Hemolytic Anemia

Epidemiology and Etiology

Epidemiology

• 5% of all cases of anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types 
• Hereditary causes present early in life.
• Autoimmune hemolytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types ( AIHA AIHA Autoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self rbcs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia) is more common in middle-aged and older adults.
• Males are predominantly affected by X-linked X-linked Genetic diseases that are linked to gene mutations on the X chromosome in humans or the X chromosome in other species. Included here are animal models of human X-linked diseases. Common Variable Immunodeficiency (CVID) hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis.

Causes

Intravascular hemolysis

• Mechanical (mechanical prosthetic valves, hemodialysis Hemodialysis Procedures which temporarily or permanently remedy insufficient cleansing of body fluids by the kidneys. Crush Syndrome)
• Transfusion reaction
• Paroxysmal nocturnal hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria Paroxysmal nocturnal hemoglobinuria (PNH) is a rare but serious acquired hemolytic anemia with periodic exacerbations. This anemia is caused by nonmalignant clonal expansion of ≥ 1 hematopoietic stem cells that have acquired a somatic mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene. Paroxysmal Nocturnal Hemoglobinuria
• Infection ( sepsis Sepsis Systemic inflammatory response syndrome with a proven or suspected infectious etiology. When sepsis is associated with organ dysfunction distant from the site of infection, it is called severe sepsis. When sepsis is accompanied by hypotension despite adequate fluid infusion, it is called septic shock. Sepsis and Septic Shock)
• Microangiopathic ( hemolytic uremic syndrome Hemolytic uremic syndrome A syndrome that is associated with microvascular diseases of the kidney, such as renal cortical necrosis. It is characterized by hemolytic anemia; thrombocytopenia; and acute renal failure. Hypocoagulable Conditions, thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura Thrombotic thrombocytopenic purpura (TTP) is a life-threatening condition due to either a congenital or an acquired deficiency of ADAMTS-13, a metalloproteinase that cleaves multimers of von Willebrand factor (VWF). The large multimers then aggregate excessive platelets resulting in microvascular thrombosis and an increase in consumption of platelets. Thrombotic Thrombocytopenic Purpura, disseminated intravascular coagulation Disseminated intravascular coagulation Disseminated intravascular coagulation (DIC) is a condition characterized by systemic bodywide activation of the coagulation cascade. This cascade results in both widespread microvascular thrombi contributing to multiple organ dysfunction and consumption of clotting factors and platelets, leading to hemorrhage. Disseminated Intravascular Coagulation)

Extravascular hemolysis

• Intrinsic hemolytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (abnormal membrane structure or shape of the RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)
  • Membrane defect:
    • Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis
  • Enzyme deficiency:
    • G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency
    • Pyruvate Pyruvate Derivatives of pyruvic acid, including its salts and esters. Glycolysis kinase deficiency
  • Hemoglobinopathy:
    • Sickle cell anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
    • Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia
• Extrinsic hemolytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types (coated RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology)
  • AIHA AIHA Autoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self rbcs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia
    • Cold agglutinin anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
    • Warm agglutinin anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types
  • ABO incompatibility ABO incompatibility Hemolytic Disease of the Fetus and Newborn, Rhesus incompatibility Rhesus Incompatibility Hemolytic Disease of the Fetus and Newborn
  • Drugs (e.g., rifampin Rifampin A semisynthetic antibiotic produced from streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits dna-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. Epiglottitis, nonsteroidal anti-inflammatory drugs, penicillin Penicillin Rheumatic Fever)
  • Infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease ( malaria Malaria Malaria is an infectious parasitic disease affecting humans and other animals. Most commonly transmitted via the bite of a female Anopheles mosquito infected with microorganisms of the Plasmodium genus. Patients present with fever, chills, myalgia, headache, and diaphoresis. Plasmodium/Malaria), gas gangrene Gas gangrene Gas gangrene, also known as clostridial myonecrosis, is a life-threatening muscle and soft tissue infection that usually develops after traumatic inoculation with Clostridium perfringens (C. perfringens), but can also develop spontaneously in association with other Clostridium species. Gas Gangrene
  • Hypersplenism Hypersplenism Condition characterized by splenomegaly, some reduction in the number of circulating blood cells in the presence of a normal or hyperactive bone marrow, and the potential for reversal by splenectomy. Splenomegaly

Pathophysiology

Hemolytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types is a normocytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types.

