Normocytic anemia (increased hemolysis) Notes


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Autoimmune hemolytic anemia

Pyruvate kinase deficiency

Sickle cell disease (NORD)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency

Hemolytic disease of the newborn

Hereditary spherocytosis

Paroxysmal nocturnal hemoglobinuria

NOTES NOTES NORMOCYTIC ANEMIA (INCREASED HEMOLYSIS) GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Inherited/acquired disorders resulting in premature destruction of normal red blood cells (RBCs) SIGNS & SYMPTOMS ▪ If hematopoietic compensation insufficient, anemic symptoms (e.g. pallor, fatigue, activity intolerance) ▪ Intravascular hemolysis → hemoglobinuria, iron deficiency ▪ Extravascular hemolysis → jaundice, splenomegaly, gallstone formation DIAGNOSIS LAB RESULTS ▪ Complete blood count (CBC) ▪ Peripheral blood smear analysis ▪ Measure plasma for hemolysis indicators ▫ Bilirubin, lactate dehydrogenase (LDH), haptoglobin ▪ Measure specific indicators of hemolysis in urine ▫ Hemoglobin, bilirubin, hemosiderin TREATMENT ▪ See individual disorders AUTOIMMUNE HEMOLYTIC ANEMIA (AHA) PATHOLOGY & CAUSES ▪ Anemia caused by immune destruction of red blood cells by autoantibodies against antigens on RBCs surface ▪ AKA AIHA TYPES Warm AIHA ▪ Most common ▪ “Warm” because optimum temperature for antibody to react with RBCs = normal body temperature (37°C/98.6°F) ▪ Predominant autoantibody: IgG (IgA and IgM may also be involved) ▪ Predominant RBC antigen: Rh ▪ Associated with immune deficiencies, malignancies, certain drugs ▪ Antibody fixes complement + binds to RBC membrane → antibody-coated RBCS destroyed in spleen ▫ Usual site of hemolysis: extravascular, by macrophages in spleen, liver OSMOSIS.ORG 425
Cold AIHA ▪ “Cold” because optimum temperature for antibody to react with RBCs = below normal body temperature (4°C/39.2°F) ▪ Predominant autoantibody: IgM ▪ Predominant RBC antigen: I, i, P ▪ Antibodies activate direct complement system attack ▪ Usual site of hemolysis: intravascular, complement-mediated ▪ Paroxysmal cold hemoglobinuria ▫ Most common in children ▫ Caused by Donath–Landsteiner antibody ▫ Associated with viral (e.g. measles, varicella) or bacterial (e.g. mycoplasma, H. influenza) infections ▪ Cold agglutinin syndrome ▫ Most common in adults > 70 years old ▫ Primarily biologically-female individuals ▫ Associated with lymphoproliferative disorders, autoimmune disorders, mycoplasma infections COMPLICATIONS ▪ Depend on type/degree of hemolysis ▪ Anemia, venous thromboembolism, cholelithiasis, renal insufficiency ▪ Older individuals: increased risk of cardiac complications SIGNS & SYMPTOMS ▪ Onset insidious/acute ▪ If hematopoietic compensation insufficient, anemic signs and symptoms (e.g. pallor, fatigue, activity intolerance) ▪ If severe anemia/underlying cardiac disease, a hyperdynamic state (e.g. bounding pulses, tachycardia, pulmonary congestion) ▪ Cold AIHA ▫ Hemoglobinuria after exposure to cold temperatures ▪ Paroxysmal cold hemoglobinuria ▫ Jaundice, hemoglobinuria, anemia after infection; pain in legs, back following exposure to cold ▪ Cold agglutinin syndrome ▫ Anemia, acrocyanosis, or Raynaud’s phenomenon DIAGNOSIS LAB RESULTS RISK FACTORS ▪ Exposure to cold ▪ Administration of offending drug ▪ Development of associated diagnosis ▫ Infection, malignancy, autoimmune disorder 426 OSMOSIS.ORG ▪ Evidence of hemolysis ▫ Increased lactate dehydrogenase (LDH) ▫ Increased indirect bilirubin ▫ Decreased haptoglobin ▪ Increased mean corpuscular volume (MCV) ▪ Low hemoglobin, hematocrit ▪ Reticulocytosis ▪ Direct antibody (DAT) ▫ Warm: positive for IgG/IgG + C3d ▫ Cold: positive for C3d ▪ Partial macrophage phagocytosis → spherocytosis
Chapter 54 Normocytic Anemia (Increased Hemolysis) TREATMENT ▪ Cold AIHA: often no treatment required MEDICATIONS ▪ Corticosteroids ▪ Monoclonal antibody: rituximab ▪ Immunosuppressants SURGERY ▪ Splenectomy (reduces hemolysis) OTHER INTERVENTIONS Figure 54.1 A peripheral blood smear from an individual with warm autoimune hemolytic anemia. There are numerous spherocytes present due to degradation of the red cell membrane by macrophages. ▪ Eliminate triggers (e.g. cold, drugs) ▪ Correct anemia ▫ Folic acid supplements to support erythropoiesis ▫ Blood transfusion GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY PATHOLOGY & CAUSES ▪ Hematological enzymopathy where deficient glucose-6-phosphate dehydrogenase (G6PD) causes premature hemolysis ▪ Inherited, X-linked mutation of G6PD gene ▪ Hemolysis can be acute/intermittent/chronic (rare) ▪ Inadequate G6PD, GSH → oxidative stress → build-up of free radicals, peroxides → precipitation of hemoglobin → disruption of cell membrane → increased cellular rigidity → extravascular hemolysis, accelerated removal of damaged RBCs by reticuloendothelial system in spleen; intravascular hemolysis may also occur ▪ Hemolysis precipitated by sources of oxidative damage that trigger hemolysis. ▫ RBCs with deficient G6PD have a decreased lifespan ▫ Certain drugs (sulfa drugs, antimalarials) and chemicals (e.g. henna compounds, aniline-based dyes, naphthalene) interact with hemoglobin + oxygen → hydrogen peroxide (H2O2), other oxidizing radicals within cell → hemoglobin precipitation ▪ Infections → possible generation of hydrogen peroxide by leukocytes/exposure to neutrophil produced oxidants → hemoglobin precipitation ▪ Ingestion of fava beans (favism) W.H.O. Classifications ▪ Based on degree of enzyme deficiency, resulting hemolysis ▪ Class I: G6PD < 10% of normal; chronic hemolytic anemia ▪ Class II: G6PD < 10% of normal; intermittent hemolysis when exposed to OSMOSIS.ORG 427
oxidative stress ▫ G6PD Mediterranean: majority of RBCs hemolyze in setting of oxidative stress; half-life of G6PD especially short (measured in hours) ▪ Class III: G6PD 10–60% of normal; intermittent hemolysis when exposed to trigger ▫ G6PD A- : only oldest RBCs hemolyze in setting of oxidative stress; G6PD halflife = 13 days (normal = 62 days) ▪ ▪ ▪ ▪ TYPES ▪ Acute hemolysis ▫ May be mild/severe (life-threatening) ▪ Kernicterus ▫ G6PD-related neonatal jaundice → kernicterus if not promptly treated ▪ Renal failure RISK FACTORS ▪ Most common in people of African, Asian, Mediterranean descent SIGNS & SYMPTOMS ▪ Generally asymptomatic until exposed to oxidative stress ▪ Acute hemolysis ▫ Pallor, jaundice, dark urine ▫ Abdominal/back pain due to increased splenic activity ▫ Renal insufficiency (severe hemolysis) ▪ Favism (potentially fatal acute hemolysis) DIAGNOSIS LAB RESULTS ▪ Decreased hemoglobin ▪ Heinz bodies ▫ Caused by precipitation of oxidized, denatured hemoglobin ▪ Bite cells ▫ Cells have bitten appearance where macrophages have removed bits of precipitated hemoglobin from RBC ▪ Blood chemistry demonstrates evidence of hemolysis 428 OSMOSIS.ORG ▪ ▫ Elevated indirect bilirubin ▫ Elevated lactate dehydrogenase (LDH) ▫ Decreased haptoglobin Reticulocytosis Hemoglobinuria, hemosiderinuria G6PD assay ▫ Directly measures G6PD activity in RBCs; false-negative if testing done during/immediately after acute hemolytic episode Screening tests ▫ Fluorescent spot test: glucose6-phosphate + NADP added to hemolysate of individual’s RBCs → fluorescence of NADPH ▫ Methemoglobin reduction test: methylene blue measures transfer of hydrogen ions from NADPH to methemoglobin → indirectly estimates NADPH generation ▫ Newborn screening: blood analyzed for biochemical, genetic markers of G6PD, other inherited disorders Confirmatory test to assay NADPH formation performed after positive screening test/as initial test ▫ Spectrophotometric analysis of RBC hemolysate + glucose-6-phosphate + NADP measures NADPH generation rate TREATMENT MEDICATIONS ▪ Folic acid supplements (support erythropoiesis) OTHER INTERVENTIONS ▪ Eliminate triggers ▪ Manage acute hemolytic episodes ▫ Hydration ▫ Transfusions ▪ Phototherapy, exchange transfusion ▫ Neonatal jaundice
Chapter 54 Normocytic Anemia (Increased Hemolysis) HEMOLYTIC DISEASE OF THE NEWBORN PATHOLOGY & CAUSES ▪ Anemia caused by hemolytic destruction of fetal/neonatal erythrocytes by maternal antibodies ▪ AKA alloimmune HDFN/erythroblastosis fetalis CAUSES ▪ Fetomaternal hemorrhage exposes maternal circulation to antigens present on fetal RBCs → maternal sensitization → formation of maternal IgG antibodies against fetal RBCs → IgG antibodies small enough to cross placenta → antibody attachment to fetal cells → agglutination (clumping) → microcirculatory impairment → hemolysis, destruction of RBCs by macrophages in reticuloendothelial system ▫ Involves Rhesus (Rh) blood group/A, B, AB, O blood groups ▪ Causes of maternal sensitization include normal delivery, spontaneous/induced abortion, chorionic villus sampling, amniocentesis, antenatal hemorrhage, maternal trauma, idiopathic ▫ Small amount (0.1mL) of fetal blood needed to induce maternal immune response ▪ Rh incompatibility ▫ Rh negative mother exposed to Rh positive fetal RBCs → maternal anti-D antibodies formed ▫ Usually will not affect first pregnancy when initial exposure occurs; adversely affects subsequent pregnancies ▫ Decreasing occurrence due to availability of Rh(D) immune globulin prophylaxis ▪ ABO incompatibility ▫ More common, less severe morbidity, mortality than with Rh incompatibility ▫ Occurs in type O mother with naturallyoccurring Anti-A and Anti-B antibodies + Type A/Type B fetus ▫ Can occur in first and all subsequent pregnancies RISK FACTORS ▪ Blood group incompatibility, fetomaternal hemorrhage COMPLICATIONS ▪ Anemia, hyperbilirubinemia, kernicterus ▪ Growth restriction, hydrops fetalis, erythroblastosis fetalis ▫ Increased immature RBCs in fetal circulation SIGNS & SYMPTOMS ▪ Hemolytic disease caused by ABO incompatibility ▫ Mild to moderate hyperbilirubinemia within first 24h of life ▫ Mild to moderate anemia ▪ Hemolytic disease caused by Rh incompatibility (more severe) ▫ Hyperbilirubinemia, kernicterus: possible ▫ Symptomatic anemia: pallor, lethargy, tachycardia, tachypnea ▫ Hydrops fetalis: related to severe anemia-induced hypoxia; subcutaneous edema, pleural/pericardial effusion, ascites, signs and symptoms of shock ▪ Antenatal presentation ▫ Intrauterine growth restriction signals problems with ongoing hemolysis, hypoxia OSMOSIS.ORG 429
DIAGNOSIS DIAGNOSTIC IMAGING Doppler ultrasound ▪ Antenatal (maternal testing) ▪ Notes growth restriction/presence of hydrops LAB RESULTS ▪ Antenatal (maternal testing) ▫ Positive indirect antiglobulin test: IAT, indirect Coombs test; demonstrates IgG antibodies in maternal serum ▫ Kleihauer–Betke test: positive if fetomaternal hemorrhage has occurred ▫ Percutaneous umbilical blood sampling (PUBS): measures hemoglobin, hematocrit, identifies fetal blood type ▫ Spectrophotometric amniotic fluid analysis: increased bilirubin if significant hemolysis has occurred ▪ Postnatal (neonatal testing) ▫ Blood typing: confirm incompatibility of maternal, neonatal blood types ▫ Positive direct antiglobulin test: DAT, direct Coombs test; evidence of maternal antibodies on RBC surface ▫ Positive indirect antiglobulin test: IAT, indirect Coombs test; evidence of maternal antibodies in serum ▫ Transcutaneous bilirubin (TcB), serum bilirubin: increased ▫ CBC: decreased RBCs, reticulocytosis, decreased hemoglobin and hematocrit ▫ Peripheral blood smear analysis: evidence of hemolysis; polychromasia, microspherocytosis (seen in ABO incompatibility) 430 OSMOSIS.ORG TREATMENT MEDICATIONS ▪ Hematopoietic agents (epoetin alfa/ darbepoetin), iron supplements ▫ Anemia OTHER INTERVENTIONS ▪ RBC transfusion ▫ Anemia, hydrops fetalis ▪ Exchange transfusion ▫ Hyperbilirubinemia, hydrops fetalis ▪ Phototherapy ▫ Hyperbilirubinemia ▪ Intravenous immunoglobulin (IVIG) ▫ Hyperbilirubinemia ▫ Reduces hemolysis, bilirubin production ▪ Pericardiocentesis, paracentesis, thoracentesis ▫ Hydrops fetalis; as indicated for pericardial effusion, pleural effusion, ascites ▪ Intrauterine RBCl transfusion ▫ Hydrops fetalis if diagnosed antenatally
Chapter 54 Normocytic Anemia (Increased Hemolysis) HEREDITARY SPHEROCYTOSIS PATHOLOGY & CAUSES ▪ Inherited RBC membrane defect causing destabilization of cellular membrane, resulting in chronic, premature extravascular hemolysis ▪ Autosomal dominant (75%) or autosomal recessive (25%) ▪ Mutations of genes encoding for proteins that secure RBC membrane skeleton to plasma membrane → membrane destabilization → rigidity, resistance to deformability → hemolysis TYPES Mild (20–30%) ▪ Mild anemia, splenomegaly, jaundice; modest reticulocytosis; normal hemoglobin ▪ Adolescents/adults most commonly diagnosed Moderate (60–70%) ▪ Moderate anemia, reticulocytosis, hyperbilirubinemia ▪ Require occasional transfusions ▪ Infants/children most commonly diagnosed Severe (5%) ▪ Marked anemia, hyperbilirubinemia, splenomegaly ▪ Regular transfusions needed RISK FACTORS ▪ Most common in people of Northern European descent COMPLICATIONS ▪ Transient aplastic crisis caused by infections (e.g. parvovirus B19) ▪ Megaloblastic anemia related to folate deficiency ▪ Neonatal icterus; non-immune hydrops fetalis with fetal death if disease = severe SIGNS & SYMPTOMS ▪ Jaundice ▪ Anemic signs and symptoms (e.g. pallor, fatigue, activity intolerance) ▪ Splenomegaly DIAGNOSIS LAB RESULTS ▪ Decreased hemoglobin ▪ Reticulocytosis ▪ Spherocytosis ▫ Morphology = sphere-shaped (normal = biconcave) ▪ Presence of schistocytes (RBC fragments) ▪ Slightly decreased to normal MCV ▫ Spherocytes: decreased MCV ▫ Reticulocytes: increased MCV ▪ Elevated mean cell hemoglobin concentration (MCHC) ▫ Secondary to dehydration, loss of cellular membrane ▪ Elevated red cell distribution width (RDW) ▪ Evidence of hemolysis ▫ Elevated indirect bilirubin ▫ Elevated lactate dehydrogenase (LDH) ▫ Decreased haptoglobin ▪ Osmotic fragility test, acidified glycerol lysis test (AGLT) ▫ Identifies spherocytes which lyse in hypotonic solutions at higher rate than normal RBCs ▪ Cryohemolysis test ▫ Uses hypertonic solution, temperature manipulation to identify spherocytes which lyse at higher rate than normal RBCs ▪ Eosin-5-maleimide (EMA) binding test ▫ Flow cytometric test to observe cell membrane protein interaction with eosin-5-maleimide dye OSMOSIS.ORG 431
