Clinical context

A young man presents to A&E with jaundice

At a glance

Stain	MGG

About G6PD deficiency in crisis

This film is a good morphological example of G6PD (Glucose 6 Phosphate Dehydrogense) deficiency in crisis. The red cell changes are due to oxidative haemolysis. This is an intravscular haemolytic process where cells that lack sufficient G6PD are unable to process NADP into NADPH in the pentose phosphate pathway. During normal physiology, the cells are usually able to function normally but when triggered by certain drugs (e.g. primaquine, rasburicase), foods (e.g. fava beans) or infections then they suffer from haemolysis. Because this is intravascular, the patients get a release of free haemoglobin which induces NO and the symptoms of a crisis such as abdominal pain are experienced.

The condition is X linked and much more common in males, but the genetics are not the best way to diagnose this as around half of diagnosed cases are with a novel mutation. The morphology of the blood film and a G6PD quantitative assay are the gold standard tests (see lab section for pitfalls on the qualitative/rapid test!).

The red cells here show features of oxidative damage, with frequent blister cells (also called hemighosts) and keratocytes. There are the normal findings in anaemia of reticulocytes and nucleated red blood cells. The red cells also show pappenheimer bodies in response to the anaemia and we see irregularly contracted cells - these are seen only in G6PD and HbC disease so this is helpful to narrow the differential. We can see reactive change throughout the white cell series in response to the anaemia (or possibly the underlying infection).

The red cells produced are initially normal as the bone marrow uses a different enzymatic pathway to produce NADPH and the reticulocytes are initially fully stocked. Once this is exhausted, the cells are unable to recycle the NADP and the other red cell changes occur.

In this patient, there is no evidence of transfusion but this would be an important feature so look out for it. The principle of management of G6PD deficiency is conservative - remove the triggers, support the patient and transfuse if necessary.

Morphological features

Anaemia

The red cells here in the mid portion of the film are far less frequent than would be expected. It is very difficult to estimate the Hb concentration from the film but this is markedly abnormal.

Reactive Neutrophilia

These neutrophils are increasd and show toxic granulation.

Nucleated Red Cell

Seen as a bone marrow response to the acute anaemia, nRBC should not normally be visible in the peripheral blood.

Blister Cell or Hemighost

This cell has retracted haemoglobin where the Hb has sepearated away from one side of the cell. These are called blister cells or hemighosts.

Pappenheimer bodies

These ferritin fragments are present here only because of the vigorous bone marrow response. These are not Heinz bodies, which are present but only visible on a supravital stain.

Irregularly Contracted Cell

This cell is irregularly contracted. Although we use the term in day to day reporting to mean any small red cell, strictly speaking these cells only occur in G6PD deficiency and Hb C disease. This is a useful and very relevant morphological lfinding.

Reticuloyte

These large, slightly purple cells are reticulocytes, immature red cells seen in any patient with anaemia and a functional bone marrow.

Blister Cells

This cluster of cells with retracted haemoglobin is characteristic of oxidative haemolysis, most likely due to G6PD.

Pappenheimer Bodies

Normal Red Cell

The haemolysis on this film is so rampant that you can't see many normal red cells - but they are there if you look.

Bite Cell or Keratocyte

The bite cell is so called because it looks like something (a splenic macrophage) has taken a bite out of the cell. It is the end results of the blister cells where the denatured haemoglobin is removed in passing through the spleen. These are thought to be strongly suggestive of oxidative haemolysis.

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