MLT 104 Hematology Past Paper PDF - May 2022

MLT 104 Hematology 04 May 2022 Topic 1: Clinical Approach to Anemias Describe the morphological classification of anemias to include the genera...

MLT 104 Hematology 04 May 2022 Topic 1: Clinical Approach to Anemias Describe the morphological classification of anemias to include the general symptoms. Anemia A condition in which red blood cells are no longer able to supply oxygen to body tissues resulting to decreased oxygen transport. Classified according to their physiology or morphological characteristics. O Morphological classification is based on red blood cell indices. O Physiological classification is based on symptoms and bone marrow response. If Microcytic/Hypochromic anemia develops, then: O MCV is less than 80 fL. O MCHC is less than 32%. O Hgb synthesis is disrupted. O RBCs appear as small cells, deficient in hemoglobin. General symptoms are: O Fatigue O Dyspnea O Angina pectoris O Syncope Patient may also experience cardiac problems: O Palpitation O Strong pulse O Heart murmurs 71  MLT 104 Hematology 04 May 2022 Topic 2: Iron Metabolism Describe iron transport from ingestion to incorporation in hemoglobin. Multiple forms of iron in the body Iron in gastrointestinal tract O Heme iron O Non-heme iron Iron in Storage O Ferritin: Found in liver, spleen, skeletal muscle, bone marrow, O Hemosiderin: Found in excreted urine Iron in Circulation O Iron and globin is recycled as a result of red blood cell senescence Figure 2.1 - Iron Cycle 72  MLT 104 Hematology 04 May 2022 Factors affecting iron levels Iron ingestion Iron absorbed (about 10% of iron ingested) Recycled hemoglobin (Hgb) components Iron stores Iron loss Factors affecting iron absorption The health of the gastric mucosa O Health of GI tract O Gastroesophageal reflux disease (GERD) O Gastrectomy O Gastric bypass The current iron stores O Decreased iron = more iron needed for the body to run optimally The erythropoietic need The amount of iron ingested O Daily intake (5%) of iron is utilized to maintain RBCs. Iron absorption enhancers Orange juice Vitamin C Pickles Soy sauce Vinegar Alcohol Iron absorption inhibitors Tea Coffee Oregano Milk 73  MLT 104 Hematology 04 May 2022 Identify the iron needs of children and adults. Infants: 70% of iron used for RBC production is recycled O As an infant develops and rapidly gains weight, there is a high demand for iron. Adequate iron stores (from diet) is paramount. O Children should absorb about 0.5 mg/day. Adults: 95% of iron used for RBC production is recycled O Men and infants should absorb about 1 mg/day O Women should absorb about 0.2 to 2.0 mg/day 74  MLT 104 Hematology 04 May 2022 Topic 3: Iron Deficiency Anemia (IDA) Table 2.1 - Stages of IDA Three Stages of Iron Deficiency Anemia (IDA) Continuum of iron depletion from marrow (Prussian blue stain will Stage I show absence of iron) Iron deficient erythropoiesis and slight microcytic, hypochromic Stage II picture A fully developed case of IDA in the peripheral circulation, Stage III microcytes and hypochromia ֎NOTE: Usually the patient will not present with symptoms until stage III anemia develops. Describe the pathophysiology and clinical symptoms of iron deficiency anemia. IDA pathophysiology Related to Increased demands O Growth spurts in infants and children O Pregnancy and nursing Related to Lack of Iron intake O Nutritional deficiency O Conditions that diminish absorption Related to Blood Loss O Gastrointestinal bleeding O Excessive menses O Hemolysis O Other causes of bleeding IDA is 50% of all anemia in the US, affecting 3.5 million IDA clinical symptoms Fatigue-extremely tired Pallor-pale Vertigo-dizziness Dyspnea (air hunger), shortness of breath 75  MLT 104 Hematology 04 May 2022 Cold intolerance Lethargy – extreme fatigue, weakness, lack of energy and motivation In Infants: O Developmental delays O Psychomotor impairment O Poor immune function O Behavioral disturbances O May lead to pre-term delivery in pregnancies or delivering a low birth weight infant Unique Symptoms O Pica – cravings