Study group discussion: Cold agglutinin disease and extravascular hemolysis in liver

We were discussing a MCQ from pathologystudent.

Here's the question:

On a routine physical examination of an elderly male patient with no other medical problems, you note that his earlobes and fingertips are pale and slightly bluish. A CBC shows a hemoglobin of 10.6 g/dL (12 – 16) and an MCV of 88 (80 -100). Numerous red blood cell agglutinates are seen on the blood smear, made by smart technologists in your laboratory. Which of the following statements is true?

1. The antibody bound to the patient’s red blood cells in this disorder is probably IgG
2. Complement is probably bound to the patient’s red cells
3. The spleen is the main site of red cell destruction in this patient
4. 1 and 3
5. 1, 2, and 3

1 is not true. It's cold agglutinin disease. The main antibody is IgM here.

2 is correct since complement is involved.

The main site of destruction is liver macrophages (Kupffer cells). Therefore, 3 is incorrect.

Is there a specific reason for it?

Liver RECs have loads of C3 specific receptors. So most extravascular hemolysis that occurs in cold agglutinin disease is in the liver.

Another common mechanism of hemolysis in cold agglutinin disease is direct complement mediated intravascular hemolysis.

There's C3b on RBC and macrophage has CR3 (Complement receptor 3).

Liver macrophages lack the capacity of spleen to sequester cells. Hence, here the RBC destruction in liver occurs by phagocytosis predominantly.

Thanks, Divya, for explaining this.