hemolytic anemia: schistocytes; spherocytosis; bite cells; blister cells

Hemolysis may be either intravascular or extravascular.

In intravascular hemolysis RBCs lyse in the circulation releasing hemoglobin into the plasma. Causes include mechanical trauma, complement fixation, and other toxic damage to the RBC. The fragmented RBCs are called schistocytes.



In extravascular hemolysis RBCs are phagocytized by macrophages in the spleen and liver. Causes include RBC membrane abnormalities such as bound immunoglobulin, or physical abnormalities restricting RBC deformability that prevent egress from the spleen. Extravascular hemolysis is characterized by spherocytes.Spherocytes are small, spherical red blood cells (RBC). Spherocytes are approximately two-thirds the diameter of normal RBC.¹ In comparison to normal erythrocytes, they have a decreased surface area to volume ratio. They are more densely hemoglobinized and lack a zone of central pallor.

Intravascular hemolysis releases hemoglobin which is immediately bound by haptoglobin.

Hemoglobin-haptoglobin is cleared almost immediately from the plasma by hepatic reticuloendothelial cells.

As intravascular hemolysis with binding to haptoglobin generally overwhelms the rate of haptoglobin synthesis, haptoglobin levels decrease.

After haptoglobin is saturated, excess hemoglobin is filtered in the kidney and reabsorbed in the proximal tubules where the iron is recovered and converted into ferritin or hemosiderin.

Hemoglobinuria indicates severe intravascular hemolysis overwhelming the absorptive capacity of the renal tubular cells.

Urine hemosiderin is another indicator that intravascular free hemoglobin is being filtered by the kidneys.

Lactic dehydrogenase (LDH) is greatly elevated in patients with intravascular hemolysis.

Note: Haptoglobin, synthesized by the liver, is decreased in patients with hepatocelIular disease.

	Intravascular	Extravascular
Peripheral smear	schistocytes	spherocytes
Haptoglobin	decrease/absent	mild decrease
Urine hemosiderin	++	negative
Urine hemoglobin	++	negative
Direct DAT	usually negative	++++
LDH	increase	increase

Bite cells are present in G6PD deficiency



blister cells in G6PD deficiency