ANEMIA

• ANEMIA – Not a disease, only a manifestation of another disease. Defined as the decrease below normal of:

  Number of red blood cells

  Hemoglobin

  Volume of packed red cells (hematocrit)
• Mechanisms of anemia include hemorrhage, hemolysis, and decreased production of erythrocytes.
• Hemorrhage is the loss of erythrocytes through bleeding and should always be the first focus in the diagnosis of anemia.
• Gastrointestinal tract is a common site for clinically significant bleeding.
• Menstruation is a significant source of blood loss in women.
• Hemolysis is a condition where the average survival time of erythrocytes is shortened and the cause is not explained by bleeding.
• The average survival time of erythrocytes after leaving the bone marrow is 120 days.
• Decreased production of erythrocytes can be caused by nutritional deficiencies such as iron, vitamin B12, or folic acid, which are common and readily correctible causes of hypo proliferative anemia.
• Kidney disease may be associated with low production of EPO.
• Normal or Decreased Reticulocyte Count:

  APLASTIC

  KIDNEY DISEASE

  ACUTE BLOOD LOSS (NOT CHRONIC)
• NORMOCYTIC, NORMOCHROMIC ANEMIAS

  (MCV and MCHC =both normal)
• Increased Reticulocyte Count:

  PNH (MACHIAVA MECHELI SYNDROME; DEF IN DAF AND MIRL; DEF IN COMPLEMENT REGULATORY PROTEIN)

  PCH (AUTO ANTI-P; AKA DONATH LANDSTEINER HEMOLYTIC ANEMIA)

  SICKLE CELL DEFICIENCY

  ENZYME DEFICIENCY (G6PD, PK DEFICIENCY)

  OTHER HEMOLYTIC ANEMIA
• APLASTIC ANEMIA - RARE BUT POTENTIALLY DEADLY (BONE MARROW FAILURE SYNDROME)

  Pancytopenia (marked ↓ in the number of RBCs, WBCs, and platelets in the blood)

  Reticulocytopenia

  Bone marrow hypocellularity

  Depletion of hematopoietic stem cells
• Acquired Aplastic Anemia - approximately 80 to 85% of aplastic anemia cases

  2 categories:

  Idiopathic acquired aplastic anemia – no known cause

  Secondary acquired aplastic anemia - identified cause

  Chemicals (ex.: insecticides, benzene)

  Viruses (ex.: Epstein-Barr virus)

  Drugs (ex.: chloramphenicol)

  Chloramphenicol = drug most frequently implicated in acquired aplastic anemia
• No known cause

  Idiopathic acquired aplastic anemia
• Identified cause

  Secondary acquired aplastic anemia
• Inherited Aplastic Anemia - approximately 15% to 20% of aplastic anemia cases

  Associated diseases:

  Dyskeratosis congenita

  Shwachman-Bodian-Diamond syndrome

  Fanconi Anemia (FA) - most common

  Chromosome instability disorder

  Characterized by: aplastic anemia, cancer susceptibility, and physical abnormalities

  Skeletal abnormalities (ex.: thumb malformations, microcephaly, scoliosis)

  Skin pigmentation (ex.: hyperpigmentation, hypopigmentation, café-au-lait lesions)

  Short stature

  Abnormalities of the eyes, kidneys, and genitals

  FA is NOT the same as Fanconi Syndrome
• PAROXYSMAL NOCTURNAL HEMOGLOBINURIA A.k.a Marchiafava Mecheli Syndrome

  Caused by deficiency of:

  DAF (decay-accelerating factor, or CD55)

  MIRL (membrane inhibitor of reactive lysis, or CD59)

  Tests for PNH:

  HAMS ACIDIFIED SERUM TEST

  SUGAR WATER TEST (SUCROSE HEMOLYSIS TEST)

  FLOW CYTOMETRY (CONFIRMATORY FOR PNH)
• MICROCYTIC, HYPOCHROMIC ANEMIAS:

  Small cells that have increased central pallor on the smear

  (MCV and MCHC = Both LOW)

  Iron level insufficient for maintaining normal erythropoiesis

  Early development of a microcytic anemia may reveal reduced iron stores, but an obvious anemia has not developed

