3. • History
• 16 month old toddler was brought to the
clinic by the mother as he is not gaining
weight, remains irritable, gets tired easily
and is a picky eater.
• O/E
• Mild pallor and minimal tachycardia
CASE 1
9. • History
• 3 year old boy referred from clinic as
labs indicated hemolytic anemia.
• Positive family history
• O/E
• Mild jaundice, Pallor, Spleenomegaly
CASE 4
13. CASE 6
• History
• 3 year old boy brought to ER with
history of fever and increasing
tenderness and swelling of hands
and feet.
• O/E
• Jaundiced, Bilateral swelling of
hands and feet
17. • History
• 9 year old girl presented with 2 day history
fever and shivering (rigors) followed by
drenching sweats, vomiting and flushing.
• O/E
• Febrile
• Jaundice, Cervical lymphadenopathy
• Her liver is palpable below the costal edge
and tender.
CASE 8
20. • History
• Petechial rashes
• Few days ago hx of bloody diarrhea
• O/E
• Pallor, jaundice , petechial rashes
CASE 9
ThrombocytopeniaHemolytic
anemia
ARF
22. • History
• 5 year old presents with bone pain, arthritis
and low grade fever for the past 2 weeks.
• O/E
• Generalized lymphadenopathy, petechial
rashes, hepatospleenomegaly
• Labs
• Anemia
• Neutropenia
• Leucocytosis
• Thrombocytopenia.
CASE 10
They have a zone of central pallor about 1/3 the size of the RBC. The RBC's demonstrate minimal variation in size (anisocytosis) and shape (poikilocytosis). A few small fuzzy blue platelets are seen. In the center of the field are a band neutrophil on the left and a segmented neutrophil on the right.
Leucocytosis is suspected when WBC >5 leucocytes/hpf and
leucopenia <2 cells/hpf.
Red blood cell numberFirst, make sure you’re in the right part of the smear. You should be a couple medium-power fields in from the “feather edge,” which is the thin edge of the smear where the cells are all spread out and there are huge empty spaces. Just give it a quick glance and make sure the red cells aren’t either piling up all over each other, or spread out too far with lots of holes in between – like the red cells in the image above. Take a look at the RBC on the CBC and make sure it fits with what you’re seeing.
2. Red cell sizeNormally, if all the red cells are roughly the same size, your eye won’t be able to tell if they’re microcytic (small) or macrocytic (large). So you have to just look at the MCV for that. What your eye can see, however, is a range of sizes. So take note and see if there are some cells that are smaller, and some that are bigger. If that’s the case, it’s called “anisocytosis” and it should be reflected in the RDW (red cell distribution width) on the CBC. The more anisocytosis (variation in size) there is, the bigger the RDW should be.
3. Red cell shapeNormally, red cells are all nice and round, like the ones in the image above. In some anemias, there are funny-shaped cells, like schistocytes (fragmented red cells), sickle-shaped cells, teardrop-shaped cells, or target cells. Your eye will naturally be drawn to these (which is why you should force yourself to follow a consistent method when looking at a smear – otherwise you just look at what your eye is drawn to!). Take note of whether there are any non-round cells, and if so, describe what kinds of shapes you see.
4. Red cell chromasia“Chromasia” refers to the amount of hemoglobin in the average red cell. Normally, there is a zone of central pallor (the white dot in the center of the cell) that comprises about 1/3 of the diameter of the cell. Check out the cute zones of central pallor in the red cells above. These cells are called “normochromic.” If there is a huge white dot, and just a thin rim of hemoglobin, then the cells are called “hypochromic.” There really isn’t a “hyperchromic” type of red cell.
5. ReticulocytesTake a look around and see if you see any polychromatophilic cells (these are slightly bigger than normal red cells, and they have a lilac tinge to them). These are just young red cells whose RNA has not yet been completely extruded (so they stain a bit blue). In normal blood, about 1% of the red cells are reticulocytes (because we’re always making new red cells). That equates to about 1-2 red cells per field. If you see more than that, it means the marrow is kicking out red cells at an increased rate.
6. Stuff inside red cellsTake a look and see if you see any red cells with stuff inside – like nuclei, Howell-Jolly bodies (little nuclear remnants that didn’t get extruded), Pappenheimer bodies (little iron granules), organisms (like malaria or babesia).
