attack complex formation following complement activation by antigen-antibody complexes. ADCC occurs when antibodies bind to cell surfaces and recruit natural killer cells to induce apoptosis. Target cell dysfunction involves antibodies altering cell surface receptors and physiology rather than directly killing cells, as seen in Graves' disease and myasthenia gravis. Examples provided include autoimmune hemolytic anemia, hemolytic disease of the newborn, Goodpasture syndrome, and drug-induced thrombocytopenia.
Child with pallor & jaundice (hemolytic anemia)Safia Sky
This document discusses causes of pallor and jaundice in a child, including hereditary spherocytosis, glucose-6-phosphate dehydrogenase deficiency, sickle cell anemia, thalassemia, and autoimmune hemolytic anemia. It provides details on the mechanisms, clinical presentations, investigations, and management of each condition. Hereditary spherocytosis is caused by a red blood cell membrane defect, resulting in destruction in the spleen. Thalassemia and sickle cell anemia are hemoglobinopathies caused by genetic defects in hemoglobin production or structure. Autoimmune hemolytic anemia occurs when antibodies destroy red blood cells. Distinguishing features, treatments including transfusions, splenectomy, and
Autoimmune hemolytic anemia (AIHA) is caused by antibodies against a person's own red blood cells, leading to their premature destruction and anemia. There are two main types - warm AIHA caused by IgG antibodies active at body temperature, and cold AIHA caused by IgM antibodies. Symptoms include jaundice and fatigue from anemia. Diagnosis involves blood tests showing low red blood cell counts and the presence of antibodies coating red blood cells. Treatment focuses on immunosuppression with corticosteroids or other drugs to reduce antibody levels and blood transfusions to manage anemia.
Hemolytic anemia is a condition where red blood cells are destroyed and removed from circulation prematurely. There are many causes of hemolytic anemia including inherited disorders like sickle cell anemia and enzyme deficiencies, immune mediated destruction of red blood cells, infections, toxins and mechanical trauma. Hemolytic anemias can be classified based on location of hemolysis (intravascular or extravascular), source of defect (intracorpuscular or extracorpuscular), and mode of onset (hereditary or acquired). Common symptoms include paleness, fatigue, fever and signs of hemoglobin in urine, blood or stool.
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kol...rightmanforbloodline
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Versio
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
TEST BANK For An Introduction to Brain and Behavior, 7th Edition by Bryan Kolb, Ian Q. Whishaw, Verified Chapters 1 - 16, Complete Newest Version
These lecture slides, by Dr Sidra Arshad, offer a quick overview of the 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 lead (limb II)
4. Differentiate between intervals and segments
5. Enlist some common indications for obtaining an ECG
6. Describe the flow of current around the heart during the cardiac cycle
7. Discuss the placement and polarity of the leads of electrocardiograph
8. Describe the normal electrocardiograms recorded from the limb leads and explain the physiological basis of the different records that are obtained
9. Define mean electrical vector (axis) of the heart and give the normal range
10. Define the mean QRS vector
11. Describe the axes of leads (hexagonal reference system)
12. Comprehend the vectorial analysis of the normal ECG
13. Determine the mean electrical axis of the ventricular QRS and appreciate the mean axis deviation
14. Explain the concepts of current of injury, J point, and their significance
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. Chapter 3, Cardiology Explained, https://www.ncbi.nlm.nih.gov/books/NBK2214/
7. ECG Basics, http://www.nataliescasebook.com/tag/e-c-g-basics
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Osteoporosis - Definition , Evaluation and Management .pdfJim Jacob Roy
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In this document , a brief outline of osteoporosis is given , including the risk factors of osteoporosis fractures , the indications for testing bone mineral density and the management of osteoporosis
Rasamanikya is a excellent preparation in the field of Rasashastra, it is used in various Kushtha Roga, Shwasa, Vicharchika, Bhagandara, Vatarakta, and Phiranga Roga. In this article Preparation& Comparative analytical profile for both Formulationon i.e Rasamanikya prepared by Kushmanda swarasa & Churnodhaka Shodita Haratala. The study aims to provide insights into the comparative efficacy and analytical aspects of these formulations for enhanced therapeutic outcomes.