for abnormal substances (toilet paper, paper, dirt, clay, ice, etc.). This is usually due to lack of iron or other substances the body needs. O Cheilitis – chapping around the edges of the mouth O Koilonychia – spooning of the nail beds Correlate the laboratory findings of an individual with iron deficiency anemia. Laboratory Testing If iron deficiency is suspected, analysis should include assessing the patient’s red blood cell status and iron status O Red Blood Cell status assessed by CBC O Iron status includes serum iron, serum ferritin, transferrin or total iron binding capacity (TIBC), and transferrin saturation Table 2.2 - Iron Profiles Iron laboratory profile Content Description Serum Iron Total iron in serum Acute phase reactant Serum Ferritin One of the most sensitive indicators of iron stores Storage of iron in tissue Transferrin Plasma protein used as an iron transport vehicle Total Iron Binding Availability of binding to transferrin Capacity (TIBC) Transferrin Saturation Serum iron / TIBC x 100 = % 76  MLT 104 Hematology 04 May 2022 Table 2.3 - Iron Reference Ranges Reference Ranges Transferrin Serum Iron Serum Ferritin TIBC Saturation 50 - 150 µg/dL Male: 15 - 250 µg/L 250 - 400 µg/dL 20% - 55% Female: 10 - 120 µg/L Relevant CBC Analytes RBC count Hgb HCT MCV MCHC Reticulocyte count Blood cell generation response to anemia Peripheral smear Microcytic, hypochromic cells, (Indicates deficiency in Hgb) Occasionally target cells, elliptocytes Iron profile Serum iron Ferritin Iron saturation TIBC 77  MLT 104 Hematology 04 May 2022 Topic 4: Anemias Related to Iron Overload Conditions Describe the iron overload conditions. Sideroblastic Anemias Accumulation of iron in the mitochondria Either Acquired or Hereditary. O Acquired as a result of: ▪ High transfusion protocol ▪ Alcoholism ▪ Lead poisoning ▪ Chloramphenicol O Hereditary (enzyme deficiency). Diagnosis: O Ringed sideroblasts ▪ Iron deposits in RBC precursors in bone marrow ▪ Siderotic granules when Prussian blue stain is utilized O Dimorphism in erythrocytes O Pappenheimer bodies ▪ Pappenheimer bodies in Wright’s stain. ▪ Confirm iron deposits with Figure 2.2 – Effects of Iron Overload Prussian blue stain O Increased serum ferritin O Increased serum iron 78  MLT 104 Hematology 04 May 2022 Describe the pathophysiology and clinical symptoms of hereditary hemochromatosis. Hereditary Hemochromatosis (HH) Rare disease compared to other blood disorders An autosomal recessive disorder O May be inherited homozygously or heterozygously. ▪ Homozygotes are more prone to iron overload while only 10% of heterozygotes. Begin to load iron excessively at a young age Caused by an abnormal gene called HFE. O HFE affects iron absorption. O Does not bind with transferrin causing iron to be continuously placed into storage. O Multiorgan damage and other symptoms over decades. Clinical symptoms: O Chronic fatigue and weakness O Cirrhosis of the liver O Hyperpigmentation O Diabetes O Impotence O Sterility O Cardiac arrhythmias O Tender swollen joints O Hair loss O Abdominal symptoms 79  MLT 104 Hematology 04 May 2022 Correlate the laboratory findings and clinical management of individuals with hereditary hemochromatosis. Diagnosis & Management of HH Table 2.4 - HH Laboratory Results Serum Iron Serum Ferritin Transferrin TIBC Transferrin Saturation elevated elevated normal normal elevated ֎Note: CDC guidelines for diagnosis = serum ferritin levels >300 µg/L and transferrin saturation levels >60% are indicative of HH (45-60% = borderline). Treatment: O Therapeutic phlebotomy O Administration of Desferal (deferrioxamine) – an iron-chelating agent Table 2.5 – Confusing Symptoms of Heredity Hemochromatosis Confusing Symptoms of Hereditary Hemochromatosis Symptom Possible Other Cause Chronic fatigue, weakness Could be seen in Iron Deficiency Anemia Cirrhosis of the liver Could be seen in alcoholism Cardiac arrhythmias Could be seen in valve problems, congestive heart failure Tender swollen joints Could be seen in collagen vascular diseases Hair loss, hyperpigmentation