Evaluation of Anemia

Hemoglobin below the normal reference level for the age and sex of the individual Reference range:  1-3 days: g/dl  6 months to 2 years: g/dl  Adult Men: g/dl  Adult Women: g/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 Syncope anorexia Dizziness/vertig o Nausea Cold intolerance Amenorrhea Decrease libido/impotenc e

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 criteria 6-23 m  10/ y  11/  12/37 MCV Lower  70 + years in age (2- 10) Upper  0.6/year + 84 (up to 96y) RDW 11.5%-14.5% Reticulocyte count Corrected 1% Mentzer index MCV/RBC <12 thal trait >13 Fe deficiency

Normal Values – Age and Gender

Clinical Manifestations of Anemia Asymptomatic Symptoms begin when HgB <7-8g/dL Vague symptoms Irritability Fatigue Dyspnea – especially with exertion Weakness Signs Pallor Tachycardia Tachypnea Congestive heart failure

The Approach Clues to the etiology are in the H&P

The Approach - History Age: Newborn period – hemolytic anemia, blood loss, Fe deficiency rare before 4-6mo old 3-6mo old – hemoglobinopathy, maybe iron deficiency 6-18mo old – iron deficiency most common, consider TEC > 18mo – differential broadens Gender Male – X-linked disease Race AA – Sickle cell disease Middle eastern, southeast asian, southern european – β thalassemia AA and southeast asians – æ thalassemia Diet Excessive cow’s milk consumption – Fe deficiency Strict vegetarian – B 12 deficiency Goat’s milk as milk protein source – folate deficiency Drug history Antibiotics, anti-inflammatory meds, anticonvulsants Infections FHx Anemia? Gallstones? Splenectomy? Transfusions?

The Approach – Physical Exam Abnormal forearm and hand, café-au-lait macules, short stature Fanconi anemia Triphalangeal thumb Diamond-Blackfan anemia Frontal bossing, maxillary overgrowth Congenital hemolytic anemia Aortic stenosis, VSD Microangiopathic hemolytic anemia Splenomegaly Inherited hemolytic anemia Ataxia and posterior column signs B 12 deficiency

Labs are Helpful – Within Reason CBC 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 = microcytosis Iron deficiency Thalassemia trait Hemoglobin EE disease (lead poisoning) (chronic disease) High MCV = macrocytosis Nutritional deficiency Bone marrow failure Aplastic 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 Labs CBC with differential and smear Red cell indices MCV and RDW = critical Reticulocyte count Not necessarily needed if H&P strongly suggest Fe deficiency as cause of anemia If an unusual hx, or age 18 mo- 2y/o, then other labs are needed**

Iron Deficiency Anemia Labs In order of changes that occur RDW increases Serum Fe levels fall MCV decreases HgB/Hct drops Other labs may be done – but not necessary

Iron studies: Ferritin TIBC FEP Iron Hgb electrophoresis: A2 and F quantification ESR, UA, stool guiac CBC and smear of parents Additional Labs

Microcytosis & Fe studies Fe deficiency Thal traitLead poisoning HgbN MCVN RDWNN FEPN Serum FeNN TIBCNN FerritinNN

Evaluation continued.. Serum Iron TIBCPeripheral smear Iron deficiency Decrease d Increased Hypochromi c Target cells Basophilic stippling Normal Increased Increased Thallasemia Diamorphi c NormalIncreasedSiderobla st Hypo/normo chromic Decrease d 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>120 B12 deficiency, Folic acid deficiency Drugs (cytotoxic, anticonvulsant, antibiotic) Without megaloblast MCV Liver disease, Alcoholism Hypothyroidism, Myelodysplastic disorders

Normocytic anemia (causes): Increased RBC loss/destruction acute blood loss, hypersplenism, hemolytic disease Decreased RBC production primary cause i.e bone marrow disorders secondary cause i.e CRF, liver disease, chronic disease Over-expansion of plasma volume pregnancy, 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 electropheresis If 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 B 12 level 3. If the the reticulocyte count is increased- Check a direct Coomb’s test 4. 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) Normocytic Macrocytic: Vitamin-related B 12, 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, continued Patient with anemia and increased reticulocyte count= HEMOLYTIC ANEMIA

Anemia Algorithm, continued Patient with anemia and increased reticulocyte count- What is the result of a Coomb’s test ?? Extrinsic red cell defect Vesse l Valve Toxin NegativPositive (autoimmune hemolytic anemia) Intrinsic red cell defect Membran e Hemoglobin Cytoplas m “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 B 12 level if folate level returns low or “indeterminate”, then begin folic acid 1 mg po qd if B 12 level returns low or “indeterminate”, then begin IM vitamin B 12

Blood Loss Anemia Excessive bleeding Injury Surgery 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

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 common Menstrual/vaginal loss Urinary tract Nosebleeds leading to anemia, but not because of it! Tachycardia and hypotension are common findings History helps the most for these

Signs and Symptoms Depend upon Rate 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

Diagnosis Confirmed 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