Like G6PD which has only ever appeared in one (disastrous) viva, sickle cell disease has only ever made one appearance, in Question 12.1 from the first  paper of 2014. If we are lucky, it will never come back. If we are slightly less lucky, the repeat question will again ask about the precipitants and the management. In brief, the precipitants can be broadly described as "stressors", and management  depends somewhat on what sort of crisis it is. They come in vasoocclusive, aplastic and sequestration flavours. All will require oxygen, analgesia and rehydration, and most will require blood transfusion.

The exam candidate with an average lifespan would likely find it wasteful to dedicate an excess of reading time to this problem. Therefore, if one were to only read a single paper on this topic,  it should be the 2004 article by Iheanyie Okpala. Or, one may safely restrict their reading to the LITFL sickle cell page.

The precipitants:

  • Infection, to which they are prone:
    • functional asplenia develops in childhood;
    • hydroxyurea used to treat the disease is an immunosuppressant
  • Hypoxia,
  • Exposure to cold
  • Dehydration
  • Physical exertion,
  • Acidosis
  • Extensive trauma or injury
  • Psychological stress

Vasoocclusive crisis

  • This is the most common presentation
  •  This crisis is characterised by skeletal or soft tissue pain of sudden onset, due to ischaemia or infarction caused by obstruction of blood vessels.
  • A variant of this is priapism, which may lead to fibrosis of the penis. Surgical caverno-venous shunts or blood vents may be required.
  •  Dehydration, due to inability of inability to concentrate urine (hyposthenuria), as well as diminished interest in food (too much pain!)
  • Hyposthenuric patients cannot excrete the sodium in normal saline;  the resulting hypernatremia and hyperosmolality facilitates crystallisation of HbS and sickling of red blood cells. 
    Thus, 5% dextrose or 4% and 1/5th saline are preferred rehydration fluids.
  • These people are adapted to anaemia, and a Hb transfusion threshold of 60g/L can be safely used.

Sequestration crisis

  • This is the is acute pooling of red cells in the spleen or liver
  • Clinically, this looks like some combination of anaemia and haemorrhagic shock: cool pale extremities, weakness and fatigue, tachycardia, and low volume pulses.
  • There is abdominal pain and distension as the liver or spleen swell, engorged with blood.
  • Circulatory collapse ensues as the larger volume of blood is sequestered in the spleen
  • This is not a gradual process: the Hb may drop to below 30g/L within five hours.
  • This circulatory collapse and anaemia looks a lot like the aplastic crisis, but can be differentiated from it by the reticulocyte count: during a sequestration crisis, the bone marrow rises to the challenge with a robust haemopoietic response, increasing the reticulocyte count. In an aplastic crisis, the reticulocyte count is depressingly low.
  • The solution is usually to transfuse PRBCs. In his article, Okpala does not mention how or why the crisis resolves; only that eventually the sequestered cells make their way back into the circulation, and the patient ends up with more haemoglobin than is usually expected from them. A more extreme solution is splenectomy, which may be unfeasible in resource-poor countries where malaria is endemic.

Aplastic crisis

  • This is a crisis of poor haematopoiesis, triggered by the infecton of immature erythroid progenitor cels by parvovirus. B19 is the specific breed of parvovirus implicated in this.
  • Normal RBCs are devoid of nuclei and therefor lack the cellular machinery for protein synthesis and viral replication; therefore the cells that end up suffering most are nucleared RBC precursors.
  • This is a gradual process, characterised by an insidious onset of fatigue over several days, as well as fever and malar rash ("slapped cheek")
  • The characteristic feature is reticulocytopenia: the reticulocyte count is usually very low.
  • Tests which identify the virus also help confirm the diagnosis.
  • Usually, only supportive transfusions are required, and the crisis runs its course over a couple of weeks. No specific treatment is possible.

Blood transfusion

Most sicle cell crisis patients will require blood transfusion. As to what kind of blood transfusion, that depends on the severity. In general,  it is reserved for people with a dropping haemoglobin, but realistically, that's all of them. "Transfusion is not recommended in uncomplicated painful crises but should be considered if there is a substantial drop in Hb from baseline (e.g. > 20 g/l or to Hb < 50 g/l), haemodynamic compromise or concern about impending critical organ complications" recommends Bernard et al (BJH Guidelines, 2016) with a Grade C level of conviction. If the addition of a little healthy haemoglobin is not effective, all the blood may need to be replaced with an exchange transfusion.

References

Okpala, Iheanyi E. "Sickle cell crisis." Practical Management of Haemoglobinopathies (2004): 63-71.

Walker, H. Kenneth, et al. "Peripheral blood smear." (1990). in Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition.

Bessis, Marcel. "Codocytes and Target Cells." Corpuscles. Springer Berlin Heidelberg, 1974. 59-64.

Jones, Kathy W. "Evaluation of Cell Morphology and Introduction to Platelet and White Blood Cell Morphology." I do not know which textbook this is form, but it is a chapter which is available for free online ... for now.

Bull, BRIAN S., J. Breton-Gorius, and E. Beutler. "Morphology of the erythron."New York, McGraw Hill (2001): 271-288. - this is an online re-posting of a chapter of Williams' Haematology, but without the figures.

Davis, Bernard A., et al. "Guidelines on red cell transfusion in sickle cell disease. Part I: principles and laboratory aspects." British journal of haematology 176.2 (2017): 179-191.

Davis, Bernard A., et al. "Guidelines on red cell transfusion in sickle cell disease Part II: indications for transfusion." British journal of haematology 176.2 (2017): 192-209.