7. Platelet numberThere should be between 7 and 21 platelets per high power field, which corresponds to a platelet count between 150 and 450 x 109/L.
8. Platelet morphologyThis doesn’t usually yield much – but take a look at the platelets anyway and make sure they’re roughly of normal size, and have some nice granules inside. There are rare platelet disorders in which the platelets are abnormally large, or lack granules, or both.
9. White blood cell countDo a quick scan of a bunch of high power fields and see how many white cells there are. There should be a few white cells per high power field. Check the WBC and see if it seems to correspond to what you’re seeing. Then, do a differential count: count a few hundred white cells (500 is best) and put them in categories (neutrophils, lymphocytes, monocytes, eosinophils, basophils). Compare this to the automated differential on the CBC, and multiply the percentages by the total WBC to get the absolute counts of each cell type. When you’re trying to determine if a patient has a normal number of a certain cell type, absolute counts are much more reliable than percentages.
10. White blood cell morphologyFinally, check the morphology of the white cells. You’ll probably do this as you’re doing your differential – your eye will be drawn to any abnormalities as you’re classifying the cells. Make sure the neutrophils and lymphocytes look normal, and keep your eye open for any weird-looking cells like blasts or circulating carcinoma cells.
A high-power field (HPF), when used in relation to microscopy, references the area visible under the maximum magnification power of the objective being used. Often, this represents a 400-fold magnification when referenced in scientific pap
Band neutrophils are an intermediary step prior to the complete maturation ofsegmented neutrophils. An increase in band neutrophils typically means that the bone marrow has been signaled to release more WBCs and increase production of WBCs, also known as a "left shift".
Hypochromic, microcytic anemia is caused by an inadequate production of hemoglobin. The most common causes of this type of anemia are iron deficiency and thalassemia.
. The prevalence of iron deficiency, the most common cause of anemia in the world, is about 9% in toddlers, 9% to 11% in adolescent girls, and less than 1% in teenage boys. Iron deficiency anemia occurs in about one third of children who are iron deficient ( Table 150-3 ). Some underprivileged minority populations in the United States may be at increased risk for iron deficiency because of poor dietary intake (see Chapter 31 ). Breastfed infants are less likely to have iron deficiency than bottle-fed infants because, although there is less iron in breast milk, this iron is more efficiently absorbed.
Slowly progressing paleness may sometimes be missed by families.
he nutritional assessment may identify some of the established risk factors for iron deficiency anemia such as low birth weight, high cow’s-milk intake, low intake of iron-rich complementary foods, low socioeconomic status, and immigrant status [37]. Similarly, we noted the carious dentition during the physical examination, which has recently been reported to be strongly associated with anemia [38].
Complete blood count
Peripheral blood smear
Reticulocyte
Urea, creatinine
Serum iron, total iron binding capacity, transferrin saturation index
Ferritin
Serum soluble transferrin receptor levela
Poikilocystosis:
Anisocytosis
Pencil shaped cells (cigar clls)
Reactive thrombocytosis
In contrast to thalassemia, target cells are usually not present, and anisocytosis and poikilocytosis are not marked In contrast to thalassemia, target cells are usually not present, and anisocytosis and poikilocytosis are not marked high reticulocyte count indicates that the bone marrow is responding to the anemia by producing red blood cells. A low reticulocyte count indicates a production problem. Anemias due to a deficiency of a substance (e.g., iron) usually have a higher RDW than anemias due to a genetic defect or bone marrow disorder.
ron deficiency is the most common nutritional deficiency in children.
Hypochromic, microcytic anemia is caused by an inadequate production of hemoglobin. The most common causes of this type of anemia are iron deficiency and thalassemia.
. The prevalence of iron deficiency, the most common cause of anemia in the world, is about 9% in toddlers, 9% to 11% in adolescent girls, and less than 1% in teenage boys. Iron deficiency anemia occurs in about one third of children who are iron deficient ( Table 150-3 ). Some underprivileged minority populations in the United States may be at increased risk for iron deficiency because of poor dietary intake (see Chapter 31 ). Breastfed infants are less likely to have iron deficiency than bottle-fed infants because, although there is less iron in breast milk, this iron is more efficiently absorbed.
Slowly progressing paleness may sometimes be missed by families.
