What's Wrong with this CBC - Medical City Dallas · PDF fileWhat’s Wrong with this CBC?...

What’s Wrong with this CBC?

Maurizio Ghisoli MDPediatric Hematology-Oncology

Texas OncologyMedical City Children’s Hospital

Pediatric Grand Round

INTRODUCTION• Overview of Components of CBC

• Red Blood Cells– Hemoglobin / Hematocrit

– Other Red Blood Cells Indices

• Platelets– PLTs Number/Morphology

• White Blood Cells– Normal variations

Complete Blood Count - CBC

• Hemoglobin: total Hb concentration per volume

• Hematocrit: proportion of Hb of total volume

• MCV: mean corpuscular volume

• MCHC / MCH: mean Hb concentration per cell

• RDW: reflect anisocytosis index

• Platelets: total number per volume

• WBC: Total number of nucleated cells per volume

CASE 1Well child visit, 4 y.o. girl.“picky eater”, with Sippy cup during clinic visitHealthy, no complains

WBC 3.6RBC 2.9HBG 8.9

HCT 26.7 Microcytosis

MCV 67 HypochromiaMCH 21.3 3+ ANISOCYTOSIS

MCHC 27.9 1+ POIKILOCYTOSIS

PLT 289

RDW 24MPV 8.3

CASE 2Well child visit, 5 y.o. boy. Parents from Jordan“picky eater”, eating chips at clinic visitHealthy, no complains



MCV 62 Target cellMCH 29.3

MCHC 30 1+ POIKILOCYTOSIS

PLT 189

RDW 14MPV 8.1

DEFINITION OF ANEMIA

PHYSIOLOGIC: when the Hb not enough to meet

the metabolic oxygen demand

STATISTICAL (PRACTICAL): Hb value 2 standard

deviation below mean value adjusted for age,

gender and race.


Anemia with high hemoglobin

3 y.o. girl with cyanotic congenital heart disease

with a Hb of 14gm/dL and HCT at 40%

No Anemia with low hemoglobin

6 weeks old premature baby with Hb at 7.5 mg/dl

7 y.o girl with hypothyroidism and Hb at 10 mg/dl


• Males 13‐18 gm/dL• Females 11.5‐16 gm/dL

• Children• Neonates : 14‐24• 2 months: 8.9‐13.2• 9‐12ys: 11.5‐15.4

Pregnancy3rd Trimester – 9.8‐13.7g/lAge5‐6th decade – falls in men rises in women

• Exercise• Altitude• Smoking

DEFINITION OF ANEMIAMALES FEMALES

MEDIAN RANGE MEDIAN RANGE

AGE 5 ‐ 9

BLACK 12.6 11.1‐14.1 12.5 11.2‐13.6

WHITE 13.0 11.6‐14.3 12.9 11.5‐14.4

AGE 10 ‐ 14

BLACK 13.1 11.5‐15.2 12.9 12.0‐14.9

WHITE 13.7 12.3‐15.5 13.4 12.0‐14.9

NORMAL RBC VALUES

DEFINITION OF ANEMIABeing practical…

ELEVEN PLUS POINT ONE RULE11 + 0.1 x (age in years) = lower limit for normal hemoglobin concentration

SEVENTY PLUS ONE RULE70 + 1 X (age in years) = lower limit of normal MCV

Normal defined as 2SD below mean

Examples:3 y.o male with Hb 11.4 mg/dl and MCV 74…6 y.o. female with Hb 11.4 mg/dl and MCV 74…

CLASSIFICATION OF ANEMIA

• PATHOPHYSIOLOGY

– Decreased production

– Acute blood loss

– Increased destruction

• ERYTHROCYTE SIZE

– Microcytic

– Normocytic

– Macrocytic

Differential Diagnosis of Microcytosis

Children and adolescents

Menstruating women

Men and non‐menstruating women

Iron deficiency anemia Iron deficiency anemia Iron deficiency anemia

Thalassemia trait Thalassemia trait Anemia of chronic disease

Other hemoglobinopathies Pregnancy Unexplained anemia

Lead toxicity Anemia of chronic disease Thalassemia trait

Chronic inflammation Sideroblastic anemia

Sideroblastic anemia

Red Cell Distribution Width (RDW)

