Hematology 1 PDF

HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 1 TOPIC OUTLINE...

HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 1 TOPIC OUTLINE Thalassemia → MICROCYTIC, A. Erythropoiesis HYPOCHROMIC B. Reticulocytes Sideroblastic anemia→ MICROCYTIC, 1. Reticulocyte count HYPOCHROMIC ANEMIA i. Methods of counting reticulocytes ○ INSUFFICIENT ERYTHROPOIESIS → Decrease in ii. Methods of reporting reticulocyte counts the number of rbc precursors in the bone marrow C. Erythrocytes 1. RBC count (resulting in low rbc production = ANEMIA) 2. RBC Metabolic Pathways Examples of conditions: D. Red Blood Cell Anomalies iron deficiency → MICROCYTIC, 1. Anisocytosis HYPOCHROMIC ANEMIA 2. Anisochromia renal disease → NORMOCYTIC, 3. Poikilocytosis NORMOCHROMIC ANEMIA 4. RBC inclusion bodies acute leukemia → NORMOCYTIC, E. Hemoglobin NORMOCHROMIC ANEMIA 1. Hemoglobinometry ○ PROGENITOR CELLS → immature hematopoietic 2. Hemoglobin electrophoresis 3. Hemoglobin Synthesis cell that is committed to a cell line but CANNOT be 4. Hemoglobin derivatives identified morphologically (makikita pero hindi F. Hematocrit and ESR makikilala) 1. Hematocrit determination EX. BFU-E, CFU-E G. Related Topics ○ PRECURSOR CELLS → immature hematopoietic 1. Rule of Three cells that is morphologically IDENTIFIABLE as 2. Erythrocyte Indices belonging to a given cell line (makikita mo na, 3. Erythrocyte sedimentation rate makikilala mo pa) H. General Overview of Anemia EX. Rubriblast, Prorubricyte 1. Morphologic Classifications 2. Pathophysiologic Classification ○ CD71→ EARLIEST marker of erythroid I. Hemoglobinopathies differentiation; transferrin receptor (in the J. ThalassemiaS erythroid cells) ○ CD34→ classical marker of the HEMATOPOIETIC ERYTHROPOIESIS STEM CELLS ERYTHROPOIESIS → process of RBC formation (takes place inside the bone marrow) HORMONES RELATED TO ERYTHROPOIESIS 50% red marrow, 50% yellow marrow HORMONE REMARKS Site of formation: red marrow Erythropoietin Chief stimulatory cytokine for Related terms: (EPO) RBCs ○ ERYTHRON → Total mass of rbc circulating in the Major hormone that stimulates peripheral blood and the bone marrow rbc the production of erythrocytes precursors Thermostable, non dialyzable, ○ RBC MASS → erythrocytes in the circulation, total glycoprotein hormones population present inside the circulation (blood Primary cell / organ source: vessel only) ○ Organ: KIDNEYS ○ ERYTHROKINETICS → a term that describes the ○ Cells: Peritubular interstitial dynamics of rbc creation and destruction cells Lifespan of RBC: 120 days EXAMPLE BOARD EXAM QUESTION: ○ INEFFECTIVE ERYTHROPOIESIS What do you call the hormone Production of defective erythroid precursor produced by the kidneys for RBC cells (These defective RBC precursors often production? undergo apoptosis (programmed cell death) A) Erythropoiesis in the bone marrow before they have a B) --- chance to mature to the reticulocyte stage.) C) --- Happens inside the RED BONE MARROW, no D) Erythropoietin longer circulate in the blood vessel = patients Primary target cells: BFU-E and suffer anemia CFU-E Examples of conditions include ○ Affected by erythropoietin Vitamin B12 deficiency → MACROCYTIC, Normally, EPO is released from the NORMOCHROMIC ANEMIA kidney into the blood in response Folate deficiency → MACROCYTIC, to hypoxia (too little tissue oxygen) NORMOCHROMIC ANEMIA Three major effects:  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 2 ○ Allowing early release of CFU-E → colony forming unit-erythroid reticulocytes from the bone NTR: marrow BFU-E & CFU-E are committed erythroid progenitor ○ Reducing the time needed for cells (makikita pero di makikilala) cells to mature and the bone It takes about 18 to 21 days for the BFU-E to mature to marrow an erythrocyte, of which approximately 6 days are ○ Preventing apoptotic death spent recognizable precursors in the bone marrow. (note: apoptosis rescue is the MAJOR way in which EPO NOMENCLATURE SYSTEMS increases rbc mass) RUBRI NORMOBLAST ERYTHROBLAST Some of the current or potential Rubriblast Pronormoblast Proerythroblast therapeutic applications: Pro rubricyte Basophilic Basophilic ○ Anemia of chronic renal Normoblast OR erythroblast OR disease Early normoblast Early erythroblast ○ Autologous donation blood Rubricyte Polychromatophi Polychromatophili collection lic normoblast c erythroblast OR ○ Anemia and hiv infection to OR Intermediate Intermediate permit use of zidovudine Normoblast Erythroblast (AZT) Metarubricyte Orthochromatic Orthochromatic “BLOOD DOPING” → Some normoblast OR erythroblast OR athletes illegally use epo injections Late normoblast Late erythroblast to increase oxygen carrying Reticulocyte Reticulocyte Reticulocyte capacity of their blood Mature Mature Mature ○ To enhance endurance and erythrocyte erythrocyte erythrocyte stamina * not a precursor ○ can lead to deadly arterial *for as long you’re using supravital stain, Reticulocyte will be and venous thrombosis called the same; it will differ in name when using Wright’s stain GROWTH Produced by: Pituitary gland HORMONE Stimulates erythropoiesis directly NTR: in the BM 5 RBC Precursors under RUBRI: Rubriblast, prorubricyte, TESTOSTERONE Produced by: Testes rubricyte, metarubricyte, reticulocyte Stimulates erythropoiesis indirectly 3 nomenclature: Rubriblast, Normoblast, Erythroblast (stimulates kidneys to produce Polychromatic and polychromatophilic are the same more erythropoietin in the BM) When reticulocytes are found in a Wright-stained smear: Male hormone Polychromatophilic erythrocytes PROLACTIN Produced by: Pituitary gland Diffusely basophilic erythrocytes Stimulates erythropoiesis directly ------------------------------------------------------------------------------- ESTROGEN Produced by: Ovaries PRO = “before” Inhibits erythropoiesis indirectly META= “after” (pinipigilan ang process of RBC production; has an effect on kidneys - inhibits the production of more erythropoietin = BM of women less stimulated to produce RBC) Bakit magkaiba RBC COUNT in males and females? ○ Because of estrogen hormones in females (inhibits erythropoiesis) = lower RBC ct. STAGES ○ Testosterone stimulates 1. RUBRIBLAST (PRONORMOBLAST) kidneys to stimulate BM to This cell (rubriblast) gives rise to 2 prorubricyte. produce MORE red cells Earliest recognizable erythroid precursor using the Female hormone light microscope Capable of mitosis= produces 2 prorubricyte each RBC STAGES OF MATURATION Moderately basophilic with nucleoli BFU-E → burst forming unit-erythroid Additional information: N:C RATIO → 8:1  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 3 ○ A morphological feature used to identify and 3. RUBRICYTE (POLYCHROMATIC/ INTERMEDIATE stage RBC and WBC precursors NORMOBLAST) ○ A visual estimate of what area of the cell is Each of this cell (rubricyte) gives rise to 2 occupied by the nucleus compared with the metarubricyte cytoplasm “POLY” = many; many colors (CHROMA) ○ If the areas occupied by the nucleus and the May be confused with the lymphocyte cytoplasm or approximately equal the N:C ratio is ○ LYMPHOCYTE 1:1 Nucleus → CRUSHED VELVET ○ If the nucleus takes up < 50% of the area of the Cytoplasm → SKY BLUE/ “ROBIN EGG” cell, the ratio is lower ( eg. 1:5 or less than 1) BLUE ○ Is the nucleus takes up > 50% of the area of the ○ RUBRICYTE cell, the ratio is higher (eg. 3:1 or 3) Nucleus → CHECKERBOARD Basophilia → pertains to the blueness (BUGHAWWW) Cytoplasm → MUDDY or GRAY of a particular part of the cell and is due to the acidic LAST stage capable of mitosis components that attract the basic stain (example: First stage in which the cytoplasm becomes PINK methylene blue) ○ Cytoplasm of rubricyte = GRAY (because of the ○ Degree of cytoplasmic basophilia correlates with mixture of pink and blue) the quantity of ribosomal rna SIZE NUCLEOLI NUCLEUS CYTOPLASM Eosinophilia or acidophilia → pertains to the 10-12 um none Round and Basophilic to pinkness of a particular part of the cell and is due to smaller, pick diffusely lilac the accumulation of more basic components that nuclear in color attract the acid stain eosin membrane, (muddy or ○ As the rbc matures, the eosinophilia of the eccentric gray), nucleus depending on cytoplasm correlates with the accumulation of hemoglobin hemoglobin. NC ratio= 4:1 content SIZE NUCLEOLI NUCLEUS CYTOPLASM 4. METARUBRICYTE (ORTHOCHROMATIC/ LATE 12 to 20 um 1 to 2 Round or Small and NORMOBLAST) slightly oval, amount, thin nuclear moderately Nucleus is extruded at this stage, and the cell membrane, basophilic, becomes a reticulocyte. central or homogeneous Last stage that the RBC has its nucleus slightly NC ratio= 8:1 ORTHO- “the same” eccentric ○ Mature red blood cell = cytoplasm: saHmon pink 2. PRORUBRICYTE (BASOPHILIC NORMOBLAST) Other names: (total number of names: 7) The prorubricyte gives rise to 4 rubricyte ○ Nucleated RBC Capable of mitosis= produces 4 prorubricyte ○ Pyknotic erythroblast No nucleoli and has cell chromatin ○ Acidophilic normoblast The color of the cell is BLUE PYRENOCYTE Most helpful criteria in distinguishing the prorubricyte from the rubriblast ○ 1) Coarser chromatin ○ 2) Absence of nucleoli (pertains to the material found inside the nucleus) Last stage with nucleolus First stage of hemoglobinization (Hb synthesis) ○ Enveloped extruded nucleus ○ Hemoglobin -> eosinophilic material (pink) ○ Engulfed by bone marrow macrophages ○ Although it starts to creates Hb, it cannot be ○ Frequently, small fragments of the nucleus are seen under the microscope because of small left behind if the projection is pinched off before amount the entire nucleus is enveloped SIZE NUCLEOLI NUCLEUS CYTOPLASM The fragments inside the cell are called 10-15 um 0-1 round, thin Appears more HOWELL-JOLLY BODIES when seen in the nuclear abundant RBCs in the circulation membrane, than in Howell-Jolly bodies are typically removed smaller, normal blast slightly because of from the rbcs by the splenic macrophage eccentric smaller pitting crosses once the enter the NC ratio= 6:1 nucleus circulation Pag nawala spleen = more HJ bodies in circulation  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 4 SPLENECTOMY- surgical removal of the SIZE NUCLEOLI & CYTOPLASM spleen NUCLEUS SIZE NUCLEOLI NUCLEUS CYTOPLASM 7-8 um None Salmon pink (with a central 8-10 um none Pyknotic salmon pink pallor occupying ⅓ of the (dense mass cell’s diameter) of the degenerated NC Ratio = 1:2 RETICULOCYTES chromatin) RETICULOCYTE COUNT 5. RETICULOCYTE (DIFFUSELY BASOPHILIC RETICULOCYTE ERYTHROCYTE) ○ Immature, non-nucleated RBC which contains >2 blue stained, granulofilamentous materials (RETICULUM) after staining (supravital stains) In Wright stain, reticulum CANNOT be seen that’s why it’s called Diffusely basophilic erythrocytes ○ Continues to generate hemoglobin (last stage) ○ Normal maturation time for reticulocytes in blood: 1 DAY ○ Production of reticulocytes: 50x10^9/L/day *wright-stained Last young stage of RBC that appear in the circulation Last stage of hemoglobin synthesis Young RBCs containing residual RNA (last immature erythrocyte stage) Spends 2-3 days in the bone marrow and 1 day in the peripheral blood before developing into a mature RBC Shift Cells (POLYCHROMATOPHILIC MACROCYTE) ○ Seen in cases of increase RBC production Stress Reticulocytes (MACRO RETICULOCYTES) RETICULOCYTE COUNT ○ Seen in more severe conditions (ex. Hemolytic ○ Permits effective assessment of RBC production by anemia the bone marrow SIZE NUCLEOLI & CYTOPLASM ○ A measure of EFFECTIVE ERYTHROPOIESIS NUCLEUS REFERENCE RANGES: 8-10 um None Cytoplasm still with small ○ Adults: 0.5 to 1.5% amounts of RNA = ○ Newborns: 1.8 to 5.8% (by 1-2 weeks of age, polychromasia (mixed pink and reference values are the same as for adults) blue staining with Golgi ○ Increased (↑) reticulocyte counts (reticulocytosis) apparatus remnants and aka: POLYCHROMASIA or POLYCHROMATOPHILIA residual mitochondria that Considered as the first sign of accelerated allows continued aerobic erythropoiesis and observed in hemolytic metabolism and hemoglobin anemias (RBCs are continually lysed in generation circulation), individuals with iron deficiency 6. MATURE ERYTHROCYTE anemia receiving iron therapy, thalassemia, Shape: biconcave disk sideroblastic anemia, and in acute and Thickness: 1.5 to 2.5 um chronic blood loss. Average life span: 120 days When RBC mass is lessened, the BM is Number of erythrocytes produced from each stimulated to produce more RBCs at a faster rubriblast: 16 rate (accelerated erythropoiesis) = manifest Normal ratio of RBCs to WBCs is approximately 600:1 as increased retics (young rbc) and the normal ratio of RBCs to Platelets is approx. ○ Decreased (↓) reticulocyte counts 15:1 (reticulocytopenia): Adult RBC contains no mitochondria (no protein or Hb Observed in aplastic anemia and and synthesis) conditions in which the bone marrow is NOT producing RBCs  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 5 MATERIALS FLOW CYTOMETRY SUPRAVITAL STAINS MILLER DISK Most rapid, accurate, and precise method of 1. New Methylene blue reticulocyte count -More preferred for In this method, the reticulocytes are counted on the staining retics basis of optical scatter or fluorescence after treatment -Composed of: with fluorescent dyes or nucleic acid stains i. Sodium oxalate- The test values in this method or reported in absolute prevents and in relative terms coagulation Example: Sysmex R-3500 ii. Sodium Chloride- Calibrated disk placed in ○ Uses auramine O (a supervital fluorescent dye) provides the ocular of the ○ Reticulocytes fall into low-fluorescence, middle isotonicity microscope fluorescence or high fluorescence regions, with Large Square (A) less mature reticulocytes showing higher 2. Brilliant Cresyl blue ○ Is used for counting fluorescence. -Provides inconsistent RETICULOCYTES ○ Immature Reticulocyte Fraction (IRF) → Sum of staining results (not Small Square (B) the middle fluorescence, or high fluorescence preferred) ○ Is used for counting ratios -Composed of: RBCs Demonstrates an early indication of i. Sodium citrate- ○ Minimum # of cells erythropoiesis (sensitive index of bone prevents that should be marrow erythropoietic activity) coagulation counted: 112 The quantity of reticulocytes with the highest ii. Sodium Chloride- ○ 1/9th of square A content of RNA provides Indicates the ratio of immature reticulocytes isotonicity to total reticulocytes in a blood sample Used together with ARC to distinguish types METHODS OF COUNTING RETICULOCYTES of anemia ROUTINE LIGHT MICROSCOPE METHOD 1. Combine equal amounts of blood and supravital stain NTR: IMPORTANT (2-3 drops or around 50 uL each), and allow to incubate New methylene blue is chemically different from at room temperature for 3 to 10 minutes. methylene blue 2. Remix the preparation Brilliant cresyl blue also stains reticulocyte but shows 3. Prepare the two blood smears. too much unpredictability and staining for routine use 4. In the region and which cells are near each other but If a patient is very anemic or polycythemic, their NOT touching, count to 1,000 RBCs under the oil proportion of dye to blood should be adjusted immersion objective lens (1000x total magnification). accordingly. For the best results, a larger proportion of NTR: blood should be added to the stain when the patient Reticulocytes are included in the total RBC count hematocrit is low. add a smaller amount of blood to Reticulocytes are counted as both an rbc and a the stain when the patient has a very high hematocrit. reticulocyte The time allowed for staining of the reticulocyte is NOT 5. To increase accuracy, have another medtech count the critical. it should not, however, be less than 10 other blood smear; count should agree within 20%. minutes. 6. Calculation: Increased blood glucose or the use of heparin as 𝑁𝑜. 𝑜𝑓 𝑅𝑒𝑡𝑖𝑐𝑠 𝑜𝑏𝑠𝑒𝑟𝑣𝑒𝑑 anticoagulant may cause the reticulocytes to show fail 𝑅𝑒𝑡𝑖𝑐 (%) = 1,000 𝑅𝐵𝐶𝑠 𝑜𝑏𝑠𝑒𝑟𝑣𝑒𝑑 𝑥 100 staining. The blood and stain should be mixed well prior to making smears. The reticulocytes have a lower specific CALIBRATED MILLER DISK METHOD gravity than mature erythrocytes and, therefore, settle Count a minimum of 112 RBCs in a small square (b). on top of the red blood cells in the mixture. Reticulocyte in square be is counted as both an erythrocyte and reticulocyte. OTHER RBC INCLUSIONS STAINED BY NMB: At this point, theoretically, the number of retics and INCLUSIONS COLOR (NMB) REMARKS 1008 RBCs has been counted. Howell-Jolly Deep purple Nuclear Computation fragments 𝑇𝑜𝑡𝑎𝑙 𝑟𝑒𝑡𝑖𝑐𝑠 𝑖𝑛 𝑆𝑞𝑢𝑎𝑟𝑒 𝐴 𝑅𝑒𝑡𝑖𝑐𝑠 (%) = (𝑇𝑜𝑡𝑎𝑙 𝑅𝐵𝐶𝑠 𝑖𝑛 𝑆𝑞𝑢𝑎𝑟𝑒 𝐵 𝑥 9) 𝑥 100 Heinz bodies Light blue green -Usually present at thePeripheral edge of the red cell  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 6 -Denatured and ○ IRF is high because BM is starting to accelerate precipitated RBC production hemoglobin CORRECTED RETICULOCYTE COUNT Pappenheimer Purple -Generally appear Sometimes referred to as: bodies as several ○ Reticulocyte index (RI) granules in a ○ Hematocrit correction small cluster ○ Poor man's bone marrow aspirate -A wright-stained The percentage of reticulocytes may appear increased or prussian blue because of early reticulocyte release into the stained smear circulation or because of a decrease in the number of may be examined mature cells in circulation. (ANEMIA may cause falsely to confirm their ↑ reticulocyte count) presence The CRC corrects the observed reticulocyte count to a -Hemosiderin in normal Hct of 0.45 L/L (average normal for both the mitochondria genders) to allow correction for the degree of patient’s Hemoglobin H Greenish-blue -Multiple small anemia. bodies dots in and form Formula: 𝐻𝑐𝑡 𝑖𝑛 𝐿/𝐿 of alpha 𝐶𝑅𝐶 = 𝑅𝑒𝑡𝑖𝑐𝑠 (%) 𝑥 0.45 𝐿/𝐿 thalassemia SAMPLE CASE METHODS OF COUNTING RETICULOCYTES Patient: Male, 29 y.o. ABSOLUTE RETICULOCYTE COUNT (ARC) Lab results: Actual number of reticulocytes in 1 liter of whole blood Hct = 28% (0.28 L/L) - anemia = low rbc mass Helps us determine what kind of anemia is present Retic ct. = 5% (MAY BE high bc of accelerated Computation: erythropoiesis or falsely elevated bc of anemia) 12 𝑅𝐸𝑇𝐼𝐶𝑈𝐿𝑂𝐶𝑌𝑇𝐸𝑆 (%) 𝑥 𝑅𝐵𝐶 𝐶𝑂𝑈𝑁𝑇 (𝑥10 /𝐿) ○ NV: 0.5-1% 𝐴𝑅𝐶 = 100 𝑥 1000 BM should produce RBC at a faster rate; accelerating Reference range: 25 to 75 X10^9/L erythropoiesis Used together with IRF to distinguish types of anemias: CONDITION ARC IRF CRC = 3.11% -> HIGH (truly ↑) Hemolytic Anemia (an anemia ↑ ↑ with ↑ marrow erythropoiesis) Hemorrhage ↑ ↑ RETICULOCYTE PRODUCTION INDEX RPI (Also known as SHIFT CORRECTION) provides a Chronic Renal Disease ↓ ↓ further refinement of the CRC. Early Response to therapy in Normal ↑ A general indicator of the rate of erythrocyte nutritional anemias to ↓ production increase above normal in anemias. Hemolytic anemia and Hemorrhage have increased: Calculation: ○ ARC → BM is compensating for the loss of RBCs in 𝐶𝑂𝑅𝑅𝐸𝐶𝑇𝐸𝐷 𝑅𝐸𝑇𝐼𝐶𝑈𝐿𝑂𝐶𝑌𝑇𝐸 𝐶𝑂𝑈𝑁𝑇 the circulation by creating more RBCs in an 𝑅𝑃𝐼 = 𝑀𝐴𝑇𝑈𝑅𝐴𝑇𝐼𝑂𝑁 𝑇𝐼𝑀𝐸 𝐼𝑁 𝑇𝐻𝐸 𝑃𝐸𝑅𝐼𝑃𝐻𝐸𝑅𝐴𝐿 𝐵𝐿𝑂𝑂𝐷 accelerated rate ○ IRF → BM is actively producing RBC (an increased HEMATOCRIT (%) MATURATION TIME (Days) IRF means BM is creating erythrocytes, because 40-45 1.0 IRF is the younger form of reticulocytes) 35-39 1.5 Chronic Renal Disease → BM of patient is not 25-34 2.0 producing enough RBC anymore (↓ ARC) 15-24 2.5 ○ Take note: Kidneys create erythropoietin, the 3 ADEQUATE BM RESPONSE also no longer stimulated to produce more RBCs. RPI 8.0 um) RBCs (diameter ⅓ of diameter spherocytosis Usually microcytic GRADING OF HYPOCHROMIA (HARMENING) POLYCHROMATOPHILIC ERYTHROCYTES 1+ Area of central pallor = ½ of diameter 2+ Area of central pallor = ⅔ of diameter 3+ Area of central pallor = ¾ of diameter 4+ Thin Rim of Hb (ANULOCYTE) ANULOCYTE ○ A.k.a. “PESSARY CELL or GHOST CELL” ○ RBC with thin rim of hemoglobin and a large, clear center When Wright’s stain is used it is called DIFFUSELY ○ May be observed in iron deficiency anemia BASOPHILIC ERYTHROCYTE Larger than normal red cells with bluish tinge (wright’s HYPERCHROMIC CELLS stain) Bluish tinge →Caused by the presence of residual RNA Large numbers: associated with decreased RBC survival, hemorrhage or erythroid hyperplastic marrow. GRADING OF POLYCHROMASIA  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 12 Grade Percentage of Polychromatophilic RBCs deficiency, hepatic Slight 1% hemangioma, neonatal hepatitis, after heparin 1+ 3% administration, post 2+ 5% splenectomy, cirrhosis 3+ 10% of the liver with 4+ >11% associated hemolytic anemia. BURR CELL RBCs with regularly Uremia - characterized “ECHINOCYTES” spiculated surface by: marked ↑ in plasma urea and POIKILOCYTOSIS other nitrogenous Increased number of red cells with variation in SHAPE waste products Acidemia RED CELL DESCRIPTION EX. OF CONDITIONS electrolyte SPHEROCYTE Almost spherical in Hereditary imbalance (K+ shape; lacks the spherocytosis, elevation) central pallor autoimmune hemolytic normocytic, anemia, burns, ABO normochromic HDN, and following anemia transfusion of stored uremic frost (dirty blood skin) NTR: generalized Hyperchromic Spherocytes me be edema wrongly reported if one foul breath examines the feathered urine-like sweat edge of the blood film Pyruvate kinase because the RBCs in deficiency the said area lack OVALOCYTE Oval-shaped RBCs Hereditary Ovalocytosis central pallor “SOUTHEAST Natural rbc death can ASIAN result to spherocytic OVALOCYTOSIS” RBC ELLIPTOCYTE Elliptical -Hereditary Rh Deficiency (cigar-shaped) RBC Elliptocytosis STOMATOCYTE Elongated RBCs with syndrome, Alcoholism, -Thalassemia “Hered. “MOUTH CELL” the slit like central Leptocytosis, pallor (may be electrolyte imbalance, severe liver diseases, Mediterranean considered as an Anemia” overhydrated More oval than that artifact) hereditary of ovalocyte stomatocytosis Dehydrated hereditary DACRYOCYTE Pear-shaped or Primary Myelofibrosis stomatocytosis “TEARDROP teardrop shaped (PMF) (previously (HEREDITARY CELLS” RBCs known as myelofibrosis XEROCYTE: with myeloid XEROCYTOSIS) → Most common form metaplasia, chronic of stomatocytosis idiopathic → Characterized by the myelofibrosis, presence of xerocytes agnogenic XEROCYTES: myelofibrosis) - a dehydrated form of - an example of an a stomatocytes MPN - appears to have (myeloproliferative puddled at one hand neoplasm) (half-dark, half-light) some of the Abetalipoproteinemia characteristics: ACANTHOCYTE RBCs with irregularly “BASSEN-KORNZWEIG -splenomegaly “THORN CELL or spiculated surface SYNDROME and -in the marrow: SPUR CELL” HEREDITARY hypercellularity, ACANTHOCYTOSIS” increased → Characterized by megakaryocytes, and defective apo B fibrosis synthesis - in the PBS: immature → VLDL, LDL, granulocytes, chylomicron: NOT normoblasts, found in plasma dacryocytes, and other bizarre RBC shapes McLeod syndrome, Pyruvate kinase Megaloblastic Anemia, myelophthisic anemia,  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 13 after Heinz body DREPANOCYTE Sickle- or Sickle cell anemia, formation induced by “SICKLE CELLS or crescent-shaped Hemoglobin SC disease, drug ingestion, MENISOCYTES” RBCs etc. tuberculosis, tumor metastasized to the Two forms of drepanocytes: bone marrow, 1.) ISC (Irreversible sickle cells) thalassemia, and some Crescent shaped with long hemolytic anemias projections When reoxygenated: may SCHISTOCYTE Fragmented RBCs Patients with artificial undergo fragmentation “SCHIZOCYTE” heart valves, uremia, severe burns, MAHAs (microangiopathic 2.) OAT-SHAPED CELLS hemolytic anemias): Less pronounced projections -group of disorders When oxygenated, they return to characterized by RBC the original biconcave disk shape fragmentation and thrombocytopenia -major MAHAs: TTP, LEPTOCYTE RBCs which show a -Liver disease Certain HELLP, HUS, and DIC “CODOCYTE, centrally stained hemoglobinopathies -characterized by PLATYCYTE, area with a thin Thalassemia (Hered. narrowing or GREEK HELMET Leptocytosis & obstruction of small outer rim of CELL, MEXICAN Mediterranean blood vessels by fibrin hemoglobin Anemia) HAT CELL, or platelet aggregates BULL’S EYE CELL, -LCAT deficiency resulting in the TARGET CELL” “Lecithin Cholesterol fragmentation of RBCs acyltransferase -Helmet cell = helmets (“lecithin cholesterol shaped schistocyte that acyltransferase”) may appear in MAHA TTP (thrombotic thrombocy- BITE CELL Demonstrate a Glucose-6-Phosphate topenic purpura) “DEGMACYTE” semicircular defect Dehydrogenase HELLP syndrome in their edge (G-6-PD) deficiency (hemoly- sis, elevated liver (resembles a bite BOARD EXAM reg. enzymes, low mark) G6PD platelet count) Poikilocyte → Bite cell HUS (hemolytic Inclusion → Heinz uremic syndrome) Bodies -associated with BISCUIT CELL Folded RBCs Hemoglobin SC disease Escherichia coli serotype SEMILUNAR -As large as Frequently seen in O157: H7 infection BODIES leukocytes malaria and in other -characterized by: -Pale-pink staining conditions causing renal failure, overt hemolysis ghost of the red cell thrombocytopenia, HbsC (the membrane schistocytes (PBS), and remaining after the severe mucocutaneous Hemorrhage contents been DIC (disseminated released) intravas- cular -Folded RBCs coagulation) BRONZE -Bipolar/ Central Sickle cell anemia *Additional information about DIC ELLIPTOCYTE distribution of Hgb “DEFIBRINATION SYNDROME and CONSUMPTION COAGULOPATHY” RBC INCLUSION BODIES Generalized over-activation of the coagulation and INCLUSION CONTENT VISUALIZATION ASSOCIATED fibrinolytic systems CONDITIONS Not a disease but a result of a particular disease OR BASOPHILIC Aggregated Wright stain -Lead manifestation of an underlying disease STIPPLING RNA (deep blue to poisoning Some of the tests: D-dimer test and PF 1+2 (Prothrombin “PUNCTATE purple) (PLUMBISM) Fragment) BASOPHILIA” Supravital stain -Arsenic related conditions: T O M A S A poisoning -Pyrimidine-5’- ○ Tissue Trauma nucleotidase ○ Obstetric complication deficiency ○ Mucus-secreting tumor -Anemias with ○ Acute infections (ex: Malaria, Gram neg. septicemia) impaired ○ Snake bites hemoglobin ○ Acute Promyelocytic Leukemia synthesis (ex:  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 14 Thalassemia) severe -Refractory hemolytic anemias episode) -Alcoholism -expected -Megaloblastic inclusion anemias bodies in Two forms of basophilic stippling: favism: HEINZ a.) Fine stippling – usually observed when there is increase BODIES polychromatophilia -Drug-induced b.) Coarse stippling – may be observed in plumbism or other disorders hemolytic with impaired Hb synthesis, in megaloblastic anemia, and in other Anemias forms of severe anemia (DIHA) SIDEROTIC Intraerythrocyt Iron stains: -Sideroblastic -Unstable GRANULES ic collections of -Perls’ reagent Anemias hemoglobin “PAPPENHEIM iron through =characterized disease ER BODIES“ Prussian Blue by a dimorphic (congenital Rxn peripheral Heinz body (described as -Called: blood picture hemolytic multiple dark SIDEROTIC (presence of anemia) blue irregular GRANULES BOTH examples of Unstable Hemoglobin Variants: 1.) Hb Köln 2.) Hb granules [in normochromic Casper/Southampton 3.) Hb Genova 4.) Hb Gun Hill 5.) Hb M-Saskatoon Prussian blue New and 6.) Hb Bristol 7.) Hb Torino 8.) Hb Seattle iron staining]) Methylene hypochromic HEMOGLOBIN Precipitated Hb Supravital Hb H Disease (a (described as Blue and RBCs in the H INCLUSION H (Hb H – an stain: (subtype of pale blue Wright stain: same blood BODY abnormal Hb - NMB alpha clusters [in -Called: smear) composed of 4 - BCB thalassemia) Wright PAPPENHEIME -Thalassemia (described as β (beta) globin staining]) R BODIES -Hemochromat small, multiple, chains) NOTE: osis or evenly (denatured Appearance of Hemosiderosis distributed β-globin RBCs with Hb H HOWELL-JOLLY Remnants of -Wright stain -Megaloblastic throughout the chains) Bodies: BODIES nuclear New anemias red cell, -NOT “PITTED GOLF (description: chromatin -Methylene -After granular, demonstrated BALL” frequently (DNA) Blue splenectomy greenish-blue using Wright’s appears singly -Feulgen -Thalassemia bodies) stain in a cell (only reaction (+) one per cell), (*histochem. usually round, staining PARASITES -Protozoa/Prot Wright stain Parasitic and 10 cells/Greek helmet cells/ (Pappenheimer platycytes) bodies) Rouleaux formation “PSEUDO AGGLUTINATION” HEMOGLOBIN Aggregation of RBCs REFERENCE RANGE Caused by a serum AGE GROUP CONVENTIONAL SI UNIT protein abnormality UNIT (↑ fibrinogen or ↑ Children (8 to 13 y.o.) 12 to 15 g/dL 120 to 150 g/L globulins) Adult (male) 14 to 18 g/dL 140 to 180 g/L Often seen in Adult (female) 12 to 15 g/dL 120 to 150 g/L MULTIPLE MYELOMA(now HEMOGLOBIN called: PLASMA Main component of the red blood cell (approximately CELL MYELOMA) 95% of the cytoplasmic content of RBCs) also known as the: RESPIRATORY PIGMENT “STACKS OF COINS” concentration of Hb within RBCs: approximately 34 appearance of red cells g/dL Rouleaux may be wrongly molecular weight: approximately 64,000 Daltons reported if one examines the Felix Seyler identified the respiratory protein thick part of the blood film Hemoglobin (in 1862) because the red blood cells in About 65% of cytoplasmic hemoglobin is produced the said area are overlapping. before the nucleus is extruded, and the remaining 35% Sickle cells Basophilic stippling Whenever present, grade as is synthesized in the early reticulocyte Pappenheimer bodies POSITIVE ONLY Single most common complex organic molecule in Howell-Jolly bodies vertebrates 1 gram of hemoglobin can carry 1.34 mL of O2. SAMPLE CRITERIA FOR RBC MORPHOLOGY EVALUATION 1 gram of hemoglobin can carry a constant 3.47 mg MORPHOLOGY WNL 1+ 2+ 3+ 4+ IRON CHARACTERISTICS + Macrocytes > 9 0-5 5-10 10-20 20-50 >50 um COMPLETE ADULT Hgb MOLECULE IS COMPOSED OF 4 Microcytes 50 DIFFERENT CONSTITUENTS: Hypochromia 0-2 3-10 1052 50-75 >75 1.) A protein component (globin) composed of two sets of 0 two different polypeptide chains. Poikilocytes 0-2 3-10 10-20 20-50 >50 Globin (protein) is made out of amino acids (generalized 2.) Four molecules of the nitrogenous protoporphyrin IX variations in with hole (ring) in the middle. shape) 3.) Four iron atoms in the ferrous form (Fe+2) that combine Burr cell 0-2 3-10 10-20 20-50 >50 with protoporphyrin IX to create the four heme molecules Acantohocytes 50 or FERROPROTOPORPHYRIN IX. Schistocytes 50 4.) One 2,3-BPG molecule as a transient resident in the Teardrop 0-2 2-5 5-10 10-20 >50 center of the hemoglobin unit. poikilocytes (dacryocytes) GLOBIN CHAIN IN HEMOGLOBIN Target cell 0-2 2-10 10-20 20-50 >50 GREEK GREEK NAME NUMBER OF AMINO ACIDS (codocytes) DESTINATION Spherocytes 0-2 2-10 10-20 20-50 >50 Alpha 141 Ovalocytes 0-2 2-10 10-20 20-50 >50 Stomatocytes 0-2 2-10 10-20 20-50 >50 Beta 146 Sickle cell A Report as 1+ to indicate (drepanocytes) presence; do not quantitate Delta 146 Polychromatophili 20 a (ADULT) YA Gamma A 146 (position Polychromatophili 1-6 7-15 15-20 20-50 >50 136: alanine) a (NB) YG Gamma G 146 (position Basophilic 0-1 1-5 5-10 10-20 >20 136: glycine) stippling E Epsilon 146 Howell-jolly A 1-2 2-5 5-10 >10 Z Zeta 141 bodies  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 16 Theta Unknown Resolved through: Centrifuge reagent-sample solution, then the supernatant is PRIMARY FUNCTION OF HEMOGLOBIN measured 1. Delivery of oxygen to the tissues 2. To carry waste product CO2 away to the lungs Lipemia (Turbidity) Caused by fatty foods 3. Binding, inactivation, and transport of NO (Nitric Oxide) Add 0.01 mL of the patient’s plasma to 5 mL of the cyanmethemoglobin reagent and using this solution as the reagent blank PROTEIN STRUCTURE OF HEMOGLOBIN Fasting is not a requirement PROTEIN STRUCTURE REMARKS Cells containing HB S and HB C Abnormal hemoglobin that PRIMARY describes the amino acid cause turbidity in sample if sequence of the polypeptide not lysed chains Make a 1:2 dilution with SECONDARY describes the chain distilled water (1 part diluted arrangements in helices and sample plus 1 part water) nonhelices. and multiplying the results TERTIARY describes the arrangement of from the standard curve by 2. the helices into a pretzel-like Abnormal globulins (such as Can easily precipitated in the configuration or formation those found in patients with solution QUATERNARY (TETRAMER) describes the complete plasma cell myeloma or Add 0.1 gram of potassium hemoglobin molecule Waldenstrom carbonate to the (complete hemoglobin macroglobulinemia) may cyanmethemoglobin reagent. molecule is spherical, has precipitate in the reagent. Commercially available four heme groups attached cyanmethemoglobin reagent to four polypeptide chains, has been modified to contain and may carry up to four KH2PO4 salt, so this problem molecules of oxygen) is NOT likely to occur. Reminders: HEMOGLOBINOMETRY (HEMOGLOBIN DETERMINATION) ○ Cyanmethemoglobin reagent is sensitive to light Measurement of hemoglobin (should be stored in a brown bottle or in a dark Reference method: Cyanmethemoglobin (HiCN) place) Method (standard, best and most widely used) ○ Another technique that has been used in some ○ Principle: Hemoglobin (Fe2+) + K3Fe (CN)6 → automated instruments involves the use of methemoglobin (Fe3+) + KCN → sodium lauryl sulfate (SLS) to transform cyanmethemoglobin hemoglobin to SLS-methemoglobin. This method ○ Ideal specimen: Fasting blood specimen (but not does NOT produce toxic wastes. required) ○ HemoCue –an example of a commercially ○ Uses Drabkin’s reagent - major components: available handheld system to measure the Potassium ferricyanide (K3Fe(CN)6) hemoglobin concentration converts the hemoglobins into Parameter: ONLY hemoglobin methemoglobin Screen potential donors → BB section Potassium cyanide (KCN) In here, hemoglobin is converted to Provides cyanide ions azidemethemoglobin and is read HiCN is measured at 540 nm (spectrophotometer) (All photometrically at two wavelengths (570 types of Hb may be measured through this method, nm and 880 nm). EXCEPT: SULFHEMOGLOBIN - cannot be converted to cyanmethemoglobin HEMOGLOBIN ELECTROPHORESIS ○ Turbid = falsely elevated Electrophoresis - movement of charged particles in an Possible source of error: electric field SOURCE OF ERROR (FALSE CORRECTION CELLULOSE ACETATE (pH 8.4-8.6) ELEVATED Hb) Considered as the primary screening procedure to High WBC count Values of High WBC (>20 x detect variant (abnormal) hemoglobins High platelet count 10^9) and High PLT ct (>700 x In an alkaline buffer (8.4 to 8.6) hemoglobin is a 10^9/L) negatively charged molecule  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 17 During electrophoresis, the Hb molecules travel toward the anode (+) because of their net negative charge ○ Positive pole - anode ○ Negative pole - cathode ○ Positively charged ions - cations ○ Negatively charged ions - anions The difference in the net charge of the Hb molecule Complementary procedure to cellulose acetate Hb defines its mobility and reveals itself by the speed electrophoresis (something that completes) with which it migrates to the positive pole. Hemoglobin exposed to acidic environment → FASTEST = Hb H (an abnormal hemoglobin; composed different charges of 4 beta globin chains; not found in normal individuals; exist in circulation of individual with Hemoglobin H disease) ○ In normal individuals, the fastest si Hb A1 ○ If ever coexisting happens (both Hb A and Hb H present), Hb H is still faster than Hb A SLOWEST = Hb C, HbA2, Hb E, Hb CHarlem, Hb OArab ○ same migration pattern → cannot identify what Some are negative charge, some are positive charge type of hemoglobin present ○ F,A,A2 might be positively charged while S and C NOTE: Hb S, Hb D and Hb G migrate to the same area might be negatively charged at cellulose acetate electrophoresis → difficult to Used to confirm variant hemoglobins and further identify what type of hemoglobin present differentiates hemoglobin S from D and G, and hemoglobin C from hemoglobins E, OArab, CHarlem ○ Ex. Patient 4 in Cellulose acetate develop band in S portion and also developed band in S portion of Citrate agar → confirmed na Hb S HEMOGLOBIN SYNTHESIS HEME SYNTHESIS HEME a.k.a. Ferroprotoporphyrin IX Belongs to class of pigments known as porphyrins Site of heme synthesis: Mitochondrion Heme biosynthesis: ○ occurs in all metabolically active cells containing mitochondria ○ most prominent in bone marrow and liver. ○ Erythroid marrow is the MAJOR heme-forming tissue, generating 85% of the daily heme requirement. Ferrochelatase - aka: Heme synthetase - enzyme needed to insert the Ferrous form of iron to the center of protoporphyrin IX Numbers: Patient sample Letters: Legend Bottom to top orientation Patient 2: hemoglobin exposed in alkaline buffer → develop a net negative charged→ hb A (same as Hb A1) Patient 4: develop a net negative charged (migrate toward the anode) → Hb S (possible but not finally) → same migration pattern as Hb D and Hb G CITRATE AGAR (pH 6.0-6.2)  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 18 FUNCTIONAL Hgb OXYHEMOGLOBIN DEOXYGENATED Hgb Symbol: HbO2 Hb w/ Fe2+, NOT Hb w/ Ferrous form of bound to oxygen iron + Oxygen Found in venous Found in arterial blood blood (Dark Red) (bright red) Conformation of Conformation of Hb in Hb in the the oxygenated state: R deoxygenated state (relaxed) state: T state MedTech does not (Tense) perform arterial puncture Glycine + Succinyl-CoA → within the mitochondrion Aminolevulinic Acid → Cytosol DYSHEMOGLOBINS Protoporphyrin IX (ring form) + Ferrous form of iron CARBOXYHEMOGLOB METHEMOGLOBIN SULFHEMOGLOBIN (FE) = heme IN Must be ferrous form Symbol: HbCO Symbol: Hi Symbol: SHb Hb w/ Fe2+ Other names: Mixture of (Ferrous ferrihemoglob oxidized, GLOBULIN SYNTHESIS form), bound in, partially Site: ribosomes in the normoblast cytoplasm to CO (carbon hemoglobin denatured Chromosome 16 = dictates the production of A and Z monoxide) Hb w/ Fe3+ forms of Hb Chromosome 11 = dictates the production of B,E,D and Carbon (ferric form), Causes: G globin chains monoxide - NOT bound to Prolonged FORMS OF HEMOGLOBIN (ACCORDING TO STAGE OF LIFE) form of O2 constipation, poison, can Color of enterogenous HgB MOLECULAR PROPORTION PROPORTION lead to death blood cyanosis, STRUCTURE (%) IN NB (%) IN ADULTS in large (methemoglo bacteremia (older than 1 quantity binemia): (caused by C. yr) CO gas Chocolate perfringens) - Has 240 times brown Color of Portland ζ2γ2 0 0 greater affinity blood: 2 zeta, 2 to Hb than O2 Mauve-Laven gamma - Tasteless, der Gower I ζ2ε2 0 0 colorless and 2 zeta, 2 odorless gas NOTE: epsilon - Color of blood In-vitro, Gower II α2ε2 0 0 and skin in HbCO sulfhemoglobin 2 apha, 2 poisoning: forms when epsilon (SHERRY) cherry hydrogen sulfide is F (Fetal Hb) α2γ2 80 37 mm/h has higher samples are then left to sediment for a specific period incidence of disease progression and death 18-degree slant of the tubes with respect to the ○ In coronary artery disease: ESR >22 mm/h in vertical axis: causes acceleration in sedimentation, white men had high risk of CAD allowing results comparable to those of Westergren at ○ In patients with known cancer: when value the 1st hour to be obtained in only 25 minutes, while exceeds 100 mm/h, metastases are usually those comparable to Westergren at the 2nd hour present. require only 45 minutes ○ ESR - indicated in establishing the diagnosis and The optoelectronic sensors automatically read the RBC in monitoring polymyalgia rheumatica and sedimentation level. temporal arteritis (rate typically exceeds 90 REFERENCE RANGE mm/hr) AGE GROUP MODIFIED WINTROBE ○ Moderate elevations - common in active WESTERGREN inflammatory disease like rheumatoid arthritis, Adult (male) 0 to 10 mm/hour 0 to 9 mm/hour chronic infections, collagen disease, and Adult (female) 0 to 15 mm/hour 0 to 20 mm/hr neoplastic disease (NOTE: ESR has little diagnostic Female - mas mabilis magfall ang RBC value in these disorders, but can be useful in STAGES OF RBC SEDIMENTATION monitoring disease activity) FIRST 10 MINS NEXT 40 MINS LAST 10 MINS REMINDERS: Lag Phase Decantation Final settling Rouleaux phase phase ESR is prone to technical errors. formation occurs Rapid and RBC ESR has low specificity and sensitivity. Therefore, it is ○ Rouleaux constant sedimentatio NOT recommended as a screening test to detect formation - RBC n is slower inflammatory conditions in asymptomatic individuals.  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 22 aggregation sedimentati Diabetes mellitus of RBC on End-stage renal ○ Increased failure Fibrinogen Hepatitis or Globulins Gout → bibilis Malignancy bagsak RBC Menstruation → mas Multiple mabilis ESR Myeloma APRs (acute Waldenstrom’s phase reactants) macroglobulinemia → proteins that Myocardial increase in infarction inflammation Rheumatic fever ○ Fibrinogen, Rheumatoid Globulins arthritis Syphilis DYSHEMOGLOBINS Temporal arteritis FACTORS ESR INCREASED ESR DECREASED Nephrosis Proteins and lipids ↑ cholesterol ↑ albumin Tuberculosis in the blood ↑ fibrinogen ↑ glucose Adults over 60 ↑ gamma globulins ↑ bile salts years of age ↓ albumin ↑ phospholipids (frequently have ↓ fibrinogen a slightly higher ↓ gamma globulins ESR value due primarily to Red blood cells Anemia Polycythemia decreased (decreased RBC) (increased RBC) concentrations of Macrocytosis Anisocytosis plasma albumin) (marked) Pregnancy Microcytosis Acanthocytosis Technique Refrigerated Clotted blood Hemoglobin C sample NOT sample Sickle cells returned to room Delay in testing Spherocytosis temperature Bubbles in ESR Thalassemia High room column temperature Low room White blood cells Leukemia Leukocytosis Vibration temperature (marked) Tilted ESR tube Narrow ESR Drugs Dextran Adrenocorticotro column diameter Heparin pic hormone Penicillamine (corticotropin) Procainamide Cortisone NTR: Theophylline Ethambutol Tilted ESR tube- “A tilt of as little as 30 from the vertical can Vitamin A Quinine cause error of up to 30 → Place on a flat surface ; tubes Salicylates must be placed in a separate stable surface/table → vibrate Clinical conditions Inflammatory Cachexia will accelerate yung pagbaba ng RBC sa bottom conditions Congestive heart (associated with failure CASE STUDY increased plasma Newborn status proteins, Because of lack of space in the laboratory, the rack of particularly, sedimentation rate tubes was placed directly on top of a fibrinogen, alpha small refrigerator. What are the three possible effects on globulins, and beta the ESR results? globulins) 1. A falsely decreased (↓) ESR– because of lower Infections (acute temperatures from air rushing out on opening the and chronic) refrigerator or freezer Subacute 2. A falsely increased (↑) ESR – because of vibrations from bacterial endocarditis opening and closing the refrigerator and freezer doors Acute heavy 3. A falsely increased (↑) ESR – because of heat released metal poisoning from the refrigerator motor Collagen vascular Must be at room temp diseases GENERAL OVERVIEW OF ANEMIA  HEMATOLOGY 1 By: RJAR Dinglasan, RMT | 23 ANEMIA ○ Described as a rare but potentially deadly bone Manifestation of the diseases marrow failure defined as the decrease below normal of one or more ○ Characteristic features: of the following: Pancytopenia (marked decrease in the ○ Number of red blood cells number of RBCs, WBCs, and platelets in the ○ Hemoglobin blood) ○ Volume of packed red cells (hematocrit) Reticulocytopenia ○ Bone marrow hypocellularity MECHANISM OF ANEMIA: Depletion of hematopoietic stem cells HEMORRHAGE ○ May be classified as: Loss of erythrocytes through bleeding must always be Acquired aplastic anemia the INITIAL FOCUS in any patient with anemia and Approximately 80% to 85% of aplastic must prompt an evaluation of the hemostatic system. anemia cases Bleeding - may be secondary to trauma, surgery, or a 2 categories disease ○ Idiopathic acquired aplastic Gastrointestinal tract - a common site for clinically anemia - no known cause significant bleeding ○ Secondary acquired aplastic Menstruation – a significant source of blood loss in anemia women Associated with an ○ Automatic ba na nagkaka anemia during identified cause menstruation? Some causes include NO especially if you are eating well (iron Chemicals (insecticides, rich food) benzene) HEMOLYSIS Viruses (Epstein-Barr shortened erythrocyte survival time NOT explained by virus) bleeding Drugs average survival time of RBCs after leaving bone (Chloramphenicol) - marrow: 120 days most frequently implicated in acquired DECREASED PRODUCTION OF ERYTHROCYTES aplastic anemia Nutritional deficiencies (iron, vitamin B12, or folic acid) Inherited Aplastic Anemia are common and readily correctable causes of Approximately 15% to 20% of aplastic hypoproliferative anemia. anemia cases Kidney disease may be associated with decreased Associated diseases: production of EPO ○ Dyskeratosis congenita ○ Shwachman-Bodian-Diamond MORPHOLOGIC CLASSIFICATION syndrome More commonly used