Could be seen in endocrine disorders 80  MLT 104 Hematology 04 May 2022 Topic 5: Thalassemia Syndromes Describe the basic defects in the thalassemia syndromes. Basic defects in Thalassemia Syndromes 2 million Americans carry the gene for thalassemia Defects of hemoglobin synthesis O Results from lack of production of alpha or beta globin chains Not enough functional hemoglobin produced Increased production of red blood cells with morphological abnormalities. O May develop to microcytic anemia and hypochromasia May require transfusions Iron status: O Not linked to iron problem 81  MLT 104 Hematology 04 May 2022 Describe the alpha thalassemic conditions with regard to gene deletions and clinical symptoms Alpha Thalassemias Each of the four (4) alpha thalassemia is a result of a deletion of one or more alpha genes O Alpha chain is critical in the formation of adult hemoglobin. High incidence in the Asian population (i.e., Thailand, Vietnam, Cambodia, Indonesia, and Laos). Also, among Saudi Arabian and Filipinos populations. Bart’s hydrops fetalis Complete absence of alpha globin chains O No Hgb A or Hgb F O Most severe Creation of Hgb Bart’s O Hgb created with 4 gamma globin (γ4) chains ▪ High O2 affinity O Incompatible with life O Leads to spontaneous abortion and stillbirth O If discovered, most pregnancies are terminated Figure 2.3 - Bart’s hydrops fetalis 82  MLT 104 Hematology 04 May 2022 Hemoglobin H disease 3 gene deletion, 1 functional gene (α chain) Hgb H (β4) formed instead of Hgb A O 5%–40% of Hgb is Hgb H O Next most severe Hgb H inclusions are formed O RBC resembles pitted golf ball when stained with supravital Clinical results O MCV > 60fL O Extremely elevated RDW O Hgb 6-8 g/dL O Reticulocytes 5%–10% O Schistocytes O Symptoms: anemia, splenomegaly, bone changes O Treatment, blood transfusion if needed Figure 2.4 - Hemoglobin H 83  MLT 104 Hematology 04 May 2022 Alpha thalassemia trait Two functional alpha gene Clinical results O 5-10% Hgb Bart’s O Mild anemia O Elliptocytes, target cells Silent carrier Three functional alpha gene Clinical results O Hematologically normal O MCV is in normal or low-normal range O Slightly microcytic O Few elliptocytes, target cells Figure 2.5 - Alpha Thalassemia Table 2.6 - Alpha Thalassemias Alpha Thalassemias Genes Condition Clinical Expression Hemoglobin Electrophoresis Deleted Bart’s hydrops 4 Stillborn, hydrops Hgb Bart’s (γ4) fetalis Microcytic, hypochromic, Hgb H Hgb H (β4) 5%-40% Hgb H disease 3 inclusions, high reticulocytes Hgb A approximately 60% Alpha Mild anemia, microcytic, Small levels of Hgb Bart’s thalassemia 2 hypochromic, elliptocytes, 5%–10% trait targets Normal hematology, with few Silent carrier 1 Normal elliptocytes, targets 84  MLT 104 Hematology 04 May 2022 Describe the beta thalassemic conditions with regard to gene mutations, clinical symptoms, and treatment Beta Thalassemia Major Cooley’s anemia or Mediterranean anemia Homozygous Little or no Beta (β) globin chain synthesis O Excess Alpha globin chains precipitate inside RBC ▪ Decrease RBC life span to 7-22 days Clinical results O Hgb 6–9 g/dL O Target cells and schistocytes O Polychromasia O High number of nRBCs O Howell-Jolly bodies O Hgb F on electrophoresis Symptoms: O No symptoms for first 3-6 months of life Figure 2.6 - Beta Thalassemia Major O Major symptoms begin at 2-4 years old ▪ Failure to thrive ▪ Changes in facial structures ▪ Pathological fractures ▪ Bossing or protrusions of the skull ▪ Enormous spleen ▪ Jaundice ▪ Anemia Treatment: O Transfusion ▪ May lead to iron overload ▪ Iron chelation O Splenectomy O Bone marrow transplantation ▪ High risk O Stem cell transplantation ▪ Depends on collected stem cells from umbilical cord 85  MLT 104 Hematology 04 May 2022 Beta Thalassemia Intermedia Beta thalassemia intermedia is a not well-defined subset of thalassemia major O Develop problems later in life Clinical symptoms O Larger spleens O Mild bone changes Treatments O Little or no need for transfusions Beta Thalassemia Trait (Minor) One abnormal beta (β) gene inherited (Heterozygous) Clinical results O Mimics IDA ▪ Except increased RBC count ▪ Increased EPO in response to anemia O May see basophilic stippling O Target cells on smear O Low Hgb and Hct levels Figure 2.7 - Beta Thalassemia Minor 86  MLT 104 Hematology 04 May 2022 Questions for Review: 1. Microcytic/Hypochromic anemia is defined by what indices and values? 