Evaluation of Anemia. Hemoglobin below the normal reference level for the age and sex of the individual Reference range: 1-3 days: 14.5 - 22.5g/dl

Evaluation of Anemia

Hemoglobin below the normal reference level for the age and sex of the individual

Reference range: 1-3 days: 14.5 - 22.5g/dl 6 months to 2 years: 10.5 - 13.5g/dl Adult Men: 13-18 g/dl Adult Women: 11.5-15.5g/dl

Clinical Features (symptoms):INFANTS

• Irritability, restlessness• Anorexia, sleepiness• Behavioral changes

Clinical Features (symptoms):ADULTS

Common• Fatigue/Muscle weakness• Headache/Lack of concentration• Faintness/dizziness

Exertional dyspnoea/palpitation

Angina/intermittent claudication

Clinical Features (signs):

Non-specific• pallor, tacycardia, flow mummer

Specific• koilonychia, angular stomatitis, glossitis• neuropathy, dementia, paraplegia• jaundice, bone deformities, leg ulcer

Anemia- Signs/Symptoms

Dyspnea on exertion

Palpitations

Angina pectoris

Intermittent claudication

Headache

SyncopeanorexiaDizziness/vertigoNauseaCold intoleranceAmenorrheaDecrease libido/impotence

Multi-system effects of Anemia

Pallor

Smooth Tongue/Glossitis

Scleral Icterus

Yellow sclera

Can be seen in hemolysis

Koilonychia (spoon nails)

History:

Physiological Inadequate

intake Blood loss Malabsorption

Comorbids Drug history Family history

Classification of Anemia (Mean Corpuscular volume):

Microcyctic – MCV < 80 fL

Macrocytic – MCV > 100 fL

Normocytic MCV 80 – 100 fL

Microcytic Anemia

Iron deficiency

Hemoglobinopathy

Lead poisoning Sideroblastic Occasionally chronic disease

If no obvious cause

Serum Ferritin:< 15ug/l : Iron deficiency

Normal or : Serum Iron / Increased (TIBC)

What’s normal?

H/H– Anemia criteria6-23 m 10/31

2-5 y 11/34

6-12 12/37

MCVLower 70 + years in age (2-10)

Upper0.6/year + 84 (up to 96y)

RDW11.5%-14.5%

Reticulocyte count

Corrected 1%

Mentzer indexMCV/RBC

<12 thal trait

>13 Fe deficiency

Normal Values – Age and Gender

Clinical Manifestations of Anemia

AsymptomaticSymptoms begin when HgB <7-8g/dLVague symptoms

IrritabilityFatigueDyspnea – especially with exertionWeakness

SignsPallorTachycardiaTachypneaCongestive heart failure

The Approach

Clues to the etiology are in the H&P

The Approach - HistoryAge:

Newborn period – hemolytic anemia, blood loss, Fe deficiency rare before 4-6mo old3-6mo old – hemoglobinopathy, maybe iron deficiency6-18mo old – iron deficiency most common, consider TEC> 18mo – differential broadens

GenderMale – X-linked disease

RaceAA – Sickle cell diseaseMiddle eastern, southeast asian, southern european – β thalassemiaAA and southeast asians – æ thalassemia

DietExcessive cow’s milk consumption – Fe deficiencyStrict vegetarian – B12 deficiencyGoat’s milk as milk protein source – folate deficiency

Drug historyAntibiotics, anti-inflammatory meds, anticonvulsants

InfectionsFHx

Anemia? Gallstones? Splenectomy? Transfusions?

The Approach – Physical Exam

Abnormal forearm and hand, café-au-lait macules, short stature

Fanconi anemiaTriphalangeal thumb

Diamond-Blackfan anemiaFrontal bossing, maxillary overgrowth

Congenital hemolytic anemiaAortic stenosis, VSD

Microangiopathic hemolytic anemiaSplenomegaly

Inherited hemolytic anemiaAtaxia and posterior column signs

B12 deficiency

Labs are Helpful – Within ReasonCBC with differential

Evaluate all cell lines

Red cell indices

MCV and RDW = critical

Peripheral smear

Reticulocyte count

Coomb’s

If smear indicates hemolysis

MCV and RDW = Critical

Low MCV = microcytosisIron deficiency

Thalassemia trait

Hemoglobin EE disease

(lead poisoning)

(chronic disease)

High MCV = macrocytosisNutritional deficiency

Bone marrow failureAplastic anemia

Drug suppression

Diamond-Blackfan

Increased RDW

Helps distinguish between iron deficiency and thalassemia trait

Iron Deficiency Anemia

Making Your Diagnosis

History and physical = most important

LabsCBC with differential and smear

Red cell indicesMCV and RDW = critical

Reticulocyte countNot necessarily needed if H&P strongly suggest Fe deficiency as cause of anemia

If an unusual hx, or age < 6 mo or >18 mo-2y/o, then other labs are needed

Iron Deficiency Anemia Labs

In order of changes that occurRDW increases

Serum Fe levels fall

MCV decreases

HgB/Hct drops

Other labs may be done – but not necessary

Iron studies:FerritinTIBCFEPIron

Hgb electrophoresis:A2 and F quantification

ESR, UA, stool guiacCBC and smear of parents

Additional Labs

Microcytosis & Fe studies

Fe deficiency

Thal trait Lead poisoning

Hgb N

MCV N

RDW N N

FEP N

Serum Fe N N

TIBC N N

Ferritin N N

Evaluation continued..Serum Iron

TIBC Peripheral smear

Iron deficiency

Decreased

Increased Hypochromic

Target cells Basophilic stippling

Normal Increased

IncreasedThallasemia

Diamorphic

NormalIncreasedSideroblast

Hypo/normo chromic

Decreased

Decreased

Chronic disease

Thallesemia Mentzer index: MCV/RBC count. <13 Hb Electrophoresis

Sideroblastic anemia Bone marrow exam

Iron deficiency anemia in men/post menopausal women Gastro-intestinal endoscopy Barium studies

Evaluation continued..

Macrocytic anemia (evaluation):

Peripheral film & Reticulocyte count

Macrocytes absent

Normal reticulocyte artifactual (hyperglycemia/natremia,

cold agglutinin, and extreme leucocytosis)

High reticulocyte hemolysis, bleeding or nutritional

response to folate/B12/iron

Evaluation continued...

Macrocytes present

With megaloblast MCV>120B12 deficiency, Folic acid deficiency

Drugs (cytotoxic, anticonvulsant, antibiotic)

Without megaloblast MCV 100-120Liver disease, Alcoholism

Hypothyroidism, Myelodysplastic disorders

Normocytic anemia (causes):

Increased RBC loss/destructionacute blood loss, hypersplenism, hemolytic

disease

Decreased RBC productionprimary cause i.e bone marrow disorders

secondary cause i.e CRF, liver disease, chronic disease

Over-expansion of plasma volumepregnancy, overhydration

Normocytic anemia (evaluation):

CBC, Peripheral smear & Retic count

Normal retic and mild anemia >9gm/dl chronic disease

Normal or decreased retic with leucopenia/thrombocytopenia/blast cell

bone marrow exam

Elevated retic count Direct Coombs test: +ve autoimmune HA

-ve mechanical or other HA

Conclusion:

Evaluation based on MCV

Microcytosis is due to iron deficiency unless proven otherwise

Megaloblast help in differentiating cause of macrocytosis

CBC and reticulocyte count essential for normocytic anemia

The Medical Student’s Approach to Anemia

1. Check the reticulocyte count to determine if the anemia is from decreased production (“hypoproliferative”, “reticulocytopenic”) or increased destruction (“hemolytic”)/acute blood loss (“reticulocytosis”)

2. If decreased production, narrow down the causes in terms of the MCV-

If the MCV is low, then do iron studies then Hb electropheresisIf the MCV is normal, check the serum creatinine and TSH, if they are WNL then consider bone marrow exam

If the MCV is high check a folate and vitamin B12 level3. If the the reticulocyte count is increased-

Check a direct Coomb’s test4. Look at the peripheral blood smear to confirm/support the diagnosis

Anemia Algorithm

Patient with anemia and decreased reticulocyte count-

What is the MCV ??

Microcytic

Fe

def.

Thal

Other: sideroblastic anemia (meds,PB,Zn excess,Cu def)

NormocyticMacrocytic:

•Vitamin-related

B12, Folate

•Non-vitamin:

•MDS

•EtOH/Liver Disease

•Hypothyroidism

Systemic Diseases

Diseases in Bone Marrow

•MDS

•Solid Tumor

•Myeloma

•Aplastic anemia

Renal vs. Liver vs. Endocrine vs.

Anemia of Inflammation

Anemia Algorithm, continuedPatient with anemia and increased reticulocyte count= HEMOLYTIC

ANEMIA

Anemia Algorithm, continuedPatient with anemia and increased reticulocyte count-

What is the result of a Coomb’s test ??

Extrinsic red cell defect

Vessel

Valve

Toxin

Negativ

Positive (autoimmune hemolytic

anemia)

Intrinsic red cell defect

Membrane

Hemoglobin

Cytoplasm

“Warm” “Cold”

The Attending’s Approach to Anemia

1. Stool guiacs x 3

2. If the MCV is low, then prescribe iron

3. If the MCV is high, then check a folate level and vitamin B12 level

if folate level returns low or “indeterminate”, then begin folic acid 1 mg po qd

if B12 level returns low or “indeterminate”, then begin IM vitamin B12

Blood Loss Anemia

Excessive bleeding InjurySurgery Problem with the blood's clotting mechanism (inherited)

Ie hemophilia

Heavy menstrual periods in teen girls and women (most common problem)

Slower, long-term blood loss Ie Intestinal bleeding and inflammatory bowel disease

http://www.innvista.com/health/ailments/anemias/bloodlos.htm

Blood Loss Anemia

GI and other malignancy

Bleeding ulcers

Bleeding hemorrhoids

Physiologic Reactions to Blood Loss

Acute – Peripheral vasoconstriction and central vasodilatation

If blood loss continues – small vessel dilatation with compensatory decreased PVR, resulting in increased CO.

Chronic - Increased plasma volume keeps intravascular volume normal

Erythropoietin released by kidneys – reticulocytes in 3-7 days.

POST HEMORRHAGIC ANEMIA

BP

ACTIVATES SNS VASCULAR RESISTANCE, HR, STROKE VOLUME

RR TO IMPROVE OXYGENATION

Anemia of Acute Blood Loss

Trauma or GI tract loss most commonMenstrual/vaginal lossUrinary tractNosebleeds leading to anemia, but not because of it!Tachycardia and hypotension are common findingsHistory helps the most for these

Signs and Symptoms

Depend uponRate of blood loss

Amount of blood lost

Age

Overall Health

Comorbid disease states

Signs and Symptoms

Weakness

Fatigue

Dyspnea

Palpitations

Orthostatic symptoms

Lethargy

Physical Exam Findings

+ Orthostatic BP’s

Tachycardia

Pallor

Systolic ejc. murmur

Widened pulse pressure

GI bleeding/Uterine bleeding

Altered Mental Status

DiagnosisConfirmed by lab values – RBC count, Hgb and Hct.

CBC may not determine specific cause – need to obtain other labs to begin appropriate workup

CBC-provides RBC indices (MCV)

Reticulocyte count

Peripheral smear

Iron studies

Folate, B12 levels