Promoting Wellbeing - Applied Social Psychology - Psychology SuperNotesPsychoTech Services
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Integrating Ayurveda into Parkinson’s Management: A Holistic ApproachAyurveda ForAll
Explore the benefits of combining Ayurveda with conventional Parkinson's treatments. Learn how a holistic approach can manage symptoms, enhance well-being, and balance body energies. Discover the steps to safely integrate Ayurvedic practices into your Parkinson’s care plan, including expert guidance on diet, herbal remedies, and lifestyle modifications.
share - Lions, tigers, AI and health misinformation, oh my!.pptxTina Purnat
• Pitfalls and pivots needed to use AI effectively in public health
• Evidence-based strategies to address health misinformation effectively
• Building trust with communities online and offline
• Equipping health professionals to address questions, concerns and health misinformation
• Assessing risk and mitigating harm from adverse health narratives in communities, health workforce and health system
Histololgy of Female Reproductive System.pptxAyeshaZaid1
Dive into an in-depth exploration of the histological structure of female reproductive system with this comprehensive lecture. Presented by Dr. Ayesha Irfan, Assistant Professor of Anatomy, this presentation covers the Gross anatomy and functional histology of the female reproductive organs. Ideal for students, educators, and anyone interested in medical science, this lecture provides clear explanations, detailed diagrams, and valuable insights into female reproductive system. Enhance your knowledge and understanding of this essential aspect of human biology.
2. Causes of Acquired hemolytic anemias
a. Mechanical
(1) Macroangiopathic (march hemoglobinuria, artificial heart valves)
(2) Microangiopathic (disseminated intravascular coagulation, DIC; thrombotic
thrombocytopenic purpura, TTP; vasculitis)
(3) Parasites and microorganisms (malaria, bartonellosis, babesiosis, Clostridium welchii, etc.)
b. Antibody-mediated
(1) Warm-type autoimmune hemolytic anemia
(2) Cryopathic syndromes (cold agglutinin disease, paroxysmal cold hemoglobinuria,
cryoglobulinemia)
(3) Transfusion reactions (immediate and delayed)
c. Hypersplenism
d. Red cell membrane disorders
(1) Spur cell hemolysis
(2) Acquired acanthocytosis and acquired stomatocytosis, etc.
e. Chemical injury and complex chemicals (arsenic, copper, chlorate, spider, scorpion, and
snake venoms, etc.)
f. Physical injury (heat, oxygen, radiation)
G. PNH
3. Classification of AIHA
Immune
• Autoimmune
– Warm Ab type
– Cold Ab type
• Alloimmune
– Hemolytic transfusion reactions
– Hemolytic disease of the newborn
– Allografts, especially marrow transplantation
• Drug associated
4. Hemolytic Anemia Resulting from
Immune Injury
• Autoimmune HA is characterized by 2 main
features:
1. shortened RBC survival and
2. presence of autoAbs directed against autologous
RBCs.
• A positive direct antiglobulin test (DAT, also known
as the Coombs test) is essential for diagnosis.
5. • Most patients with AHA (80%) exhibit warm-
reactive antibodies of the IgG isotype.
• Most of the remainder of patients exhibit cold-
reactive autoAbs. Two types of cold-reactive
autoAbs to RBCs are recognized:
Cold agglutinins (IgM)
Cold hemolysins (IgG)
6. • About half of patients with AHA have no underlying
associated disease (primary).
7. Classification of Hemolytic Anemia as a Result of
Immune Injury
I. Warm-autoantibody type:
autoAb maximally active at body temperature (37°C).
A. Primary or idiopathic warm AHA
B. Secondary warm AHA
1. Associated with lymphoproliferative disorders (e.g., HD, lymphoma)
2. Associated with the rheumatic disorders, particularly SLE
3. Associated with certain nonlymphoid neoplasms (e.g., ovarian
tumors)
4. Associated with certain chronic inflammatory diseases (e.g.,
ulcerative colitis)
5. Associated with ingestion of certain drugs (e.g., -methyldopa)
8. II. Cold-autoantibody type:
autoantibody optimally active at temperatures <37°C .
A. Mediated by cold agglutinins
1. Idiopathic (primary) chronic cold agglutinin disease
2. Secondary cold agglutinin hemolytic anemia
a. Postinfectious (e.g., Mycoplasma pneumoniae or infectious
mononucleosis)
b. Associated with malignant B cell lymphoproliferative disorder
B. Mediated by cold hemolysins
1. Idiopathic (primary) paroxysmal cold hemoglobinuria (very rare)
2. Secondary
a. Donath-Landsteiner hemolytic anemia, usually associated with an acute
viral syndrome in children (relatively common)
b. Congenital or tertiary syphilis in adults (very rare)
9. III. Mixed cold and warm autoantibodies
A. Primary or idiopathic mixed AHA
B. Secondary mixed AHA
1. Associated with the rheumatic disorders, particularly SLE
IV. Drug-immune hemolytic anemia
A. Hapten or drug adsorption mechanism
B. Ternary (immune) complex mechanism
C. True autoantibody mechanism
10. Warm-antibody AHA
Epidemiology
• The frequency of primary warm-antibody AHA is 50%
of all cases.
• Careful follow up of patients with primary AHA is
essential,
– because hemolytic anemia may be the presenting finding
in a patient who subsequently develops overt evidence of
an underlying disorder.
• Warm-antibody AHA has been diagnosed in people of
all ages, from infants to the elderly. The majority of
patients are older than 40 years.
11. Etiology
• The etiology of AHA is unknown.
• In warm-antibody AHA, the autoantibodies that
mediate RBC destruction are predominantly IgG
with high binding affinity for RBCs at 37°C.
• As a result, the major share of plasma autoantibody
is bound to the patient's circulating RBCs.
12. • Normal subjects sometimes have a positive DAT
when they volunteer to donate blood (one in
10,000).
• The positive DAT in these normal donors often
results from warm-reacting IgG autoAbs.
• Although many of these donors remain Coombs
positive without developing overt hemolytic
anemia, a few have been documented to
develop AHA.
13. Pathogenesis
• In warm-antibody AHA, the patient's RBCs typically
are coated with IgG autoAbs with or without
complement proteins.
• autoAb-coated RBCs are trapped by macrophages in
the spleen and, to a lesser extent, by Kupffer cells in
the liver.
• The process leads to generation of spherocytes and
fragmentation and ingestion of antibody-coated
RBCs.
14. • The macrophage has surface receptors for
– the Fc region of IgG and
– opsonic fragments of C3 (C3b and C3bi) and C4b.
• When present together on the RBC surface, IgG
and C3b/C3bi appear to act cooperatively as
opsonins to enhance trapping and phagocytosis.
15. Interaction of a trapped RBC with splenic macrophages
may result in:
1. Phagocytosis of the entire cell.
2. More commonly, a type of partial phagocytosis results
in spherocyte formation.
– portions of RBC membrane are internalized by the
macrophage. Because membrane is lost in excess of
contents, the noningested portion of the RBC assumes a
spherical shape.
– Spherical RBCs are more rigid than normal RBCs and are
fragmented further and destroyed in the spleen.
16. • Spherocytosis is a consistent and diagnostically
important hallmark of AHA,
• and the degree of spherocytosis correlates well with
the severity of hemolysis.
19. • Direct complement-mediated hemolysis with
hemoglobinuria is unusual in warm-antibody AHA.
• GPI-linked erythrocyte membrane proteins, such as
DAF(CD55) and HRF (CD59), may limit the action of
autologous complement on autoAb-coated RBCs.
20. • DAF inhibits the formation and function of
cell-bound C3-converting enzyme, thus
indirectly limiting formation of C5-converting
enzyme.
• HRF, on the other hand, impedes C9 binding
and formation of the C5b–9 membrane attack
complex.
21. Autoimmune hemolytic anemia: Warm antibody type (WAIHA)
Reaction at normal temperature (37 C)
= Antibody usually IgG type
= Antigenic determinant
Cell membrane
modified
Cell becomes
microspherocytes
With consequences similar to
hereditary spherocytosis-
early sequestration in spleen (RE)
22. Clinical Features of warm AHA
• Presenting: Usually anemia, occasionally jaundice.
• Symptom onset usually is slow and insidious, but
occasionally sudden onset of severe anemia and jaundice.
• In secondary AHA, the symptoms and signs of the
underlying disease may overshadow the hemolytic anemia.
• In idiopathic AHA, physical examination may be normal or
only modest splenomegaly.
• However, in very severe cases, patients may present with
fever, pallor, jaundice, hepatosplenomegaly, hyperpnea,
tachycardia, angina, or heart failure.
23. Laboratory Features
General Features
i. By definition, patients with AHA present with
anemia,
the severity of which ranges from life threatening to
very mild.
24. • Patients with warm-antibody AHA may present with:
hematocrit levels less than 10 percent or
compensated hemolytic anemia and a near-normal
hematocrit.
• For the latter patients, the predominant laboratory
features are:
1. an increased reticulocyte count and
2. a positive DAT.
25. ii. Platelet counts typically are normal.
Rarely, severe immune thrombocytopenia is
associated with warm-antibody AHA. This is
termed Evans syndrome.
26. Cold agglutinin disease
Epidemiology
• Cold agglutinin disease is less common than
warm-antibody AHA, only 10 to 20 % of all
cases of AHA.
• Paroxysmal cold hemoglobinuria constitutes 2
to 5 % of all cases of AHA.
27. Overview
• Cryopathic hemolytic syndromes are caused
by autoantibodies that bind RBCs optimally at
temperatures less than 37°C and usually less
than 31°C.
28. • Two major types of "cold antibody" may produce
AHA:
1. Cold agglutinins mediate cold agglutinin disease.
2. The Donath-Landsteiner autoAb, which is not an
agglutinin but a potent hemolysin, mediates
paroxysmal cold hemoglobinuria.
