IX. Anemias

Pg: 269-277

Anemia

dec. in RBCs and Hgb, resulting in dec. oxygen delivery to the tissues.

How are anemias classified?

• morphologically using RBC indices

• etiology/cause: Hgb: <12 g/dL in men or <11 g/dL in women

Relative (pseudo) anemia

• plasma vol. is inc

• Reticulocyte count normal

  • normocytic/normochromic anemia

  • Ex: Pregnancy

Absolute anemia

• RBC mass is decreased

• Mechanisms:

  • DECREASED delivery → reticulocytopenia

  • INCREASED loss of red cells → reticulocytosis

Iron-deficiency anemia

Most common type of anemia

• Laboratory: Microcytic/hypochromic anemia

• LOW: serum iron, ferritin, Hgb/HCT, RBC indices, & retic

• RDW and TIBC high

  • show ovalocytes/pencil forms

• Clinical symptoms: Fatigue, dizziness, pica, stomatitis (cracks in the corners of the mouth), glossitis (sore tongue), and koilonychia (spooning of the nails)

Anemia of Chronic Disease (ACD)

2nd most common type of anemia

• Inability to use available iron

• Impaired release of storage iron w/ inc. hepcidin lvls

  • Liver hormone; + acute-phase reactant

  • Levels inc.; dec. iron release from stores

Anemia of Chronic Disease (ACD) Lab

• Lab: Normo/normo, or slightly micro/hypo

  • inc. ESR; N to inc. ferritin; low serum iron and TIBC

• Persistent infections, chronic inflammatory disorders (SLE, rheumatoid arthritis, Hodgkin lymphoma, cancer)

Sideroblastic anemia

• caused by blocks in the protoporphyrin pathway

  • defective Hgb synthesis and iron overload.

• Characterized by ringed sideroblasts (Pappenheimer bodies on Wright stained smears)

• 1° (irreversible) dimorphic

• 2° (reversible)

Siderocytes are best demonstrated using what stain?

Prussian Blue

Sideroblastic Anemia Lab

Microcytic/hypochromic anemia

• increased ferritin and serum iron

• Total iron binding capacity (TIBC) dec.

Lead poisoning

• Normocytic/normochromic anemia w/ basophilic stippling

• MULTIPLE blocks in protoporphyrin pathway

• gum lead line from blue/black deposits of lead sulfate

Lead Poisoning Lab

Normocytic/normochromic anemia w/ basophilic stippling

Porphyrias

group of INHERITED disorders characterized by A block in protoporphyrin pathway of heme synthesis.

• Clinical symptoms: Photosensitivity, abdominal pain, CNS disorders

Megaloblastic anemias

• Defective DNA synthesis

• Megaloblastic

• either a vitamin B12 or folic acid deficiency

Megaloblastic Anemias’ Lab

macrocytic/normochromic anemia

Vitamin B12 deficiency (cobalamin)

• Pernicious anemia

  • deficiency of intrinsic factor

• achlorhydria (stomach does not produce enough HCl acid)

• Clinical symptoms: CNS problems

Pernicious

having a harmful effect, especially in a gradual or subtle way

• ex: Pernicious anemia → body's immune system attacks cells in the stomach that produce intrinsic factor, a protein needed for vitamin B12 absorption → Vitamin B12 deficiency

Folic Acid and Vitamin B12 Deficiency both cause Megaloblastic anemia…

How do they differ?

Vit. B12 defic.

• CNS involvement

• pernicious anemia (intrinsic factor defic.)

• achlorhydria

Folic Acid defic.

• no CNS involvement

• methotrexate (anti-folic drug)

Non-megaloblastic macrocytic anemias

anemias include alcoholism, liver disease, and cause accelerated erythropoiesis.

Non-megaloblastic macrocytic vs megaloblastic macrocytic anemias

round RBCs vs oval RBCs

Aplastic anemia

• BM failure → pancytopenia

• Lab: dec. in Hgb/HCT and retics

• normocytic/normochromic anemia

• Treatment: BM or SC transplant and immunosuppression

• Can be genetic, acquired, or idiopathic

Genetic aplastic anemia (Fanconi anemia)

• Autosomal RECESSIVE

• inc. risk of malignancy (especially acute lymphoblastic leukemia).

Acquired aplastic anemia (secondary)

~30% from drug exposure.

Idiopathic (primary) aplastic anemia

50–70% have no known cause

Diamond-Blackfan anemia

• True red cell aplasia (WBCs and PLTS normal)

• Autosomal inheritance

Myelophthisic (marrow replacement) anemia

• Hypoproliferative anemia caused by replacement BM hematopoietic cells

• Lab: Normocytic/normochromic anemia

Hemochromatosis

A genetic disorder causing excessive iron absorption and accumulation in the body, leading to tissue damage.

Acute blood loss anemia vs. Chronic blood loss anemia

SUDDEN loss of blood vs GRADUAL, long-term loss of blood

Acute blood loss anemia

• sudden blood loss

• Clinical symptoms: Hypovolemia, rapid pulse, low blood pressure, pallor

• Lab: Normocytic/normochromic anemia

  • inc. in PLT, leukocytosis w/ left shift

  • dec. in Hgb/HCT and RBC

Chronic blood loss anemia

• gradual, long-term loss of blood

• Lab: Initially normo/normo anemia

• gradual loss of iron →

  micro/hypo anemia

• Hgb/HCT dec.

Hemolytic Anemias Due to Intrinsic Defects all cause…?

normocytic/normochromic anemia

Types of Hemolytic Anemias Due to Intrinsic Defects

• Hereditary..

  • spherocytosis

  • elliptocytosis/ovalocytosis

  • stomatocytosis

  • acanthocytosis (abetalipoproteinemia)

• GP6D deficiency

• Pyruvate kinase (PK) deficiency

• Paroxysmal nocturnal hemoglobinuria (PNH)

Hereditary spherocytosis

Most common membrane defect

• Spherocytes on PBS

• Dec. surface area-to-vol ratio

• MCHC > 37 g/dL (hyperchromia)

Hereditary elliptocytosis (ovalocytosis)

• Autosomal DOMINANT

• >25% ovalocytes

Hereditary stomatocytosis

• Autosomal DOMINANT

• up to 50% stomatocytes

Hereditary acanthocytosis (abetalipoproteinemia)

• Autosomal RECESSIVE

• 50-100% acanthocytes

G6PD Deficiency

• Sex-linked (X) enzyme defect

• most common enzyme deficiency in the hexose monophosphate shunt

• results: Hgb to methemoglobin (Fe3+ = Ferric) → unable for RBCs to bind to O2

  • forms Heinz bodies

Pyruvate Kinase (PK) deficiency

• Autosomal RECESSIVE

• Embden-Meyerhof pathway defect → reduced life span of RBC (deformed, severe)

Paroxysmal nocturnal hemoglobinuria (PNH)

• ACQUIRED membrane defect

• Inc. sens. to complement-mediated lysis of RBCs,

• Pancytopenia and chronic intravascular hemolysis

• Diagnosed via Ham’s and sugar water tests; inc. leukemia risk.

• leads to hemolysis & hemoglobinuria

Types of Hemolytic Anemias Due to Extrinsic/Immune Defects

• Warm autoimmune hemolytic anemia (WAIHA)

• Cold autoimmune hemolytic anemia (CAIHA or cold hemagglutinin disease)

• Paroxysmal cold hemoglobinuria (PCH)

• Hemolytic transfusion reaction

• Hemolytic disease of the newborn (HDN/HDFN)

Hemolytic Anemias Due to Extrinsic/Immune Defects all cause…?

• normocytic/normochromic anemia

• acquired disorder

• accelerated destruction w/ reticulocytosis

Warm autoimmune hemolytic anemia (WAIHA)

• RBCs coated w/ IgG and/or complement

  • Macrophages phagocytize these

• Lab: Spherocytes, MCHC >37 g/dL, increased osmotic fragility, bilirubin, reticulocyte count, occasional nRBCs (DAT).

Cold autoimmune hemolytic anemia (CAIHA or cold hemagglutinin disease)

• RBCs coated w/ IgM and complement at temps BELOW 37C

• Can be idiopathic or secondary to M. pneumoniae

• MCHC >37 g/dL

• Inc. bilirubin & retic count

• Positive DAT (complement-coated RBCs)

• Warm sample to 37°C for accurate results if high antibody titer

CAIHA vs WAIHA (Antibody Type and Cause)

IgG ± complement; reacts at 37°C, 60% idiopathic
vs.
IgM + complement; reacts below 37°C, Idiopathic, Secondary to Mycoplasma pneumoniae

CAIHA vs WAIHA (Laboratory)

Laboratory Finding	Warm AIHA (WAIHA)	Cold AIHA (CAIHA/CAD)
DAT	IgG ± complement (C3d)	complement only (C3d)
Peripheral smear	Spherocytes	RBC clumping (macro/microscopic)
MCHC	Increased	Increased
Sample handling	Normal processing	Must warm to 37°C if high cold agglutinin titer

Paroxysmal cold hemoglobinuria (PCH)

• IgG biphasic Donath-Landsteiner Ab w/ P specificity fixes complement to RBCs in cold (< 20°C); the complement-coated

• RBCs lyse when warmed to 37°C.

• Can be idiopathic, or secondary to viral infections

• Laboratory: inc. bilirubin and plasma HgB, dec. haptoglobin, Donath-Landsteiner test positive

Hemolytic transfusion Rxn

• Recipient has Abs to Ags on donor RBCs → donor cells are destroyed.

• ABO incompatibility:

  • Usually IgM Abs

  • Can trigger DIC

• Lab: + DAT, inc. plasma HgB

Hemolytic disease of the newborn (HDN/HDFN)

• Rh (ABO) incompatibility (erythroblastosis fetalis)

  • Rh(-) woman (group O) exposed to Rh(+) fetal blood → forms IgG Abs

  • IgG crosses placenta in subsequent pregnancies → coated RBCs are phagocytized

• Lab

  • Severe anemia

  • nRBCs

  • (+) DAT

  • High bilirubin → risk of kernicterus (brain damage)

• Use of Rh immunoglobulin (RhoGam) for prevention

Types of Hemolytic Anemias Due to Extrinsic/Nonimmune Defects

• Microangiopathic hemolytic anemias (MAHAs)

  • Disseminated intravascular coagulation (DIC)

  • Hemolytic uremic syndrome (HUS)

  • Thrombotic thrombocytopenic purpura (TTP)

• March hemoglobinuria

• Other causes: Infectious agents, mechanical trauma, thermal burners

Hemolytic Anemias Due to Extrinsic/NONimmune Defects all…?

• All cause a normocytic/normochromic anemia

  • caused by trauma to the RBC.

• All are acquired disorders that cause intravascular hemolysis

  • schistocytes and thrombocytopenia.

Disseminated intravascular coagulation (DIC)

1. Systemic clotting due to toxins triggers coagulation, causing organ failure and RBC fragmentation.

2. Fibrin is deposited in small vessels, causing RBC fragmentation.

Hemolytic uremic syndrome (HUS)

1. Occurs most often in children following a gastrointestinal infection (e.g., E. coli)

2. Clots form, causing renal damage

Thrombotic thrombocytopenic purpura (TTP)

1. occurs most often in adults.

2. deficiency of the enzyme ADAMTS-13 (breaks down vWF → dec.)

von Willebrand factor

• Mediates platelet adhesion & stabilizes factor VIII for clotting.

• Uncleaved multimers: microthrombi → leads to:

  • RBC damage (→ schistocytes/MAHA)

  • Neurologic symptoms (→ CNS involvement in TTP)

March hemoglobinuria

Transient hemolytic anemia that occurs after forceful contact of the body with hard surfaces (e.g., marathon runners and tennis players)

Other causes of Hemolytic Anemias Due to Extrinsic/Nonimmune Defects

• Infectious agents (e.g., Plasmodium falciparum, Clostridium perfringens)

• Mechanical trauma (e.g., prosthetic heart valves/"Waring blender syndrome")

• Thermal burns (especially third-degree)

  • Cause direct RBC membrane damage → acute hemolysis

Aplasia meaning and significance

the failure of an organ or tissue to develop or to function normally → dec. in RBCS due to failure of the BM to produce them

Pyruvate Kinase (PK) Deficiency Lab

• Normocytic anemia

• Reticulocytosis

• ↑ unconjugated bilirubin

• Echinocytes/Burr

• Negative DAT (non-immune hemolysis)

Positive DAT vs Positive IAT

• + DAT = Abs are attached to the RBCs → suggesting autoimmune hemolytic anemia

• + IAT = Abs in the serum that may react with RBCs → used for blood typing or crossmatching

Donath-Landsteiner test

detects the presence of the Donath-Landsteiner Ab

• → IgG Ab that binds to RBCs at low temp and then triggers their destruction when warmed

  • Paroxysmal Cold Hemoglobinuria (PCH).

Paroxysmal

Sudden onset or sudden recurrence of symptoms; a sudden attack or burst of activity

→ hemolytic episodes can happen suddenly

Iron Studies Chart

Serum iron reflects the amount of iron circulating in the blood, TIBC measures the blood's capacity to transport iron, and ferritin indicates the body's iron storage levels