Blood Smear

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(Red cell size >85 fL) (Red cell size 72-79 fL) 1-2

Normal newborn Increased erythropoiesis* Post splenectomy Liver disease1 Obstructive jaundice1" Aplastic anemia Hypothyroidism Megaloblastic anemias Down syndrome Syndromes with elevated Hgb F

Myelodysplastic syndromes Diamond-Blackfan anemia Fanconi anemia Dyskeratosis Congenita Pearson syndrome

Paroxysmal nocturnal hemoglobinuria Drugs (methotrexate, mercaptopurine, Phenytoin)

Fig. 1-1. An approach to the diagnosis of anemia by examination of the blood smear. +Spurious macrocytosis (high MCV) may be caused by macroagglutinated red cells (e.g., Mycoplasma pneumonia and autoimmune hemolytic anemia). 'Increased number of reticulocytes.

tOn the basis of increased membrane, resulting in an increased membrane/volume ratio. Increased membrane results from exchanges between red cell lipids and altered lipid balance in these conditions.

Iron-deficiency anemia Thalassemia, a or p Sideroblastic anemia Chronic disease Infection Cancer Inflammation Renal disease Lead toxicity Hemoglobin E trait Atransferrinemia Inborn errors of iron metabolism Copper deficiency Severe malnutrition

MCV NORMAL (Red cell size 72-79 fL)

Acute blood loss Infection Renal failure

Connective tissue disorder Liver disease Disseminated malignancy Early iron deficiency Aplastic anemia Bone marrow infiltration Dyserythropoietic anemia Hemolysis

RBC enzyme deficiency RBC membrane defects Hypersplenism Drugs

Table 1-2. Specific Red Cell Morphologic Abnormalities

I. Target cells

Increased surface/volume ratio Thalassemia Hemoglobinopathies Hb AC or CC Hb SS, SC, S-Thal Liver disease

Postsplenectomy or hyposplenic states

Severe iron deficiency

Hb E (heterozygote and homozygote)

LCAT deficiency: congenital disorder of lecithin/cholesterol acyltransferase deficiency (corneal opacifications, proteinuria, target cells, moderately severe anemia) Abetalipoproteinemia

II. Spherocytes

Decreased surface/volume ratio, hyperdense (>MCHC) Hereditary spherocytosis

ABO incompatibility: antibody-coated fragment of RBC membrane removed Autoimmune hemolytic anemia: antibody-coated fragment of RBC membrane removed

Microangiopathic hemolytic anemia (MAHA): fragment of RBC lost after impact with abnormal surface SS disease: fragment of RBC removed in reticuloendothelial system Hypersplenism

Burns: fragment of damaged RBC removed by spleen


Pyruvate kinase deficiency

Water-dilution hemolysis: fragment of damaged RBC removed by spleen

III. Acanthocytes (spur cells)*

Cells with 5-10 spicules of varying length; spicules irregular in space and thickness, with wide bases; appear smaller than normal cells because they assume a spheroid shape

Liver disease

Disseminated intravascular coagulation (and other MAHA) Postsplenectomy or hyposplenic state Vitamin E deficiency Hypothyroidism

Abetalipoproteinemia: rare congenital disorder; 50-100% of cells acanthocytes; associated abnormalities (fat malabsorption, retinitis pigmentosa, neurologic abnormalities) Malabsorptive states

IV. Echinocytes (burr cells)*

10-30 spicules equal in size and evenly distributed over RBC surface; caused by alteration in extracellular or intracellular environment Artifact Renal failure Dehydration Liver disease

Pyruvate kinase deficiency

Peptic ulcer disease or gastric carcinoma

Immediately after red cell transfusion

Rare congenital anemias due to decreased intracellular potassium

*May be morphologically indistinguishable

Table 1-2. (Continued)

V. Pyknocytes*

Distorted, hyperchromic, contracted RBC; can be similar to echinocytes and acanthocytes

VI. Schistocytes

Helmet, triangular shapes, or small fragments. Caused by fragmentation on impact with abnormal vascular surface (e.g., fibrin strand, vasculitis, artificial surface in circulation)

Disseminated intravascular coagulation (DIC) Severe hemolytic anemia (e.g., G6PD deficiency) Microangiopathic hemolytic anemia Hemolytic uremic syndrome

Prosthetic cardiac valve, abnormal cardiac valve, cardiac patch, coarctation of the aorta

Connective tissue disorder (e.g., SLE) Kasabach-Merritt syndrome Purpura fulminans Renal vein thrombosis

Burns (spheroschistocytes as a result of heat) Thrombotic thrombocytopenia purpura Homograft rejection

Uremia, acute tubular necrosis, glomerulonephritis Malignant hypertension Systemic amyloidosis Liver cirrhosis

Disseminated carcinomatosis

Chronic relapsing schistocytic hemolytic anemia

VII. Elliptocytes

Elliptical cells, normochromic; seen normally in less than 1% of RBCs; larger numbers occasionally seen in a normal patient Hereditary elliptocytosis

Iron deficiency (increased with severity, hypochromic)

SS disease

Thalassemia major

Severe bacterial infection

SA trait

Leukoerythroblastic reaction Megaloblastic anemias

Any anemia may occasionally present with up to 10% elliptocytes Malaria

VIII. Teardrop cells

Shape of drop, usually microcytic, often also hypochromic Newborn Thalassemia major Leukoerythroblastic reaction Myeloproliferative syndromes

IX. Stomatocytes

Has a slit-like area of central pallor Normal (in small numbers) Hereditary stomatocytosis Artifact Thalassemia

*May be morphologically indistinguishable


Classification and Diagnosis of Anemia During Childhood 7 Table 1-2. (Continued)

Acute alcoholism

Rh null disease (absence of Rh complex)

Liver disease


X. Nucleated red blood cells

Not normal in the peripheral blood beyond the first week of life Newborn (first 3-4 days) Intense bone marrow stimulation

Hypoxia (especially postcardiac arrest) Acute bleeding

Severe hemolytic anemia (e.g., thalassemia, SS hemoglobinopathy) Congenital infections (e.g., sepsis, congenital syphilis, CMV, rubella) Postsplenectomy or hyposplenic states: spleen normally removes nucleated RBC Leukoerythroblastic reaction: seen with extramedullary hematopoiesis and bone marrow replacement; most commonly leukemia or solid tumor—fungal and mycobacterial infection may also do this; leukoerythroblastic reaction is also associated with teardrop red cells, 10,000-20,000 WBC with small to moderate numbers of metamyelocytes, myelocytes, and promyelocytes; thrombocytosis with large bizarre platelets Megaloblastic anemia Dyserythropoietic anemias

XI. Blister cells

Red cell area under membrane, free of hemoglobin, appearing like a blister G6PD deficiency (during hemolytic episode) SS disease Pulmonary emboli

XII. Basophilic stippling

Coarse or fine punctate basophilic inclusions that represent aggregates of ribosomal RNA

Hemolytic anemias (e.g., thalassemia trait) Iron-deficiency anemia Lead poisoning

Pyrimidine 5'-nucleotidase deficiency

XIII. Howell-Jolly bodies

Small, well-defined, round, densely stained nuclear-remnant inclusions; 1 |im in diameter; centric in location

Postsplenectomy or hyposplenia Newborn

Megaloblastic anemias Dyserythropoietic anemias

A variety of types of anemias (rarely iron-deficiency anemia, hereditary spherocytosis)

XIV. Cabot's Ring bodies

Nuclear remnant ring configuration inclusions Pernicious anemia Lead toxicity

XV. Heinz bodies

Denatured aggregated hemoglobin Thalassemia Asplenia

Chronic liver disease Heinz-body hemolytic anemia

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  • henri
    What is 10 to 30 spicules evenly distributed over the surface of an rbc?
    8 years ago

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