29. • In both cryopathic syndromes, the complement
system plays a major role in RBC injury;
• however, much greater potential exists for direct
intravascular hemolysis than in warm-antibody–
mediated AHA.
30. i. Cold agglutinin disease: chronic AHA in which the
autoantibody directly agglutinates human RBCs at
temperatures below body temperature, maximally
at 0 to 5°C.
• Cold agglutinins typically are IgM, although
occasionally may be other Igs.
31. ii. The Donath-Landsteiner antibody is responsible
for complement-mediated hemolysis in:
PCH, a very rare form of AHA in adults. The
disorder is characterized by recurrent episodes of
massive hemolysis following cold exposure.
more commonly in children as an acute, self-
limited single postviral episode hemolytic process.
– Thus, rather than PCH, a proposed term for this latter
entity is Donath-Landsteiner hemolytic anemia
32. Pathogenesis
• Most cold agglutinins are unable to agglutinate
RBCs at temperatures higher than 30°C.
• The highest temperature at which these antibodies
cause detectable agglutination is termed the
thermal amplitude.
• The value varies considerably among patients.
• Generally, patients with cold agglutinins with higher
thermal amplitudes have a greater risk for cold
agglutinin disease.
33. • The pathogenicity of a cold agglutinin depends upon
its ability to bind host RBCs and to activate
complement. This process is called complement
fixation.
• Although in vitro agglutination of the RBCs may be
maximal at 0 to 5°C, complement fixation by these
antibodies may occur optimally at 20 to 25°C and may
be significant at even higher physiologic temperatures.
• Agglutination is not required for the process.
34. • Cold agglutinins may bind to RBCs in superficial
vessels of the extremities, where the temperature
generally ranges between 28 and 31°C.
• Cold agglutinins of high thermal amplitude may
cause RBCs to aggregate at this temperature,
thereby impeding RBC flow and producing
acrocyanosis.
• In addition, the RBC-bound cold agglutinin may
activate complement via the classic pathway.
35. • Once activated complement proteins are deposited onto the RBC
surface,
the cold agglutinin must remain bound to the RBCs for hemolysis to
occur.
Instead, the cold agglutinin may dissociate from the RBCs at the higher
temperatures in the body core and again be capable of binding other
RBCs at the lower temperatures in the superficial vessels.
• As a result,
patients with cold agglutinins of high thermal amplitude tend toward a
sustained hemolytic process and acrocyanosis.
In contrast, patients with antibodies of lower thermal amplitude require
significant chilling to initiate complement-mediated injury of RBCs.
36. • This sequence may result in a burst of hemolysis
with hemoglobinuria.
• Cold agglutinins of the IgA isotype, an isotype that
does not fix complement, may cause acrocyanosis
but not hemolysis.
37. Autoimmune hemolytic anemia : Cold antibody type
Reaction at temperatures usually below 30 C
they occur in peripheral circulation and in cold weather.
Antibody
combines
with RBC
Reactions
= Antigenic determinant
Agglutination
Clinically present as painful
hand and feet
Amboceptor effect
Ag/Ab activates complement
Acute intravascular hemolysis
usually of IgM type
38. • Complement fixation by cold agglutinins may effect
RBC injury by two major mechanisms:
(1) direct lysis and
(2) opsonization for hepatic and splenic macrophages.
39. 1. Direct lysis requires propagation of the full C1-
to-C9 sequence on the RBC membrane leading
to intravascular hemolysis with hemoglobinemia
and hemoglobinuria.
• Intravascular hemolysis of this severity is
relativey rare because GPI-linked RBC membrane
proteins (DAF and HRF) protect against injury by
autologous complement components.
40. 2. Thus, the complement sequence on many RBCs is
completed only through the early steps, leaving opsonic
fragments of C3 (C3b/C3bi) and C4 (C4b) on the cell
surface.
• Activated macrophages may ingest C3b-coated particles
avidly.
• Accordingly, RBCs heavily coated with C3b (and/or C3bi)
may be removed from the circulation by macrophages
either in the liver or, to a lesser extent, the spleen.
• The trapped RBCs may be ingested entirely or released
back into the circulation as spherocytes after losing
plasma membrane.
41. Clinical features
• Most patients with cold agglutinin hemolytic anemia
have chronic hemolytic anemia with or without
jaundice. In other patients, the principal feature is
episodic, acute hemolysis with hemoglobinuria
induced by chilling.
• Acrocyanosis and other cold-mediated vasoocclusive
phenomena affecting the fingers, toes, nose, and ears
are associated with sludging of RBCs in the cutaneous
microvasculature.
