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258 Cards in this Set
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- 3rd side (hint)
What is Anisocytosis? |
It's a variation in cell SIZE |
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What part of a CBC is increased with anisocytosis? |
Red cell distribution width (RDW) |
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What classifies an RBC as microcytic? |
When it's < 80 fL |
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In what diseases do you see microcytosis? |
-Iron deficiency anemia -thalassemia -Chronic blood loss i.e. bleeding ulcers or GI bleeds |
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What does a blood smear look like with microcytic cells? |
It's thinner blood so its spread out more on the smear |
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What is macrocytosis? |
When the MCV is >100 fL |
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In what disorders would you see you macrocytic cells? |
- vitamin b12 deficiency enter - folate deficiency - liver disease - hypothyroidism - myelodysplastic disorders |
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What does polychromatophilic mean & what causes it? |
It means variation in color - other - red or blue - due to artifactual changes from staining and pH
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What is dimorphism? |
- 2 populations of cells - indicative of blood transfusions |
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What is polychromasia? |
When ribosomal RNA gives RBCs a blue tinge i.e. reticulocytes stained with super vital stain new methylene blue to confirm (but not always) |
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What are reticulocytes stained with and what do they look like? |
- not artefactual because they are not refractive - have to have at least two inclusions or it could be Heinz bodies - stained with new methylene blue |
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What are schistocytes? |
Fragmented red blood cells |
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What are helmet cells |
Another name for schistocytes |
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What is poikilocytosis? |
Change in red cell SHAPE |
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In what dIseases do you see target cells? |
- B12 / folate deficiency - thalassemia - hemoglobin C disease - liver disease |
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What are red cells called that have 2-10 spiny or thorny projections? |
Acanthocytes |
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In what dIseases do you see acanthocytes? |
- lipid metabolism disorders - liver disease - spleen removal - alpha beta lipoproteinemia |
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What are the RBCs called that have >30 short pointed evenly spaced projections? - also called echinocytes |
Burr/crenated cells |
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What causes burr cells? |
- when there's a chemical change in the blood - renal disease from toxins building up - can be from drying artifacts and water in stain |
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What causes schistocytes to form? |
- mechanical hemolysis i.e. heart valve replacement - DIC = dissociated intravascular coagulation - 3rd & 4th degree burns |
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In what conditions do you see spherocytes? |
- hereditary spherocytosis - autoimmune hemolytic anemia - burn patients |
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What are Dacrocytes? |
Teardrop cells |
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In what conditions do you see teardrop cells? |
- megaloblastic anemia (B12/folate) - myelofibrosis: RBCs are being infiltrated in the bone marrow so they are being 'squeezed' - bone marrow metastasis |
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In what conditions do you see elliptocytes and/or ovalocytes? |
- hereditary elliptocytosis and Ovalocytosis - megaloblastic anemia - microcytic anemia ( iron deficiency & thallasemia) |
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What is another name for a sickle cell? |
Oat cells... Because they have 2 pointed ends |
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What causes cells to be sickled? |
- Issue with hemoglobin S or C - decreased oxygen tension in the blood (running marathons or high altitudes) |
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What body part removes sickled cells? |
The spleen |
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What are the cells that have an elongated central pallor that looks like a mouth? |
Stomatocytes |
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What causes stomatocytes to form? |
- membrane abnormalities - liver disease - hereditary stomatocytosis |
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What are Howell Jolly bodies? |
Inclusions made of very dense chromosomal DNA remnants |
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How can you tell HJ bodies apart from platelets? |
Platelets will push away from the hgb causing a halo effect and will be more in focus than HJ bodies |
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What is 1 condition that causes HJ bodies? |
There will be an increase in these inclusions with a spleenectomy |
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Inclusions that look like a stack of cannonballs with smaller dots aggregated together are called... |
Pappenheimer bodies |
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What conditions do you see pappenheimer bodies form in? |
- chemical intoxication - heavy metal exposure - sideroblastic anemia - spleen dysfunction |
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What are pappenheimer bodies made of? |
Non-heme iron deposited in RBC mitochondria |
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What stain do you use to find/see pappenheimer bodies? |
Prussian blue |
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What causes basophilic stippling? |
- lead poisoning - thalassemia |
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What are fine to coarse granules of polyribosome aggregates evenly distributed in cell with mitotic spindles? |
Basophilic stippling |
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What are inclusions that look like lined up dots/stippling and are mitotic spindle remnants? |
Cabot rings |
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What conditions cause Heinz bodies to form? |
- thalassemia - Hemoglobin S & H - G6PD shunt defect - Exposure to oxidizing drugs (aspirin, vit. C, anti-malarial meds) - fava bean reaction |
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What are Heinz bodies made of? |
Denatured precipitated hgb |
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What stain do you use to display Heinz bodies? |
Supravital stain |
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How are hgb crystals formed? |
Formed in-vitro (in test tube) due to drying process |
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What is made from sodium citrate additive & are dense & rigid? |
Hemoglobin C crystals |
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What's another name for hgb C crystals? |
Washington monument crystals |
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What inclusions look like a gloved hand & are rigid? |
Hemoglobin SC crystals |
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What does it mean when bacteria/fungi (yeast)/parasites are found in the blood? |
It's a sign a patient Is septic and you report it immediately |
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What organism causes accole form rings on RBC edges? |
Plasmodium falciparum |
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What organism causes Schuffner's dots to form? |
Plasmodium vivax |
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What causes water artifacts to form? |
-humidity - not drying a slide completely before staining - they are very refractive and shiny |
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This cytoplasmic change causes larger/darker staining granules & is the body's response to bacterial infection |