▪ Osmotic gradient ektacytometry ▫ Measures surface area to volume, cell hydration, membrane deformability TREATMENT SURGERY ▪ Splenectomy OTHER INTERVENTIONS ▪ Blood transfusions ▪ Phototherapy, exchange transfusions ▫ Neonatal hyperbilirubinemia ▪ Folic acid supplements ▫ Support hematopoiesis Figure 54.2 A peripheral blood smear demonstrating sphere shaped erythrocytes in an individual with hereditary spherocytosis. The erythrocytes have lost their biconcave shape. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH) PATHOLOGY & CAUSES ▪ Inherited, X-linked hematologic stem cell disorder resulting in nocturnal hemolysis, hemolytic anemia, bone marrow failure, thrombosis CAUSES ▪ Mutation of PIGA gene in hematopoietic stem cells ▫ PIGA required for synthesis of glycosylphosphatidylinositol (GPI) protein on cell surface ▫ GPI anchors glycoproteins on erythrocyte surface, protecting cell from lysis by attenuating activity of complement ▪ GPI protein absence or deficiency → ↑ 432 OSMOSIS.ORG susceptibility to complement activity → complement-mediated intravascular hemolysis ▪ Three phenotypes of RBCs categorized according to amount of GPI-anchored proteins on cell surface ▫ Type I: normal ▫ Type II: decreased ▫ Type III: absent RISK FACTORS ▪ Hemolysis in PNH cases increases in setting of increased complement activation ▫ Infections ▫ Surgery ▫ Blood transfusions ▫ Strenuous exercise ▫ Excessive alcohol use
Chapter 54 Normocytic Anemia (Increased Hemolysis) COMPLICATIONS ▪ Intravascular, extravascular hemolysis → anemia ▪ Consequences of hemoglobin-mediated nitric oxide scavenging ▫ Intravascular hemolysis → free hemoglobin → ↑ consumption of nitric oxide → smooth muscle dystonia, vasospasm (abdominal pain, esophageal spasm, erectile dysfunction) ▪ Venous, arterial thrombosis ▫ Multifactorial etiology related to proinflammatory complement activity, decreased availability of nitric oxide with resulting vasoconstriction, endothelial cell activation, associated platelet aggregation/clot formation ▫ Hepatic vein thrombosis (Budd–Chiari syndrome) → hepatomegaly, jaundice, ascites, gastric and/or esophageal varices ▫ Intestinal vein thrombosis → ischemic colitis ▫ Cerebral vein thrombosis → headache, neurologic effects ▪ Microvascular hemolysis + iron deposits in renal tubules → chronic kidney disease ▪ Bone-marrow failure, aplastic anemia related to hematopoietic stem cell injury ▪ Eculizumab treatments associated with Increased risk of life-threatening neisserial infections SIGNS & SYMPTOMS ▪ Variable according to degree of GPIanchored protein loss → hemolysis ▪ Intermittent episodes (paroxysms) of hemoglobinuria ▫ Dark urine ▫ Hemolysis during night ▪ Clinical manifestations of anemia; e.g. pallor, fatigue, exertional dyspnea DIAGNOSIS LAB RESULTS ▪ Range from normal to abnormal according to degree of GPI-anchored protein loss, resulting hemolysis ▪ RBCs normal morphologically (pancytopenia may be evident in setting of bone marrow failure) ▪ Occasional poikilocytosis, anisocytosis ▪ Normochromic ▪ Normal to extremely decreased serum hemoglobin ▪ Reticulocyte count ranges from normal to decreased ▪ Evidence of hemolysis ▫ Elevated bilirubin ▫ Decreased haptoglobin ▫ Elevated LDH ▪ Direct antiglobulin (DAT/Coombs) positive ▪ Hemoglobinuria, hemosiderinuria OTHER INTERVENTIONS ▪ Bone marrow examination may indicate hypocellularity ▪ Flow cytometry TREATMENT MEDICATIONS ▪ Eculizumab ▫ Monoclonal antibody, reduces complement-mediated hemolysis ▫ Vaccinate against Neisseria meningitidis ▪ Iron, folic acid supplements support erythropoiesis ▪ Therapeutic anticoagulation and/or thrombolysis, as indicated for thrombosis ▪ Immunosuppressive therapy if aplastic anemia present SURGERY ▪ Allogeneic hematopoietic stem cell transplant OTHER INTERVENTIONS ▪ Red blood cell transfusions as needed OSMOSIS.ORG 433
PIRUVATE KINASE DEFICIENCY PATHOLOGY & CAUSES ▪ Hematological enzymopathy caused by deficient pyruvate kinase, resulting in chronic, premature hemolysis of RBCs, hyperactive erythropoiesis ▪ Inherited, autosomal recessive mutation of (PK-LR) pyruvate kinase-LR (liver-red cell) gene ▫ Homozygous for single PK-LR mutation/ heterozygous for two mutations ▪ Hemolysis primarily extravascular (within spleen); intravascular hemolysis variable ▪ Pyruvate kinase ▫ Tetramer enzyme, catalyzes transphosphorylation of phosphoenolpyruvate into pyruvate, ATP during glycolysis ▫ Pyruvate kinase deficiency-related block in glycolysis → accumulation of 2,3-bisphosphoglycerate (2,3-BPG) → shifts oxyhemoglobin dissociation curve to right → improved oxygen delivery to tissues → better tolerance of hemolytic anemia CAUSES ▪ Hemolytic mechanism is unclear; possibly ▫ ATP deficiency ▫ Apoptosis of erythroid progenitors in spleen (ineffective erythropoiesis) RISK FACTORS ▪ Most common in white people of Northern European descent, Asian people of Chinese descent, genetically-isolated communities of Swiss/German descent COMPLICATIONS ▪ Pigmented gallstone formation ▪ Iron overload-associated organ damage ▪ Megaloblastic anemia related to folate deficiency 434 OSMOSIS.ORG ▪ Accelerated hemolysis during pregnancy/ with oral contraceptive use ▪ Neonatal icterus/non-immune hydrops fetalis ▪ Transient aplastic crisis induced by infections (e.g. parvovirus B19) SIGNS & SYMPTOMS ▪ Variable presentation ranging from compensated disease to transfusiondependent anemia ▪ Anemic signs and symptoms ▫ Pallor, shortness of breath, activity intolerance ▪ Jaundice, splenomegaly DIAGNOSIS LAB RESULTS Decreased RBC count, reticulocytosis Increased serum glycolytic 2,3-BPG Hemoglobinuria, hemosiderinuria Evidence of hemolytic anemia with one or both of ▫ Low levels of erythrocytic PK enzymatic activity ▫ PK-LR gene mutation ▪ Evidence of hemolysis ▫ Elevated indirect bilirubin ▫ Elevated lactate dehydrogenase (LDH) ▫ Decreased haptoglobin ▪ ▪ ▪ ▪ OTHER DIAGNOSTICS ▪ Clinical evidence of hemolysis ▫ Jaundice, pigmented (bilirubin) gallstones
Chapter 54 Normocytic Anemia (Increased Hemolysis) TREATMENT SURGERY ▪ Splenectomy ▫ Reduces hemolysis ▪ Allogeneic hematopoietic cell transplantation ▫ May be curative OTHER INTERVENTIONS ▪ RBC transfusions ▫ Often chronic ▪ Chelation therapy ▫ Reduces iron-related organ damage ▪ Folic acid supplementation ▫ Supports erythropoiesis ▪ Phototherapy, exchange transfusion ▫ Treats neonatal jaundice SICKLE-CELL ANEMIA PATHOLOGY & CAUSES ▪ Hemolytic anemia caused by sickle-cell disease (SCD) ▪ A group of inherited hemoglobinopathies caused by point mutation of beta globin gene → produces hemoglobin S (HbS) ▪ RBCs containing HbS tend to polymerize, deform into sickle/crescent-shaped forms when deoxygenated ▫ Triggers for deoxygenation: cold, dehydration, insomnia, alcohol consumption, stressful situations, overexertion, hormonal changes ▫ Deoxygenation may be idiopathic ▪ Sickled cells less deformable than normal RBCs ▫ Decreased lifespan due to hemolysis TYPES HbSS ▪ Sickle-cell disease ▫ Homozygous for HbS ▫ Chronic hemolytic anemia HbSC ▪ Milder form of sickle-cell disease ▫ Heterozygous for HbS + abnormal hemoglobin C HbSA ▪ Sickle-cell trait/benign carrier state ▫ Heterozygous for HbS + hemoglobin A (normal hemoglobin) HbS beta thalassemia ▪ Heterozygous for HbS + one beta thalassemia gene HbSD, HbSE, HbSO ▪ Rare ▪ Heterozygous for HbS + one other abnormal hemoglobin (D, E, or O) COMPLICATIONS ▪ Affect all body systems ▪ Hematologic ▫ Anemia related to aplastic crisis involving temporary arrest of erythropoiesis ▪ Pain ▫ Vaso-occlusion, tissue ischemia, infarction; dactylitis (acute pain in small bones of hands/feet especially in children) ▪ Increased risk of infection ▫ Related to hyposplenism/asplenism, decreased tissue perfusion ▪ Central nervous system ▫ Ischemic/hemorrhagic stroke; transient ischemic attack, seizures OSMOSIS.ORG 435
▪ Cardiovascular ▫ Myocardial infarction, dysrhythmias, cardiomyopathy, heart failure, venous thromboembolism, leg ulcers, sudden death ▪ Respiratory ▫ Acute chest syndrome (fever, chest pain, hypoxemia, wheezing, cough, respiratory distress), pulmonary hypertension, disordered breathing during sleep with nocturnal hypoxemia ▪ Genitourinary, reproductive ▫ Priapism, erectile dysfunction; pregnancy complications, fetal/neonatal or maternal (e.g. intrauterine growth restriction, fetal death, low birthweight; preeclampsia, thromboembolic events) ▪ Endocrine ▫ Delayed growth, development ▪ Skeletal ▫ Osteoporosis, bone infarction ▪ Sensory ▫ Proliferative retinopathy, retinal detachment ▪ Systemic ▫ Multiorgan failure related to ischemia and/or infarction SIGNS & SYMPTOMS ▪ Mild to moderate anemia (e.g. fatigue, activity intolerance, extertional dyspnea) ▪ Hypersplenism ▪ Pain from acute vaso-occlusive crisis DIAGNOSIS ▪ Findings variable depending on inheritance pattern, degree of hemolysis ▪ Pain indicates cell sickling, vaso-occlusion LAB RESULTS ▪ Vaso-occlusion, hemolysis, splenic sequestration → decreased hemoglobin, hematocrit, RBC count ▪ Reticulocytosis ▪ Increased white blood cell (WBC) count ▪ Peripheral blood smear analysis 436 OSMOSIS.ORG ▪ Mostly normochromic, normocytic cells; polychromasia may be present secondary to reticulocytosis ▪ Sickled cells present in SCD but not sicklecell trait ▪ Canoe-shaped (partially sickled) RBCs ▪ Howell Jolly bodies ▫ Related to hyposplenia ▪ Normal-to-increased mean corpuscular volume (MCV) ▪ Target cells ▪ Diagnostic tests to determine organ damage (e.g. urinalysis → hematuria, albuminuria from renal papillary damage) ▪ Evidence of hemolysis ▫ Elevated unconjugated bilirubin ▫ Elevated lactate dehydrogenase (LDH) ▫ Low haptoglobin ▪ Positive solubility test (Sickledex) ▪ Hemoglobin electrophoresis provides definitive diagnosis (90–95% HbS) TREATMENT ▪ Prevent/reduce occurrence of crises (e.g. immunizations to prevent infection, manage stress, prevent deoxygenation) MEDICATIONS ▪ Hydroxyurea ▫ Increases cell deformability, decreases RBC endothelial adhesion, increases hemoglobin F levels; reduces sickling ▪ L-glutamine ▫ Reduces sickling ▪ Pain management ▫ Analgesics, adjunctive, nonpharmacological therapies SURGERY ▪ Hematopoietic cell transplantation OTHER INTERVENTIONS ▪ Blood transfusions ▪ Folic acid supplements ▪ Manage iron deficiency
Chapter 54 Normocytic Anemia (Increased Hemolysis) Figure 54.3 A recoloured scanning electron micrograph demonstrating a sickled erythrocyte. Figure 54.4 An abdominal CT scan in the axial plane demonstrating autosplenectomy in an individual with sickle cell disease. The splenic remnant is densely calcified. Figure 54.5 A peripheral blood smear containing sickled erythrocytes in an individual with sickle cell disease. OSMOSIS.ORG 437

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This Osmosis High-Yield Note provides an overview of Normocytic anemia (increased hemolysis) essentials. All Osmosis Notes are clearly laid-out and contain striking images, tables, and diagrams to help visual learners understand complex topics quickly and efficiently. Find more information about Normocytic anemia (increased hemolysis) by visiting the associated Learn Page.