• The hemolysis is self-limited, lasting 1 to 3 weeks
• Splenomegaly, a characteristic finding in
lymphoproliferative diseases or infectious
mononucleosis, may be observed in idiopathic cold
agglutinin disease.
42. • In paroxysmal cold hemoglobinuria, constitutional
symptoms are prominent during a paroxysm.
• A few minutes to several hours after cold exposure, the
patient develops aching pains in the back or legs,
abdominal cramps, and perhaps headaches.
• Chills and fever usually follow.
• The first urine passed after onset of symptoms typically
contains hemoglobin.
• The constitutional symptoms and hemoglobinuria
generally last a few hours.
• Raynaud phenomenon and cold urticaria sometimes
occur during an attack; jaundice may follow.
43. The blood film in acute paroxysmal cold
haemoglobinuria showing spherocytosis and
red cell agglutination.
44. Cold agglutinins
• Antibody not detected by the DAT because
they are readily dissociated from the RBCs
• Complement components however are more
securely bound
• Majority of cold agglutinins are anti I/i
45. • Cold agglutinins are distinguished by their ability to
directly agglutinate saline-suspended human RBCs at
low temperature, maximally at 0 to 5°C. The reaction is
reversible by warming.
• The DAT result is positive with anticomplement
reagents. The antibody itself, however, is not detected
by the DAT because the cold agglutinins readily
dissociate from the RBCs both in vivo and during the
washing steps of the standard antiglobulin procedure.
46. Drug mediated immune injury
• Major Mechanisms of Drug-Related Hemolytic
Anemia and Positive Direct Antiglobulin Tests:
1. Three mechanisms of drug-mediated
immune injury to RBCs.
2. Mediate protein adsorption to RBCs by
nonimmune mechanisms, but RBC injury
does not occur.
47. Drug-induced immune haemolytic
anaemias
Drugs may cause immlme haemolytic anaemias via three mechanisms:
1. Antibody directed against a drug-red cell membrane complex (e.g.
penicillin, ampicillin);
2. Deposition of complement via a drug-protein (antigen)-antibody
complex onto the red cell surface (e.g. quinidine, rifampicin); or
3. A true autoimmune haemolytic anaemia in which the role of the
drug is unclear (e.g. methyldopa).
In each case, the haemolytic anaemia gradually disappears when the
drug is discontinued but with methyldopa the autoantibody may
persist for several months.
48. Nonimmunologic Protein
Adsorption
Autoantibody Binding
Ternary Complex
Formation(Drug–
Antibody–Target Cell
Interaction)
Hapten/Drug Adsorption
Cephalothin
-Methyldopa
Quinidine
Penicillin
Prototype drug
Possibly alters red cell
membrane
Induces formation of
antibody to native red
cell antigen
Forms ternary complex
with antibody and red
cell membrane
component
Binds to red cell
membrane
Role of drug
Absent
Absent
Present
Present
Antibody to
drug
49.
50. • Significantly, not all patients receiving high-
dose penicillin develop a positive DAT reaction
or hemolytic anemia because only a small
proportion of such individuals produce the
requisite antibody.
51. Clinical features
• A careful history of drug exposure should be
obtained from all patients with hemolytic
anemia and/or a positive DAT.
• As in idiopathic AHA, the clinical picture in
drug-immune hemolytic anemia is quite
variable. The severity of symptoms largely
depends upon the rate of hemolysis.
52. Laboratory features of IHA
• General features
I. Blood film:
1. Polychromasia indicates a reticulocytosis.
2. Spherocytes are seen in patients with moderate to severe
hemolytic anemia. Hereditary spherocytosis should be
excluded.
3. RBC fragments, nucleated RBCs, and occasionally
erythrophagocytosis by monocytes may be seen in severe
cases.
4. Most patients have mild leukocytosis and neutrophilia.
5. Patients with cold-antibody AHA may exhibit RBC
autoagglutination in the blood film and in chilled
anticoagulated blood.
53.
54. II. The reticulocyte count usually is elevated.
• Nevertheless, early in the course of the disease,
more than one third of all patients may have
transient reticulocytopenia despite a normal or
hyperplastic erythroid marrow. The mechanism is
unknown
55. III. Marrow examination:
1. erythroid hyperplasia and
2. may provide evidence of an underlying
lymphoproliferative disorder.
56. IV. Hyperbilirubinemia (chiefly unconjugated) is
highly suggestive of hemolytic anemia,
although its absence does not exclude the
diagnosis.
57. V. Urinary urobilinogen is increased regularly, but bile is
not detected in the urine unless serum conjugated
bilirubin is increased.
VI. Usually, serum haptoglobin levels are low, and LDH
levels are elevated.