2. Adults recycle % of iron for RBC production? 3. Your CBC shows decreased results in RBC count, Hgb, HCT, MCV and MCHC. What will you expect on a peripheral smear? 4. Alpha Thalassemia is the result of a deletion of one or more? 5. A patient is microcytic/hypochromic, has a high retic count and inclusions that give their RBCs a golf-ball look. What condition does the patient have? 87  MLT 104 Hematology 04 May 2022 Lesson: 2.2 Macrocytic Anemias Objective: 2.2.1 Differentiate the characteristics of Macrocytic Anemias. Topics: Megaloblastic Anemias Non-Megaloblastic Macrocytic Anemias Topic Objectives: Describe megaloblastic anemia as a macrocytic anemia. Describe the pathway of vitamin B12 and folic acid from ingestion through incorporation into the red cell. List the causes of vitamin B12 and folic acid deficiency. Describe red blood cell maturation during megaloblastic anemia to include the morphological changes seen in the peripheral smear Describe the clinical symptoms of a patient with megaloblastic anemia. Define pernicious anemia and its clinical and laboratory findings. Describe the laboratory tests used in diagnosing megaloblastic anemia. Describe treatments for megaloblastic anemias. Differentiate the anemias that are macrocytic but are not megaloblastic. 88  MLT 104 Hematology 11 June 2022 Topic 1: Megaloblastic Anemias Describe megaloblastic anemia as a macrocytic anemia Megaloblastic Anemia An anemia caused by a deficiency in vitamin B12 and/or folic acid This deficiency leads to impaired DNA synthesis A serious condition which affects: O All dividing cells ▪ Hematopoietic cells ▪ Epithelial cells ▪ Skin cells O With dramatic effects on the bone marrow. ▪ MCV >110 fL and normal MCHC Describe the pathway of vitamin B12 and folic acid from ingestion through incorporation into the red cell. Vitamin B12 (cobalamins) Found in: O Liver O Meat O Fish O Eggs O Dairy products Long term storage capacity Minimum requirement is 2.0 µg/day O Daily average consumption of 5-30 µg/day ▪ 1-2 mg is stored in the liver Vitamin B12 into storage Process described as follows: O Vitamin B12 is separated from food by salivary enzymes O Transported to the stomach ▪ B12 combines with intrinsic factor (IF) ▪ B12 requires functional IF for transport through the stomach O B12 /IF complex is transported to the ileum 89  MLT 104 Hematology 11 June 2022 O B12 is absorbed into the plasma to form a complex with transcobalamin II (TCII) for transportation through circulation ▪ IF is degraded in the ileum O B12 is transferred to the liver, bone marrow and other tissues for storage. Folic acid Found in: O Green leafy vegetables O Fruit O Broccoli O Dairy products Short term storage capacity Minimum requirement is 200 µg/day O Can be depleted within months ▪ 5-10 mg in the liver Folic Acid into storage Described as follows O Folic Acid movement into the circulation occurs with a little more ease O Upon ingestion, folic acid is absorbed through the small intestine O It is then reduced to methyl tetrahydrofolate (THF) by the action of mucosal cells enzyme, dihydrofolate reductase O Methyl group (reduced form of folic acid) is delivered to the tissues for storage O In tissue, methyl group combines with homocysteine, converting to methionine ▪ Flawed folate or Vitamin B12 metabolism causes homocysteine accumulation which may lead to thrombosis. Role of Vitamin B12 and Folic Acid in DNA synthesis Creation of Thymidine triphosphate (TTP) O Key component of DNA synthesis ▪ Enough Vitamin B12 and folic acid is needed to form TTP O TTP needs the methyl group derived from methyl tetrahydrofolate (MTH) to be synthesized O Vitamin B12 helps as a cofactor to transfer the methyl group to TTP O If