  ASSOCIATED CONDITIONS: (CTAILS)

  CHRONIC BLOOD LOSS

  THALASSEMIA

  ANEMIA OF CHRONIC INFECTION

  IRON DEFICIENCY ANEMIA

  LEAD POISONING (PLUMBIASM)

  SIDEROBLASTIC ANEMIA
• Anemia of chronic inflammation (ACI) - Originally called ACD (Anemia of Chronic Disease)

  Most common anemia among hospitalized patients

  Tuberculosis, chronic inflammatory conditions such as rheumatoid arthritis, and tumors

  Body stores have ABUNDANT iron; red cells are DEFICIENT in iron

  Sideropenia (↓ serum iron) despite abundant iron stores

  PBS shows normocytic, normochromic; ADVANCED states: microcytic, hypochromic

  Acute phase reactants (APRs) that contribute to ACI: (HLF)

  HEPCIDIN

  LACTOFERRIN

  FERRITIN
• HEPCIDIN - Master regulatory hormone for systemic iron metabolism Inactivates FERROPORTIN

  TRANSPORT IRON FROM TISSUE TO BLOOD
• Sideroblastic anemias - DEVELOPED when the production of protoporphyrin or the incorporation of iron into protoporphyrin is prevented

  Iron is trapped in the mitochondria

  Dimorphic peripheral blood picture (normochromic and hypochromic RBCs)
• SIDEROBLAST – Nucleated RBC precursor with cytoplasmic iron granules
• SIDEROCYTE – Anucleate RBC w/ iron granules
• Ring sideroblasts – Hallmark of the sideroblastic anemias

  The “rings” in ring sideroblasts = Mitochondria loaded with iron
• Iron deficiency anemia (IDA) - Most common anemia

  Blood loss (especially menstruating women)

  Nutritional deficiency (infants)

  ↑iron demand (pregnancy, lactation, adolescence)

  Malignancies of gastrointestinal tract

  Hookworm infections
• TIBC - Indirectly measures the concentration of transferrin by measuring its ability to bind iron
• Serum Ferritin Test -Reveals the body’s tissue iron stores

  Good indicator of iron storage status

  Useful in diagnosing iron deficiency (generally the first laboratory test to become abnormal when iron stores begin to decline)

  Measured using radioimmunoassay

  Expensive
• MACROCYTIC, NORMOCHROMIC ANEMIAS

  (MCV= HIGH, MCHC=NORMAL)
• MEGALOBLASTIC ANEMIA:

  Vitamin B12 deficiency may be caused by:

  Inadequate intake

  Increased need (occurs during pregnancy, lactation and growth) Competition (ex.: D. latum infection)

  Lack of intrinsic factor (IF) (ex.: gastrectomy, H. pylori infection, Pernicious Anemia)
• NONMEGALOBLASTIC ANEMIA:

  Liver disease

  Alcoholism (Chronic)

  Bone marrow failure
• Anemia associated with CHRONIC ALCOHOLISM:

  MACROCYTIC, NORMOCHROMIC, NON MEGALOBLASTIC TYPE
• Pernicious Anemia:

  Antibodies directed against PARIETAL CELLS

  Antibodies directed against INTRINSIC FACTOR (IF)
• Parietal cells:

  Stomach

  Produce HCL and Intrinsic Factor
• Folate deficiency:

  Inadequate intake

  Increased need

  Renal dialysis
• Presence of hyper segmented neutrophils (with > 6 lobes)

  MEGALOBLASTIC ANEMIA: MERON

  NON MEGALOBLASTIC ANEMIA: WALA
• Shape of the macrocytes:

  MEGALOBLASTIC ANEMIA: OVAL

  NON MEGALOBLASTIC ANEMIA: ROUND
• Presence of megaloblasts in the bone marrow:

  MEGALOBLASTIC ANEMIA: MERON (GIANT RBC PRECURSORS IN BM)

  NON MEGALOBLASTIC ANEMIA: WALA
• Impaired DNA synthesis:

  ROOT CAUSE NG MEGALOBLASTIC ANEMIA
• Vitamin B12 is also known as Cobalamin.

  Folate is the general term used for any form of the folic acid