Hemolytic Anemia Table PDF

INTRACORPUSCULAR DEFECTS: INCREASED RBC DESTRUCTION (INTRINSIC) HEREDITARY DEFECTS OF THE RBC MEMBRANE Disorder Cause/Epidemiology/Pathophysiology Symptoms...

INTRACORPUSCULAR DEFECTS: INCREASED RBC DESTRUCTION (INTRINSIC) HEREDITARY DEFECTS OF THE RBC MEMBRANE Disorder Cause/Epidemiology/Pathophysiology Symptoms Lab Findings Treatment Accute: Decreased Hb Mean Hgb level of 12- - Defect in vertical interactions between transmembrane proteins and Fatigue 13 g/dL 25% no anemia (fully the cytoskeleton Pallor compensated) - decreased membrane surface area and decreased deformability Jaundice increased MCHC (cellular Vaccines Hereditary - AD transmission ~ 2/3 of total hemolysis with dehydration; >36%) splenectomy (full or partial depending on Spherocytosis 25-30% sporadic mutations without family history infections increased reticulocyte count severity) ▪ Randomly happens in 1 family member w/out history of HS aplastic crisis spherocytes, polychromasia on - Autosomal Recessive cases often more severe (5%) Chronic: peripheral smear - Most common congenital hemolytic anemia (1/2000) splenomegaly Extravascular Hemolysis gallstone ↑ Indirect bilirubin, ↑ LDH - abnormal spectrin heterodimer association (SPTA, SPTB, horizontal interactions) - Autosomal dominant pattern (1/2000-1/4000) Three Types: 1. Common HE: 90% Asymptomatic ▪ Low MCV (25% elliptical, cigar- shaped RBCs Most are asymptomatic Hereditary Subtypes Special subtypes on smear Not typically needed, splenectomy may be but some have Elliptocytosis 1. HHP 1. Southeast Asian slight reticulocytosis; decreased considered in severe cases hemolytic anemia ▪ Decreased thermal stability ovalocytosis Haptoglobin ▪ Marked RBC fragmentation upon ▪ Rigid heating ▪ Band 3 mutations ▪ Severe form of HE ▪ Stamatocytes and 2. Leach Phenotype ovalocytes ▪ Lack the Gerbich antigen, ▪ Mild hemolysis Glycoprotein C and D 2. Alpha Lely ▪ Defect in the interaction between ▪ Reduced alpha spectrin GPC and Protein 4.1R ▪ HE modifier microcytic MCV (55-74 fL) Bizarre shaped RBCs on smear (similar Hereditary Severe hemolysis in - Spectrin abnormalities to thermal burn) Treatment for severe hemolysis in childhood Pyropoikilocytosis early childhood that - autosomal recessive Can be confirmed with molecular then HE later in life (HPP) lessens with age testing (spectrin mut)  INTRACORPUSCULAR DEFECTS: INCREASED RBC DESTRUCTION (INTRINSIC) INHERITED DISORDERS OF RBC CATION PERMEABILITY DEFECT Disorder Cause/Epidemiology/Pathophysiology Symptoms Lab Findings - Rare, autosomal dominant - Failure of Na & K pumps; increase in intracellular water - Influx of Na exceeds the loss of K → cells swell → less dense → Macrocytes Hereditary Stomatocytic Moderate to severe hemolytic anemia reduced K and increased Na Stomatocytosis - Lack of stomatin on band 7.2b – supports or regulates an stomatocytes on smear unidentified ion channel - Increased osmotic fragility, low 2,3 DPG - Thrombotic complications - increased intracellular Na+ = overhydrated RBCs Macrocytes Increased MCV - Inheritance: Autosomal Dominant Pattern Decreased MCHC Overhydrated Reduced K and Increased Na Hereditary - Ion movement: Excessive permeability to Sodium and Stomatocytosis Potassium Acquired Stomatocytosis: Drying artifact in Wright’s - Water movement: More water enters the cell stain - Structural defect: Mutation in RhaG gene Rh null disease: Absence of Rh membrane proteins Decreased osmotic fragility ektacytometry - Intracellular K+ loss = dehydrated RBC assessing cation leak or molecular testing - Excessive permeability to potassium leading to water loss from the Mild to moderate anemia cell Reticulocytosis - AD mutation in PIEZO1 or Gardos channel (KCCN4) jaundice Hereditary