no TTP is produced, it is replaced with DTP (deoxyuridine triphoshphate) which leads to: ▪ Nuclear fragmentation ▪ Destruction of cells ▪ Impaired cellular division 90  MLT 104 Hematology 11 June 2022 List the causes of vitamin B12 and folic acid deficiency. Dietary deficiency Vitamin B12 deficiency O Very rare O Causes: ▪ Vegetarians/vegans ▪ Infants of vegetarian mothers who did not take supplements Folic acid deficiency O Increased requirement ▪ Pregnancy/Infancy O Lack of availability ▪ In elderly ▪ Alcoholics Malabsorption syndromes Vitamin B12 deficiency: O Stomach malabsorption ▪ Helicobacter pylori or excessive antacid use ▪ Inhibits acid production so B12 is not released from food ▪ Lack of IF due to gastrectomy ▪ B12 is denatured by stomach enzymes O Intestinal malabsorption ▪ Blind loop syndrome ▪ Overgrowth of bacteria using vitamin B12 before it can be adsorbed. ▪ Fish tapeworm (Diphyllobothrium latum) which competes for vitamin B12. Folic Acid deficiency: O Tropical Sprue ▪ From tropical areas like Haiti, Cuba, and Puerto Rico. O Chemotherapy drugs ▪ Patients taking methotextrate which affects DNA synthesis 91  MLT 104 Hematology 11 June 2022 Describe red blood cell maturation during megaloblastic anemia and the morphological changes seen in the peripheral smear RBC Maturation Asynchronous maturation of red blood cell precursors O Makes it appear as though the nucleus and the cytoplasm are at different maturation stages ▪ Cytoplasm develops at the proper pace ▪ Nucleus develops slower ▪ Slows the maturation of the red blood cell, ending in a macrocytic RBC Ineffective Erythropoiesis O Premature destruction of red cell precursors before entering circulation O The bone marrow is unable to respond to anemic stress. ▪ Bone marrow becomes hypercellular ▪ Myeloid:erythroid ratio is 1:1 to 1:3 − Indicates erythroid hyperplasia O Consequences of Ineffective Erythropoiesis ▪ Intramedullary Hemolysis ▪ Increase in bilirubin and LDH. ▪ Lack of nRBCs and reticulocytes in peripheral smear. CBC MCV will be initially high, between 100 to 140 fL RDW is increased Pancytopenia Low reticulocyte count Peripheral smear Red blood cells O Macrocytes O Macro-ovalocytes O Schistocytes O Target cells O Teardrop cells O Inclusions ▪ Basophilic stippling (RNA) ▪ Howell-Jolly bodies (DNA) – Larger and more fragmented than normal 92  MLT 104 Hematology 11 June 2022 White blood cells O Hypersegmented neutrophils (>= 6 lobes) O Morphological indicator of megaloblastic anemias Describe the clinical symptoms of a patient with megaloblastic anemia. Symptoms of megaloblastic anemia includes: Shortness of breath Light-headedness Extreme weakness Pallor Glossitis (sore or enlarged tongue) Dyspepsia (indigestion) Diarrhea Neurologic involvement may be seen: O Numbness O Vibratory loss (paresthesias) O Difficulties in balance and walking Personality changes: O Mania O Disorientation O Depression O Impaired memory Demyelinization of the peripheral nerves, the spinal column, and the brain. O Spasticity O Paranoia Jaundice O Due to destruction of the red blood cells within 75 days; (Average is 120 days life span.) O Bilirubin will be elevated and LDH, indicating hemolysis. 93  MLT 104 Hematology 11 June 2022 Describe pernicious anemia and its clinical and laboratory findings. Pernicious anemia Lack of the intrinsic factor (IF), which is significant in the absorption of Vitamin B12. O IF may be blocked, neutralized, or not being secreted. ▪ Gastrectomy ▪ Atrophic gastritis ▪ Immune factors causing production of antibodies against IF. Laboratory findings lead to frequent diagnosis of diabetes, thyroid conditions and autoimmune disorders to affected individuals. Clinical and hematological findings are similar to all megaloblastic anemias: O Pancytopenia O Increased MCV O Hypersegmented neutrophils O Increased bilirubin O Hyperplasia in the bone marrow O Reticulocytopenia Describe the laboratory tests used in diagnosing megaloblastic anemia. Serum Vitamin B12 and Folic Acid Levels Radioimmunoassay (B12) O Value less than 200 ng/L indicates need for additional testing. Serum Test (Folate) O Chemiluminescence technique measures folate stored. Serum Methylmalonic Acid and Homocysteine Metabolites Methylmalonic Acid (MMA) and homocysteine are elevated when vitamin B12 is deficient. O They can detect even mild B12 deficiency O Important diagnostic indicators that, when used together, can differentiate B12 and folate deficiency. 