Approach to the Patient with Anemia   Author: Márcia Datz MD, Pediatrician

Introduction

Anemia is a commonly encountered clinical condition that is caused by an acquired or hereditary abnormality of red blood cells (RBC) or its precursors, or may be a manifestation of an nonhematologic disorder.

Definition

Anemia is defined as a decrease in the circulating RBC mass and a corresponding decrease in the oxygen-carrying capacity of the blood.
Normal values of the hemogram:

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TEST	            WOMEN	            MEN
           ----------------------------------------------------------           
Ht (%)	            36-48	            40-52
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Hg (g/dl)	    12-16	            13,5-17,7
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Hem	            4,0-5,4	            4,5-6,0
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VCM	            80-100	            80-100
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A decrease in any of this values (Ht, Hg, Hem) is called anemia. They can be altered by the plasmatic volumes.Diference between women and men values are due to androgen hormones.

Signs and Symptoms

The clinical manifestations vary with the age, degree and rapidity of onset, presence of subjacent illness and other factors. Mild anemia are often assymptomatic. The main symptoms are exercise dyspnea, fatigue, palpitation, pica (consumption of substances such as ice, starch or clay, frequently found in iron deficiency anemia), syncope (particularly following exercise) and bounding pulse. Dizziness, headache, syncope, tinnitus or vertigo, irritability, difficulty sleeping or concentrating are more frequent in severe chronic anemia.

Common signs are pallor (color of skin, palms, oral and conjunctival mucous membrane and nail beds), tachycardia, ejection sistolic murmur, mild peripheral edema and venous hums and wide pulse pressure. In old people, angina pectoris can be an important clinical manifestation. Females commonly develop abnormal menstruation, both amenorrhea and increased bleeding.Males can develop decrease in libido and impotence.

Cardiovascular Adaptations in Anemia

The main consequence of anemia is tissue hypoxia. If anemia has developed rapidly, there may not be adequate time for compensatory adjustments to take place, so there is a sudden marked contraction of intravascular volume, resulting in postural hypotension, fall in cardiac output, shunting of blood from skin to central organs, sweating, restlessness, thirst and air hunger. If anemia has slowly instalation, many adaptations occur for the oxygen mantainance, such as increasing of plasmatic volume and right shift of the oxygen-hemoglobin dissociation curve.

History and Physical Examination

In the hystory is important to ask about duration and time of onset, other subjacent illness, associated symptoms related with one specific etiology, family history, hemotransfusion, blood loss and drug exposure.Physical findings can inclue jaundice, splenic enlargement, neurologic symptoms (loss of vibration sensibility, abnormal march), tongue atrophy, lynphadenopathy, evidence of blood in feces or vomit, leg ulcers, petechiae and myriad signs of primary diseases that may cause a secondary anemia.

Basic Laboratory Exams

• Complete blood count (with reticulocyte count, platelet count, mean cellular volume-VCM- and diferencial leukocyte count).
• Peripheral blood smear can confirm size and color of RBC, variation in red cell size (anisocytosis) or shape (poikilocytosis).Particularly important in evaluating a patient with hemolysis.
• Serum ferritin level, serum iron and total iron binding capability (TIBC).
  OBS: Bone marrow aspiration is useful and critical in the workup of any unexplained anemia, specially in underproductions anemia.

   

  Initial Evaluation of Anemia

   

  The first exam to see after detecting the anemia is count of reticulocyte.If it is increased, it means anemia with increased red blood cell loss or destruction.If it is decreased, means anemia associated with decreased red blood cell production.

   

  Cause	Reticulocyte Number(normal:50.000-100.000/ml)
  Bone Marrow Failure	Low or Normal
  Hemolysis or Acute Blood Loss	High

   

  Then, if the diagnostic is bone marrow failure, it is important to classifie anemia based on mean cellular volume (VCM).It can be microcytic, normocytic and macrocytic, with low, normal or high VCM, respectively).

  Normocytic Anemias

  Chronic disease anemia Iron deficiency Secundary anemias (hepatic, renal or endocrine disorders) Primary bone marrow disorders (aplasia, myelodisplasia, myelofibrose, hematologic and solid tumors, HIV infection, granulomas)

   

  Microcytic Anemias

  Iron Deficiency Chronic Disease Anemia Thalassemia

   

   

  Macrocytic Anemias

  Megaloblastic anemias ( folic acid and cobalamin deficiency and congenital disorders ) Alcoholism Drugs Liver diseases Primary bone marrow disorder Hypothyroidism Splenectomy High VCM by artefacts

   

  Anemias due to Decreased RBC Production

  RBC indexes	Marrow	Additional lab tests	Diagnosis
  Hipochromic microcytic (Low VCM)	No iron	Low Fe, High TIBC	Iron Deficiency
  	+ iron	High HbA2 or High HbF	beta-Thalassemia
  	Ring sideroblasts	Low HbA2	Sideroblastic anemia
  Macrocytic Hyperchromic( High VCM)	Megaloblastic	Low Serum B12	Vitamin B12 deficiency
  		Achlorhydria	Pernicious anemia
  Normocytic, normochromic	normal	Low Serum folate	Folic acid deficiency
  		Low Fe and TIBC	Anemia of chronic inflammation
  		High Crestinine	Anemia of uremia
  		Abnormal liver function tests	Anemia of liver disease
  		Low T4	Anemia of myxedema
  Normoblasts, Teardrops
  	Aplastic	Pancytopenia	Aplastic anemia
  	Fibrosis	Alkaline Phosphatase	Myeloid Metaplasia
  	Infiltrated: tumor, lymphoma, etc.	High leukocyte count	Myelophtisic

  If the number of reticulocytes is high (hemolysis), it’s important to confirm the presence and assess the magnitude of hemolysis, asking for serum unconjugated bilirrubin (increased), haptoglobin (decreased), urine hemosiderin (present), urine hemoglobin (present) and serum lactate dehydrogenase (increased).

   

  Hemolytic Anemia

   

  Blood Smear	Additional Lab Tests	Diagnosis
  Schistocytes, Helmet Cells	Positive Coombs test	Traumatic hemolytic anemiaImmunohemolytic anemia
  Spherocytes	High Osmotic Fragility	Hereditary spherocytosis
  Spur Cells	Abnormal LFT+ sucrose lysis	Spur cell anemia, Paroxysmal nocturnal hemoglobinuria
  Sickle cell	+ sickle prep.	Sickle cell syndromes
  Target cell	Abnormal Hb eletrophoresis	HbC, D, etc...
  Heinz bodies	Abnormal Hb eletropheresis Low G6PD	Congenital Heinz body hemolytic anemiaG6PD deficiency