Sickle Cell for Healthcare Professionals


A North American physician, James Herrick, was the first to describe sickle cell disease in western medical literature in 1910. A medical student named Walter Clement Noel, who originated from Grenada in the West Indies complained of frequent episodes of pain in his joints and limbs and was noted to be prone to fever which often warranted medical intervention (Bloom 1995). On examination of Clement’s blood Herrick noted crescent shaped peculiar red blood cells resembling the shape of ‘sickle’ which is a farmer’s cutting tool implement.

Although this was the first formally reported case in western medical literature there is evidence that many families in Africa were able to trace the disease through many generations of their families (Konotey-Ahulu 1991) and they had tribal names for what was thought to be a rare disease in the west but common in Africa; the tribal names often describe what is now known to be classic symptoms of the disease, for example, the Yoruba people of southern Nigeria called it ‘arun romolegungun’, which means ‘disease that aches the child’s bones’, a common description of one of the classic symptoms of sickle cell crisis pain.

The significant migration of people from the West Indies, Africa and Asia during the 1950’s and onwards accounts for the high incidence of sickle cell disease in the UK. Approximately 12,000 with sickle cell disease live in the UK and 9,000 of these live in London (Streetly et al 1997).

To appreciate the problems associated with sickle cell disease health care professionals working in all care settings need to understand the aetiology, biology, genetics, epidemiology, clinical and psycho-social implications of living with this debilitating and potentially fatal genetic disease.

Composition of Blood

  • Plasma, which is mainly fluid
  • Formed cells, of which there are:
    • Red blood cells
    • White blood cells
    • Platelets

Red blood cells (RBC) are responsible for transporting oxygen; white blood cells are the body’s defence against infection, platelets are responsible for clotting to arrest bleeding arresting whilst plasma contain chemical and particles and its main function is to transport the formed blood cells around the body.

Haemoglobinopathies of which sickle is the most common type are genetic conditions affecting the red blood cell haemoglobin gene; therefore, the focus of this section will be on the red blood cells and sickle cell disease.

Diagram 1: Normal Red Blood Cells

A normal RBC is a biconcave, flexible disc which is pliable, spongy and soft (see diagram). It travels easily, even through the tiniest blood capillaries without damage to its own structure. It is manufactured in the bone marrow, primarily the long bones during childhood, and the flat bones during adulthood. RBCs live approximately 120 days in circulation before they are destroyed by the reticulo- endothelial cells in the spleen (Tortora & Grabowski 2003).

RBCs contain millions of haemoglobin molecules, which are responsible for attracting oxygen in the lungs and transporting it to the body tissues; normal haemoglobin molecules are water soluble and remain separate in the red blood cell (diagram 1). Haemoglobin is made up of two parts, haem which is the iron compound that binds with oxygen, and globin, which are proteins. Different haemoglobins predominate at different stages of human development, from embryonic to fetal to adulthood, see Haemoglobin.

Adult haemoglobin is made up of a pair of alpha (α2) and a pair of beta (β2) globin chains. Synthesis of the alpha globin chain is controlled by a pair of genes located on chromosome 16 and the beta globin chain is controlled by genes on chromosome 11 (diagram 2). The chromosomes controlling the α and β gene is unrelated even though their end product (globin chain) unite, with iron to form the adult haemoglobin.

146 amino acids link together in a predetermined sequence to form the alpha globin chain and 141 amino acids form the beta globin chain (Gelehter & Collins 1990).

The body is constantly manufacturing new RBCs and destroying aged or damaged RBCs. When RBCs are destroyed the haem (iron) is released, stored in the liver to be later released to the bone marrow for the manufacture of new RBCs. The globin (protein) is converted into bile and stored in the gall bladder to aid digestion; bile gives urine its yellow pigment and faeces its brown pigment (Thibodeau & Patton 1993, Tortora & Grabowski 2003).

Inheritance of Normal and Abnormal Haemoglobin

The type of adult haemoglobin which an individual has is genetically inherited, one from each parent. Where an individual inherits two normal adult beta globin genes and two normal alpha globin genes they have βA βA and α α / α α, this is commonly written Hb AA, see Inheritance of Haemoglobin and Interpreting Sickle Cell / Thalassaemia Test Results.

Those who inherit one normal and one abnormal beta globin gene are said to have a ‘trait’, for example, sickle cell trait βA βS commonly written (Hb AS), Beta Thalassaemia trait βA βThal commonly written (Hb AβThal), Haemoglobin C trait βA βC commonly written (Hb AC), haemoglobin D trait βA βD commonly written (Hb AD) and Haemoglobin E trait βA βD commonly written (Hb AE). These are the most common combinations seen in the UK with sickle haemoglobin being the most common. There are over 1000 genetic mutations of haemoglobin identified in humans to date (Bain 2001).

Haemoglobinopathies are regarded as structural / qualitative defects of haemoglobin because individuals produce the correct amount of the globin chain but the quality of it could be affected; whilst Thalassaemia is a synthesis / quantitative defect of haemoglobin where there is a reduction in the amount of the globin chain synthesised but the quality may not be affected.

Individuals with sickle cell trait or any other haemoglobin trait are referred to as ‘healthy carriers’ because under normal circumstances they do not have any symptoms. But because they are healthy they will not know that they carry this unusual haemoglobin gene unless they have been tested for it specifically.

These genetic conditions are autosomal (non-sex linked) recessive, which means the genetic mutation can be inherited by male and females equally and an individual will need to inherit the mutation on both chromosomes, one from each parent, in order to have a disease state. For example, where a person inherits two sickle cell gene mutations they will have sickle cell anaemia (Hb SS) and if they inherit two beta zero Thalassaemia mutations they will have Beta Thalassaemia Major (Hb βThalβThal.)

The production of sickle haemoglobin occurs as a result of a genetic mutation on the 6th point of the beta globin chain where glutamic acid is replaced by another amino acid called valine. This amino acid substitution causes a change in the beta globin chain sequence and consequently in its ability to bind with oxygen and release oxygen to the tissues effectively (Embury et al 1994, Steinberg et al 2001).

Diagram 2 - Double Helix and Haemoglobin Tetramer

NB:  (Mutation GAG → GTG result in amino acid substitutionβ6 Glutamic acid → Valine = Sickle)
(Mutation GAG → AAG result in amino acid substitution β6 Glutamic acid → Lysine = Hb C)
(Mutation GAA → CAA result in amino acid substitution β121Glutamic acid → Glutamine = Hb DPunjab also known as Hb DLos Angeles)
(Mutation GAG → AAG result in amino acid substitution β26 Glutamic acid → Lysine = Hb E)
(Mutation GAA→ AAA result in amino acid substitution β121 Glutamic acid → Lysine = Hb OArab)

There are more than 400 mutations of the beta globin gene and any of these can be co-inherited with each other to result in a benign, mild, moderate or severe disease state.

Sickle cell disease is inherited either in a homozygous state resulting in Sickle Cell Anaemia (Hb SS) or in a compound heterozygous state, for example, Sickle Haemoglobin C disease (Hb SC), Sickle Beta Thalassaemia disease (Hb SβThal), Sickle Haemoglobin E disease (Hb SE), Sickle Haemoglobin D disease (Hb SD) and Sickle Haemoglobin Hb OArab disease (Hb SOArab). There are reports of dominant forms of the sickle gene mutation which give rise to sickle related symptoms even in the carrier state (Higgs & Weatherall 1993, Steinberg et al 2001), but these are exceptionally rare.

Inheritance of haemoglobin

For illustrations of inheritance see Inheritance of Haemoglobin and for interpreting Sickle Cell / Thalassaemia test results see Interpreting Sickle Cell / Thalassaemia Test Results.

Health care professionals must have an understanding of how to explain the inheritance of haemoglobin. Two simple methods that can be used in this instance are the family tree and the punnet square.

Example of family tree

In this instance each of parent one’s haemoglobin needs to be matched with both of the other parents two haemoglobin.

If one parent has sickle cell trait (Hb AS) and the other has haemoglobin C trait (Hb AC) using the genetic tree pattern of explaining inheritance, these are the possibilities for the couple’s offspring:

Step 1 matching parent 1 first haemoglobin with parent 2 two haemoglobins:

Step 2 matching parent 1 second haemoglobin with parent 2 two haemoglobins:

When these are combined to complete the illustration it will resemble the completed family tree below:

In each and every pregnancy, there is a 1 in 4 (25%) chance the child could inherit normal haemoglobin (Hb AA), a 1 in 4 chance (25%) the child could inherit sickle cell trait (Hb AS), a 1 in 4 chance (25%) the child could inherit Haemoglobin C trait (Hb AC) and or a 1 in 4 chance (25%) the child could inherit sickle Haemoglobin C disease (Hb SC).

The same couple using the Punnet square:

Parent 1


The general principle in the Punnet square is that each haemoglobin must appear in the two boxes directly in front of it but it must not travel diagonally.

These methods of explaining inheritance can be used to determine the haemoglobin type that a couple’s child can inherit provided the couple’s haemoglobin type is known and has been confirmed by a laboratory diagnosis.


Using the same methods as given in the inheritance pattern examples work out the four possible chances for the following couple’s children:
Parent 1   Parent 2   Child could inherit one of the following:
a) Hb AS Hb AE
b) Hb AS Hb AβThal
c) Hb AβThal Hb AD
d) Hb AC Hb AC
e) Hb AβThal Hb AβThal

All newborn babies have a high level of fetal haemoglobin (Hb F) at birth. It is produced during intrauterine development and makes up approximately 80-90% of the total haemoglobin at this stage of the baby’s development. By the age of one year the synthesis of fetal haemoglobin declines to <1% and remains at this level right through adult life. Hb F is a normal fetal haemoglobin, which all unborn babies have during intrauterine life irrespective of the type of adult haemoglobin that the child has inherited from both parents.

If a newborn has inherited the genes for normal adult haemoglobin, at birth the blood test result will indicate the presence of fetal haemoglobin F and the normal adult Haemoglobin A (Hb FA), although Haemoglobin A2 is also present this is often not reported as part of a routine newborn screening test, but in adult tests the A2% is reported.

For information on interpreting haemoglobin results and actions required, see Interpreting Sickle Cell / Thalassaemia Test Results.

Sickle Cell

Incidence of the Sickle Gene

There is often a misconception that sickle cell affects Black people only. Having a genetic mutation of haemoglobin is not dependent on skin colour but on the haemoglobin gene that an individual has inherited from their parents. Sickle cell occurs most commonly among people whose ancestors originate from Africa, Asia, Middle East and the Mediterranean. Migration accounts for its presence in the Caribbean, South America and other parts of the world, including Britain. All people of non-Northern European origin are therefore considered to be at greater risk of inheriting genetic mutations of haemoglobin, but it is not exclusive to these populations and can affect people of any race, colour or ethnic origin (Lehmann & Huntsman 1974).

The incidence of sickle cell trait is approximately:

  • 1 in 4 West Africans
  • 1 in 10 Black African-Caribbean
  • 1 in 20 - 50 Asians
  • 1 in 100 Northern Greeks

Since introducing a comprehensive neonatal screening programme in the former North West Thames Regional Health Authority in 1989, a number of White English new born babies have been identified with sickle cell trait, but a larger proportion have been identified with other haemoglobinopathies including haemoglobin C, D, E, J and a myriad of other novel haemoglobin carriers states, some of which are rare in Black and other minority ethnic populations; this is similar to the findings of Chami et al (1995) on an examination of the blood samples of French Caucasian populations attending a hospital in France.

Sickle Cell Trait

Sickle cell trait (Hb AS) is a healthy carrier state which does not give rise to a significant clinical presentation (LINK TO HAEMOGLOBIN S). However it is reported that those with sickle cell trait are less able to concentrate their urine (hypostheuria) in view of this there is an increased tendency and risk of dehydration and these individuals should be advised to maintain an adequate fluid balance. There is increased rate of bacteriuria, pyelonephritis and haematuria especially during pregnancy, screening is essential and a positive result needs to be treated with antibiotics promptly and rigorously (Embury et al 1994, Serjeant & Serjeant 2001).

Sickle Cell Disease

Sickle cell disease is a collective name for a group of genetically inherited conditions where sickle haemoglobin is inherited in a homozygous form resulting in Sickle Cell Anaemia (Hb SS) or inherited with another beta globin gene mutation resulting in a compound heterozygous state, for example, Haemoglobin C, resulting in sickle Haemoglobin C disease (Hb SC). This condition affects the globin chain structure and consequently the red blood cells structure and inability to transport oxygen and function effectively.

Red blood cells (RBC), which contain a significant proportion of sickle haemoglobin is insoluble. When deoxygenated the haemoglobin molecules crystallise, forming long stiff rods (tactoids), which distort the membrane of the RBC. These stiff rods exert pressure on the wall of the RBC membrane causing it to collapse and distort into a variety of shapes including the classic shape of a farmer’s sickle, from which the condition derived its name. When re-oxygenated in the lungs the RBCs will regain their original round shape. However with repeated sickling (deoxygenation) and unsickling (oxygenation) there is increasing crystallization and formation of these stiff rods within the RBCs; they become increasingly hard, brittle and consequently irreversibly sickled; these cells are fragile, they break easily and are rapidly destroyed by the reticulo- endothelial cells in the spleen, thereby shortening their life span from the normal 120 days to about 5 – 20 days (Higgs & Weatherall 1993).

Diagram 3 - Sickled Red Blood Cells

This shortened life span of sickle RBCs is the cause of the haemolytic anaemia associated with this condition. It is important to note that the anaemia is not due to iron deficiency. The iron content of destroyed RBCs, even sickled red blood cells, is extracted by the body, transported to the liver for storage to be later released to the bone marrow for the manufacture of new red blood cells. Evidently the quantity of iron obtained and stored from normal RBCs, which live for 120 days, will be less than that obtained and stored from sickle RBCs that only live 5 - 20 days. Therefore iron supplements or medications are not recommended unless blood investigations prove there is genuine iron deficiency. Unnecessary self medication or prescriptions of iron may cause an individual to become iron overloaded and this can cause other medical complications such as diabetes.

Sickling Crisis

The major problem with sickle red blood cells is their shape, rigidity and inability to transport oxygen efficiently. They are unable to manoeuvre through small venous capillaries and are likely to cause obstruction in blood flow this is called a vaso-occlusion which can cause a debilitating pain known commonly as a sickle cell crisis pain, this is an episode which range from a mild to moderate or severe excruciating pain. The majority of mild to moderate pain episodes abate spontaneously with bed rest, intake of extra fluids and analgesia and patients manage these at home using pain medications. In some cases there is increasing and excruciating pain which require medical intervention and hospitalization. Untreated complications can cause long term handicap and can prove fatal (Serjeant & Serjeant 2001).

Diagram 4 – Vaso-occlusion

A number of factors may precipitate a sickle cell crisis, these include:

  • Hypoxia
  • Acidosis
  • Dehydration
  • Infection
  • Extreme Fatigue
  • Trauma
  • Temperature Changes (sudden)
  • Stress / Anxiety
  • Increase physical / physiological demand (Pregnancy, physical exercise)

Although these may precipitate a sickling crisis many occur with no known specific cause or identifiable precipitating factor.

There are a number of short and long term complications associated with sickle cell disease and although many of these can be minimised with good self and medical management and activities to prevent and treat complications however long term and chronic damage to tissues and body organs is often inevitable and these shorten the life span of those with sickle cell disease (diagram 5).

Diagram 5 - Clinical Implications and Complications of Sickle Cell Disease


In describing the nature of sickle cell disease Jones stated:

Life threatening infections that were once the leading cause of death for children with the disorder have been reduced by 85%. One often cited study found that 50% of patients survived beyond their 50th decade…Patients who experience three or more painful events or episodes of the acute chest syndrome per year are at greatest risk for death before the age of 40…Chronic haemolytic anaemia and vaso-occlusion that cause ischaemia, tissue injury and end stage organ damage are hall marks of the disease in adults…if you are not looking for the signs, you’re not going to see them until the damage is already done. The lungs, liver and kidneys are especially vulnerable…Evaluating for end stage organ damage every 3 to 6 months, depending on the severity of the disease is critical. By closely monitoring patients, a physician can identify early sings of organ damage and take steps to treat it before more serious complications develop…A child born today with sickle cell disease can expect to live well into adulthood; you couldn’t say that 20 years ago. Jones 1998:1055-6


The occurrence of complications can sometimes be avoided but this depends on how well the individual and their family learn about the condition and their ability to master its day-to-day management, for example, by learning to avoid precipitating factors and seeking prompt medical care when required, adhering to prescribed medical care such as taking penicillin twice daily especially during childhood. Another important aspect for improving survival rate is the ability and competence of health care providers to assess, accurately diagnose and treat symptoms and complications when the client presents at the GP surgery, Accident & Emergency department, day care unit or whilst an in-patient in hospital.

