Hemolytic Anemia

Pediatrics

Approach to Hemolytic Anemia

CLASSIFICATION OF HEMOLYTIC ANEMIAS

	Intra Corpuscular Defects	Extra Corpuscular Factors
Hereditary	• Hemoglobinopathies • Enzymopathies • Membrane-cytoskeletal defects	• Familial hemolytic uremic syndrome
Acquired	• Paroxysmal nocturnal hemoglobinuria	• Mechanical destruction (microangiopathic) • Toxic agents • Drugs • Infectious • Autoimmune

classification of haemolytic disorders

Inherited hemolytic disorders

1. Defects in the structure of the red cell membrane:

   • Hereditary spherocytosis
   • Hereditary elliptocytosis
   • Hereditary stomatocytosis

2. Defects of erythrocyte metabolism:

   • G6PD deficiency
   • Pyruvate kinase deficiency
   • Other enzyme disorders

3. Qualitative haemoglobin disorders:

   • Stable variants, such as sickle cell disease
   • Unstable variants

4. Quantitative haemoglobin disorders:

   • Impaired globin chain synthesis
   • Thalassaemias

Hemolytic Anemia Diagnosis

Two main principles:

1. Confirm hemolysis
2. Determine the etiology

The Key To The Etiology Of Hemolytic Anemia

• The history
• The peripheral blood film

How to diagnose hemolytic anemia

• New onset pallor or anemia
• Jaundice
• Splenomegaly
• Gall stones - Calciumbilirubinate stones
• Dark colored urine (hemoglobinuria)
• Leg ulcers (poor circulation and microinfarcts, healing is delayed and infection becomes established).

Patient History

• Acute or chronic
• Medication/Drug precipitants
• G6PD
• AIHA
• Family history
• Concomitant medical illnesses
• Clinical presentation

---

GENERAL FEATURES OF HEMOLYTIC DISORDERS

• General Examination: Jaundice, Pallor, Bossing Of Skull
• Physical Findings: Enlarged Spleen
• Hemoglobin: From Normal To Severely Reduced
• MCV: Usually Increased
• Reticulocytes: Increased
• Bilirubin: Increased [mostly Unconjugated]
• LDH: Increased
• Haptoglobulin: Reduced To Absent

Laboratory Diagnosis of Hemolytic Anemia:

Evidence for Red cell Destruction

• i) PERIPHERAL BLOOD SMEAR → - Burr Cell - Tear drop cell (Intravascular Hemolysis) - Fragmented cell ⇒ Spherocytes - Spherocytes → H. spherocytosis - Malaria → Malaria parasite - Sickle cells → Sickle cell anemia
• ii) Plasma haptoglobin & Plasma hemopexin → ↓
• iii) Plasma Hb ↑
• iv) Serum LDH & Serum Carboxy Hb → ↑
• v) Indirect bilirubin & urobilinogin → ↑
• vi) Red cell survival → ↓ Using Chromium 52

Evidence of Red cell Generation:

1. Peripheral blood smear
   • Polychromasia
   • Nucleated red cells
2. Reticulocyte count → ↑

Laboratory Evaluation of Hemolysis

Laboratory Evaluation of Hemolysis	Extravascular	Intravascular
HEMATOLOGIC
Routine blood film	Polychromatophilia	Polychromatophilia
Reticulocyte count	↑	↑
Bone marrow examination	Erythroid hyperplasia	Erythroid hyperplasia
PLASMA OR SERUM
Bilirubin	Unconjugated ↑	Unconjugated
Haptoglobin	↓, Absent	Absent
Plasma hemoglobin	N/↑	↑↑
Lactate dehydrogenase	↑ (Variable)	↑↑ (Variable)
URINE
Bilirubin	+	+
Hemosiderin	0	+
Hemoglobin	0	+ → severe cases

---

---

---

FM

Hemolytic Anemia

Hereditary Anemias

• Membrane: hereditary spherocytosis, hereditary elliptocytosis
• Metabolism: G6PD deficiency, pyruvate kinase deficiency
• Hemoglobin: genetic abnormalities (Hb S, Hb C, unstable)

Acquired Anemias

• Immune:

  • Autoimmune: warm antibody type, cold antibody type
  • Alloimmune: hemolytic transfusion reactions, hemolytic disease of the newborn, allografts (especially stem cell transplantation)
  • Drug-associated

• Red Cell Fragmentation Syndromes

• Infections: malaria, clostridia

• Chemical and Physical Agents: drugs, industrial/domestic substances, burns

• Secondary: liver and renal disease

• Paroxysmal Nocturnal Hemoglobinuria

Definition

• A group of disorders leading to anemia caused by a reduction in red cell life span.

• RBC’s normally survive 100 - 120 days.

• Bone marrow has the capacity to increase erythropoiesis 6 - 8 times than normal.

• Anemia is the result of premature destruction of red cells exceeding the erythropoietic capacity of the bone marrow.

Clinical Manifestations of Hemolytic Anemia

• Onset may be acute or insidious

• Symptoms and signs of anemia

• Jaundice

• Symptoms and signs specific to the type of hemolytic anemia

• Symptoms related to the underlying disease

• Splenomegaly

• Cholelithiasis (gall stones) symptoms

• Leg ulcers (sickle cell, spherocytosis)

• Skeletal abnormalities (thalassemia)

• Crises (chronic hemolytic disease)

  • Aplastic crises
  • Hemolytic
  • Megaloblastic

• Changes in urine color

Laboratory Findings

I- Increased RBC Destruction

• Decreased RBC life span
• Increased haem(heme) catabolism
• Increased serum LDH
• Absence or decrease of serum haptoglobin
• > 1 g /dl /week fall in blood Hb level
• Reduced glycosylated Hb
• Signs of intravascular hemolysis
  • Hemoglobinemia
  • Hemoglobinuria

Treatment

• The principal form of treatment is splenectomy although this should not be performed unless clinically indicated because of anemia.

• Splenectomy lengthens the life span of red cells, corrects anemia, prevents haemochromatosis, but does not affect the character of red cells.

G6PD Deficiency

Glucose-6-phosphate Dehydrogenase
(Enzyme to maintenance of RBC life)

• Mediterranean and middle eastern groups have high frequencies of G6PD deficiency.

G6PD Deficiency (Clinically)

• Usually no evidence of hemolysis is apparent until 48-96 hours after the patient has ingested a substance which has oxidant properties.

  • (Antipyretic, Sulfonamide, Anti-malarial, or fava beans) producing an acute and severe hemolytic syndrome called FAVISM, Z
  • Hb level becomes very low,
  • presence of hemoglobinemia /-uria,
  • mild jaundice,
  • splenomegaly and increased reticulocyte count.

Oxidant Stress and Hemolysis

• Most common type of oxidant stress is infections and not drugs as sulfa, primaquine, dapsone, quinidine, and nitrofurantoin.

• A sudden, severe, intravascular hemolysis can occur including jaundice, dark urine, weakness, and tachycardia.

• Heinz bodies are precipitated hemoglobin inclusions seen in red cells. Bite cells are seen on smear indicating the removal of the Heinz bodies.

Treatment

• Treatment: There is no specific therapy beyond hydration and transfusion if the hemolysis is severe.
• The main therapy is to avoid oxidant stress in the future.