ANEMIA

Pamela L. Charity, MD, FHMMedical University of South CarolinaMay 23, 2013

ObjectivesDefine AnemiaUnderstand variables between

certain populationsDescribe both kinetic and

morphologic approach to determining cause of anemia

Obtain pertinent history, physical and indicated studies

Interpret studies for accurate differential diagnosis

AnemiaDefinition: reduction in one or

more of the major RBC measurements

◦HGB: major oxygen carrying pigment in whole blood

◦HCT: percent of sample of whole blood occupied by intact RBC

◦RBC: number of cells contained in volume

Normal RangeAnemia: Values > 2 standard

deviations below the meanOther proposed definitions:

◦WHO criteria based on international nutrition

◦WHO/National Cancer Institute’s criteria based on malignancy

◦NHANES III and Scripps-Kaiser studies based on sex, age, and race

VariablesVolume status

Special populations◦High altitude◦Carboxyhemoglobin◦African-Americans vs Caucasion◦Population with high incidence chronic

disease◦Pregnancy

SymptomsFactors:

◦Decreased oxygen delivery to tissues Oxyhemoglobin dissociation curve O2 extraction baseline 25%, up to 60% SV X HR = CO

◦Possible hypovolemia with marked acute bleeding

SymptomsOccurs generally when:

◦ HGB < 5 at rest, or ◦ higher with exertion or ◦ with cardiac decompensation

Primary symptoms: ◦ exertional dyspnea◦ dyspnea at rest◦ fatigue◦ hyperdynamic state◦ confusion◦ high output heart failure

Causes of Anemia

Kinetic Approach Morphologic ApproachDecreased RBC

production

Increased RBC destruction

Blood loss

Based on measurement of RBC size

◦ Normocytic◦ Microcytic◦ Macrocytic

Evaluation of the Patient with AnemiaAnemia is never normal and is

one of the major signs of disease.◦Bleeding?◦RBC destruction?◦Bone marrow suppression?◦Iron deficient?◦Deficiency B12 or Folic Acid?

Evaluation of the Patient with AnemiaHistory:

◦Symptoms or medical condition associated with anemia?

◦Acute or lifelong? ◦Inherited hemoglobinopathy ,

hereditary spherocytosis, etc.◦Ethnicity and country of origin

Physical ExamAssess severity and find signs of organ

or multisystem involvement.

◦Tachycardia◦Dyspnea◦Fever◦Postural hypotension◦ Jaundice◦Pallor◦Petechiae, ecchymoses◦Stool for occult blood

Laboratory EvaluationCBC to include WBC differential, platelet

count, and reticulocyte count.

Blood smear reviewed

Laboratory Evaluation

Reticulocyte Count WBC Count and Differential

• High reflects increased erythropoietic response

• Low reflects decreased production of RBC, is pancytopenia present?

Leukopenia:◦ bone marrow suppression◦ Hypersplenism◦ deficiencies

Leukocytosis:◦ Infection◦ Inflammation◦ malignancy

Evaluation for Iron Deficiency Anemia (IDA)

Iron is necessary for erythrocyte production and maturation:

DNA synthesis, cellular respiration, and oxygen transport

History: blood loss, malabsorption, increased need

Microcytosis, anisopoikilocytosis

Measure: Iron, IBC (transferrin), Transferrin saturation, and Ferritin (<15)

Evaluation for B12 DefeciencyNeeded for DNA synthesisTransferred from R-binders to intrinsic factor in ileumStored in reticuloendothelial system with large

hepatic reservoirPernicious anemia involves antibodies directed

toward parietal cell membrane, reducing intrinsic factor

Glossitis, weight loss, neurologic and psychiatric symptoms

Measure cobalamin, folate, homocysteine, methylmalonic acid *

May present as hemolysis pictureTreatment now with oral B12

Evaluation for Folate DeficiencySmall stores of folate in bodyMalnutrition, alcohol dependence,

pregnancyDrugs: triamterene, phenytoinSmall bowel disease: Celiac, IBD,

AmyloidosisHomocysteine levels > 90% sensitivity

and specificity when MMA normalExclude B12 Deficiency before starting

treatment as neurologic symptoms will progress

Inflammatory AnemiaChronic infections , malignancy,

collagen vascular diseasesErythropoetin production

inhibited Increased levels of inflammatory

cytokines: TNF, IL-6 (hepcidin causes decreased iron absorption), IL-1, interferon

Typically, Hbg > 8

Inflammatory Anemia vs IDA

Anemia of Kidney DiseaseDecreased renal cortical mass ,

decreased erythropoetinNormochromic/normocyticPeripheral smear may show Burr cellsESA to achieve target Hbg levels 10 –

12ESA can lead to HTN, Thrombosis, MI,

CVAIron stores improve efficacy, Ferritin

> 100

Evaluation for Hemolysis• Rapid fall in HGB• Reticulocytosis• Abnormally shaped RBC

Measure: LDH, Indirect bilirubin, Haptoglobin

Hemolytic AnemiasDiverse group of diseases sharing

accelerated erythrocyte destructionCongenital:

◦ Hereditary Spherocytosis◦ G6PD Deficiency ◦ Thalassemia◦ Sickle Cell Syndromes

Acquired:◦ Autoimmune◦ Microangiopathic◦ Paroxysmal Nocturnal Hemoglobinuria◦ Infectious, chemical agents

Hemolytic Anemias

Spherocyte

Schistocytes

Target Cells

Sickle Cells

Bone Marrow ExaminationIndications:

◦ Pancytopenia◦ Abnormal cells

(blasts)

Diagnoses:◦ Aplastic Anemia◦ Myelodysplasia◦ Malignancy◦ Myeloproliferative

D

Key MessagesApply your understanding of

clinical history and physical before ordering extensive laboratory studies

Evaluating the blood smear will always provide important information

Anemia is never normal

ReferencesMKSAP 16, Hematology and

Oncology, pp 18 – 35.Up to Date; Approach to the adult

patient with Anemia; Schrier, Stanley, Jan 2013.

ESRD Network II, Medical Review Committee 2011 goals.

Questions?