NURS 212: Week 15 - Hematology Part 1

• Hemophilia


  Inherited hemorrhagic disease, serious bleeding disorders
• Hemophilia


  • First signs by age 3 to 4 years include episodes of persistent bleeding from minor injuries, prolonged bleeding with circumcision could be a sign of hemophilia
  • Inherited as an X-linked recessive disorder
  • Affects mostly males, females are usually asymptomatic carriers
• Hemophilia A


  Factor VIII deficiency, 1/10,000 males
• Hemophilia B


  Deficiency of factor IX, 1/50,000
• Hemophilia A and B are clinically indistinguishable because factor VIII and IX function together to activate factor X. Severity of clinical bleeding depends on the level of factor VIII and IX activity.
• Hageman Factor


  1. Thromboplastin from subendothelial cells (tissue factor)

  2. Faster

  3. Slower
• Hemophilia A


  Factor VIII deficiency
• Hemophilia B


  Factor IX deficiency
• Clinical Manifestations of Hemophilia


  • May have no symptoms with mild hemophilia unless stressed with surgery or trauma
  • Prolonged bleeding from trauma
  • Occasional spontaneous episodes of bleeding
  • Hemarthrosis is hallmark symptom (elbows, knee or ankle joints most commonly affected)
  • Bleeding into joint causes inflammation of synovium with pain and swelling
  • With recurrent joint bleeding may have fibrosis and contractures, can become major disability
• Hemoglobin (Hb)


  Protein contained in red blood cells that is responsible for delivery of oxygen to the tissues
• Normal Hemoglobin level


  For males: 14 to 18 g/dl, For females: 12 to 16 g/dl
• Anemia


  Reduction in the total number of circulating erythrocytes or a decrease in the quality or quantity of hemoglobin
• Causes of Anemia


  • Impaired erythrocyte production
  • Blood loss
  • Increased erythrocyte destruction
  • Combination of the above
• Decreased RBC production


  • Conditions include: Aplastic anemia, Chronic renal failure -↓ erythropoietin, bone marrow cell depression, deficiency of vitamins and minerals (Iron, B12, folate)
  • Inherited disorders leading to anemia: Sickle cell anemia, thalassemia, deficiency, glucose-6-dehydrogenase deficiency (G6PD)
  • RBC destruction disorders: Hemolytic disease of the newborn, antibody-mediated drug reactions
  • Acute Blood Loss: Trauma, surgery, or disease
• General Effects of Anemia


  • Tissue hypoxia due to the low O2-carrying capacity of the blood leads to compensatory mechanisms to restore tissue oxygenation
  • ↑ Cardiac and Respiratory function and increased O2 extraction at tissue
  • May cause shortness of breath (SOB), a rapid and pounding heartbeat, dizziness, and fatigue
  • In mild, chronic cases: symptoms may be present only when there is an increased O2 demand (physical exertion)
  • In severe cases, symptoms may be experienced even at rest
  • Mild to Moderate Anemia - Hemoglobin (Hgb) > 8g/dl
  • Moderate to Severe Anemia - Hemoglobin below 8g/dl
  • Hgb 9-11 g/dl in elderly patients or patients with cardiovascular or pulmonary disease may have symptoms
• Anemia Classification based on Morphology


  Mean Corpuscular Volume (MCV): reflects the size, or volume of RBC

  Microcytic - small

  Macrocytic - large

  Normocytic –normal size

  Mean Corpuscular Hemoglobin Concentration (MCHC): reflects concentration (or proportion) of Hgb in each cell

  Hyperchromic - ↑ Hgb

  Hypochromic - ↓ Hgb

  Normochromic (Hgb accounts for the color of RBCs)

  Mean Corpuscular Hemoglobin (MCH): reflects mass of RBCs (less useful in classifying anemia)
• Macrocytic - Normochromic Anemia


  Large, abnormally shaped erythrocyte with normal Hgb concentration
• Macrocytic Anemias


  • Pernicious Anemia: Lack of Vit B12, abnormal DNA and RNA synthesis in RBC, premature cell death

  Folate deficiency Anemia: Lack of folate, premature cell death
• Pernicious Anemia


  Caused by lack of intrinsic factor (IF) – the transporter required for absorption of dietary Vit B12 (required for DNA synthesis)
• Causes of Pernicious Anemia