Xerocytosis Macrocytosis = Increased MCV splenomegaly (Dehydrated Increased MCHC Dehydrated stomatocytes: artifact, acute ethanol intoxication, liver fetal loss stomatocytosis) stomatocytes on smear disease, Rh null disease, Tangier disease hydrops fetalis - Ion Movement: Excessive permeability to Potassium neonatal hepatitis - Water movement: Water is lost from the cell - Structural defect: Abnormal gene 16q 23-24 Complications: Marked increased risk of thrombosis after splenectomy  INTRACORPUSCULAR DEFECTS: INCREASED RBC DESTRUCTION (INTRINSIC) ENZYMOPATHIES Disorder Cause/Epidemiology/Pathophysiology Symptoms Lab Findings Treatment - Decreased NADPH: inability to maintain reduced glutathione = ↓ antioxidant level - Most common RBC enzymopathy, affects millions globally. - Protective against malaria - X-linked (hemizygous females can have findings) Pathophysiology: normochromic, normocytic anemia - Reduces NADP; oxidizes G-6P WBC count slightly elevated, varied platelet - Regenerates NADPH; if absent RBC is vulnerable to oxidative damage count - RBCs with normal G-6PD activity are able to detoxify the oxidative Heinz bodies and blister cells on smear compounds and safeguard the Hb. Reticulocytosis (30%) - In deficiency – oxidation of membrane thiols, Heinz bodies, increase of Episodic hemolysis/anemia with Hemoglobinuria G6PD Deficiency Avoid oxidative triggers leak rates of Na, K; bite cells – Hb separates from RBC membrane oxidative exposure Jaundice Wright-stained blood smear: Anisocytosis, Hemolytic Process Poikilocytosis, Spherocytosis, and Schistocytosis Clinical syndromes associated with G6PD: Chemistry test results: Based on reduction of ▪ AHA – resulting from drug exposure or infection NADP to NADPH by change in absorbance at ▪ Favism 340 nm ▪ Neonatal jaundice ▪ Chronic non-spherocytic hemolytic anemia ▪ In association with DKA & hypoglycemia, infection, oxidative drug exposure ▪ Oldest RBCs have the lowest amount – 1st to lyse ▪ Plasmodium falciparum infections protections Pathophysiology: Severe anemia in infants - PK is an important enzyme: Conversion of PEP to Pyruvate to form ATP Reticulocytosis markedly pronounced after compensated hemolysis in - ↓ PK = ↓ RBC ATP: loss of membrane stability = hemolysis splenectomy (retics may increase from 10-15% Splenectomy may Pyruvate Kinase adults ▪ Decreased RBC Lifespan to 30-70%) with only partial amelioration of reduce transfusion Deficiency may require regular - ↑ 2,3-DPG: increased O2 off-loading anemia → risk of gallstones and aplastic crisis requirement transfusions until - Significant hemolysis of reticulocytes: highest ATP needs, rely on persists splenectomy mitochondria for ATP but cannot in hypoxic spleen  INTRACORPUSCULAR DEFECTS: INCREASED RBC DESTRUCTION (INTRINSIC) OTHER ENZYMOPATHIES Disorder Cause/Epidemiology/Pathophysiology Lab findings/Symptoms Treatment - Epidemiology/Lab findings: AR, compound Glucose Phosphate hemolysis and its complications Splenectomy can reduce transfusion heterozygous or homozygous; 2nd most common Isomerase Deficiency neurologic impairment requirement glycolytic enzyme defect hemolysis, occasional neurologic findings - Pathophysiology: P5’N catalyzes degradation of cytidine and uridine. Diagnosis through screening for ↑ Pyrimidine Pyrimidine 5’ Pyrimidine degradation products are impermeable to membrane unless nucleotides in RBCs and molecular testing Nucleotidase Deficiency exposed to P5’N Blood smear: Basophilic stippling (can be seen - Rare but most common enzymopathy affecting nucleotide metabolism if the cytidine and uridine is not degraded)  PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (INTRINSIC) Disorder Cause/Epidemiology/Pathophysiology Symptoms Lab findings treatment Acquired clonal stem cell mutation that lacks glycosylphosphatidylinositol (GPI)- anchored proteins - Associated with sleep: Decreases pH of the blood → Lysis of RBCs - Also known as Marchiava-Micheli syndrome - Ham’s Acidified Serum Test and Sugar H2O test for detection - Abnormalities of the red cell membrane Mild to severe anemia - Highly sensitive to complement-mediated hemolysis Normocytic, normochromic Leukopenia - Strongly associated with aplastic anemia Thrombocytopenia anemia - Decreased LAP (leukocyte alkaline phosphatase) activity Anemia classification: Chronic slight macrocytosis Eculizumab -monoclonal Paroxysmal intravascular hemolysis due to increased reticulocytes antibody that binds with C5 History and etiology Nocturnal hemosidenuria hemosiderin in urine supportive care - Acquired clonal stem cell mutation that lack Hemoglobinuria Bone Marrow evaluation: increased indirect bilirubin with Median Survival Rate: 10 - glycosylphosphatidylinositol (GPI)- anchored proteins such as CD55 and Erythroid Hyperplasia hemoglobinuria years CD59 - Role of complement Hemoglobinuria decreased haptoglobin - Onset: Young adulthood Budd-Chiari syndrome (hepatic negative Coombs test - Age most at risk: Childhood and advanced age vein thrombosis) Pathophysiology - Main defect: mutation in PIG-A gene Subpopulations of cells ▪ PNH-I: normal CD55 and CD59, little or no hemolysis ▪ PNH-II: partial deficiency; relatively resistant to hemolysis ▪ PNH-III: sensitive to hemolysis 1. Sugar Water Test Positive ham’s test must demonstrate the following characteristics: Sucrose hemolysis test (sugar water test) initial screening test; ▪ Haemolysis occurs with the patient’s cells and not with control cells Positive: will show 10% to 80% lysis; less than 5% is considered negative ▪ Haemolysis is enhanced by acidified serum and does not occur with - Ham’s Test or acidified serum lysis test heat-inactivated serum utilizes acidified serum which activates complement via the alternative pathway 2. Flow cytometry and allows binding of C3 to the red cell membrane causing lysis of the PNH red - GPI-anchoring proteins cells (deficient in the GPI-anchor proteins) - Utilizes monoclonal antibodies against Protein CD 55 and CD 59 ▪ Deficiency of CD59, CD55, CD24, and CD15 - Urine Hemosiderin  EXTRACORPUSCULAR DEFECTS: INCREASED RBC DESTRUCTION (EXTRINSIC) NON-IMMUNE CAUSES Disorder Description Clinical Findings/Symptoms/Diagnosis Laboratory Findings - Thrombotic Thrombocytopenic Purpura - Hemolytic Uremic Syndrome - Malignant Hypertension - Disseminated Intravascular Coagulopathy & Differential diagnosis: Disseminated Carcinoma DIC, TTP, HUS - Chemotherapy-Induced Microangiopathic Hemolytic Microangiopathic Kasabach-Merritt Syndrome Anemia Syndrome Hemolytic Anemia - Microangiopathic Hemolytic Anemia Syndrome Burns (MAHA) Bone Marrow Transplant (allogeneic > autologous) Associated with Transplantation - RBC fragmentation in circulation → intravascular hemolysis Drugs: Cyclosporine A, tacrolimus - RBC passes thru luminal fibrin deposits - Shearing of red cells in small vessels (schistocytes) Classical Pentad: Lab findings: Thrombocytopenia intravascular hemolysis - abnormal von Willebrand factor-cleaving protease. The renal dysfunction thrombocytopenia ADAMTS13 gene encodes this enzyme neurological changes - Upshaw-Schulman Syndrome: Congenital absence of normal PT/PTT/fibrinogen Fever enzyme MAHA blood smear with schistocytes Thrombotic - Acquired autoantibody to the vWF cleaving protease: Hemoglobin: Usually < 10 g/dL8 idiopathic or secondary to rheum, pregnancy, infections Reticulocytosis Thrombocytopenic Diagnosis Purpura (TTP) Clinical diagnosis based on symptoms and lab nRBC, basophilic stippling findings Platelet