Complete blood count
Peripheral blood smear
Reticulocyte
Urea, creatinine
Serum iron, total iron binding capacity, transferrin saturation index
Ferritin
Serum soluble transferrin receptor levela
• Infants and toddlers—occurs especially if the diet is predominantly human
milk (low in iron). Children in this age group also have an increased requirement
for iron because of accelerated growth. It is most common between 6
months and 3 years of age
• Adolescents—rapid growth
Anemia is typically defined as a hemoglobin concentration that is 2 standard deviations (SD) or more below the mean for a healthy population of the same gender and age. The World Health Organization (WHO) uses the following hemoglobin thresholds to define anemia [3]:
•Children 6 months to <5 years: 11 g/dL
•Children 5 to <12 years: 11.5 g/dL
•Children 12 to <15 years: 12 g/dL
Blood fi lm: microcytic, hypochromic RBCs; target cells often present.
Basophilic stippling especially in Mediterraneans (see Fig 2.8).
Target cells (codocytes) have a centrally located disk of hemoglobin surrounded by an area of pallor with an outer rim of hemoglobin adjacent to the cell membrane giving the cell the appearance of a target. Leptocytes (or wafer cells) are thin, flatcells with the hemoglobin at the periphery of the cell.
Basophilic stippling, also known as punctate basophilia, is the presence of numerous basophilic granules that are dispersed through the cytoplasm of erythrocytes in a peripheral blood smear. They can be demonstrated to be RNA: They are composed of aggregates of ribosomes; degenerating mitochondria and siderosomes may be included in the aggregates. In contrast to Pappenheimer bodies, they are negative with Perls' acid ferrocyanide stain for iron (i.e no iron in basophilic stippling). Basophilic stippling is indicative of disturbed erythropoiesis. It can also be found in some normal individuals.
marked anisopoikilocytosis, target cells, and nucleated
red cells
It results from accentuated vertical trabeculae between the inner and outer tables of the skull because of excessive bone marrow hyperplasia.
Blood fi lm shows ii spherocytic RBCs (see Fig 2.10).
• Anaemia, ireticulocytes, iLDH, unconjugated bilirubin, urinary
urobilinogen with d haptoglobins.
• DAT−ve.
• If typical family
RBC changes include oval macrocytosis, poikilocytosis, basophilic
stippling, Howell–Jolly bodies, circulating megaloblasts.
• Hypersegmented neutrophils.
• Leucopenia and thrombocytopenia common.
DNA synthesis is impaired in these cases because of inadequate amounts of metabolically active folate derivatives necessary for DNA base synthesis. Megaloblastic changes affect all 3 hematopoietic cell lines. Thrombocytopenia, leukopenia, and anemia are all observed to varying extents.
Causes (almost all cases are due to impaired absorption)
1. Pernicious anemia (lack of intrinsic factor)—most common cause in the Western
hemisphere
2. Gastrectomy
3. Poor diet (e.g., strict vegetarianism); alcoholism
4. Crohn disease, ileal resection (terminal ileum—approximately the last 100 cm)
5. Other organisms competing for vitamin B12
a. Diphyllobothrium latum infestation (fish tapeworm)
b. Blind loop syndrome (bacterial overgrowth)
Here is a hypersegmented neutrophil that is present with megaloblastic anemias. There are 8 lobes instead of the usual 3 or 4. Such anemias can be due to folate or to B12 deficiency. The size of the RBC's is also increased (macrocytosis, which is hard to appreciate in a blood smear).Here is a hypersegmented neutrophil that is present with megaloblastic anemias. There are 8 lobes instead of the usual 3 or 4. Such anemias can be due to folate or to B12 deficiency. The size of the RBC's is also increased (macrocytosis, which is hard to appreciate in a blood smear).
Blood fi lm shows marked variation in red cell size with prominent
sickle cells and target cells; basophilic stippling, Howell–Jolly bodies, and
Pappenheimer bodies (hyposplenic features after infancy)
Infants with SCD may develop hand-foot syndrome, a dactylitis presenting as exquisite pain and soft tissue swelling of the dorsum of the hands and feet. The syndrome develops suddenly and lasts 1-2 weeks. Hand-foot syndrome occurs between age 6 months and 3 years; it is not seen after age 5 years because hematopoiesis in the small bones of the hands and feet ceases at this age. Osteomyelitis is the major differential diagnosis.