• Extravascular hemolysis
  • Normal breakdown of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology occurs in the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy every 120 days.
  • An increased splenic clearance occurs in:
    • IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis/ IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions tagging of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology in auto-immune conditions
    • Intrinsically defective RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology: sickle cell, spherocytosis, G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency
  • Increased breakdown results in increased heme which is converted into bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism.
  • Excessive bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism →  unconjugated bilirubinemia and jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
  • Iron Iron A metallic element with atomic symbol fe, atomic number 26, and atomic weight 55. 85. It is an essential constituent of hemoglobins; cytochromes; and iron-binding proteins. It plays a role in cellular redox reactions and in the transport of oxygen. Trace Elements from the breakdown also begins to accumulate in the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy.
  • Excessive functioning and clearance results in splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly.
• Intravascular hemolysis
  • RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology become fragmented when passing through narrowed vessel lumen (microangiopathic) or prosthetic valves (macroangiopathic).
  • Splitting Splitting Defense Mechanisms of the RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology results in schistocytes Schistocytes Hemolytic Uremic Syndrome in the smear.
  • Hemoglobin in the bloodstream binds to haptoglobin.
  • Excessive heme also presents in the urine as hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma/ hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions.

Clinical Manifestations

• Jaundice Jaundice Jaundice is the abnormal yellowing of the skin and/or sclera caused by the accumulation of bilirubin. Hyperbilirubinemia is caused by either an increase in bilirubin production or a decrease in the hepatic uptake, conjugation, or excretion of bilirubin. Jaundice
• Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly (mainly in extravascular causes)
• Cholelithiasis Cholelithiasis Cholelithiasis (gallstones) is the presence of stones in the gallbladder. Most gallstones are cholesterol stones, while the rest are composed of bilirubin (pigment stones) and other mixed components. Patients are commonly asymptomatic but may present with biliary colic (intermittent pain in the right upper quadrant). Cholelithiasis
• Hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma/ hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions
• Symptoms of anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types:
  • Shortness of breath Shortness of breath Dyspnea is the subjective sensation of breathing discomfort. Dyspnea is a normal manifestation of heavy physical or psychological exertion, but also may be caused by underlying conditions (both pulmonary and extrapulmonary). Dyspnea
  • Fatigue Fatigue The state of weariness following a period of exertion, mental or physical, characterized by a decreased capacity for work and reduced efficiency to respond to stimuli. Fibromyalgia
  • Syncope Syncope Syncope is a short-term loss of consciousness and loss of postural stability followed by spontaneous return of consciousness to the previous neurologic baseline without the need for resuscitation. The condition is caused by transient interruption of cerebral blood flow that may be benign or related to a underlying life-threatening condition. Syncope
  • Tachycardia Tachycardia Abnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia. Sepsis in Children
• Sickle cell patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with acute pain Pain An unpleasant sensation induced by noxious stimuli which are detected by nerve endings of nociceptive neurons. Pain: Types and Pathways syndromes.
• Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency and patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship with paroxysmal nocturnal hemoglobinuria Paroxysmal Nocturnal Hemoglobinuria Paroxysmal nocturnal hemoglobinuria (PNH) is a rare but serious acquired hemolytic anemia with periodic exacerbations. This anemia is caused by nonmalignant clonal expansion of ≥ 1 hematopoietic stem cells that have acquired a somatic mutation of the phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIG-A) gene. Paroxysmal Nocturnal Hemoglobinuria present with episodic hematuria Hematuria Presence of blood in the urine. Renal Cell Carcinoma.
• AIHA AIHA Autoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self rbcs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia (cold) patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with cold sensitivity.

Diagnostics

General

• ↓ Hb Hb The oxygen-carrying proteins of erythrocytes. They are found in all vertebrates and some invertebrates. The number of globin subunits in the hemoglobin quaternary structure differs between species. Structures range from monomeric to a variety of multimeric arrangements. Gas Exchange, N-MCV, N-MCH
• Reticulocytosis (≤ 3%)
• Decreased hematocrit Hematocrit The volume of packed red blood cells in a blood specimen. The volume is measured by centrifugation in a tube with graduated markings, or with automated blood cell counters. It is an indicator of erythrocyte status in disease. For example, anemia shows a low value; polycythemia, a high value. Neonatal Polycythemia
• Increased lactate dehydrogenase Lactate Dehydrogenase Osteosarcoma
• Decreased haptoglobin
• Increased unconjugated bilirubin Bilirubin A bile pigment that is a degradation product of heme. Heme Metabolism

Intravascular hemolysis

• Hemoglobinuria Hemoglobinuria The presence of free hemoglobin in the urine, indicating hemolysis of erythrocytes within the vascular system. After saturating the hemoglobin-binding proteins (haptoglobins), free hemoglobin begins to appear in the urine. Transfusion Reactions/hemosiderinuria: hemoglobin that exceeds haptoglobin binding (most sensitive) 
• Schistocytes Schistocytes Hemolytic Uremic Syndrome on blood film 
• Indirect Coombs test (positive for complements)

Extravascular hemolysis

• Direct Coombs test (positive for IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions/ IgG IgG The major immunoglobulin isotype class in normal human serum. There are several isotype subclasses of igg, for example, igg1, igg2a, and igg2b. Hypersensitivity Pneumonitis)
• Blood film: spherocytes, sickle cell anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, agglutination (in IgM IgM A class of immunoglobulin bearing mu chains (immunoglobulin mu-chains). Igm can fix complement. The name comes from its high molecular weight and originally being called a macroglobulin. Immunoglobulins: Types and Functions AIHA AIHA Autoimmune hemolytic anemia (AIHA) is a rare type of hemolytic anemia characterized by antibody production against self rbcs, leading to destruction of these cells in the spleen and other reticuloendothelial tissues. The disease is generally categorized as warm or cold, depending on the thermal reactivity of the autoantibodies. Autoimmune Hemolytic Anemia)

Treatment

• Manage underlying cause.
• Supplement with folic acid to boost compensatory erythrocytosis.
• Manage hyperkalemia Hyperkalemia Hyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs. Hyperkalemia due to increased cell breakdown.
• Splenectomy Splenectomy Surgical procedure involving either partial or entire removal of the spleen. Rupture of the Spleen for extravascular hemolytic diseases

