RBC inclusions: Heinz bodies and Howell-Jolly bodies

The college loves Heinz bodies and Howell-Jolly bodies. RBC inclusion bodies have appeared in several SAQs, and are usually associated with a question on post-splenectomy vaccination. Most often, the question is worth 10-20% of a multi-part question, and represents easy marks for the person who can remember a handful of differentials. Thus far, the college has not ask anything about siderocytes or  basophilic stippling.

Representative SAQs include the following:

• Question 3.2 from the first paper of 2021 (Post-splenectomy Howell-Jolly bodies)
• Question 7.2 from the first paper of 2016 (Post-splenectomy Howell-Jolly bodies)
• Question 12.2 from the second paper of 2012 (Post-splenectomy Howell-Jolly bodies)
• Question 24.3 from the second paper of 2010 (Heinz bodies in G6PD)
• Question 18 from the second paper of 2007 (Post-splenectomy film)

Howell-Jolly bodies

Howell-Jolly bodies are bits of lefteover DNA in the erythrocytes. The name is usually hyphenated (Howell-Jolly), but does not have to be, as these intracellular inclusions are named after William Howell and Justin Jolly (i.e not a single person with a double-barrelled hyphenated name).  Normally, the spleen would view these as defective, and they would be removed. They are typically seen in patients who have had a splenectomy.

Other associations include the following conditions:

• Pernicious anaemia
• Macrocytosis of any cause
• Corticosteroid use

Question 3.2 from the first paper of 2021 also asked for other possible blood film abnormalities associated with splenectomy. These are numerous: the spleen is responsible for policing the circulating blood cells, and in its absence the bloodstream becomes full of weird-looking cellular rejects. It is hard to find a peer-reviewed reference which lists all of these, so here's an incomplete list from learnhaem.com:

• Pappenheimer bodies
• Acanthocytes
• Target cells
• Spherocytes
• Stomatocytes
• Thrombocytosis
• Platelet anisocytosis
• Lymphocytosis

• Heinz bodies

Heinz bodies, also known as Heinz-Ehrlich bodies are essentially little lumps of denatured haemoglobin within the red cells. They typically indicate some sort of oxidative stress. This sort of abnormality is usually seen in disorders of red cell metabolism and haemoglobinopathies. Additonally, a normal individual probably has a few RBCs with Heinz bodies, but they are rapidly cleaned up by splenic macrophages (and thus after splenectomy they begin to accumulate).

Increased oxidative stress due to toxins

• Primaquine
• Toxic solvents, eg. aniline, benzene, naphthalene
• Quinidine

Unstable haemoglobins

• Chronic liver disease
• Alpha-thalassaemia
• Certain congenital "Heinz body anaemias"
• Methylene blue methaemoglobinaemia

Deranged RBC metabolism

• Dapsone toxicity
• Glucose-6-phosphate dehydrogenase deficiency
• Trimethoprim-sulfamethoxazole (Bactrim)

Decreased clearance of defective RBCs

• Post splenectomy

Miscellaneous RBC inclusion bodies:

Blister cells: blebs on the surface of RBCs, suggestive of oxidative damage; seen with G6PD deficiency as well as in various oxidative stress states, eg. dapsone or primaquine toxicity. Within the same film one might expect a few Heinz bodies.

Pappenheimer bodies: hemosiderin-containing granules seen in sideroblastic anaemia

Basophilic stippling: altered ribosomes in the cytoplasm; seen with lead poisoning. This was a clever sideways glance by the examiners in Question 3.2 from the first paper of 2021, where its presence in the follow-up blood film of a gunshot trauma victim was used to imply that some bullet fragments remained in situ, and were causing systemic lead toxicity.   Garcés & Ortuz (2012), writing for Colombia Médica, observed the increasing prevalence of this condition in their increasingly lawless country as a sign of the times.