94  MLT 104 Hematology 11 June 2022 Parietal Cell and Intrinsic Factor (IF) Antibodies Parietal cell antibodies are not specific for pernicious anemia but is seen in 90% of patients during initial diagnosis. Intrinsic Factor antibodies either block the binding of B12 to IF or prevents the IF- B12 complex from attaching to the small intestines. Describe treatments for Megaloblastic anemias. Administration of Vitamin B12 and Folic Acid Therapeutic vitamin B12 in the form of cyanocobalamin or hydroxycobalamin O Orally O Intramuscularly O Subcutaneously Lifelong treatment For patient with pernicious anemia: O 6,000 µg Vit B12 as initial dose over a 6-day period O If good response to the therapy, symptoms will diminish, and rapid reticulocyte response within 2 to 3 days. O Maintenance therapy follows for 1 to 2 months. For folate, this is a short term therapy with 1 to 5 mg/day for 2 to 3 weeks. 95  MLT 104 Hematology 11 June 2022 Topic 2: Non-Megaloblastic Macrocytic Anemias Differentiate the anemias that are macrocytic but are not megaloblastic. Megaloblastic features Macrocytes are large, and oval They have thick exterior membrane They lack hypochromia - Normochromic Non-Megaloblastic features: Round hypochromic macrocytes O Alcoholism O Hypothyroidism O Liver disease Blue-tinged macrocyte (Reticulocytes) O Seen in neonate response to anemic stress O Response to anemic stress Figure 2.8 - Differences in Macrocytes 96  MLT 104 Hematology 11 June 2022 Questions for Review: 1. In the stomach, B12 combines with what for transport? 2. What leads to the creation of nuclear fragmentation, destruction of cells and impaired cellular division? 3. Pancytopenia, increased RDW, and MCV between 100 to 140 fL may be indicative of? 4. Pernicious anemia is caused by what in 90% of patients? 5. Round, hypochromic macrocytes are typically seen in what type of anemia? 97  MLT 104 Hematology 11 June 2022 Lesson: 2.3 Normochromic Anemias Objective: 2.3.1 Differentiate the characteristics of Normochromic Anemias. Topics: Hereditary Membrane Disorders Hereditary Enzyme Disorders Topic Objectives: Describe the red cell membrane defect in hereditary spherocytosis. Relate the clinical findings and laboratory data to include red cell morphology in patients with hereditary spherocytosis. Describe the osmotic fragility tests and its clinical usefulness. Relate the red cell membrane defects, clinical findings, and laboratory data to include RBC morphology in hereditary stomatocytosis Relate the red cell membrane defects, clinical findings, and laboratory data to include RBC morphology of hereditary elliptocytosis (ovalocytosis) to include the various subtypes. Describe the mutations and ethnic distinctions in pyruvate kinase deficiency. Describe the mutations and ethnic distinctions in glucose-6- phosphate dehydrogenase deficiency 98  MLT 104 Hematology 11 June 2022 Topic 1: Hereditary membrane disorders Describe the red cell membrane defect in hereditary spherocytosis. Hereditary Spherocytosis (membrane defects) Common among Northern Europeans (1:5000) Inherited as 75% autosomal dominant and 25% autosomal recessive. Pathophysiology O The defect is represented by a deficiency in membrane proteins Spectrin & Ankyrin: ▪ Responsible for elasticity and deformability of the red cell membrane. ▪ Average red blood cell with 6 to 8 microns in size, must be able to pass through much smaller circulatory spaces. ▪ Protein band 3 ▪ Protein band 4.2 Spherocytes O Formed in the spleen O Cell ion and gas transportation is disrupted O Cells are unable to expand normally O Cell lacks flexibility to deform in microvasculature O The membrane is stretchable but less