The pain can affect any body part. It often involves the abdomen, bones, joints, and soft tissue, and it may present as dactylitis (bilateral painful and swollen hands and/or feet in children), acute joint necrosis or avascular necrosis, or acute abdomen. [30] With repeated episodes in the spleen, infarctions and autosplenectomy predisposing to life-threatening infection are usual. The liver also may infarct and progress to failure with time. Papillary necrosis is a common renal manifestation of vaso-occlusion, leading to isosthenuria (ie, inability to concentrate urine).
Blood fi lm shows marked variation in red cell size with prominent
sickle cells and target cells; basophilic stippling, Howell–Jolly bodies, and
Pappenheimer bodies (hyposplenic features after infancy)
During maturation in the bone marrow, late erythroblasts normally expel their nuclei; but, in some cases, a small portion of DNA remains. Its presence usually signifies a damaged or absent spleen, because a healthy spleen would normally filter this type of red blood cell.
During maturation in the bone marrow, late erythroblasts normally expel their nuclei; but, in some cases, a small portion of DNA remains. Its presence usually signifies a damaged or absent spleen, because a healthy spleen would normally filter this type of red blood cell.
In steady state (i.e. no haemolysis) the RBCs appear normal.
• Heinz bodies in drug-induced haemolysis (methyl violet stain).
• Spherocytes and RBC fragments on blood fi lm if severe haemolysis. chronic Heinz body intravascular haemolysis
with dapsone or sulafasalazine in G6PD defi cient people or unstable
Hb (and normals if dose high enough). Film: bite cells (RBC). Heinz
bodies not prominent if intact spleen. Haemolysis well compensated.
Denatured hemoglobin
www.labce.com
Heinz bodies appear as small round inclusions within the red cell body, though they are not visible when stained with Romanowsky dyes. They are visualized more clearly with supravital staining (e.g., with new methylene blue, crystal violet or bromocresol green).
In P. falciparum infections, red blood cells (rbcs) are normal in size. Typically only rings and gametocytes are seen unless the blood sat before the smears were prepared.
Rings may possess one or two chromatin dots. They may be found on the periphery of the RBC (accolé, appliqué) and multiply-infected RBCs are not uncommon. Ring forms may become compact or pleomorphic depending on the quality of the blood or if there is a delay in making smears. There is usually no enlargement of infected RBCs.
Classic findings in hemolytic-uremic syndrome (HUS) include anemia and thrombocytopenia, with fragmented RBCs (eg, schistocytes, helmet cells, burr cells), as shown in the image below
Burr cells characterisitc of uremia
Diagnosis
• FBC—usually shows leucocytosis, anaemia, and thrombocytopenia.
Can show pancytopenia
• Blood fi lm—usually contains blasts.
• BM aspirate—≥20% blasts (see Figs. 4.1–4.5).
• Trephine biopsy—to exclude fi brosis and multilineage dysplasia.
• Immunophenotyping to diff erentiate AML from ALL: CD3,
CD7, CD13, CD14, CD33, CD34, CD64, CD117, cytoplasmic
myeloperoxidase (MPO).
• Cytochemistry—MPO or Sudan Black (SB), combined esterase.
• Cytogenetic analysis—to identify prognostic group.
• Molecular analysis—RT-PCR and FISH in selected cases.
Acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) is the most common childhood malignancy.
The WBC's seen here are lymphocytes, but they are blasts--very immature cells with scant cytoplasm and large nuclei that contain nucleoli. Such abnormal lymphocytes are indicative of acute lymphoblastic leukemia (ALL). ALL is more common in children than adults. Many cases of ALL in children respond well to treatment, and many are curable.
Acute lymphoblastic leukemia/lymphoblastic lymphoma (ALL/LBL) is the most common childhood malignancy.
The WBC's seen here are lymphocytes, but they are blasts--very immature cells with scant cytoplasm and large nuclei that contain nucleoli. Such abnormal lymphocytes are indicative of acute lymphoblastic leukemia (ALL). ALL is more common in children than adults. Many cases of ALL in children respond well to treatment, and many are curable.
Confi rmed by BM examination and classifi ed by immunophenotyping
and cytogenetic/molecular genetic analysis.