Sickle Cell Anaemia

Sickle cell anaemia is the most common haemoglobinopthy. The Hb S gene is a single point mutation which changes one amino acid (the sixth AA from glutamic acid to valine) and individuals are only affected if they have two HbS genes (called HbSS) or a combination of haemoglobin S with another abnormal haemoglobin (e.g Hb SC or Hb S BThal). The change in the haemoglobin structure is enough that the haemoglobin crystallises under low oxygen tension and as the cells cycle through high and low oxygen tension they eventually crystallise completely into sickle cells.

These sickle cells cause chronic microinfarcts in organs throughout the body, and also exacerbations such as acute vaso-occlusive crises where the patient may present with pain or an acute chest syndrome. The trigger for VOC may be anything from cold weather to infections. The phenotype is varied amongst individuals 

Outside of a VOC, sickle patients may have a much less exciting blood film with some target cells, sickle cells and nRBC. During a crisis however, the film appears like this.

There are frequent sickle cells and boat cells - these are cells where the crystallisation is ongoing and has not yet completed. There is anaemia and the consequences of this including reticulocytosis and nucleated red blood cells. There is dyserythropoiesis with those nRBC looking unhappy, evidence of abnormal haemoglobinisation and also with frequent pappenheimer bodies. Target cells are frequently seen. 

In patients with a severe crisis (some people say especially those with a chest crisis), there is evidence of retracted haemoglobin. This is not the same process as during a G6PD crisis but the intiation of the Hb crystallisation process drawing the haemoglobin away from the membrane. It occurs more frequently in patients who are unwell because the rate of crystallisation is increased in these ptients..

Patients with sickle cell disease get infarcted spleens early on in life, so almost universally outside of paediatrics, patients are hyposplenic with howell-jolly bodies. The white cell series is often reactive, either due to the infective trigger or the bone marrow stress.

Target cell