Approach to Anemias

Objectives At the end of this session you should be able to: describe history and physical examination findings pertinent to anemia describe the basic diagnostic tests used in working- up anemia describe an approach to classification of anemias Use this approach to arrive at underlying etiology of anemia in various clinical scenarios

Definition Decrease in circulating RBC mass Decrease in hemoglobin or hematocrit Affected by plasma volume

General Symptoms and Signs Vary with Age Degree rapidity of onset presence of other illness

Symptoms Shortness of breath ‘palpitations’ – ‘heart racing’ dizziness headache fatigue

causes-for-anemia.aspx

Anemia and Fatigue What’s the link? Hemoglobin in RBCs Iron-containing oxygen transport protein Function to transport oxygen to every tissue in the body ~250 million Hb molecules in one RBC

signs Pallor (skin, palms, oral and conjunctival mucosa, nail beds) dyspnea Tachycardia ejection systolic murmur wide pulse pressure hypotension

History: getting at the root cause Duration, time of onset family history previous transfusion blood loss drug exposure other illnesses abdominal pain Diet, EtOH

Physical Exam: Getting at the root cause Vital signs Jaundice, pallor splenic enlargement Lymphadenopathy nail beds tongue neurologic changes

Basic laboratory exam CBC Reticulocyte count Peripheral blood smear/film

Electron Microscopy Facility at The National Cancer Institute at Frederick (NCI-Frederick)

Basic Lab Exam: CBC Hemoglobin MCV Hematocrit RDW WBC, platelets

Basic Lab Exam – Initial Approach Hb – reduction defining anemia Mean corpuscular volume (MCV)  Size Reticulocyte count – young RBCs Film – details on morphology

MCV MCV < 80 microcytic anemia MCV normocytic anemia MCV >100 macrocytic anemia MCV

Microcytic anemias iron deficiency chronic disease hemoglobinopathy sideroblastic anemia MCV < 80 microcytic anemia MCV normocytic anemia MCV >100 macrocytic anemia MCV

Macrocytic anemias MCV < 80 microcytic anemia MCV normocytic anemia megaloblastic anemias, alcholism, drugs, liver disease, primary marrow disorder, hypothyroidsm, high reticulocyte count MCV >100 macrocytic anemia MCV

Normocytic anemias MCV MCV < 80 microcytic anemia MCV normocytic anemia reticulocyte count increased evidence of hemolysis (morphology, biochemistry, Coombs test) yes immunenon immune no recent bleed normal or decreased renal, endocrine or chronic disease? yes anemia of chronic inflammation no primary marrow problem MCV >100 macrocytic anemia

A little help from a friend: The Kidneys Erythropoietin A natural hormone that stimulates the marrow to produce more RBCs as they are needed Produced by the kidneys Kidney disease Lowered production of erythropoietin  anemia

Reticulocyte count endocrine failure, microcyticnormocyticmacrocytic MCV bone marrow problem anemia of chronic inflamation evidence of renal failure, or chronic inflammation? low or normal blood loss or hemolysis high reticulocyte count

Peripheral blood film MorphologyLab testsDiagnosis Hypochromic, microcyticLow Fe, high TIBC, low ferritin Iron deficiency Hypochromic, microcyticHigh Hb A2 or high Hb FBeta- thalassemia MacrocyticLow B12 or low folateB12 or folate deficiency Macrocytic, other cell lines abnormal Normal B12,folate, low WBC, low plt Myelodysplasia (other possibilities) Normocytic, normochromic Low Fe, low TIBC, abnormal liver, abnormal kidney, high ESR, normal or high ferritin Anemia of chronic inflammation

Peripheral blood film MorphologyLab testsDiagnosis Nucleated RBC, Teardrops Other cell lines, marrow aspirate and biopsy Myelofibrosis, Marrow infiltration SchistocytesCoombs test, PTT, INR, fibrinogen Microangiopathic hemolytic anemie, ie. DIC SpherocytesCoombs test, Osmotic fragility Immune hemolysis, Hereditary spherocytosis Sickle cellsSickle prep.Sickle cell syndromes Target cellsAbnormal Hb electrophoresis HbC, D, thalassemia

Anemia Easy to identify Present with associated symptoms or signs Complete blood count (CBC): low Hb/RBC count Anemia is not a disease itself A condition caused by some other problem Diagnosis of the underlying cause may be difficult  referral to a hematologist Treatment: Sometimes easy Nutrient deficiencies Depends on underlying cause

Case presentation#1 74 year old male presents with fatigue, SOB, weakness History: diet is good, no medications, no previous history of anemia, no family history of anemia Physical exam shows: pallor, no jaundice, tachycardia, cachexia CBC: Hb 65, WBC 5.8, plt 487 What do you want to know next? MCV: 75, low reticulocyte count

Peripheral blood film

Case # 1 continued What other lab tests would you order? Low serum iron, high TIBC, low ferritin Diagnosis?

Case #2 45 year old female presents with fatigue and jaundice History: mechanical mitral valve, on warfarin, no other medications, no previous history of anemia, no family history Physical exam shows: scleral icterus, hr 125, bp 102/65, loud holosystolic murmur

Case # 2 continued CBC: Hb 56, WBC 6.4, plt 432 What do you want to know next? MCV 102, reticulocyte count high

Peripheral blood film

Case #2 continued What other lab tests would you order? Haptoglobin low, indirect bilirubin high, Coomb’s test negative Echocardiogram shows large circumferential paravalvular leak around the mechanical valve

Case # 3 24 year old female presents with fatigue and joint pain History: previously well, no medications, no family history, 6 weeks of finger, wrist, and ankle pain, associated with joint stiffness and swelling Physical exam: swelling of all MCP and PIP joints, swollen ankles, joints tender to touch, vitals normal

Case # 3 continued CBC: Hb 108, WBC 4.5, plt 684 What do you want to know next? MCV is 87, reticulocyte count is low

Peripheral blood film

Case # 3 continued What other tests might be useful? ESR is 45, ferritin is 364, TIBC is low, serum iron is low, RF is high

Questions?

Case #4  60 year-old male presents with worsening fatigue, palpitations, shortness of breath with minimal exertion  CBC: Hb 50, WBC 7.0, platelets 400,  MCV 100  High reticulocyte count

Peripheral blood film

Case #4 continued  What is the differential diagnosis?  What other tests would you order?  Haptoglobin low, indirect bilirubin high  Direct antibody test (Coomb’s test) positive  Antibody specification: non-specific IgG autoantibody  Diagnosis?

Objectives At the end of this session you should be able to: describe history and physical examination findings pertinent to anemia describe the basic diagnostic tests used in working- up anemia describe an approach to classification of anemias Use this approach to arrive at underlying etiology of anemia in various clinical scenarios

Discovered how blood is truly amazing!