  • Congenital IF deficiency

  Autoimmune gastritis (may be due secondary to H pylori infection)

  Chronic gastritis (excessive alcohol or hot tea ingestion and smoking)

  Gastrectomy – partial or complete

  Drugs - Proton pump inhibitors
• Pernicious Anemia


  • Develops slowly over 20-30 years

  Vague symptoms early in development

  Classic symptoms (Hgb ↓ 7 – 8 g/dl): Weakness, fatigue, Neurologic pathology: paresthesias of feet and fingers, difficulty walking, loss of appetite, abdominal pain, weight loss, and sore tongue that is smooth and beefy red

  Tx: Replace vit B12 (cobalamin) by injection
• Folate


  Essential for RNA and DNA synthesis in maturing erythrocytes
• Dietary intake of 50-200 mg/day of folate is required
• Sources of Folate


  • Vegetables (especially dark green leafy vegetables), fruits and fruit juices, nuts, beans, peas, dairy products, poultry and meat, eggs, seafood, and grains. Spinach, liver, yeast, asparagus, and Brussels sprouts are among the foods with the highest levels of folate.
• Folate Deficiency


  • Clinical symptoms similar to person with pernicious anemia except with no neurologic issues

  Specific manifestations include cheilosis (scales and fissures of the mouth), stomatitis (inflammation of the mouth), painful ulcerations of the buccal mucosa and tongue characteristic of burning mouth syndrome

  Tx – dietary intake of folate, manifestation of anemia disappear within 1 to 2 weeks
• Microcytic-Hypochromic Anemia


  Abnormally small erythrocytes that contain abnormally reduced amounts of hemoglobin
• Disorders causing Microcytic-Hypochromic Anemia

  • Disorders of iron metabolism

  Disorders of porphyrin and heme synthesis

  Disorders of globin synthesis
• Iron Deficiency Anemia


  Lack of iron for hemoglobin; insufficient hemoglobin
• Sideroblastic Anemia


  Dysfunctional iron uptake by erythroblasts and defective porphyrin and heme synthesis
• Thalassemia


  Impaired synthesis of alpha or beta chain of hemoglobin A; phagocytosis of abnormal erythroblasts in marrow
• Iron Deficiency Anemia


  • Most common nutritional deficiency in the world

  Unavailable iron for hemoglobin synthesis

  Low iron levels due to chronic blood loss, decreased absorption, increased requirements

  Hypochromic, microcytic RBCs, ↓MCV, MCH, and MCHC
• Forms of Dietary Iron


  • Heme iron: derived from hemoglobin, found in animal foods

  Nonheme iron: found in plant foods, less efficiently absorbed
• Glossitis


  • Tongue of individual with iron deficiency anemia has bald, fissured appearance caused by loss of papillae and flattening
• Pallor and Iron Deficiency


  • Pallor of the skin, mucous membranes, and palmar creases in an individual with a hemoglobin level of 9 g/dl. Palmar creases become as pale as the surrounding skin when the hemoglobin level approaches 7 g/dl.
• Normocytic-Normochromic Anemia


  Relatively normal erythrocytes in size and hemoglobin content but insufficient number
• Causes of Normocytic-Normochromic Anemia


  • Aplastic

  Posthemorrhagic

  Acquired hemolytic

  Anemia of chronic inflammation
• Aplastic Anemia


  • Stem cell disorder (decreased hematopoietic tissue in the bone marrow)

  Results in pancytopenia (decrease in RBCs, WBCs, and platelets) – anemic and susceptible to infection and difficulty clotting

  Acquired or familial

  Acquired: due to physical or chemical agents and viruses, e.g. post cancer chemotherapy

  Familial: hereditary defect
• Hemolysis of RBCs


  Lysis of RBCs - Hemoglobin released

  Globin is broken down into amino acids and iron is recycled

  Heme is reduced to bilirubin, which is transported to the liver and conjugated by the glucuronyl transferase

  Excessive lysis - Hepatocytes cannot conjugate and excrete bilirubin as rapidly as it is formed, so bilirubin enters the bloodstream, causing unconjugated hyperbilirubinemia and bilirubin deposits in tissues causing Jaundice
• RBC lysis and heme pathway
• the spleen filters blood to remove old or damaged red cells, bacteria, and other foreign particles from circulation.