elastic; can only expand up to 3% before it ruptures Figure 2.9 - Spherocyte Structure 99  MLT 104 Hematology 11 June 2022 Relate the clinical findings and laboratory data to include red cell morphology in patients with hereditary spherocytosis. Hereditary Spherocytosis Clinical symptoms O Anemia O Jaundice O Splenomegaly O Cholelithiasis (Gall bladder Stone) Laboratory data O Increased bilirubin O Retic count 3% - 10% O Increased spherocytes in 97% of patients O MCV is normal O 50% of patients have MCHC >36% O RDW slightly elevated Describe the osmotic fragility tests and its clinical usefulness. Osmotic fragility test Confirmatory test for the diagnosis of Hereditary Spherocytosis. Cells are tested at varying salt concentrations, from isotonic saline (0.85% NaCl) to distilled water (0.0% NaCL) O Under isotonic condition, normal RBCs reach equilibrium and show little hemolysis. O As the solution becomes more hypotonic, less salt more water, initial hemolysis occurs as RBCs rupture. O Normal RBCs initially hemolyze at 0.45% NaCl O HS Patients are less able to tolerate an influx of water and lyse at 0.65% NaCl RBCs from patients with HS have a decreased surface: volume ratio and an increased osmotic fragility 100  MLT 104 Hematology 11 June 2022 Relate the red cell membrane defects, clinical findings, and laboratory data to include RBC morphology in hereditary stomatocytosis Hereditary Stomatocytosis Pathophysiology O Hereditary Stomatocytosis is a rare hemolytic disorder O Autosomal dominant O Red cell membrane has a deficiency of a protein, stomatin O The active-passive transport of ions (Na+ and K+) is disrupted O Stomatocytosis can also be seen in patients with Rh null disease ▪ Individuals that lack Rh antigens Clinical findings O Patients may display mild, moderate, or marked anemia that may be corrected by splenectomy Laboratory data O 10-30% stomatocytes present in the peripheral smear O RBCs appear as if the cells have slits or bars in the center, as if the cell is smiling ▪ Na+ in the RBC increases, followed by increased water and red cell swelling ▪ Decreased MCHC ▪ Increased MCV Relate the red cell membrane defects, clinical findings, and laboratory data to include RBC morphology of hereditary elliptocytosis (ovalocytosis) including the various subtypes. Hereditary Elliptocytosis (HE) Pathophysiology O All racial and ethnic groups O Autosomal dominant O The red cell membrane has a defective or deficient spectrin ▪ associated with alpha and beta regions Four Clinical subtypes O Common hereditary elliptocytosis O Southeast Asian Ovalocytosis O Spherocytic hereditary elliptocytosis O Hereditary pyropoikilocytosis 101  MLT 104 Hematology 11 June 2022 General clinical finding O Red blood cell deformability is affected with degrees of hemolysis General Laboratory data O Elliptocytes are present in varying degrees in each of the subtypes O Decreased MCV Clinical Subtypes of Hereditary Elliptocytosis Common Hereditary Elliptocytosis O Mild common HE ▪ Elliptical cells are present in 30-100% patients ▪ No clinical symptoms O Severe Common HE ▪ Seen more often in infants – as patient ages, disease converts to mild HE in presentation ▪ Moderate hemolysis ▪ Jaundice ▪ Fragmented cells ▪ May require transfusions Southeast Asian Ovalocytosis O Melanesia/Malaysian population O Autosomal Dominant ▪ Band 3 defect O Laboratory data ▪ Provides mild protection against malaria ▪ Cells strongly resistant to heat and rigid ▪ Cells may be spoon shaped ▪ Cells appear to have two bars across their center Spherocytic Hereditary Elliptocytosis O Northern European ancestry O Autosomal dominant O A cross between Hereditary Spherocytosis and Hereditary Elliptocytosis O Laboratory data ▪ Spherocytes and elliptocytes present ▪ Mild hemolysis ▪ Increased osmotic fragility ▪ Gallbladder disease and splenomegaly 102  MLT 104 Hematology 11 June 2022 Hereditary Pyropoikilocytosis O Rare and autosomal recessive, unlike most HE subtypes O Laboratory data ▪ Red cell budding, rare elliptocytes, and spherocytes in circulation ▪ Hemoglobin: