Evaluation of Anemia

Introduction

a low RBC mass manifested by ß Hct or ß Hgb for a person’s age, sex, or physiologic state.

normal values:

male hematocrit: 41-47%
male hemoglobin: 13.5-15.5 g/dl
female hematocrit: 36-41%
female hemoglobin: 12-14 g/dl

Rule of Thumb – hematocrit is around 3 times the hemoglobin

Women have a lower hematocrit because of menstrual blood loss and a lower testosterone level. Testosterone Ý hemoglobin

Physiologic states that lower hematocrit but do not result in functional anemia include:

Plasma volume expansion (e.g. pregnancy)
Hypothyroidism (anemic but tissues have adequate O₂ delivery because of reduced metabolic demand)
Low O₂ affinity hemoglobinopathies

Clinical Manifestations of Anemia

more likely to be symptomatic if the onset of anemia is acute

Symptoms - reflect hypoxia; fatigue, dyspnea on exertion, HA, confusion, chest pain

Signs – very non-specific until anemia is severe; pallor (skin, conjuctiva, mucosa, nail beds)

Diagnosing the Cause of Anemia

history Onset of anemia, Concurrent illnesses, GI blood loss, change in bowel habits, Neurologic complaints (B₁₂), Family History, Social History (EtOH, IDU), Medications (Bactrim, ASA), Occupational exposure (Pb), Travel History (Malaria), Diet (folate)

PE Orthostatic hypotension, Fever, Jaundice, Icteric sclera, Vitaligo (assc. with pernicious anemia), Leg ulcers, Splenomagaly, lymphadenopathy, Neurological deficits (B₁₂), Hemoccult (+) stool (GI bleed)

Labs

Reticulocyte count – counts young RBCs. Normal is < 1%. As patient becomes anemic Ý Epo leads to Ý RBC production and RBCs are released earlier causing the Reticulocyte count to be elevated. A normal reticulocyte takes one day to mature in the bloodstream. Early release RBCs take 2-3 days in the blood stream to appear mature therefore in the presence of polychromasia (blueish color of reticulocytes released early) the reticulocyte count needs to be corrected. Also in acute blood loss of very rapid hemolysis the body needs 48 hours to mount a reticulocyte response so the reticulocyte count may not be increased at first.

Corrected Reticulocyte Count (in case of Anemia) = patient’s reticulocyte count x patient’s Hct/normal Hct

Ex: 2% x 20/40, for a man with a Hct of 20 and reticulocyte count of 2%
if corrected reticulocyte index is <2: probable lack of production
if corrected reticulocyte index is >3: probable hemolysis or bleed

Absolute Reticulocyte Count = RBC count x Retic %. Doesn’t need to be corrected for anemia. Correct for polychromasia as follows: divide absolute retic count by 2 for Hct > 20, or by 3 for Hct < 20

normal RBC count = 4-6 million / m L

normal reticulocyte count 40-60,000 / m L

Absolute reticulocyte count > 100,000: probable RBC loss

Absolute reticulocyte count < 50,000: probable underproduction

Bilirubin and LDH – most bilirubin comes form the degradation of Hgb from old RBCs. Indirect (unconjugated) bilirubin is a good indicator of RBC destruction. LDH also rises with RBC destruction but is less specific.

Hypoproliferation: ß retic, normal bilirubin and LDH

Ineffective erythropoeisis (B₁₂ deficiency): ß retic, Ý bilirubin and LDH

Hemolysis: Ý retic, Ý bilirubin and LDH

Blood loss: Ý retic, normal bilirubin and LDH

Peripheral Blood Smear –

Look for polychromasia

RBC morphology

Þ "tear drop" cells – occur in conditions where RBCs are pushed out of the bone marrow

Þ nucleated RBCs are abnormal in the adult and occur when RBCs are pushed out of the marrow early

Þ spherocytes are seen in auto-immune hemolytic anemia

Þ "Rouleaux" (staking of RBCs) is seen in multiple myeloma.

WBC morphology (hypersegmented PMNs in B₁₂ def)

Smear review can confirm RBC indicies

RBC Indices – and normal values

MCV mean corpuscular volume

normal: 80-96 fL

MCH mean corpuscular Hgb

normal: 27.5-33 pg

ß MCH in hypochromatic

MCHC mean corpuscular Hgb concentration

normal: 33.4-35.5 g/dL
Useless clinically except in Hereditary spherocytosis

RDW red cell distribution width

normal: 11.5-13.4
Helpful, an index of variation in the size of the RBCs

RBC count

normal: 4.5 – 5.5. x 10⁶ / m L

Types of Anemias

(1) Hypoproliferative Anemias

Fe deficiency

Microcytic, hypochromic RBCs (late manifestation), Ý RBW shows up first

Low serum iron, high TIBC (=transferrin), low ferritin

Absent Fe stores in bone marrow

Anemia of chronic disease (Cytokine-mediated diminished release of stored Fe from phagocytes)

Microcytic or normocytic
Low Fe, low TIBC, high ferritin
Adequate Fe stores in bone marrow

Renal disease (diminished erythropoietin production)

Myelophthisic processes (marrow replacement with non-marrow elements)

Leukoerythroblastic smear (tear drops, nucleated RBCs, early myeloid cells)
Bone marrow is diagnostic (solid tumor cells, leukemia, fibrosis, many others)

Multiple myeloma

Rouleaux on smear
Normochromic, normocytic

Lead poisoning

Microcytic
Prominent, coarse basophilic stippling

Aplastic anemia and pure red cell aplasia

High Fe and high transferrin saturation (Fe/TIBC)
Markedly diminished to absent RBC precursors on bone marrow biopsy

(2) Ineffective Erythropoiesis

Vitamin B₁₂ and folate deficiencies

Macrocytosis, hypersegmented neutrophils
Megaloblastic changes in bone marrow

Myelodysplastic syndromes (may also appear hypoproliferative without elevated LDH and bili-, depending on the degree of ineffective erythropoiesis)

Macrocytosis, usually mild
Dysplastic findings on peripheral smear (hypogranular PMNs, pseudo-Pelger Huet cells)

Thalassemias (also associated with peripheral hemolysis)

Chemotherapy agents

(3) Hemolysis

Thalassemias (inherited forms of diminished globin production)

Microcytosis
High RBC count (as opposed to Fe deficiency)

Hemoglobinopathies, due to globin chain mutations associated with abnormal polymerization

Smear often diagnostic (sickled cells in sickle cell, crystals in hemoglobin C)
Hemoglobin electrophoresis

Autoimmune hemolysis

Direct Coomb’s test positivity
Spherocytes on smear

Microangiopathic

Fragmented RBCs (schistocytes)
DIC, TTP, mechanical heart valve

Inherited RBC membrane disorders

Smear helpful (hereditary spherocytosis, elliptocytosis)

RBC enzyme deficiencies (i.e. G6PD deficiency)

Smear sometimes helpful ("bite cells")

(4) Bleeding

Additional studies directed at site of bleeding
May need evaluation of hemostatic function

The Value Of Red Blood Cell Morphology In Diagnosis Of Hemolytic Anemia

Morphology	Cause	Syndromes
Spherocytes	Loss of membrane	Hereditary spherocytosis, autoimmune hemolytic anemia
Target cells	Increased ratio of RBC surface area to volume	Hemoglobin disorders: thalassemias, hemoglobin S, C, etc.; liver disease
Schistocytes	Traumatic disruption of membrane	Microangiopathic conditions, intravascular prostheses
Sickled cells	Polymerization of hemoglobin S	Sickle cell syndromes
Acanthocytes	?Abnormal membrane lipids	Severe liver disease (spur cell anemias)
Agglutinated cells	Presence of IgM antibody	Cold agglutinin disease
Heinz bodies	Precipitated hemoglobin	Unstable hemoglobin, oxidant stress