VII. Hemoglobinuria is encountered in
– rare patients with warm-antibody AHA and hyperacute
hemolysis,
– more commonly in patients with cold agglutinin disease,
and characteristically in patients with PCH
– with drug-immune hemolytic anemia mediated by the
ternary complex mechanism.
58. VIII.Direct Antiglobulin Test Pattern
Diagnosis of AHA or drug-immune hemolytic
anemia requires demonstration of
immunoglobulin and/or complement bound
to the patient's RBCs.
61. • Three possible major patterns of direct
antiglobulin reaction in AHA and drug-immune
hemolytic anemia exist:
(1) RBCs coated with only IgG,
(2) RBCs coated with IgG and complement
components, and
(3) RBCs coated with complement components
without detectable immunoglobulins (When the
RBCs are coated chiefly with complement
proteins, a positive DAT depends upon the
presence of anticomplement (principally anti-C3)
in the antiglobulin reagent.)
62. Therapy
• General: Transfusion.
• Therapy of Warm-Antibody Autoimmune Hemolytic
Anemia:
1. Glucocorticoids
2. Splenectomy
3. Rituximab
Rituximab is a monoclonal antibody directed against the
CD20 antigen expressed on B lymphocytes and used for
treatment of B cell lymphoma. It eliminates B lymphocytes,
including presumably those making autoantibodies to RBCs.
4. Immunosuppressive Drugs
5. Cytotoxic drugs such as cyclophosphamide to suppress
synthesis of autoantibody.
63. • Therapy of Cold-Antibody Hemolytic Anemia
1. Keeping the patient warm, particularly the
patient's extremities, is moderately effective in
providing symptomatic relief.
64. • Therapy of Drug-Immune Hemolytic Anemia
1. Discontinuation of the offending drug often is the only
treatment needed. This measure is essential.
2. the drug need not be discontinued because of a
positive direct antiglobulin reaction alone but only in
the presence of overt hemolytic anemia.
65. Alloimmune Hemolytic Disease of the
Newborn
• Alloimmune hemolytic disease of the fetus and
newborn is caused by the action of transplacentally
transmitted maternal immunoglobulin IgG antibodies
on paternally inherited antigens present on fetal red
cells but absent on the maternal red cells.
• Maternal IgG antibodies bind to fetal red cells, causing
hemolysis. As a consequence of the hemolytic process,
anemia, extramedullary hematopoiesis, and neonatal
hyperbilirubinemia sometimes result in fetal loss or
neonatal death or disability.
66. Definition
erythroblastosis fetalis was caused by immunization
of an Rh-negative mother by the red blood cells
from an Rh-positive fetus.
Antibodies produced by the sensitized mother
crossed the placenta in the next pregnancy and
coated the fetal Rh-positive cells, leading to
hemolysis and thus to anemia, hydrops, and
severe neonatal jaundice secondary to hemolysis.
67. Hemolytic Disease of the New born (HDN)
2. Incompatibilities with in the Rh blood group system
Allo-immune hemolytic anemia
Subsequent pregnancies
Maternal anti-Rh antibodies IgG type
Pass placental barrier
Enter fetal circulation and destroy fetal red cells
(agglutination and hemolysis)
Placenta
Uterus
68. • Postpartum and antepartum anti-D prophylaxis to
prevent Rh sensitization led to the most dramatic
reduction in the incidence of Rh hemolytic disease
of the newborn.
69. • Other than the Rh blood group system
However, the disease has not disappeared, and cases
of HDN resulting from red cell Abs directed toward
Ags other than the Rh blood group system are being
increasingly recognized.
70. Etiology and Pathogenesis
Causative Antibodies
• More than 40 different red cell antigens are associated
with maternal alloimmunization.
• These antibodies can be categorized into three main
classes:
(1) antibodies directed against the D antigen in the Rh
blood group system,
(2) antibodies directed against the A and B antigens, and
(3) antibodies directed against the remaining red cell
antigens (non-D Rh antibodies (c, C, e, E, cc, and Ce)
and antibodies belonging to the Kell, Duffy, Kidd, and
MNS systems ).
71. 1.Rh Hemolytic Disease
• Immunization:
1. Asymptomatic transplacental passage of fetal red cells occurs in 75%of
pregnant women at some time during pregnancy or during labor and
delivery.
2. The presence of D-positive red cells in a D-negative mother initially
provokes a primary immune response that is weak and slow and consists
of IgM antibodies that do not cross the placenta.
3. Subsequently, anti-D IgG antibodies capable of crossing the placenta are
produced.
4. Repeated exposure to Rh-positive fetal red blood cells, as in a second Rh-
positive pregnancy in a sensitized Rh-negative woman, produces a
secondary immune response marked by rapid production of large
amounts of anti-D IgG antibody by maternal memory B lymphocytes.
72. • In the absence of Rh Ig prophylaxis, sensitization
occurs in
– 7 to 16% of women at risk, after delivery of the first Rh-
positive ABO-compatible fetus,
– 2 % after delivery of an ABO-incompatible fetus.
• The reason why most women who are at risk for
development of anti-D are not sensitized is unclear.
73. • Hemolysis
Binding of transplacentally transferred maternal anti-
D IgG Abs to D-antigen sites on the fetal red cell
membrane is followed by
adherence of the coated RBCs to the FcR of
macrophages leading to
extravascular noncomplement-mediated lysis in the
spleen.
74. The blood film of a baby with Rh haemolytic
disease of the newborn showing spherocytosis
75. 2.ABO Hemolytic Disease
• ABO hemolytic disease of the newborn is limited to
mothers who are blood group type O and whose
babies are group A or B.
• Although far more common than Rh hemolytic
disease of the newborn, ABO hemolytic disease of
the newborn usually is mild.
76. • may affect the first-born ABO incompatible infant
because IgG anti-A and anti-B antibodies may be present normally in
group O adults.
• The low incidence of ABO hemolytic disease of the
newborn may be because most anti-A and anti-B antibodies are of
the IgM type incapable of crossing the placenta.
• Only a small proportion of group O individuals produce
anti-A and anti-B of the IgG type that can cross the
placenta.
77. The blood film of a baby
with ABO haemolytic disease of the
newborn showing marked
spherocytosis and an NRBC
78. 3.Hemolytic Disease Caused by Other
Red Cell Antibodies
When the D antibodies are excluded,
• the non-D Rh antibodies (E, C, and c) and
• those belonging to the Kell, Duffy, Kidd, and MNS
systems are most frequently involved.
79. Clinical Features of HDN
• Hallmarks of hemolytic disease of the newborn:
1. Anemia,
2. jaundice, and
3. hepatosplenomegaly
• An important complication of elevated serum
indirect bilirubin in the neonate is bilirubin
encephalopathy (kernicterus)is caused by bilirubin
pigment deposition, leading to neuronal necrosis,
marked by lethargy, poor feeding, and hypotonia.
80. Prevention of HDN
• Transfusion of blood compatible not only with the D
antigen but also with Kell and other Rh antigens for
premenopausal women to prevent alloimmunization.
• Use of Rh Ig is the mainstay of prevention of maternal
D immunization. (Postpartum nonsensitized Rh-
negative women who deliver an Rh-positive infant).
• Every obstetric patient should undergo ABO and RhD
typing and be tested for irregular serum antibodies at
the initial prenatal visit.
81. • However 1.8 % of Rh-negative women
apparently are sensitized from small
transplacental hemorrhages during pregnancy.
• Antepartum Rh Ig prophylaxis at 28 weeks'
gestation (this is the current standard
recommendation in the United States).
82. • The mechanism by which Rh Ig prevents
sensitization to the D antigen is not
understood.
• One theory proposes passively administered
anti-D attaches to the D-antigen sites on Rh-
positive red blood cells in the circulation and
interferes with the host's primary immune
response to the foreign antigen.
83. Hemolytic Anemia Resulting from
Chemical and Physical Agents
1. Arsenic, lead, copper, chlorates, and a variety of other
chemicals can cause severe red cell destruction.
– Arsenic may cause hemolysis by interacting with sulfhydryl
groups.
– Lead inhibits a variety of red cell enzymes, including several
enzymes of porphyrin metabolism and pyrimidine 5'-
nucleotidase. The anemia that it produces is usually not
primarily hemolytic in nature.
– Copper inhibits a number of red cell enzymes and catalyzes the
oxidation of intracellular reduced glutathione (GSH).
– Chlorates produce methemoglobin and Heinz bodies.
2. Many drugs: by poorly defined mechanisms.
3. Animal toxins, such as those of insects, spiders, and snakes.
4. Severe burns, probably as a result of direct damage to
erythrocytes by heat.
84. Hemolytic Anemia Resulting from
Infections with Microorganisms
1. Malaria, Babesia, and Bartonella, which directly invade the
erythrocyte.
• Malaria is probably the most common cause of hemolytic anemia.
• Falciparum malaria, in particular, can cause severe fatal hemolysis
(blackwater fever).
2. Other organisms cause hemolytic anemia by producing a
hemolysin (e.g., Clostridium Welchii),
3. by stimulating an immune response (e.g., Mycoplasma
pneumoniae),
85. Organisms causing haemolytic anemia
1. Cytomegalovirus
2. Epstein-Barr virus
3. Hepatitis A, B, C
4. Human immunodeficiency virus
5. Influenza A virus
6. Parvovirus B19
7. Plasmodium falciparum
8. Salmonella
86. Red cell fragmentation syndromes
• These arise through physical damage to red cells either
1. on abnormal surfaces (e.g. artificial heart valves or
arterial grafts),
2. arteriovenous malformations
3. or as a microangiopathic haemolytic anaemia.
This is caused by red cells passing through abnormal
small vessels due to
– deposition of fibrin associated with DIC or
– platelet adherence as in TTP or
– vasculitis as PAN (endoth damage).
87.
88. • Microangiopathic hemolytic anemia:
In childhood, the commonest cause is
enteric infection, most often by a verocytotoxin
secreting Escherichia coli, resulting in HUS.
In adults, the commonest causes are
idiopathic TTP,
pregnancy-associated hypertension
carcinoma.
89. • Blood film and count
1. microspherocytes, keratocytes and schistocytes
2. polychromasia.
3. In microangiopathic HA, there is associated
thrombocytopenia and large platelets.
90. • In the postdiarrhoeal HUS of childhood there is
leucocytosis and neutrophilia,
– the severity of which correlates with associated renal
damage.
• Blood films of microangiopathic HA and of
haemolytic anaemia caused by large vessel or
valvular diseases or prostheses cannot be readily
distinguished.
91. • Haemolysis in the microangiopathic and mechanical
haemolytic anaemias is intravascular the resultant
haemoglobinuria can lead to complicating iron deficiency,
the features of which are then apparent on the blood film.
• It should be noted that, although red cell fragmentation is
often a feature of chronic DIC, it is quite uncommon in
acute DIC. Examination of a blood film is therefore not a
useful screening test if this diagnosis is suspected.
• Conversely, blood film examination is very important if TTP
or HELLP syndrome is suspected.
92. Further tests
• The speedy recognition of HUS by the lab is of critical importance
for optimal management.
• assess the severity of haemolysis:
– Bilirubin and
– LDH estimations
– reticulocyte count
• Demonstrate intravascular haemolysis in chronic mild cases:
– detection of haemosiderin in urinary sediment
93. March haemoglobinuria
• This is caused by damage to red cells between
the small bones of the feet, usually during
prolonged marching or running. The blood
film does not show fragments.
95. The blood film of an Afro-
Caribbean patient with iron
deficiency as a complication of
mechanical haemolysis from a
defective prosthetic valve. The film
shows fragments, hypochromia,
microcytosis and one target cell. The
patient also had haemoglobin C trait.
96. Several keratocytes (in microangiopathic haemolytic anaemia);
keratocytes are sometimes called ‘bite cells’
98. The blood film of a patient with PNH showing polychromatic
macrocytes
99. The blood film of a patient with terminal liver disease of
unknown aetiology showing numerous acanthocytes (‘spur cell’
haemolytic an)
100. Hypersplenism
Hypersplenism usually is associated with the
triad of:
1. splenomegaly,
2. blood cytopenias, and
3. compensatory marrow hyperplasia;
it is characteristically corrected by splenectomy.
102. Laboratory Features
• The blood cell morphology usually is normal,
although a few spherocytes may result from
metabolic conditioning of red cells during
repeated slow transits through the expanded
red pulp.
103. Miscellaneous causes of acquired
haemolytic anaemia
Haemolytic anaemia with
• a negative direct and indirect antiglobulin test
and with
• no specific morphological features
has been described as a transient phenomenon,
sometimes accompanied by
thrombocytopenia, in patients with hepatitis C
infection.
104.
105. Anemia Algorithm
• Patient with anemia and increased reticulocyte count-
What is the result of a Coomb’s test ??
Extrinsic red
cell defect
Vessel Valve
Toxin
Negative Positive
(autoimmune hemolytic anemia)
Intrinsic red
cell defect
Membrane
Hemoglobin
Cytoplasm
“Warm” “Cold”
108. • MCQ 5 An increased cold agglutinin titre is a
recognized feature of
(a) Non-Hodgkin’s lymphoma
(b) Paroxysmal nocturnal haemoglobinuria
(c) Mycoplasma pneumoniae infection
(d) Alpha-methyl dopa-induced haemolytic
anaemia
(e) Infectious mononucleosis
109. • MCQ 8 A positive direct antiglobulin
(Coombs’) test is characteristic of
(a) Hereditary spherocytosis
(b) Hereditary elliptocytosis
(c) Haemolytic disease of the newborn
(d) Delayed haemolytic transfusion reaction
(e) Warm autoimmune haemolytic anaemia
110. • Q10 The following are usually associated
with spherocytes in the blood film:
1 Severe iron deficiency anaemia
2 Combined deficiency of vitamin B12 and folic
acid
3 Severe burns
4 Autoimmune haemolytic anaemia
5 Polycythaemia rubra vera