Differential Diagnoses

• Sickle cell anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types: a hereditary hemoglobinopathy due to a deficiency is the beta-globin chain. It is an autosomal recessive Autosomal recessive Autosomal inheritance, both dominant and recessive, refers to the transmission of genes from the 22 autosomal chromosomes. Autosomal recessive diseases are only expressed when 2 copies of the recessive allele are inherited. Autosomal Recessive and Autosomal Dominant Inheritance disease and presents with symptoms of hemolysis in hypoxic conditions.
• Thalassemia Thalassemia Thalassemia is a hereditary cause of microcytic hypochromic anemia and results from a deficiency in either the α or β globin chains, resulting in hemoglobinopathy. The presentation of thalassemia depends on the number of defective chains present and can range from being asymptomatic to rendering the more severely affected patients to be transfusion dependent. Thalassemia: a hereditary hemoglobinopathy due to a deficiency of either alpha or beta-globin chain. Results in an array of symptoms based on which and how many gene deletions Gene Deletions A genetic rearrangement through loss of segments of DNA or RNA, bringing sequences which are normally separated into close proximity. This deletion may be detected using cytogenetic techniques and can also be inferred from the phenotype, indicating a deletion at one specific locus. Blotting Techniques have occurred. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship have chronic hemolysis and present with symptoms of hemolytic anemia Anemia Anemia is a condition in which individuals have low Hb levels, which can arise from various causes. Anemia is accompanied by a reduced number of RBCs and may manifest with fatigue, shortness of breath, pallor, and weakness. Subtypes are classified by the size of RBCs, chronicity, and etiology. Anemia: Overview and Types, rendering them transfusion-dependent.
• G6PD deficiency G6PD Deficiency Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a type of intravascular hemolytic anemia. The condition is inherited in an X-linked recessive manner. Patients have episodic hemolysis due to an oxidative stressor that causes damage to red blood cells, which lack sufficient NADPH to protect them from oxidative injury. Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency: an enzyme deficiency linked to a deficiency of glucose-6-phosphate Glucose-6-phosphate An ester of glucose with phosphoric acid, made in the course of glucose metabolism by mammalian and other cells. It is a normal constituent of resting muscle and probably is in constant equilibrium with fructose-6-phosphate. Gluconeogenesis dehydrogenase activity. Patients Patients Individuals participating in the health care system for the purpose of receiving therapeutic, diagnostic, or preventive procedures. Clinician–Patient Relationship present with episodic hemolysis Episodic Hemolysis Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency due to exposure to an oxidative stress Oxidative stress A disturbance in the prooxidant-antioxidant balance in favor of the former, leading to potential damage. Indicators of oxidative stress include damaged DNA bases, protein oxidation products, and lipid peroxidation products. Cell Injury and Death agent.
• Hereditary spherocytosis Hereditary Spherocytosis Hereditary spherocytosis (HS) is the most common type of hereditary hemolytic anemia. The condition is caused by a cytoskeletal protein deficiency in the RBC membrane. This results in loss of membrane stability and deformability of the RBC, giving the cell its spherical shape (spherocyte). Hereditary Spherocytosis: an inherited deficiency in cytoskeletal and membrane proteins Proteins Linear polypeptides that are synthesized on ribosomes and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of amino acids determines the shape the polypeptide will take, during protein folding, and the function of the protein. Energy Homeostasis that stabilize an RBC. The deficiency results in loss of biconcave shape Biconcave shape Erythrocytes: Histology to a spherical shape.
• Hemolytic uremic syndrome Hemolytic uremic syndrome A syndrome that is associated with microvascular diseases of the kidney, such as renal cortical necrosis. It is characterized by hemolytic anemia; thrombocytopenia; and acute renal failure. Hypocoagulable Conditions: a triad of hemolysis, renal failure Renal failure Conditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate. Crush Syndrome, and low platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology usually secondary to Escherichia coli Escherichia coli The gram-negative bacterium Escherichia coli is a key component of the human gut microbiota. Most strains of E. coli are avirulent, but occasionally they escape the GI tract, infecting the urinary tract and other sites. Less common strains of E. coli are able to cause disease within the GI tract, most commonly presenting as abdominal pain and diarrhea. Escherichia coli (O157:H7) infection. Microangiopathic hemolysis is due to platelet adherence to vascular walls.
• Disseminated intravascular coagulopathy: an imbalance of plasmin Plasmin A product of the lysis of plasminogen (profibrinolysin) by plasminogen activators. It is composed of two polypeptide chains, light (b) and heavy (a), with a molecular weight of 75, 000. It is the major proteolytic enzyme involved in blood clot retraction or the lysis of fibrin and quickly inactivated by antiplasmins. Hemostasis and thrombin Thrombin An enzyme formed from prothrombin that converts fibrinogen to fibrin. Hemostasis leads to intravascular coagulation. There is an excessive consumption of platelets Platelets Platelets are small cell fragments involved in hemostasis. Thrombopoiesis takes place primarily in the bone marrow through a series of cell differentiation and is influenced by several cytokines. Platelets are formed after fragmentation of the megakaryocyte cytoplasm. Platelets: Histology, coagulation factors Coagulation factors Endogenous substances, usually proteins, that are involved in the blood coagulation process. Hemostasis, and fibrinogen Fibrinogen Plasma glycoprotein clotted by thrombin, composed of a dimer of three non-identical pairs of polypeptide chains (alpha, beta, gamma) held together by disulfide bonds. Fibrinogen clotting is a sol-gel change involving complex molecular arrangements: whereas fibrinogen is cleaved by thrombin to form polypeptides a and b, the proteolytic action of other enzymes yields different fibrinogen degradation products. Hemostasis due to thrombus formation. Thrombosis Thrombosis Formation and development of a thrombus or blood clot in the blood vessel. Epidemic Typhus results in the fragmentation Fragmentation Chronic Apophyseal Injury of RBCs RBCs Erythrocytes, or red blood cells (RBCs), are the most abundant cells in the blood. While erythrocytes in the fetus are initially produced in the yolk sac then the liver, the bone marrow eventually becomes the main site of production. Erythrocytes: Histology.
• Splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly: Enlargement of the spleen Spleen The spleen is the largest lymphoid organ in the body, located in the LUQ of the abdomen, superior to the left kidney and posterior to the stomach at the level of the 9th-11th ribs just below the diaphragm. The spleen is highly vascular and acts as an important blood filter, cleansing the blood of pathogens and damaged erythrocytes. Spleen: Anatomy due to increased workload is seen in hemolytic anemias. There are many other causes of splenomegaly Splenomegaly Splenomegaly is pathologic enlargement of the spleen that is attributable to numerous causes, including infections, hemoglobinopathies, infiltrative processes, and outflow obstruction of the portal vein. Splenomegaly: infiltration, abnormal blood flow Flow Blood flows through the heart, arteries, capillaries, and veins in a closed, continuous circuit. Flow is the movement of volume per unit of time. Flow is affected by the pressure gradient and the resistance fluid encounters between 2 points. Vascular resistance is the opposition to flow, which is caused primarily by blood friction against vessel walls. Vascular Resistance, Flow, and Mean Arterial Pressure, and immunological disorders.