Hematology: Anemia

Anemia

Causes

  • Microcytic Anemia (MCV < 80 fL)
    • Iron Deficiency Anemia (IDA)
      • Can Be from Chronic Blood Loss
    • Anemia of Chronic Disease
    • Thalassemia
  • Normocytic Anemia
    • Acute Blood Loss Anemia
    • Hemolytic Anemia
      • Autoimmune Hemolytic Anemia
      • Hereditary Spherocytosis
      • Sickle Cell Anemia
      • G6PD Deficiency
    • *Any Cause of Microcytic or Macrocytic Anemia Can Also Present with Normocytic Anemia – Especially if Early in the Disease Course
  • Macrocytic Anemia (MCV > 80 fL)
    • Folate (B9) Deficiency
    • B12 Deficiency
    • Anaplastic Anemia
    • Fanconi Anemia
    • Diamond Blackfan Anemia

General Transfusion Thresholds

  • Goal Hgb:
    • General Population: 7.0 g/dL
    • Preexisting Coronary Artery Disease: 8.0 g/dL
      • Debated – Some Newer Literature Suggests 7.0 g/dL
  • Outside of Massive Transfusion Blood Should Be Transfused One Unit at a Time
  • Can Recheck Hgb as Early as 15 Minutes After Transfusion Completion
    • High Correlation of Hgb at 15 Minutes, 1 Hour & 2 Hours

Autoimmune Hemolytic Anemia (AIHA)

Definitions

  • Definition: Hemolytic Anemia Due to Autoantibodies to a Patient’s Own Red Blood Cells
  • Classification:
    • Warm-Reactive – IgG Autoantibodies Bind Red Cells at 37°C
      • Most Common (60-90%)
      • Hemolysis Primarily in the Spleen (Splenectomy Can Improve)
      • Generally a More Chronic Course
    • Cold Agglutinin – IgM Autoantibodies Bind Red Cells at Lower Temperatures
      • Hemolysis Primarily in the Liver & Intravascular (Splenectomy/Steroids Do Not Effect)
      • Generally Self-Limiting
  • Can Be Associated with Other Autoimmune Diseases (SLE, Scleroderma, etc.)

Labs

  • Anemia
  • Signs of Hemolysis: High Indirect Bilirubin, Low Haptoglobin, High LDH
  • Blood Smear: Spherocytes

Diagnosis

  • Diagnosis: Direct Antiglobulin (Coombs) Test
  • Cold AIHA: Hemolytic Anemia & Direct Antiglobulin Test Positive for Bound Complement & Negative for IgG
  • Warm AIHA: Hemolytic Anemia & Direct Antiglobulin Test Positive for IgG
    • May or May Not Be Positive for Bound Complement

Treatment

  • Cold AIHA: Avoid the Cold
    • If Fails: Rituximab
    • Plasmapheresis Can Remove Antibodies in the Acute Setting
  • Warm AIHA: Steroids
    • If Fails: Splenectomy or Rituximab
  • *Severe Anemia Requires Urgent Red Blood Cell Transfusion

Hereditary Spherocytosis (HS)

Basics

  • The Most Common Cause of Hemolytic Anemia
  • Caused by a Defect in the Red Blood Cell Membrane
    • Variant Membrane Protein Defects: Spectrin, Ankyrin, Band 3 & Band 4.2
  • Can Present at Any Time in Life

Classification

  • HS Trait: Normal Hgb, Bilirubin & Reticulocyte Count
  • Mild HS: Hgb 11-15 g/dL, Bilirubin 1-2 mg/dL or Reticulocyte Count 3-6%
  • Moderate HS: Hgb 8-12 g/dL, Bilirubin > 2 mg/dL or Reticulocyte Count > 6%
    • Most Common (60-75%)
  • Severe HS: Hgb 6-8 g/dL, Bilirubin > 3 mg/dL or Reticulocyte Count > 10%

Presentation

  • Anemia
  • Jaundice
  • Pigmented (Bilirubin) Gallstones – Rare in Children Under 10 Years Old
  • Splenomegaly
  • Leg Ulcers – Rare

Diagnosis

  • Lab Findings (Not Diagnostic):
    • Spherocytes on Blood Smear
    • High MCHC
    • Coombs-Negative Hemolysis
  • Definitive Diagnosis:
    • Osmotic Fragility Test –
    • EMA (Eosin-5-Maleimide) Binding Test
    • AGLT (Acidified Glycerol Lysis Test)

Treatment

  • Mild-Moderate Hemolysis: Supportive Measures (Folic Acid Supplementation & Blood Transfusion PRN)
  • Severe Hemolysis: Splenectomy
    • Concomitant Cholecystectomy if Gallstones Present – All Patients Should Have a Preoperative US to Evaluate
    • Timing: After Age 5-6 (Allow Early Immune System Development to Avoid Sepsis)

Sickle Cell Disease

Definition

  • Definition: Hemoglobin-S Gene Mutation on ≥ One Beta Globin Gene
  • Mutation Increases Risk of Erythrocytes to Sickle (Become Rigid & Elongated)
  • Sickle Erythrocytes Cause Deoxygenation, Hemolysis & Polymerization (Clumping)

Classification

  • Sickle Cell Anemia – Homozygous Mutation (HbSS/SCA-)
  • Sickle Cell Trait – Heterozygous Mutation (HbAS)
    • Rarely is Symptomatic
  • Hemoglobin SC Disease – Both a Hgb-S & Hgb-C Genes Coinherited (HbSC)

Presentation

  • Hemolytic Anemia
  • Vaso-Occlusive Phenomena
    • Acute Chest Syndrome
    • Stroke
    • Renal Infarction
    • Myocardial Infarction
    • Priapism
    • Hand-and-Foot Syndrome – Peripheral Occlusion
  • Sequestration Crisis – Pain, Hypotension & Profound Anemia
  • Increased Risk of Infection
  • Chronic Complications:
    • Pain
    • Anemia
    • Pulmonary Disorders
    • Renal Impairment
    • Seizures
    • Leg Ulcers

Triggers of Acute Events

  • Dehydration
  • Stress
  • Cold Temperature
  • High Altitude
  • Alcohol
  • Menstruation

Acute Chest Syndrome (ACS)

  • Definition: Pulmonary Sequestration of Sickled Erythrocytes
  • High Mortality: 4.3% in Adults (Lower in Peds)
    • Most Common Cause of Mortality in Sickle Cell Disease
  • 50% of Patients with Sickle Cell Disease Will Have an Episode of ACS
  • 78% are Secondary to Vaso-Occlusive Pain Episodes
    • Most Common Cause: Fat Embolism
  • Effects:
    • Lung Infarction
    • Inflammation & Atelectasis
    • Ventilation-Perfusion Mismatch
  • Definition: New Radiographic Evidence of Pulmonary Infiltrate & ≥ One Of:
    • Chest Pain
    • Fever > 38.5° C
    • Respiratory Symptoms:
      • Tachypnea
      • Intercostal Retractions or Accessory Muscle Use
      • Cough
      • Wheezing or Rales
    • Relative Hypoxemia (> 2% Decrease in SpO2)
  • Treatment:
    • Aggressive Immediate Pain Control
    • Fluid Resuscitation
    • Pulmonary Hygiene:
      • Incentive Spirometry
      • Supplemental Oxygen
      • Intensive Chest Physiotherapy
    • Empiric Antibiotics
    • Consider Blood Transfusion

Hemolytic Disease of the Newborn (HDN)

Pathophysiology

  • Alloimmunization: Rh-Negative Mother Develops Rh Antibodies
    • From Exposure to Rh Antigens
  • IgG Passes Through Placenta
  • Causes Hemolysis During a Subsequent Pregnancy
  • *Rh-Positive & Rh-Negative Nomenclature Describes the RhD Antigen Specifically Although in Reality there are Numerous Other Rh Antigens (D, d, C, c, E, e & G)

Sources of Exposure

  • Delivery
  • Abortion – Mother May Not Even Be Aware
  • Ectopic Pregnancy

Maternal Prevention

  • Prevention: Anti-D Immune Globulin (RhoGAM)
  • Indications:
    • D-Negative Mother
    • Negative Anti-D Antibody Screen
    • One of the Following:
      • 28 Weeks Gestation
      • After Delivery of a D-Positive Newborn
      • Antepartum Event Associated with an Increased Risk of Fetomaternal Bleeding:
        • Abortion (Spontaneous or Induced)
        • Blunt Abdominal Trauma
        • Ectopic Pregnancy
        • Invasive Prenatal Procedures
  • Dose: 300 mcg
    • May Consider 50 mcg if in the First-Trimester