Anemia

1. Assess the risk of decompensation of anemic patients (e.g., volume status, the presence of congestive heart failure [CHF], angina, or other disease states) to decide if prompt transfusion or volume replacement is necessary.
2. In a patient with anemia, classify the anemia as microcytic, normocytic, or macrocytic by using the MCV (mean corpuscular value) or smear test result, to direct further assessment and treatment.
3. In all patients with anemia, determine the iron status before initiating treatment.
4. In a patient with iron deficiency , investigate further to find the cause.
5. Consider and look for anemia in appropriate patients (e.g., those at risk for blood loss [those receiving anticoagulation, elderly patients taking a nonsteroidal anti-inflammatory drug]) or in patients with hemolysis (mechanical valves), whether they are symptomatic or not, and in those with new or worsening symptoms of angina or CHF.
6. In patients with macrocytic anemia:
   1. Consider the possibility of vitamin B12 deficiency.
   2. Look for other manifestations of the deficiency (e.g., neurologic symptoms) in order to make the diagnosis of pernicious anemia when it is present.
7. As part of well-baby care, consider anemia in high-risk populations (e.g., those living in poverty) or in high-risk patients (e.g., those who are pale or have a low-iron diet or poor weight gain).
8. When a patient is discovered to have a slightly low hemoglobin level, look carefully for a cause (e.g., hemoglobinopathies, menorrhagia, occult bleeding, previously undiagnosed chronic disease), as one cannot assume that this is normal for them.
9. In anemic patients with menorrhagia, determine the need to look for other causes of the anemia.

See iron deficiency, vitamin B12 deficiency.

General Overview

• Usually defined as low hemoglobin or hematocrit (Approximately Hb <135 for men <120 for women)
• Restrict transfusions if stable, consider maintain Hb>70-80 (if underlying cardiovascular disease, planned surgery)
  • Consider transfusions in symptomatic, unstable, ongoing losses
    • If transfused, may repeat post-transfusion hemoglobin levels even after 15 minutes (1pRBC usually raises Hb by 10g/L)

Microcytic (MCV <80: TAILS)

• Thalassemia (alpha, beta)
  • Africa, Mediterranean, Southeast Asia
  • Mild Splenomegaly
• Anemia of chronic disease
• Iron deficiency
  • Nutrition
  • Chronic blood loss (GI, celiac, menstruation)
• Rare
  • Lead poisoning
  • B6 deficiency
  • Copper or Zinc deficiency
  • Sideroblastic (iron metabolism defect)

Normocytic (MCV 80-100: ABCD)

• Acute blood loss
• Bone marrow failure
• Chronic disease
  • ESR, CRP, creatinine
• Destruction (Hemolysis)
  • Inherited:
    • Hemoglobinopathy: Sickle cell, Thalassemia, Unstable Hb
    • Membrane: Spherocytic
    • Metabolic: HMP shunt, glycolytic
  • Acquired
    • Immune
    • Infection
    • MAHA
    • Oxidative

Macrocytic (MCV>100: FATRBC)

• Folate / Fetus (pregnancy)
• Alcoholism / Liver disease
• Thyroid (hypo) / Endocrine
• Reticulocytosis
• B12 deficiency
• Cytotoxic Drugs / Dysplasia

Kinetic Approach

• Decreased RBC production
  • Nutrients (B12, iron)
  • Bone marrow disorder/suppression
  • Low trophic hormones (EPO, thyroid hormone, androgens)
  • Note: Inflammation reduces available iron, EPO, and RBC lifespan
• Increased RBC destruction
  • Extravascular (spleen/liver)
    • Inherited (spherocytosis, sickle, thalassemia)
    • Acquired (autoimmune, thrombotic thrombocytopenic purpura, malaria, paroxysmal nocturnal hemoglobinuria)
    • Hypersplenism
  • Intravascular
    • MAHA
    • Paroxysmal nocturnal hemoglobinuria
    • Cold agglutinin
• Blood loss

Investigations

• CBC
  • Serial hemoglobin and hematocrit
  • RBC indices
    • MCV as above, MCH (similar to MCV)
    • Increased MCH concentration (mean corpuscular hemoglobin concentration) occur almost exclusively in congenital/acquired spherocytosis or other congenital hemolytic anemias (sickle cell, Hb C, xerocytosis)
  • WBC (monocytosis may suggest myelodysplasia)
  • Platelets
    • Rule out pancytopenia (bone marrow infiltration, aplasia or destruction/sequestration)
• Reticulocyte
• Blood smear
  • Red cell fragmentation ("helmet cells," schistocytes) in microangiopathic hemolysis
  • Microspherocytes in autoimmune hemolytic anemia
  • Teardrop RBC in myelofibrosis
  • Leukoerythroblastic pattern in bone marrow infiltration or replacement
  • RBC parasites in malaria or babesiosis
• Iron profile (consider if blood loss or low MCV, low MCH, high RDW)
  • Ferritin
  • TIBC (transferrin)
• Hb electrophoresis
• Hemolysis work-up
  • LDH
  • Bilirubin (indirect)
  • Haptoglobin (reduced in hemolysis)
  • Consider Coombs' test
  • Consider urinary hemoglobin and hemosiderin for intravascular hemolysis in paroxysmal nocturnal hemoglobinuria
• Bone marrow biopsy
  • Usually indicated in pancytopenia or blast cells (rule out malignancy)
• TSH/B12/Folate
• INR
• DIC panel (fibrinogen, D-dimer)

Anemia in Children

History

• Lethargy, tachycardia, pallor
• Signs of hemolysis (urine color, scleral icterus, jaundice)
• Failure to thrive
• Bleeding history
• PMH (birth, jaundice, anemia, medical conditions)
• Family History
  • Bleeding disorder, hemoglobinopathy, IBD
• Poverty
• Non-iron-fortified formula
• Ethnicity
  • Hb S and C in black/Hispanic
  • Thalassemia in Mediterranean/Southeast Asian
  • G6PD in Sephardic Jews/Filipinos/Greeks/Sardinians/Kurds/black
• Whole cow's milk diet
• Exclusive breastfeed after 6 months of age
• Poorly controlled maternal diabetes

By Age

• 0-3 months:
  • Newborns: Blood loss, hemolysis (Rh or ABO incompatibility), congenital infection, twin-twin transfusion, congenital hemolytic anemia (spherocytosis, G6PD deficiency)
  • Physiologic anemia (nadir of 110 at 6-9w of age due to decrease in EPO)
• 3-6 months:
  • Hemoglobinopathy (thalassemia, sickle cell)
• 9-12 months:
  • Acquired (iron deficiency anemia)
  • WHO recommends screening in all children 9-12 months
    • Consider targeted screening if risk factors (poverty, poor weight gain, excessive milk intake + low iron-rich foods [malnutrition], malabsorption, GI blood loss, obesity)