Because a few of these patients are frequent ‘fliers’ and are admitted as in-patients on a regular basis health carers may become complacent and fail to recognise the potentially fatal complications of sickle cell disease (NCEPOD 2008). This can and often leads to sudden unexpected death especially among young people and adults. A patient that appears to be making a recovery may be relegated to the status of self-caring, nurses then assume that they no longer require nursing care or maintenance of observations, such patients may suddenly deteriorate and develop unexpected complications which can prove fatal, much to the astonishment of health carers, maintaining vigilance is the key message for the health care professionals looking after this patient group.

Focus on Children

The commonest cause of illness and hospitalisation in children is infection precipitated crisis and the subsequent bodily response to this, which may include, fever, dehydration, loss of appetite, swelling and pain in the affected part, restlessness, anxiety and lassitude. Less common causes, which can be fatal, are acute splenic sequestration, stroke and aplasia of the bone marrow (aplastic crisis). Aplastic crisis is often due to a viral infection caused by the parvovirus. In the case of a stroke the parents or nurse may be the first to observe a child’s reluctance or inability to use a limb, or holding a limb awkwardly, the rate of stroke in children with sickle cell disease is reported to be approximately 8 - 10% (Ohene-Frempong et al 1998).

Historically the highest death rate in sickle cell disease occurs in children under the age of five and splenic sequestration is one of the major causes of death. Parents need to be educated about how and why it is important to observe their child daily. They must be taught how to palpate their child’s spleen to note any increase in the size of the spleen. An enlargement in the spleen from its usual size is often the first signs of splenic sequestration. They must also observe the palm of the hands, lips and conjunctiva of the eyes for increasing pallor. This general observation must be incorporated as part of the routine daily care of the child. This can be done during bath time so as not to focus the child’s attention on their illness. Daily palpation of the spleen enables parents to have some control in managing their child’s illness and this practice can actually save their child’s life (Serjeant & Serjeant 2001).

It is recommended that children with sickle cell disease have the full course of childhood immunisations; twice daily low dose penicillin is also recommended, folic acid may or may not be recommended, other specialist medication and immunisations are also advised, for more information see Management of People with Sickle Cell Disease.

As part of routine care it is also recommended that children have Transcranial Doppler (TCD) scanning of the brain from the age of three years and every year thereafter; this is in order to identify narrowing of blood vessels and areas of small cerebral infarctions which are signs of Trans Ischaemic Attacks [TIA]) that may be missed because they have not resulted in an obviously debilitating stroke but in time is likely to cause a stroke. TCDs are done routinely in order to identify children who will benefit from having long term blood transfusion in an attempt to prevent the occurrence of a stroke and a consequent serious handicap (UK Forum 2006).

Focus on Adults

In adults the commonest cause of hospital admission is acute vaso-occlusive sickle cell crisis and the most common cause of death is sickle lung often precipitated by an acute chest infection.

Chest infections may not be apparent radiologically until the condition worsens. Laboured or rapid respiration may be the only indication that is observed by a vigilant family member or nurse. This observation may be the only warning sign, which determines whether the patient receives the urgent medical attention required to prevent a fatality. It is always important for family members and carers to observe for mood changes, unresponsiveness or behaviour that appears unusual and take immediate action as this may indicate poor oxygenation of the brain increasing hypoxia or a stroke. For example, a patient who is normally compliant and co-operative may become unresponsive because of lack of oxygen to the brain.

Leg Ulcers

Leg ulceration is one of the less well understood complications of SCD. It affects a proportion of older children and adults with sickle cell disease especially in the Caribbean and in tropical areas of the world. Leg ulcers are much less common in the UK and the USA but it does occur, especially in patients with less severe forms of sickle cell disease such as Hb SC (Koshy et al. 1989). It accounts for a great deal of pain, absence from school and work and reduced physical activity.

Leg ulcers are probably caused when minor cuts and abrasions fail to heal properly because of poor circulation to the lower limbs. Treatment consists of careful cleaning and dressing over a period of weeks or even months, but there remains a high risk of recurrence (Serjeant & Serjeant 2001, Steinberg et al 2001). Skin grafting may be required at a later stage. Ulcers are one of the few visible and unsightly complications of sickle cell disease, increasing the potential for stigmatization in those affected and leading to embarrassment and inhibition about dress and social activities especially because it is seen most commonly among teenagers and young adults; this being a vulnerable developmental phase of life.


Priapism is a persistent and abnormal erection of the penis accompanied by pain, tenderness and swelling. It may or may not be associated with sexual arousal, but unlike a normal sexual erection priapism is not relieved by sexual activity. Sickling causes priapism by occluding the circulatory spaces and small blood vessels of the penis and obstructing the drainage of blood from the corpora cavernosa (Steinberg et al 2001, Serjeant & Serjeant 2001, Akinyanju & Olujohungbe 2006). Episodes can last for hours, days or even weeks and can be among the most frightening and disturbing complications of sickle cell disease. Prolonged episodes can lead to partial, or complete, impotence. In extreme causes, exchange blood transfusion and even surgery may be needed to drain blood from the penis to relieve engorgement and pain. Early presentation and therapeutic intervention yield a successful outcome.

Fertility and childbirth

Women and to a lesser extent, men with sickle cell disease are potentially vulnerable to complications which may precipitate infertility and in women who are fertile complications are increased during pregnancy and childbirth (Howard et al 1993, Eboh, van Den Akker 1994, Adams 1996). In males, lower semen volume, sperm count, and sperm motility have been observed (Davis 1988), which may relate to sickling in the testes.

There is no hard evidence that female fertility is affected by sickle cell disease, however Tuck (1985) suggest a slight risk but as medical care of these patients have been improving in the last four decades the data observed in 1985 is now improved Tuck et al (1998). Pregnancy can pose a greater health challenge and the pregnant woman with sickle cell disease need specialist obstetric and haematology care Oni et al (2002). See Midwives focus on Sickle Cell.


Choices about contraception methods may be more difficult for women with sickle cell disease because the intrauterine contraceptive device may result in an increased susceptibility to heavy painful periods and the contraceptive pill can be unpredictable in its effect in this client group. Several studies have demonstrated that oestrogen has a beneficial effect on the red cell membrane, giving females of reproductive age a marginal advantage over males (Platt et al 1991). Hence the use of inject able contraceptive preparations such as Depo-Provera is popular among women of reproductive age because it is reported to reduce the occurrence of vaso occlusive crisis whilst offering reliable contraception.

Some women have reported an increase in episodes of painful crisis during their menstrual periods.

The teenage years are a time of rapid growth and development, the hormonal changes of pubertal development may contribute to increasing episodes of crisis and pain.

Management of people with sickle cell disease

For general care and management of people with sickle cell disease see Management of People with Sickle Cell Disease.

Long term effect of sickle cell disease

The hormonal changes occurring during puberty and early adulthood can pose a physical challenge for those with sickle cell disease. The long-term effects of sickle cell disease often begin to emerge during the teenage years and this may be a time of increased episodes of sickle cell crisis, especially in young men. This evidently can have a major impact on education, career, future employment prospects, and social relationships.

With improvements in health and social status especially access to health care the life span of those with sickle cell disease has improved tremendously and many are living into their fifth and sixth decade, especially in the UK where access to a National Health Service, which is free at point of access, allows people with sickle cell disease to get access to appropriate and prompt medical care.


Contact the local specialist Sickle Cell & Thalassaemia centre. Find out if there is an established patient / parent support group. Arrange to attend one of their meetings to identify some of the issues affecting the clients in their community OR visit one of the voluntary organisations to arrange to meet some of their members and perhaps attend a local meeting.

Request an opportunity to talk to a parent of a child or an adult with sickle cell disease or Thalassaemia major, find out, for example:

  • What it is like to live with the condition.
  • What impact the condition has on the life of each family member.
  • Experience of hospitalisation during an acute illness.
  • As a parent how has their child’s illness affected their social circumstance, e.g. relationships, employment, social status?

Record your findings in a reflective diary. This will be useful for meeting professional development requirements.

Respect the patients / family’s right to privacy and confidentially and only do this exercise where there is an opportunity and consent, remember to anonymize any written report.

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