Toxic granulation |
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This cytoplasmic change is found in the cytoplasm as residual RNA |
Dohle Bodies |
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This morphology is caused from coag & bleeding disorders b/c they don't like sticking together - exhibit hypogranular platelets (lg) and neutrophils (polymorphonuclear) |
Cytoplasmic agranulartiy |
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Intracellular bacteria |
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This is a dying/dead cell & it's starting to break down & dissolve |
Pyknotic cells |
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- These have 6+ lobes - Associated with Megaloblastic Anemia - Even 1 can be significant |
Hypersegmented neutrophils |
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Atypical Lymphs- just means it's moving away from normal morphology |
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These are seen in VIRAL RXNS i.e. Infectious Mono |
Reactive Lymphocytes |
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These are fragile, look like lymphs that are broken apart - Common in Chronic Lymphocytic Leukemia (CLL) |
Smudge Cells |
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Abnormal platelets |
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These are agranular, the size of RBCs or larger, found in leukemias - If more than 1 is found in 5 oil immersions fields- REPORT IT |
Giant, agranular platelets |
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Budding platelets from a megakaryoblast/cyte |
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platelet clumping: seeing this means clots are starting to form - Do we need to redraw the patient? |
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Platelet satellitosis: Plts adhere to neutrophil surfaces. - To prevent this, draw blood in Na+ citrate tube. |
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This is a group of disorders that have a hgb synthesis defect due to iron deficiency or abnormal iron utilization |
Microcytic Hypochromic anemias |
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This group of disorders include: - Fe+ deficiency anemia - Anemia of Chronic Disease - Sideroblastic anemia |
Microcytic hypochromic anemia |
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Anemia of Chronic disease includes what? |
1) Chronic Infection 2) Autoimmune diseases 3) Chronic Inflammation 4) Malignancies |
There are 4 |
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This is a type of microcytic hypochromic anemia that has a globin chain synthesis disorder |
Thalassemia(s) |
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- Cellular growth - Oxygen transport - RBC proliferation ** what are these 3 things indicative of? |
Normal Iron Requirements |
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What is the Avg. adult iron content in the body? |
3500-4000 mg |
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Where are the primary areas in the body that iron is stored in? |
- 2/3 in hemoglobin - 1/3 in BM, liver & spleen |
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How much iron is stored as ferritin or hemosiderin? |
~90% |
It's a percentage |
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What are the daily requirements of iron? |
- Infants: 1.0 mg - Children: 0.5 mg - Menstruating women: 2.0 mg - Pregnant/lactating women: 3.0 mg - Adult men/women: 1.0 mg |
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How much iron is absorbed from your diet? |
5-10% |
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What are some foods that ⬆ Fe+ absorption? |
- Acidic foods - Vitamin C |
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What kind of foods are iron rich? |
- Meat - Legumes - Green veggies i.e. spinach - Cereal (fortified) - Prunes - Whole grain bread/ oatmeal - Oysters/shrimp |
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What are some things that affect iron absorption? |
- Amount & type of iron in diet - Current iron stores - Erythropoietic needs (if you're anemic, the body needs more) |
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Where is Transferrin + Fe +3 located? |
Plasma |
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This is an iron binding transport protein found in plasma & extracellular fluid |
Transferrin |
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This is a receptor mediated ferric transferrin |
Transferrin receptor |
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Used for iron storage |
Ferritin |
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This binds w/ transferrin receptors... reducing the affinity for transferrin |
hemochromatosis gene protein (HFE) |
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This is an iron transport protein from GI lumen into the duodenal mucosal cell Erythroblast --> cytoplasm |
Divalent metal transporter 1 (DMT 1) |
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This is involved in iron metabolism. - ⬆ in iron overload - ⬇ in iron deficiency |
Hepcidin |
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This is a measure of transferrin bound iron Males: 65-170 ug/dL Females: 50-170 ug/dL *Morning specimens preferred due to diurnal variation |
Serum Iron |
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This is the total amount of iron that can be bound by transferrin in plasma or serum - Range: 250-450 ug/dL - 1/3 is normally saturated - It's an indirect measurement of transferrin concentration |
Total Iron Binding Capacity (TIBC) |
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This is measured as the max. amount of iron that's bound to plasma or serum - <16% indicates iron deficiency Males: 20-50% Females: 15-50% |
Transferrin Saturation |
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What is the formula for calculating Transferrin Saturation? |
% Saturation= (serum iron/TIBC) x 100% |
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This is directly proportional to the amount of stored iron & is a better measurement than TIBC or serum iron |
Ferritin |
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What is Ferritin's normal reference range? |
12-30 ng/mL |
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This is inversely proportional to the amount of body iron - ⬆ in iron deficiency ONLY when iron stores are depleted - No increase w/ Anemia of Chronic Disease |
Transferrin Receptor |
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This is a heme precursor that incorporates iron into the hgb molecule |
Free Erythrocyte Protoporphyrin (FEP) |
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This component inversely correlates w/ ferritin levels |
Zinc Protoporphyrins (ZPP) |
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This is available when iron is not. Excess protoporphyrins form & complex w/ zinc to form zinc protophyrins |
Free Erythrocyte Protoporthyrin (FEPs) Zinc Protoporthyrin (ZPPs) |
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This is the most common type of anemia |
Iron defiency anemia |
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This may occur b/c of: - ⬆ iron demands & blood loss - Abnormal iron utilization - Poor diet/ Malabsorption |
Iron Defiency Anemia (IDA) |
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What is involved in Stage 1 Iron Defiency Anemia (IDA)? - Stage 1 = Iron depletion |
- Asymptomatic - BM iron stores & ferritin: ⬇ - Hemosiderin: ⬇ or absent - TIBC & RDW: ⬆ - CBC & Morphology: Normal |
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What is involved in Stage 2 Iron Defiency Anemia (IDA)? - Stage 2 = Iron-Deficient Erythropoiesis |
- Ferritin, Iron, Hgb & Hct: ⬇ - ZPP, TIBC: ⬆ - Morphology: Microcytic - TfRs- ⬆ on RBC surfaces |
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What is involved in Stage 3 Iron Defiency Anemia? - Stage 3 = IDA development |
- Hgb & Hct: ⬇ - Erythropoietin levels: ⬆ - Morphology: Micro/hypo - BM: 'Ragged' erythroid precursors - Iron: Severely ⬇ |
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What are the clinical symptoms of IDA?
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- Fatigue, irritability, weakness - Headache - Shortness of breathe, tachycardia - Pale skin color - Pica |
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What are symptoms of severe IDA? |
- Doilonychias (Nail smoothing) - Muscle dysfunction - Pharyngeal webs - Glossitis (tongue inflammation) - Cheilitis (lip inflammation) |
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What are symptoms of infants/ children w/ IDA? |
- Developmental delays (motor/ behavioral) - Irritability, memory loss, poor growth - Increased chance of infections |
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What are the lab findings of someone with IDA? |
- Serum iron, ferritin: ⬇ - TIBC, FEP, serum soluble transferrin receptor levels: ⬆ - Morphology: Micro/hypo - Anisocytosis, storage iron & sideroblasts: ⬇ - Ringed sideroblasts: absent |
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These are used to treat this disease: - Find primary cause - Oral supplements (ferrous sulfate, gluconate, fumerate) - Parenteral- IV or intramuscular - Blood trx |
Iron Defiency Anemia (IDA) |
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This is seen after therapy: - Retics: ⬆ in 3-5 days/ max in 8-10 days - Hgb: ⬆ in 2-3 weeks/ normal in 6 weeks - Microcytosis: ~4 months to resolve - Normal cell pop. ~6-10 weeks - Iron stores: ~6 months for replenishment - Iron therapy response: 1 g Hgb ⬆ in 1 month |
Iron Defiency Anemia (IDA) |
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This is the 2nd most common form of anemia |
Anemia of Chronic Disease (ACD) aka Anemia of Inflammation (AOI) |
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This disease is common with these infections - TB - Chronic osteomyelitis - Fungal infections |
Anemia of Chronic Disease (ACD) |
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These neoplasms are associated w/ this disease state: - Carcinomas - Malignant lymphoma - Multiple myeloma |
Anemia of Chronic Disease (ACD) |
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These autoimmune disorders are associated w/ this disease: - Lupus (SLE= Systemic lupus) - Rheumatoid Arthritis (RA) - Sarcoidosis |
Anemia of Chronic Disease (ACD) |
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This chronic disease is said to block transfer of storage iron to erythroid precursors in BM. Possible causes: 1) Shortened RBC survival 2) BM fails to increase RBC production 3) Impaired Fe+ release from RES (Reticuloendothelial System) |
Anemia of Chronic Disease (ACD) |
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This disease state allows T-cells to become activated, makes more cytokines = ⬇ iron = ⬇ available RBC production |
ACD |
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- Normocytic, but may be hypo/normo - BM RBC precursors: normal - M:E ratio: 4:1 - Retic %: Not reflective - WBC/Plt counts: Normal - iron storage: Increased - Sideroblasts: decreased- w/ very coarse iron aggregates - Ringed sideroblasts: rare or absent - Low Erythropoietin levels |
ACD morphology findings |
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This disease shows: - Anemia present for months - Mild-moderate anemia - Normo/Normo: 60-70% - Micro/hypo: 30-40 % - Related to underlying cause |
ACD clinical features |
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This disease shows: - Iron, TIBC, % transferrin saturation: ⬇ - TfR: Normal - Ferritin: Normal/ ⬆ (due to trapped iron in RES cells in BM) |
ACD lab test findings |
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Ways of treating this disease: - Treat underlying cause 1st - Need to counteract effects of cytokines & stimulate iron uptake & heme synthesis - Blood trx (severe cases) |
ACD |
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This is a rare inherited condition - Congenital (sex-linked) - Autosomal recessive OR - is primary (idiopathic)- Acquired: Myelodysplasia OR- Secondary from lead, alcohol, or drugs |
Sideroblastic Anemia |
NEED to know if it's hereditary or acquired to treat it. |
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This disease has abnormalities of heme synthesis enzymes i.e. - Delta 5-aminolevulinic acid synthetase - Uroporphyrinogen decarboxylase Characterized by: Ringed Sideroblasts |
Sideroblastic Anemia |
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What significant RBC morphology is present in lead poisioning? |
Basophilic stippling - Mitochondrial aggregates or polyribosomes |
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This condition will cause these clinical findings: - People usually >50 yrs old - Weakness, pallor, fatigue (associated w/ anemia) |
Sideroblastic anemia |
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This condition will cause these morphologies: - Moderate-Severe anemia - Dimorphic RBC population - RDW: Increased (Aniso) - Hypochromia, basophilic stippling, pappenheimer bodies, target cells, poik - Hypercellular BM w/ RBC hyperplasia - >15% ringed sideroblasts |
Sideroblastic Anemia |
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These lab findings are present in this condition: - Iron, Ferritin, % saturation: ⬆ - TIBC & TfR: Normal or ⬇ |
Sideroblastic Anemia |
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This condition is acquired by lead poisoning or is hereditary from a single enzyme deficiency - Is a RARE disease w/ light sensitivities & there are a lot of them |
Porphyrias |
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This is an accumulation of excess iron in reticuloendothelial cells. - It's Inherited or secondary to chronic anemias & their treatments |
Iron Overload |
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- This is a clinical disorder from excess iron. - It has ⬆ intestinal iron absorption that leads to excess iron in tissue from tissue damage |
Hemochromatosis |
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These conditions cause excess iron to be stored in the liver, heart & pancreas- therefore- causing organ damage |
Iron Overload & Hemochromatosis |
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This condition is recessive, most frequent genetic disease in caucasians (affects 1 in 300 Irish, Scottish, Welsh descents) |
Hereditary Hemochromatosis (HH) |
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This rare genetic condition affects chromosome 6, short arm, HFE gene - Is a single base substitution of HFE protein, which alters the protein conformation & interferes w/ iron absorption regulation |
Hereditary Hemochromatosis (HH) |
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These symptoms are caused by gradual iron accumulation: - Chronic liver disease - Arthritis, diabetes - pituitary damage, congestive heart failure, cardiac arrhythmias |
Hereditary hemochromatosis pathophysiology |
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This condition absorbs 2-3x more dietary iron than normal (~3 mg/day) |
Hereditary Hemochromatosis |
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Stage 1: Genetic predisposition w/ no abnormality other than ⬆ serum transferrin saturation
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Hereditary Hemochromatosis |
The 1st of 4 stages of this condition |
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Stage 2: 2-5 g of iron overload w/o symptoms |
Hereditary Hemochromatosis |
The 2nd of 4 stages of this condition |
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Stage 3: Iron overload w early symptoms of lethargy & joint pain |
Hereditary Hemochromatosis |
The 3rd of 4 stages of this condition |
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Stage 4: Iron overload w/ organ damage & cirrhosis. Hepatomegaly is present in 95% of cases |
Hereditary Hemochromatosis |
The 4th of 4 stages of this condition |
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These are the early symptoms of this condition: - Fatigue - Joint Pain (most common) - Bronze skin discoloration - ED |
Hereditary Hemochromatosis |
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These are the chronic symptoms of this condition: - Enlarged liver, cirrhosis & fibrosis of liver, cardiomyopathy from iron deposits, diabetes, hypo-pituitary, -gonadism, -parathyroidism |
Hereditary Hemochromatosis |
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Lab results in this disease: - Erythropoiesis & TIBC: Normal - ALT, AST, Iron, ferritin, transferrin: Increased - Hallmark: % transferrin saturation increased >50% females & >60% Males |
Hereditary Hemochromatosis |
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Analyzing the HFE gene is diagnostic in confirming this disease |
Hereditary Hemochromatosis |
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The treatment of this disease is to remove excess iron - Usually by therapeutic phlebotomy - Or using desferrioxamine, a chelating agent |
Hereditary Hemochromatosis |
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The removal of 500 mL of blood 1-2x/week until decrease in % transferrin saturation (<30%) & serum ferritin (<50 ug/L)... then is done 2-4x/year |
Therapeutic phlebotomy |
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This is acquired or secondary to other anemias - It displays: anemia, iron overload, ineffective erythropoiesis - from trx, leads to iron storage increase (iron then can't be excreted) - Treatment: Iron chelation therapy |
Secondary Hemochromatosis |
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This is a macrocytic anemia caused by impaired DNA synthesis which causes defective nuclear maturation Result: Megaloblasts in BM & macro-ovalocytes in blood & WBC precursors are larger |
Megaloblastic Anemia |
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This condition is caused when DNA lacks bonding w/ dTTP & binds to dTDP instead |
Megaloblastic Anemia |
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These deficiencies cause this disease: - Vitamin B12 - Folic Acid ** Or combination of both |
Megaloblastic Anemia |
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This condition can cause mild- severe anemia -Symptoms: Weakness, fatigue, shortness of breath, dizzy - Congestive heart failure may be present if severe enough - ⬆ bilirubin = causes jaundice |
Megaloblastic anemia: Clinical manifestations |
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This condition's MCV = >100 fL - Ineffective erythropoiesis - Hemolysis - Ineffective granulopoiesis |
Megaloblastic Anemia |
Look on pg. 182 for more in-depth explanation |
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Bone marrow in this disease is hypercellular M:E ratio is 1:1-1:3 - Megaloblasts present - Giant bands & metamyelocytes - Megakaryocytes |
Megaloblastic Anemia |
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This condition is macrocytic/ normochromic - Pancytopenia (RBC/WBC/Plts) may all be decreased eventually - Macro-ovalocytes - Hypersegmented neutrophils - Schistocytes, teardrops, spherocytes, targets - Howell Jolly bodies - Basophilic stippling - Cabot rings - Megaloblasti nucleated RBCs |
Peripheral blood found in Megaloblastic anemia |
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Lab findings of this condition: -MCV: 100-160 fL - MCH, RDW: ⬆ - MCHC: Normal - Hgb: Normal or ⬇ - Abs. Retic count: ⬇ - RPI: <2.0 (Ineffective) |
Megaloblastic Anemia |
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What binds to vitamin B12 so it can be stored in the liver? |
TC II: Transcobalamin ** I & III bound to 70-90% ** II bound to 10-25% |
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These cause this deficiency: - Vegan diets - Malabsorption: Pernicious anemia, Blind loop syndrome, fish tapeworm, ileum disease - AIDS/HIV, hemodialysis - Drugs: Alcohol, nitrous oxide |
Causes of vitamin B12 deficiency |
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What is the definition of pernicious anemia? |
It lacks the intrinsic factor (caused from parietal cell atrophy) & is the most common form of vitamin B12 deficiency |
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This disease is most common in Scandinavian, English & Irish descent. More common in women @ 4:1 (>50 yrs of age) |
Pernicious anemia |
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This congenital form of the disease is seen as autosomal recessive & is primarily seen in children <2 yrs old |
Pernicious Anemia |
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This disease produces autoantibodies to Parietal Cells, Intrinsic Factor, thyroid tissue, & has increased association w/ other autoimmune disorders |
Pernicious Anemia |
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This disease involves autoantibodies binding to 2 types of Intrinsic Factor (IF): 1) Blocks Ab's, bind to vit. B12 binding site of IF 2) Binds Ab's, to vit. B12:IF complex Ab |
Pernicious Anemia-- Immunological factors |
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This disease has an insidious onset. Symptoms are: - Weakness, lightheaded, shortness of breath, appetite loss, Lemon-yellow pallor, Glossitis, Paresthesias, problems w/ fine motor movement & leads to neurological damage |
Pernicious Anemia |
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What is glossitis? |
Tongue Inflammation |
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What does paresthesias mean? |
Burning/numbiness/prickling sensation |
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What does Insidious mean? |
Slow onset |
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The early stages of this disease include: - Peripheral nerves affected - Pins & needles sensation in toes 1st, then moves to all limbs |
Pernicious Anemia |
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The later stages of development of this disease include: - Posterior spinal column degeneration - Clumsiness/ uncoordinated gait |
Pernicious Anemia |
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Severe symptoms of this disease include: - Severe weakness/ limb stiffness - Impaired memory - Retinal bleeding - Thrombocytopenia possible - Hallucinations, paranoia, stupor, severe depression |
Pernicious Anemia |
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This disease's severe neurological symptoms (paranoia, hallucinations, severe depression, stupor) are reversible if they've been experiencing them <3 months. If >3 months... not very reversible |
Pernicious Anemia |
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This deficiency is water soluble & has high turnover time & high rate of loss compared to vit. B12, so you see changes within a few months |
Folic Acid Deficiency |
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This nutrient is found in high concentrations in green leafy veggies, dairy, cereal, liver & kidneys |
Folic Acid |
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This nutrient's RDA= 50-100 ug/day. - Absorbed through duodenum & jejunum where ~80% is absorbed |
Folic Acid |
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A lack of this nutrient in the mother during pregnancy can cause the Spina Bifida birth defect |
Folic Acid Defiency |
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Causes of this deficiency include: - Decreased dietary intake (poverty, old age, alcoholism, chronic disease, malapsorption, tropical sprue, gluten sensitivity, celiac's disease) - Increased need (Pregnancy, infancy, malignancy, contraceptives) - Anti-malarial drugs |
Folic Acid Defiency |
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What is tropical sprue? |
Associated w/ folic acid deficiency, it's an infection that causes parietal cell atrophy - Causes: weakness, weight loss, fatty stools |
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This deficiency causes same issues as vit. B12 manifestations. - Insidious onset - Megaloblastic anemia in BM & blood - Do NOT see neurological issues in this (like B12 does) |
Folic Acid defiency |
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You do these lab tests to diagnose this deficiency: - CBC/Diff/RBC morphology - Retic Index - Lactate dehydrogenase (LD enzymes) - Iron Studies - BM aspirate (not often) |
Folic Acid Deficiency |
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Lab findings for this deficiency: - <200 (Normal: 200-500 ng/L) - Gastric Auto Ab's - Gastric atrophy test - Serum cobalamin binding proteins - Serum & urine methylmalonic acid (⬆100x) - Total homocysteine: ⬆ |
Vitamin B12 deficiency |
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These are found in the severe form of this deficiency: Serum folate: ⬆ RBC folate: ⬇ |
Vitamin B12 deficiency |
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These are lab findings for this deficiency: - Serum & RBC folate: ⬇ - Normal ranges: 5-16 ng/mL - Serum homocysteine |
Folic Acid deficiency |
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What 3 other tests evaluate for Macrocytic Anemia? |
1) Schilling's Test 2) dU suppression test 3) Holo TC II (used more often) |
Review on pg. 192 |
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This deficiency requires lifelong vitamin therapy (sometimes doses are 1000-2000 ug/day)
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Vitamin B12 deficiency |
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This deficiency requires oral therapeutic dosages of 1-5 mg/ day for 2-3 weeks. * Lifelong therapy not required |
Folic Acid deficiency |
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These deficiencies show a positive response when these show: - ⬆ retic count (3-10 days) - Megaloblastic morphology in BM disappears (24-48 hrs) - Hct: ⬆ (5-7 days) & normal in 4-8 weeks - Giant metamylocytes & hypersegmented neutros are gone in 2 weeks - Entire response: 3-6 weeks |
Megaloblastic Anemias: - Vitamin B12 - Folic Acid |
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This deficiency has a refractory or regenerative processing issue & BM is unable to respond to cytopenia in blood ** ⬇ cells/ ⬆ fat** |
Aplastic Anemia |
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This is the definition of this anemia: - Marrow of <25% normal cells - At least 2 cytopenias present: - Neutrophils: <500/uL - Platelets: <20,000/uL - Anemia w/ corrected retic count: <1% |
Aplastic Anemia |
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This disease is acquired in ~95% cases & ~40-70% is idiopathic - Congenital: <5%--> Very rare - Fanconi's anemia - Dyskeratosis Congenita |
Statistics of Aplastic Anemia |
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What are some secondary causes of Aplastic Anemia? |
- Chemical agents (insecticides, arsenic) - Drugs - Ionizing radiation (DNA breakage/genetic abnormalities) - Infections (Acute/Chronic hepatitis) - Miscellaneous immune based |
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- Pancytopenia over time - Malformed fingers, small head, stunted growth, mental retardation, CML development, die from hemorrhages or infection... all characteristic of what? |
Fanconi's Anemia, which is a severe, congenital form of Aplastic Anemia |
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What is Dyskeratosis congenita? |
A form of congenital Aplastic Anemia--- from short telomeres & is X-linked |
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This disease is insidious, occurs in all age groups - has progressive fatigue, dyspnea, palpitations, bleeding, infection, pallor, petechiae, purpura, mucosal bleeding |
Aplastic Anemia |
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These labs are needed for this condition: - CBC w/ diff - Retic count - BM exam - Liver & renal function tests - Cultures & serological tests |
Aplastic Anemia |
More info on pg. 197 |
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This is characteristic of what condition? |
This is a dry bone marrow tap-- no cells, just fat (Aplastic Anemia) |
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If this disease is left untreated a poor prognosis results-- Get lethal infections or bleeding |
Aplastic Anemia
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These are the standard treatments for this disease: - Support therapy: blood trx or steroids to stimulate hematopoiesis - BM or stem cell transplants (<50 yrs old) |
Aplastic Anemia treatment |
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This is a rare disorder where RBCs in BM are selectively destroyed |
Pure Red Cell Aplasia |
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This is characterized by: - Severe, chronic, normocytic- slightly macrocytic - Retics: ⬇ /absent - No hemolysis or hemorrhage - WBCs & Plts: Normal - BM: No RBC precursors - Erythropoietin Levels: ⬆ |
Pure Red Cell Aplasia |
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Causes of this disease includes: ACQUIRED - Parvovirus B19 infection: 5th's Disease (Hand/foot/mouth) - Aplastic crisis - Immunocompromised patients - Malnutrition, drugs, Direct toxicity, neoplasms |
Pure Red Cell Aplasia |
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Causes of this disease includes: CONGENITAL - Anemia: Chronic,mod.-severe - Onset: Early infancy - Retic Count: decreased - BM: erythroid hypoplasia & normocellular - Head & upper limb abnormalities - Spontaneous remission |
Pure Red Cell Aplasia |
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This disease causes spontaneous remission: - In 25% of patients - Many respond to steroids or trx - Increased AML incidence - Age of onset, severity & course of disease (variations) |
Pure Red Cell Aplasia |
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Type 1 of this disease includes: - Mild-mod. macrocytic anemia - Aniso & poik present - BM: 1-3% erythroblasts are binucleated / chromatin bridges - Autosomal recessive - Skeletal defects & skin hypopigmentation |
Congenital Dyserythropoietic Anemias (CDAs) |
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Type 2 of this disease includes: - HEMPAS: Hereditary Erythroblast Multinuclearity w/ Positive Acid Serum test ** Most common CDA - Autosomal recessive - Mild-severe normocytic anemia - BM: 10-50% bi- or multinucleated erythroblasts - Strongly agglutinated by anti-i - Ham's Test: RBCs lyse in acidified serum |
Congenital Dyserythropoietic Anemias (CDAs) |
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Type 3 of this disease includes: - Mild-mod. macrocytic anemia - 30% gigantoblasts (multinucleated erythroblasts w/ ~12 nuclei) - Autosomal dominant (monoclonal gammopathy) - Sporadic occurance: mental retardation & lymphoma related |
Congenital Dyserythropoietic Anemias (CDAs) |
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This is a rare, stem cell disorder characterized by recurrent episodes of hemoglobinuria & clots - Associated w/ aplastic anemia |
Paroxysmal Nocturnal Hemoglobinuria |
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This disease is caused by a mutation on the X chromosome by either insertion or deletion & causes a fringe area & INTRAvascular hemolysis |
Paroxysmal Nocturnal Hemoglobinuria |
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This mutation has a complete/partial deficiency of cell surface anchor protein glycophosphatidylinositol (GPI) - RBCs: Highly sensitive to complement mediated hemolysis |
Paroxysmal Nocturnal Hemoglobinuria |
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This disease state is found on the phosphatidyl inositol glycan A (PIG-A) gene |
Paroxysmal Nocturnal Hemoglobinuria |
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This disease state uses Flow Cytometry to test for presence/absence of markers - Also cannot bind to complement so it binds to & attacks RBCs |
Paroxysmal Nocturnal Hemoglobinuria |
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Clinical findings of this disease: - Insidious onset - Adults usually affected - Anemia: mild-severe (from chronic hemolysis) |
PNH |
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You diagnose this disease by collecting a 1st morning specimen: contains gross hematuria (25%) - During sleep, decreased pH (acidic) causes cell lysis |
PNH |
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This disease happens w/ infection, surgery, trx - And you verify w/ microscopic exam- there will be NO intact RBCs - Venous thrombosis (~33%) - Leukopenia @ some pt. |
PNH |
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This disease has hemosiderinuria as a constant feature & leads to IDA; hemolysis possibly leads to chronic renal failure due to tubular damage |
PNH |
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Lab findings of this disease: - Anemia: mild-severe - Blood smear: Normal w/ possible schistocytes -Retics: ⬆⬆ (5-10%) - Abs. retic: Possibly ⬇ - leukopenia: ⬇b/c WBCs more complement sensitive - Thrombocytopenia: 50-100,000 ⬇⬇⬇ - BM: Erythroid hyperplasia from chronic hemolysis - Indirect bilirubin: ⬆ |
PNH |
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This disease uses Sugar Water Test (Sucrose hemolysis test): - Sucrose med-low ionic strength - Promotes (C3) complement binding - Normal cells unaffected, but 10-80% RBC lysis |
PNH |
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This disease uses the Ham's Test to confirm after using the Sugar water Test |
PNH |
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This is the 'acidified serum lysis' test. The acidified serum activates complement via ALTERNATIVE pathway & allows C3 binding |
Confirmatory Ham's Test for PNH |
pg. 206 in notes |
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This disease lacks GPI anchor proteins & normal cells are unaffected. |
Ham's Test for PNH |
pg. 206 in notes |
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This test assesses presence or absence of GPI anchor proteins - uses monoclonal Ab's to CD55 & CD59 - Decrease/absence of expression is indicative of this disease |
Flow Cytometry testing used for Paroxysmal Nocturnal Hemoglobinuria (PNH) |
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This disease needs supportive treatment (blood trx- long term) - BM transplant is considered a cure - Chronic disease: many survive ~20-40 yrs after diagnosis (avg. ~10) - Death: results from blood clots, or hemorrhage - Some will go into remission or progress into AML |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
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This level rarely exceeds 3-4 mg/dL in uncomplicated hemolytic states |
Indirect (unconjugated) bilirubin |
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What is the normal level for serum haptoglobin? |
40-336 mg/dL |
-Reflects rapid clearance by RES of Hgb/haptoglobin complex |
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What other tests are done to test for hemolytic states? |
-Urine dipstick: hemoglobinuria & microscopic exam -Urine sediment: hemosiderinuria using Prussian Blue - Retic counts - RPI: >2.5 indicative of hemolytic state |
There are 4 other options to look at for finding hemolysis |
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What are some forms of hereditary hemolytic anemia that is due to an intrinsic defect? |
- RBC membrane & enzyme defects - Hemoglobinopathies - Thalassemia |
There are 4 main ones * structural defects are ALWAYS hereditary |
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What is 1 form of acquired hemolytic anemia that is due to an intrinsic defect? |
Paroxysmal Nocturnal Hemoglobinuria (PNH) |
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What are some forms of hemolytic anemia that are caused from extracorpuscular defects? |
- Immune hemolytic anemia - Infections - Exposure to chemicals, toxins, physical agents - Micro/macroangiopathic hemolytic anemia - Spleenic sequestering |
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What are some main features of RBC membrane structure? |
- membrane proteins provide strength & flexibility - Surface area to volume ratio - Cytoplasmic viscosity - Elastic properties (structural/ functional skeleton integrity) |
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What are the main protein components of a red blood cell? |
- SPECTRIN, ankyrin, adducin, band 4.1, band 3, band 4.2 - Hexagonal lattice shape |
**More details on pg. 211 of notes |
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This disease is autosomal dominant, common in N. European descent, usually deficient in SPECTRIN, ankyrin, Band 3 & 4.2 |
Hereditary Spherocytosis (HS) |
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This disease loses surface to volume ratio-- results: stomatocytes & spherocytes, cells have decreased deformability - Protein defects weaken vertical interactions w/ skeleton & lipid bilayer |
Hereditary Spherocytosis (HS) |
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This disease shows jaundice, anemia & enlarged spleen - Acholuric jaundice: lacking bile pigment & many have pigment gallstones - 1/4 of people asymptomatic - Age variable - Severe: Aplastic crisis from infection (parvovirus B19) & chronic leg ulcers |
Hereditary spherocytosis |
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Lab findings of this disease: - Increased bilirubin, retics, polychromasia, spheros, stomatos - MCV, MCH: normal - MCHC: >36% (~50% of cases) - Uses Osmotic Fragility Test |
Hereditary Spherocytosis |
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This tests an RBCs surface to volume ratio. It's a series of graded hypotonic salt solutions - Water enters cells, if hgb leaks out or cells burst- determines how tolerable a cell is to swelling |
Osmotic fragility test for hereditary spherocytosis |
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This hereditary disease state causes a 'shift to the right' b/c a cell lyses at higher salt concentrations than normal (since they're already full) |
Osmotic fragility test for hereditary spherocytosis |
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This test measures structural & metabolic integrity w/ glucose depletion conditions - Need to incubate RBCs 48 hrs @ 37 degrees in own plasma - In HS, autohemolysis of 10-50% |
Autohemolysis Test for HS |
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This is a rapid test similar in sensitivity & specificity to osmotic fragility - Lysing occurs within 5 min. vs. 30 min for osmotic fragility |
Acidified Glycerol Lysis Test for HS |
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This test shows SDS-PAGE... shows quantitative defects |
RBC Membrane Studies in HS |
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Treatment for this disease includes: - Splenectomy- but not recommended in children <6 yrs (can cause sepsis) - Children instead get prophylactic antibiotics |
Hereditary Spherocytosis (HS) |
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This disease is autosomal dominant & has an abnormality on the RBC membrane skeleton involving spectrin & band 4.1 - There are 3 phenotypes |
Hereditary Elliptocytosis (HE) |
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This is 1 of the phenotypes of this disease: - MOST COMMON FORM- especially in African populations - Hereditary Pyropoikilocytosis (HPP) - Retics: ⬆ - Haptoglobin: ⬇ |
Hereditary Elliptocytosis |
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This is 1 of the phenotypes of this disease: - It's rare and is a hybrid form of HE & HS |
Spherocytic Hereditary Elliptocytosis |
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This is 1 of the phenotypes of this disease: - It has a protective effect against malaria & is common in Melanesian/ southeast asian & South African populations |
Southeast Asian Ovalocytosis (SAO) |
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This is a very rare, severe hemolytic disease-- results from vertical AND horizontal defects - Has 2 genetic defects |
Hereditary Pyropoikilocytosis (HPP) |
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The 2 genetic defects of this disease are: - Mutant alpha or beta spectrin that impairs spectrin dimers - ⬇ synthesis of alpha spectrin (makes microspherocytes) |
Hereditary Pyropoikilocytosis (HPP) |
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The lab findings of this disease: - Microspherocytes, micropoikilocytes, fragments, maybe a few elliptocytes - MCV: ⬇ - MCHC: ⬆ - Osmotic fragility: pre & post incubation period ⬆ - Autohemolysis Test: ⬆ & unaffected by glucose |
Hereditary Pyropoikilocytosis (HPP) |
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These 2 diseases have horizontal molecular defects between proteins & skeletal membrane - Defective spectrin dimers or band 4.1 deficiency: means weak skeleton, distorted cells, cells lose ability to retain original shape |
Hereditary Elliptocytosis AND Hereditary Pyropoikilocytosis |
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This disease is very mild autosomal dominant hemolytic anemia. Has gene mutation for Band 3 - ⬆cell membrane rigidity & malaria resistance - found in southeast Asian malarial zones |
Southeast Asian Ovalocytosis |
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Lab findings of this disease: - >30% elliptocytes - MCV: normal or slight increase - MCH & MCHC: normal - Osmotic fragility: Normal - Autohemolysis test: Normal |
Southeast Asian Ovalocytosis |
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Treatments for this disease include splenectomy if it's uncompensated, otherwise there's no treatment in the compensated version |
Southeast Asian Ovalocytosis |
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What are 2 disease states that have membrane cation permeability (Na+/K+) defects? |
1) Hereditary Stomatocytosis 2) Hereditary Xerocytosis |
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This disease is also called hydrocytosis, have very swollen cells - 5-50% stomatocytes, Macrocytic - MCV: ⬆ (110-150 fL) - RBC K+ conc. ⬇ - RBC Na+ conc. ⬆ - Osmotic fragility: ⬆ |
Hereditary Spherocytosis (HST) |
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This disease has many target cells, RBCs look dehydrated - MCHC: ⬆ - Echinocytes w/ Hgb concentrated in 1 part of cells (it pools on 1 side of the cell) - Excessively permeable to K+ so it leaks out BUT is not replaced by Na+, so the cation conc. is ⬇ (meaning water loss in cell) - Osmotic Fragility: ⬇⬇ |
Hereditary Xerocytosis (HX) |
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What is the most common enzyme deficiency? |
G6PD |
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This disease state affects >400 million worldwide (highest #'s in dark pigmented ethnic groups) - X Chromosome mutation (men= full expression when inherited from mother & women= full expression when 2 mutant genes are inherited) |
G6PD deficiency of the hexose monophosphate pathway |
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This disease is mainly asymptomatic & 20% of activity is considered sufficient for normal RBC function & survival - See bite & helmet cells - Symptoms: back pain, hemoglobinuria & jaundice - Have sensitivity to fava beans: develop severe hemolysis after eating these beans or inhaling the plant's pollens |
G6PD defiency of the hexose monophosphate pathway |
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This disease has to account for family & drug history - RBC count: ⬇ 2-3 days after taking drugs (if drug induced) - Retics: ⬆ - Haptoglobin: ⬇ / absent - Normocytic/ Normochromic, Heinz bodies, bite/ helmet cells |
G6PD defiency of hexose monophosphate pathway |
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Tests for this disease include: 1) Methemoglobin reduction test 2) Fluorescent spot test |
G6PD deficiency |
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This test is done when RBCs fail to reduce metHgb in presence of methylene blue |
Methemoglobin reduction test in G6PD deficiency |
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This test is positive in G6PD ONLY deficiency - Mix G6PD+saponin+buffer+ blood sample put on filter paper - G6PD converts NADP-->NADPH - View under fluorescent light - If deficient in G6PD: Fails to fluoresce (+ test) - If the test fluoresces: (- test) |
Fluorescent Spot Test in G6PD deficiency |
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This disease is autosomal recessive (2 variants usually inherited, 1 from each parent) & both genders equally affected - Pennsylvania Amish has high frequency - Decreased ability to make ATP (lack of ATP results in cell water loss, shrinkage, distorted, rigid, early destruction) |
Embden-Meyerhof pathway enzyme PYRUVATE KINASE DEFICIENCY |
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This deficiency's severity depends on mutation & are true homozygotes--> anemic & jaundice @ birth, need trx throughout life - Anemia increases w/ infection or stress: jaundice, enlarged spleen, pigmented gallstones - RBC 2,3-DPG levels ⬆ =⬇ oxygen affinity |
Pyruvate Kinase Deficiency Embden- Meyerhof pathway enzyme deficiency |
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Lab findings of this disease include: - Normo/Normo, polychromasia, nRBCs, Poik & aniso - Retics: varied - Hgb, Hct, Haptoglobin: ⬇ - Unconjugated bilirubin: ⬆ |
Pyruvate Kinase Deficiency **Embden- Meyerhof pathway enzyme deficiency |
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Lab tests of this disease: - Fluorescent spot test: if blood lacks enzyme= NADH won't be oxidized =fluorescence lasts 45 min-1 hr. IF enzyme is present =fluorescence is gone in ~15 min - Quantitative: 5-25% normal - Osmotic fragility: ~normal - Autohemolysis: No correction w/ glucose addition |
Pyruvate Kinase Deficiency ** Embden- Meyerhof pathway enzyme deficiency |
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This disease state reduces ferric -->ferrous iron (+3 --> +2) - Methemoglobinemia occurs w/ decreased enzyme activity, production exceeds reducing capacity, Hgb M disease - Cyanosis occurs w/ increased metHgb levels - Normal metHgb: <1% |
Methemoglobin Reductase Pathway |
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This disease's congenital form is autosomal recessive & hetero zygotes are asymptomatic until drugs express them - The acquired form is induced by drugs/toxic substances that oxidize Hgb in circulation |
Methemoglobin Reductase Pathway |
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