Hematologic Pathology p36-47

RBC Disorders

Tues. 10/19/10

Erythropoiesis:

Goal: formation of RBCs – oxygen transport Site: bone marrow Main growth factor: erythropoietin Duration: 5 days (from proerythroblast to reticulocyte) Lifespan of RBC: 120 days Test q: The normal lifespan of RBCs in peripheral blood is: 120 days.

Anemia vs. Polycythemia: Anemia: Decrease in Hgb and hematocrit levels in relation to age- and sex-adjusted normal ranges. - Signs: Pallor, Fatigue, Dizziness, Tachycardia, Shortness of breath Polycythemia: Increase in hemoglobin and hematocrit as compared to normal ranges - Signs: Headache, Pruritus, Dizziness

Red cell indices: - Hemoglobin (Hb) : concentration, in g/dL - Hematocrit (Hct) : proportion of blood volume that is occupied by RBCs - Mean cell volume (MCV) : average volume of RBC expressed in femtoliters - Mean cell hemoglobin (MCH) : average mass of hemoglobin per RBC, in picograms - Mean cell hemoglobin concentration (MCHC) : average concentration of hemoglobin in dL of packed RBCs, g/dL - RBC distribution width (RDW) : CV of RBC volume, size variability Can separate RBCs from the rest of the blood.

Determining the Concentration of Hemoglobin:

RBC distribution width (RDW):

 Figure: The potassium ferricyanide oxidizes hemoglobin to hemiglobin (Hi; methemoglobin), and potassium cyanide provides cyanide ions (CN-) to form HiCN, which has a broad absorption maximum at a wavelength of 540 nm. Figure: RDW  Abnormal in anisopoikilocytosis (abnormally shaped RBCs).

Adult Reference Ranges for RBCs: The reference ranges for the laboratory providing the result should always be used in interpreting the test result. Advantages of the electronic cell counter  - Speed of performance - elimination of visual fatigue of the technician - Improved precision are decisive Morphologically discernable stages of erythroid development: • Proerythroblast • Basophilic erythroblast • Polychromatophilic erythroblast • Orthochromatic erythroblast • Reticulocyte • Mature RBC

Bone marrow

Blood

Maturation:

When passing through bone marrow sinus, nucleus is extruded.

Reticulocyte count: • Enumeration of reticulocytes indicates production of new red blood cells by the marrow – Manual using supravital dye to precipitate residual RNA – Automated in a cell counter • Corrected reticulocyte count: actual patient value corected with an expected release of reticulocytes in health Polychromasia:

Reticulocyte: Wright-Giemsa

Supravital Live-nonfixed cells Methylene blue/brilliant cresyl blue

Polychromasia (purple tinge)

Polychomatophilic – more purplish/bluish

Substantia reticulofilamentosa (Amount of precipitated RNA decreases w/age of the reticulocyte.)

Reticulocytes – Supravital stain:

Automated Reticulocyte count: RNA binding dye

Reticulocyte count: Decreased • Iron deficiency • B12/folate deficiency • Anemia of chronic disease • Primary marrow neoplasms • Aplastic anemia

Test q: Reticulocytes are DECREASED in all of the following EXCEPT: Hemolytic anemia. (Other choices: Aplastic anemia, Iron deficiency anemia, Leukemia, and Folate deficiency.) Test q: A healthy 19F suffered blunt abdominal trauma in a motor vehicle accident. On admission to the hospital, her initial hematocrit was 33%, but over the next hour, it dropped to 28%. A paracentesis yielded serosanguineous fluid. She was taken to surgery, where a liver laceration was prepared and 1 L of bloody fluid was removed from the peritoneal cavity. She remained stable. A CBC performed 3 days later is most likely to show which of the following morphologic findings in RBCs in the peripheral blood? Reticulocytosis. (= increase in reticulocytes)

Increased • Hemolytic disorder • Treatment of iron or B12/folate deficiency with response • Bleeding

Anemia: • Reduction of the total circulating red cell mass below normal limits • reduces the oxygen-carrying capacity of the blood, leading to tissue hypoxia • In practice, the measurement of red cell mass is not easy, and anemia is usually diagnosed based on a reduction in the hematocrit and the hemoglobin concentration of the blood to levels that are below the normal range

Anemia: Clinical features • Pale, weakness, malaise, and easy fatigability • ↓O2 → dyspnea, fatty change in the liver, myocardium, and kidney • Hypoxia – Myocardial → angina pectoris, particularly when complicated by pre-existing coronary artery disease – CNS →headache, dimness of vision, and faintness

Anemia according to underlying mechanism: • BLOOD LOSS • INCREASED RED CELL DESTRUCTION (HEMOLYSIS) • DECREASED RED CELL PRODUCTION

Anemia – paleness of mucosa and skin.

Classification of anemia based on MCV and RDW: MCV

             

High RDW

Microcytic 100 fL

– Aplastic anemia – Myelodysplastic syndromes

– B12/folate deficiency – Liver disease – Alcohol – Thyroid insufficiency – Myelodysplastic syndromes

Above: Different problems correlate with different steps in maturation.

ANEMIAS OF BLOOD LOSS: Acute Blood Loss – loss of intravascular volume – massive -cardiovascular shock, and death. – rate of hemorrhage, external or internal bleeding – ↓O2 →↑erythropoietin from the kidney → proliferation of committed erythroid progenitors (CFU-E) in the marrow →5 days →reticulocytes

Normal RDW

ANEMIAS OF BLOOD LOSS: Chronic Blood Loss – Chronic blood loss induces anemia only when the rate of loss exceeds the regenerative capacity of the marrow or when iron reserves are depleted and iron deficiency anemia appears Microcytosis pattern: – Normal RBC size ~ nucleus of small lymphocyte – Most common causes: – Iron deficiency – Hemolysis – Thalassemia (globin synthesis defect)

Iron deficiency: – Most common cause of anemia across the age groups – Most common nutritional deficiency world-wide – US: toddlers, adolescent girls, and women of childbearing age – Iron present as: – Functional (hemoglobin, myoglobin. enzymes) – Storage iron (ferritin, hemosiderin) – 15-20% total  Intracellular ferritin (aggregates form hemosiderin) and plasma ferritin  Hemosiderin prominent in iron overload  Transferrin as transporter of iron in plasma

Microcyte: