Hemolytic anemias (HAs)
Definition:
- Hemolysis is the premature breakdown of red blood cells. When bone marrow activity cannot compensate for the loss of red blood cells, it can lead to hemolytic anemia.
- Any disorders which lead to a reduction in the mean lifespan of the red cell is a hemolytic disorder.
- Due to red blood cell proliferation and the anatomical expansion of the bone marrow, red blood cell destruction may increase several times before the patient becomes anemic.
- After the normal adult bone marrow is fully expanded, it can produce red blood cells at 6-8 times the normal rate.
– Thus, HA may not be seen until the red cell lifespan is less than 30 days.
Classification of HA
The HA can be classified in various ways:
1- Site of hemolysis:
- The macrophages of the reticuloendothelial system in extravascular hemolytic disorders
- Within the circulatory system in intravascular hemolytic disorders
- In many cases, there is both extra and intravascular hemolysis.
Extravascular hemolysis:
- Red cell destruction usually takes place in the cell of the reticuloendothelial system. Causes include abnormal RBC membranes (such as bound immunoglobulin) or physical abnormalities. Extravascular hemolysis is characterized by spherocytes.
Intravascular hemolysis:
- Destruction of red cells take place inside the blood vessels. Caused by mechanical trauma, complement fixation, and other toxic damage to the RBC.
2- Site of defect:
- Intrinsic defect (intracorpuscular)- structural or functional defect in the red blood cell.
- Extrinsic defect (extracorpuscular)- an abnormality in the red cell environment. E.g. Toxins, infections, March hemoglobinuria.
3- Inherited or acquired:
- Inherited HAs are commonly caused by an intrinsic defect.
- While acquired HA is caused by an external defect.
- However, there are some exceptions: Paroxysmal nocturnal hemoglobinuria (PNH) which is an acquired intrinsic defect, and severe hereditary G6PD enzyme deficiency which requires external triggers like the antimalarial drug for the intrinsic defect to manifest.
Inherited & acquired HA
● Hereditary HA:
- Membrane defects e.g. hereditary spherocytosis, elliptocytosis.
- Metabolic defect e.g. G6PD deficiency, Pyruvate Kinase Deficiency.
- Hemoglobin defects e.g. sickle cell disease, Thalassemia.
● Acquired HA:
▪ Immune
-Autoimmune e.g. AIHA
-Alloimmune e.g. Hemolytic disease of the newborn, Hemolytic Transfusion Reaction.
▪ Red cell fragmentation syndromes
▪ March hemoglobinemia
▪Infections
▪ Chemical and physical agents.
▪ PNH
Approach to the diagnosis of hemolytic anemias.
Patient’s history:
Good history is essential to guide the diagnosis of hemolytic disorders. The following points should not be neglected:
- Family history: hereditary conditions, mode of inheritance.
- Ethnic origin: G6PD deficiency is most common in the Mediterranean and Chinese populations.
- Past medical history: may be indicative of congenital conditions as Hereditary spherocytosis or G6PD deficiency.
- Triggering events: a history of drugs, infections.
Clinical features
- The pallor of the mucous membranes.
- Mild fluctuating jaundice.
- Splenomegaly.
- Dark urine.
- Pigment gall stones.
- Ulcers around the ankle.
- A plastic crisis may complicate viral infections.
- Growth retardation.
- Hypertrophic skeletal changes.
Leg ulcers in patients with severe congenital hemolytic disease. e.g. sickle cell anemia.
Skeletal changes in patients with β thalassemia.
Laboratory findings:
The lab. Findings are divided into 3 groups:
1- Features of increased red cell breakdown.
2- Features of increased red cell production.
3- Damaged red cells.
1-Features of increased red cell breakdown:
- Increased Serum bilirubin, unconjugated, and bound to albumin.
- Increased urine urobilinogen.
- Increased fecal stercobilinogen.
- Absent Serum haptoglobins (saturated with Hb and removed by the reticuloendothelial system cells).
2-Features of increased red cell production:
- Nucleated RBCs in the peripheral blood
- Reticulocytosis: Increased reticulocytes in the peripheral blood which appear as Polychromatic cells.
- Bone marrow erythroid hyperplasia.
3-Damaged red cells:
- Morphology: microspherocytes, elliptocytes, fragments.
- Special tests: Osmotic fragility, autohemolysis.
- Red cell survival is shortened; this is best shown by 51Cr labeling with the study of the sites of destruction.
- Reticulocytosis is a characteristic of increased red blood cell production. The new methylene blue is used to stain reticulocytes.
- Fragmented cells and bitten cells are sings of damaged cells occurring in hemolysis.
Intravascular hemolysis:
- Free hemoglobin will be released from damaged red blood cells.
- This free Hb will rapidly saturate plasma haptoglobins. The complex will be removed by the liver.
- The excess free Hb is filtered by the glomerulus, and free Hb will enter the urine, as iron is released, the renal tubules become loaded with hemosiderin.
- Methemalbumin and hemopexin are also found in the process of IV hemolysis.
The process of intravascular hemolysis
- The liberation of free Hb.
- Filtered through the kidney.
- Appear in urine as hemoglobinuria.
Lab features of intravascular hemolysis:
1. Hemoglobinemia & hemoglobinuria.
2. Hemosiderinuria (iron storage protein in the spun deposit of urine).
3. Methemalbumin (detected by Schumm’s test).
Hemoglobinuria:
- Notice the dark color of urine compared to the normal color in the other container.
- This is a sign of intravascular hemolysis.
General Complications of Chronic Hemolytic Anemias:
• Depressed immunity-infections.
• Chronic non – healing ulcers.
• Gallstone formation, cholecystitis.
• Hypersplenism if huge splenomegaly.
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