• Degree of variation in size of RBC: N <14

• Increased RDW corresponds with anisocytosis:

• Iron deficiency

– Increased RDW

– Anisocytosis precedes the anaemia

• Thalassemia trait– normal RDW

Number of Red Blood Cells (RBC)

• Total number of red blood cell per volume

• Decreased RBC corresponds with hypoproductive anemias:

• Iron deficiency

– Decreased RBC

– Goes along with decreased in Hb and is proportional

• Thalassemia trait– normal RBC

Laboratory tests in the Differential Diagnosis of

Microcytosis

CASE 1Well child visit, 4 y.o. girl.“picky eater”, with Sippy cup during clinic visitHealthy, no complains



MCV 67 HypochromiaMCH 21.3 3+ ANISOCYTOSIS

MCHC 27.9 1+ POIKILOCYTOSIS

PLT 289

RDW 24MPV 8.3

Iron Deficiency

• Most common cause of microcytosis• Clinical Clues• Iron Studies– Iron– Total Iron Binding Capacity– Ferritin

IRON STUDIES

Serum Iron TIBC Ferritin

Iron Deficiency Low Elevated Low

Sideroblastic Elevated Nml Elevated

Thalassemia Elevated Nml Elevated

Anemia of ChronicDisease

Low Elevated Elevated

Causes of Iron Deficiency Anaemia

• Dietary deficiency

• Increased Whole Milk intake

• Blood loss

• Malabsorption - Celiac disease; gastrostomy, post-NEC

• Increased utilisation – parasites (Rare in US)

• End Stage Renal Disease

Iron Supplementation

• Elemental Iron at 6 mg per kilo per day

• May divide dose twice a day

– Once a day intolerant , TID non-complaint

• Elemental iron: Ferrous Sulfate + 1:5 ratio

• As soon as 2 weeks Hb corrected

• First changes in RDW and some times PLTs

• Treat for 3-4 month after correction of Hb

CASE 2Well child visit, 5 y.o. boy. Parents from Jordan“picky eater”, eating chips at clinic visitHealthy, no complains



MCV 62 Target cellMCH 29.3

MCHC 30 1+ POIKILOCYTOSIS

PLT 189

RDW 14MPV 8.1

Major Types of Hemoglobins

Alpha ThalassemiaVariant Chromosome 16 Signs and symptoms

Alpha thalassemia silent carrier

One of four gene deletions Asymptomatic

Alpha thalassemia trait Two of four gene deletions Asymptomatic

Hemoglobin Constant Spring Reduced output of alpha globin

Silent or mildly symptomatic

Alpha thalassemia intermedia(hemoglobin H disease)

Three of four gene deletions Moderate to severe hemolytic anemia, modest degreeof ineffective erythropoiesis, splenomegaly, variablebone changes

Alpha thalassemia major Four of four gene deletions Causes nonimmune hydrops fetalis, usually fatal

Beta ThalassemiaVariant Chromosome 11 Signs and Symptoms

Beta thalassemia trait One gene defect Asymptomatic

Beta thalassemia intermedia Two genes defective (mild to moderatedecrease in beta globin synthesis)

Variable degrees of severity of symptoms of thalassemia major

Beta thalassemia major Two genes defective (severe decrease inbeta globin synthesis)

Abdominal swelling, growth retardation,irritability, jaundice, pallor, skeletal abnormalities,splenomegaly; requires lifelong blood transfusions6

Hemoglobin Studies

1. Normal adult 2. HPFH (heterozygote)3. Hb S--HPFH 4. Hb C--HPFH 5. Normal newborn

A/F/S/C control

Hb ElectrophoresisAlpha and Beta Thalassemia

• Beta Thalassemia:– Increased HbA2, reduced HbA, and probably increased HbF

• Alfa Thalassemia:– Normal

– Newborns: may have HbH or Hb Bart’s

– Alfa trait Diagnosis of exclusion

Remember: Fe deficiency may have reduced HbA2

Case 3: 2 y.o. female, pale , brought in because weak , not playful. Mother strict vegan.


HCT 31.4 3+ Macrocytosis

MCV 109 hyper segmentationMCH 26.3

MCHC 29.9

PLT 139

RDW 19MPV 8.5

Case 4:7 y.o. boy, pale , brought in because last week had fever, and erythematous rash. You remember last year CBC and was normal.


HCT 31.1 Hypochromia

MCV 103MCH 28.3 2+ ANISOCYTOSIS

MCHC 32.9

PLT 105

RDW 19MPV 10.5

Differential Diagnosis of Macrocytosis

Megaloblastic (vitamin B12 and/or folate deficiencies)

• Strict vegan diets• Atrophic gastritis• Enteral malabsorption• Human immunodeficiency

virus treatments• Anticonvulsants (folate

depletion)

Nonmegaloblastic•Primary bone marrow disorders•Medications•Acquired Aplastic Anemia•Hypothyroidism•Liver disease•Chronic Bronchopulmonary Disease

False elevations•Cold agglutinins•Hyperglycemia•Marked leukocytosis

Megaloblastic Anemia• Hyper segmented Neutrophils

–Any neutrophil with > six segments or

–More than five percent with five segments or

–Majority of cells with four segments

• Presence of Macroovalocytes

–Egg - shaped cells

The combination is a result of absence of terminal divisionsof marrow precursors

Investigations

1. Serum vitamin B12

2. Red cell folate (serum folate)

3.Reticulocyte count (BM erythroid function)

4.Liver function

5.Parvovirus serology

6.Bone marrow examination

Medications That May CauseMacrocytosis

• Treatments for human immunodeficiency virus: reverse transcriptase inhibitors (e.g., stavudine [Zerit], lamivudine [Epivir], zidovudine [Retrovir])

• Anticonvulsants (e.g., valproic acid [Depakote], phenytoin [Dilantin])

• Folate antagonists (e.g., methotrexate)• Chemotherapeutics (e.g., alkylating agents, pyrimidine, purine

inhibitors)• Trimethoprim/sulfamethoxazole (Bactrim, Septra)• Biguanides (e.g., metformin [Glucophage]), cholestyramine

(Questran)

Case 3:2 y.o. female, pale , brought in because weak , not playful. Mother strict vegan.


HCT 31.4 3+ Macrocytosis

MCV 109 hyper segmentationMCH 26.3

MCHC 29.9 Vitamin B12

PLT 139 < 100 pg/ml

RDW 19MPV 8.5

Case 4:7 y.o. boy, pale , brought in because last week had fever, and erythematous rash. You repeat CBC 2 weeks later.


HCT 29.7

MCV 109MCH 29.3 2+ ANISOCYTOSIS

MCHC 31.9

PLT 123

RDW 16MPV 10.3

Case 5:8 y.o. boy, pale , brought in because jaundice and dark urine. Last week had a UTI, mother gave ABX.


HCT 24.1

MCV 92MCH 31.3 2+ Poikylocytosis

MCHC 30.9 Bite cells

PLT 123

RDW 18MPV 8.3

Case 6:9 y.o. girl, pale , brought in because jaundice and dark urine. Last week had a UTI, mother gave ABX.


HCT 24.1

MCV 89MCH 33.3 2+ spherocytes

MCHC 36.9 Polychromasia

PLT 123

RDW 17MPV 9.3

Normocytic Anaemia

• Reduced red cell survival/Increased Destruction

• Blood loss

• Intrinsic defects (Enzyme; membrane)

• Extrinsic defects (immune hemolysis)

• Primary marrow production defect

• Bone Marrow infiltration

Investigations• Biochemistry:

– Bilirubin 100 μmol/L (<20)

– Other LFT Normal

– LDH 1,500 U/L (120-240)

– Haptoglobin <0.1

• Hematology:

– Reticulocyte count

– Direct anti-globulin (Coombs) test: Positive

– Enzymes

– Hereditary spherocytosis screen

– G6PD testing

Case 5:8 y.o. boy, pale , brought in because jaundice and dark urine. Last week had a UTI, mother gave ABX.

WBC 14.5RBC 4.4 G6PDHBG 8.1 <1 mmol

HCT 24.1

MCV 92MCH 30.3 2+ Poikylocytosis

MCHC 31.9 Bite cells

PLT 123

RDW 18MPV 8.3

Case 6:9 y.o. girl, pale , brought in because jaundice and dark urine. Last week had a UTI, mother gave ABX.


HCT 24.1

MCV 89MCH 34.3 2+ spherocytes

MCHC 35.9 Polychromasia

PLT 123

RDW 17MPV 9.3

Case 7:5 y.o. girl, coming from school parents noticed multiple bruises in legs, arms and shoulders. Healthy.


HCT 33.6

MCV 79MCH 31.3

MCHC 32.9

PLT 15

RDW 16MPV 11.3

Case 8:5 y.o. girl, well child visit. Healthy. No bleeding

WBC 4.5 3.7RBC 3.8 4.0HBG 12 11.8

HCT 34.6 33.6

MCV 79 80MCH 31.3 32

MCHC 32.9 31.1

PLT 67 53

RDW 16 16MPV 8 8.4

Finger Stick Venous

Is it real???

• Poor sample, not adequate anticoagulant proportion

• The sample has been “sitting” on lab

• Clotted blood, specially in finger stick samples

• Clumped in EDTA – blood film

• EDTD-Ab mediated clumping

**If at all possible confirm with a repeat sample

Is this isolated thrombocytopenia?More than one cell line vs.. Isolated low platelets

1. When associated with other cells lines often bone marrow infiltrative process or BMF

2. Virus (CMV, EBV, HSV, others) may induce transient BM suppression.

3. Follow up closely, consider referral to hematologist

4. Remember: <PLT with neuro symptoms TTP/HUS

Usually benign process.

ITP most common cause of isolated thrombocytopenia.

Expect spontaneous resolution.Drugs, pregnancy, large spleen / portal hypertension.

EDTA medicated clumping under Dx.

Platelet volume very helpful

• Large MPV relates to increased destruction (generally ITP).

• Small PLT often associated with Congenital PLT disorders.

• Normal MPV seen in BM infiltrative processes.

Normal range: <8.0 and >10

Thrombocytopenia

Case 7:5 y.o. girl, coming from school parents noticed multiple bruises in legs, arms and shoulders. Healthy. Next day had significant nose bleeding, oral blisters. Admitted for IVIG


HCT 30.6 Large PLT reported

MCV 79MCH 31.3

MCHC 32.9

PLT 90

RDW 16MPV 12

Case 8:5 y.o. girl, well child visit. Healthy. No bleeding

WBC 4.5 3.7 3.8RBC 3.8 4.0 4.1HBG 12 11.8 11.9

HCT 34.6 33.6 33.5

MCV 79 80 81MCH 31.3 32 31

MCHC 32.9 31.1 30.2

PLT 67 53 187

RDW 16 16 15MPV 8 8.4 8.9

Finger Stick CitrateVenous

Case 9:13 y.o. boy, African-American. New to your practice. Routine visit. Never ill.


HCT 41.6 ANC

MCV 87 905MCH 31.3

MCHC 32.9

PLT 327

RDW 16MPV 12

Isolated Neutropenia

• Not always easy to identify a cause!

• Most of time benign and transient

• Always think drugs (idiopathic vs. dose)

• Viral infection

• Auto-immune disease

• Marrow causes. (sepsis / very ill)

• Don’t forget

– Racial variation

– In child, think congenital

• Investigations will depend on clinical presentation

– Chance finding vs. ill patient

– Viral serology may be indicated (hepatitis, EBV etc –Think HIV!)

– Autoimmune

– Serial blood counts

– Referral may be required

Isolated Neutropenia

Case 9:13 y.o. boy, African-American. New to your practice. Routine visit. Never ill.Requested medical records showed neutropenia since several years ago.

Last case is only “show and tell”…

WBC 1750.0RBC 3.25HBG 11.0

HCT ANC

MCV 10.660 (1%)MCH Other cells

MCHC 99%

PLT 38

RDWMPV 8.4

Case 10:1 day old full term. Perinatal uneventful. Respiratory distress few hours after was born…

Two years later…

Thanks

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